Compositions and methods for selective expansion of immune cells

Abstract

Compositions and methods for the selective activation and / or proliferation of immune cells. The methods involve engineering immune cells (e.g., through base editing) to express an interleukin 2 receptor, beta (IL2Rβ) polypeptide variant capable of being selectively bound by a bispecific antibody containing an antigen-binding domain capable of selectively binding the IL2Rβ polypeptide and an antigen-binding domain capable of specifically binding a wild-type IL2Rγ polypeptide. The methods further involve contacting the engineered immune cells with the bispecific antibody. Base editor systems for use in preparing the engineered immune cells as well as bispecific antibodies and VHH domains capable of selectively binding the IL2Rβ polypeptide and specifically binding a wild-type IL2Rγ are also provided.

Description

[0001] ATTORNEY DOCKET NO. 180802-049202 / PCT

[0002] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0003] COMPOSITIONS AND METHODS FOR SELECTIVE EXPANSION OF IMMUNE CELLS

[0004] CROSS REFERENCE TO RELATED APPLICATIONS

[0005] The present application claims priority to U. S. Provisional Application No. 63 / 745,509 filed January 15, 2025, the entire contents of which are hereby incorporated by reference.

[0006] SEQUENCE LISTING

[0007] This application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. The Sequence Listing XML file, created on January 13, 2026, is named 180802-049202PCT_SL.xml and is 1,334,645 bytes in size.

[0008] BACKGROUND

[0009] Cellular therapy is a form of immunotherapy that uses immune cells, such as T cells, as a treatment for a disease or disorder (e.g., a cancer). In cellular therapies, immune cells are typically isolated from a donor (e.g., a patient to be treated), expanded and, in some cases, engineered to enhance their abilities to treat the disease or disorder (e.g., eliminate cancer). One kind of cellular therapy referred to as “tumor infiltrating lymphocyte (TIL) therapy” may be used to treat a tumor in a subject. TIL therapy involves expanding and / or engineering lymphocytes penetrating within a tumor (i.e., TILs) of a subject to enhance their abilities to eliminate cancer cells in the subject. Typically, TIL therapy involves collecting TILs from a tumor in a subject, expanding the TILs in vitro, and subsequently administered the cells back to the subject. This approach to treating cancer in a subject presents a number of challenges, such as the requirement for tumor resection, ex vivo cell manufacturing, lymphodepletion, and hospitalization.

[0010] Accordingly, there is an ongoing need for improved methods for TIL therapies.

[0011] SUMMARY

[0012] As described below, the present disclosure features compositions and methods for the selective activation and / or proliferation of immune cells. In various aspects, the methods involve modifying a surface protein (e.g., an IL receptor, G protein-coupled receptor (GPCRs), ion channel receptor, enzyme-linked receptors, IL-2, or any other protein displayed on the surface of a cell) on a cell (e.g., an immune cell, a t-cell, Treg cell, an NK cell, a macrophage, CAR-T, CAR-Macrophage, CAR-NK, or any other cell type that may or may not be an immune cell) so that the cell can be selectively targeted by an agent (e.g., an antibody, small molecule, peptide)ATTORNEY DOCKET NO. 180802-049202 / PCT

[0013] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0014] either in vivo or ex vivo. In some aspects, methods involve engineering immune cells (e.g., through base editing) to express an interleukin 2 receptor, beta (IL2RP) polypeptide variant (e.g., a variant containing an amino acid alteration listed in Table 1 or an epitope tag, such as a BC2 tag) capable of being selectively bound by a bispecific antibody containing an antigen-binding domain capable of selectively binding the IL2RP polypeptide and an antigen-binding domain capable of specifically binding a wild-type IL2Ry polypeptide. The methods further involve contacting the engineered immune cells with the bispecific antibody. The present disclosure also provides base editor systems for use in preparing the engineered immune cells. The present disclosure further provides bispecific antibodies and VHH domains capable of selectively binding the IL2RP polypeptide and specifically binding a wild-type IL2Ry.

[0015] In one aspect, the disclosure provides a method for the selective activation and / or expansion of an immune effector cell. The method involves contacting an immune effector cell engineered to express an IL2RP polypeptide variant containing an amino acid alteration selected from one or more of R107G, W48R, Q50R, Q60R, H62R, W64R, D66G, R67G, D102G, I103V, W116R, N129S, and F217S or containing an epitope tag with a bispecific antibody, thereby selectively activating and / or expanding the immune effector cell. The bispecific antibody contains an antigen binding domain capable of selectively binding to the IL2RP polypeptide variant and an antigen binding domain capable of specifically binding to an IL2Ry polypeptide expressed by the cell.

[0016] In another aspect, the disclosure provides a method for treating a neoplasia in a subject in need thereof. The method involves selectively activating and / or expanding an immune effector cell in the subject according to the method of any aspect of the disclosure, or embodiments thereof.

[0017] In another aspect, the disclosure provides a base editor system. The base editor system contains a base editor containing an adenosine deaminase domain and a nucleic acid programmable DNA binding (napDNAbp) domain, and a guide RNA, or one or more polynucleotides encoding the base editor system or a component thereof. The guide RNA directs the base editor to effect a nucleotide alteration in an IL2RP polynucleotide to yield an IL2RP polynucleotide encoding an IL2RP polypeptide variant containing an amino acid alteration selected from one or more of W48R, Q50R, Q60R, H62R, W64R, D66G, R67G, D102G, I103V, R107G, W116R, N129S, and F217S.

[0018] In another aspect, the disclosure provides a method for preparing an immune effector cell expressing an IL2RP polynucleotide encoding an IL2RP polypeptide variant containing an amino acid alteration selected from one or more of W48R, Q50R, Q60R, H62R, W64R, D66G, R67G,ATTORNEY DOCKET NO. 180802-049202 / PCT

[0019] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0020] D102G, I103V, R107G, W116R, N129S, and F217S. The method involves contacting the cell with the base editor system of any aspect of the disclosure, or embodiments thereof.

[0021] In another aspect, the disclosure provides an immune effector cell prepared according to the method of any aspect of the disclosure, or embodiments thereof.

[0022] In another aspect, the disclosure provides a polynucleotide or set of polynucleotides encoding the base editor system of any aspect of the disclosure, or embodiments thereof.

[0023] In another aspect, the disclosure provides a vector or set of vectors containing the polynucleotide or set of polynucleotides of any aspect of the disclosure, or embodiments thereof.

[0024] In another aspect, the disclosure provides a lipid nanoparticle containing the base editor system of any aspect of the disclosure, or embodiments thereof.

[0025] In another aspect, the disclosure provides a method for treating a neoplasia in a subject in need thereof. The method involves intratumorally administering to the subject the lipid nanoparticle of any aspect of the disclosure, or embodiments thereof, or a lentiviral vector encoding an IL2RP polypeptide variant containing an epitope tag, and subsequently administering to the subject the bispecific antibody defined in any aspect of the disclosure, or embodiments thereof.

[0026] In another aspect, the disclosure provides a method for treating a neoplasia in a subject in need thereof. The method involves administering to the subject an immune effector cell engineered to express an IL2RP polypeptide variant containing an epitope tag or the amino acid alteration R107G and subsequently administering to the subject the bispecific antibody defined in any aspect of the disclosure, or embodiments thereof.

[0027] In another aspect, the disclosure provides a bispecific antibody containing 1) an antigen binding domain capable of selectively binding to an IL2RP polypeptide variant containing an R107G amino acid alteration or to an epitope tag containing the amino acid sequence PDRKAAVSHWQQ (SEQ ID NO: 690) and 2) an antigen binding domain capable of specifically binding to a wild-type IL2Ry polypeptide. The antigen binding domains are VHH domains.

[0028] In another aspect, the disclosure provides a VHH domain, or an antigen-binding fragment thereof, capable of selectively binding to an IL2RP polypeptide variant containing an R107G amino acid alteration. The VHH domain contains cluster of differentiation (CDR) 1, CDR2, and CDR3 amino acid sequences of an IL-2RP VHH domain amino acid sequence listed in Table A corresponding to CDR1, CDR2, or CDR3 sequences listed in Table B and calculated using a numbering method selected from Chothia, AbM, Kabat, Contact, and IMGT.

[0029] In another aspect, the disclosure provides a VHH domain, or an antigen-binding fragment thereof, capable of selectively binding to a wild-type IL2Ry polypeptide. The VHH domainATTORNEY DOCKET NO. 180802-049202 / PCT

[0030] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0031] contains cluster of differentiation (CDR) 1, CDR2, and CDR3 amino acid sequences of an IL-2Ry VHH domain amino acid sequence listed in Table A corresponding to CDR1, CDR2, or CDR3 sequences listed in Table C and calculated using a numbering method selected from Chothia, AbM, Kabat, Contact, and IMGT.

[0032] In another aspect, the disclosure provides a polynucleotide encoding the VHH domain of any aspect of the disclosure, or embodiments thereof.

[0033] In another aspect, the disclosure provides a VHH antibody containing an amino acid sequence listed in Table A.

[0034] In another aspect, the disclosure provides a polynucleotide encoding the VHH antibody of any aspect of the disclosure, or embodiments thereof.

[0035] In another aspect, the disclosure provides a bispecific antibody containing an amino acid sequence listed in Table E.

[0036] In another aspect, the disclosure provides a polynucleotide encoding the bispecific antibody of any aspect of the disclosure, or embodiments thereof.

[0037] In another aspect, the disclosure provides a kit containing the base editor system, the immune effector cell, the polynucleotide or set of polynucleotides, the vector or set of vectors, the lipid nanoparticle, the bispecific antibody, the VHH domain, or the VHH antibody of any aspect of the disclosure, or embodiments thereof, and a container.

[0038] In another aspect, the disclosure provides a composition containing a polynucleotide encoding a base editor. The base editor contains an adenosine deaminase domain selected from one or more of TadA*8e, TadA*8.20, TadA*9.1, or TadA*9.52 and an SpCas9 nickase domain containing a D10A amino acid alteration, and a guide RNA containing a spacer containing a spacer sequence listed in Table 1.

[0039] In another aspect, the disclosure provides a lipid nanoparticle containing mRNA encoding a base editor. The base editor contains an adenosine deaminase domain selected from one or more of TadA*8e, TadA*8.20, TadA*9.1, or TadA*9.52 and an SpCas9 nickase domain containing a D10A amino acid alteration, and a guide RNA containing a spacer containing a spacer sequence listed in Table 1.

[0040] In another aspect, the disclosure provides a method for treating a neoplasia in a subject in need thereof. The method involves intratumorally administering to the subject a lipid nanoparticle containing mRNA encoding a base editor. The base editor contains an adenosine deaminase domain selected from one or more of TadA*8e, TadA*8.20, TadA*9.1, or TadA*9.52 and an SpCas9 nickase domain containing a D10A amino acid alteration, and a guide RNA containing a spacer containing a spacer sequence listed in Table 1.ATTORNEY DOCKET NO. 180802-049202 / PCT

[0041] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0042] In another aspect, the disclosure provides a method for the selective activation and / or expansion of an immune effector cell. The method involves contacting an immune effector cell with a polynucleotide encoding an IL2RP polypeptide variant containing an epitope tag or containing an amino acid alteration selected from one or more of R107G, W48R, Q50R, Q60R, H62R, W64R, D66G, R67G, D102G, I103V, W116R, N129S, and F217S. The method further involves contacting the cell with a bispecific antibody containing an antigen binding domain that selectively binds the IL2RP polypeptide variant and an antigen binding domain capable of specifically binding to a an IL2Ry polypeptide expressed by the cell, thereby selectively activating and / or expanding the immune effector cell.

[0043] In another aspect, the disclosure provides a method for the selective activation and / or expansion of an immune effector cell. The method involves contacting an immune effector cell with a base editor system containing a base editor containing an adenosine deaminase domain and a nucleic acid programmable DNA binding (napDNAbp) domain, and a guide RNA, or one or more polynucleotides encoding the base editor system or a component thereof. The guide RNA directs the base editor to effect an edit in a polynucleotide encoding an IL2RP polypeptide to generate an IL2RP polypeptide encoding an IL2RP polypeptide variant. The variant contains an amino acid alteration selected from one or more of R107G, W48R, Q50R, Q60R, H62R, W64R, D66G, R67G, D102G, I103V, W116R, N129S, and F217S. The method further involves contacting the cell with a bispecific antibody containing an antigen binding domain that selectively binds the IL2RP polypeptide variant and an antigen binding domain capable of specifically binding to a an IL2Ry polypeptide expressed by the cell, thereby selectively activating and / or expanding the immune effector cell.

[0044] In another aspect, the present disclosure features a method for the selective activation and / or expansion of an immune effector cell. The method involves contacting an immune effector cell engineered to express an IL2RP polypeptide variant containing an R107G amino acid alteration with a bispecific antibody containing an antigen binding domain capable of selectively binding to the IL2RP polypeptide variant and an antigen binding domain capable of specifically binding to an IL2Ry polypeptide expressed by the cell. The bispecific antibody contains an amino acid sequence with at least 90% identity to the following sequence:

[0045] QVQLVESGGGLVQAGGSLRLSCAASRRTSSYYVMGWFRQAPGKEREFVAGITWGVGDTYYKDGVKGRFTISRDNAKNTVYLQMSSLKPEDTAVYYCATADVWPSALSYDYTYWGQGTQVTVSSGGGGS QVQLVESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSVKGRFTISRDNAKNTVSLQMNSLKPEDTAVYYCAALRRGVVQRRGGPYEVDTWGQGTQVTVSSPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 1062). The antigen binding domain capable of selectively binding to the IL2Rβ polypeptide variant contains a cluster of differentiation 1 (CDR) 1 containing the amino acid sequence TQTFTSY (SEQ ID NO: 1063), a CDR2 containing the amino acid sequence NWSGS (SEQ ID NO: 1064), and a CDR3 containing the amino acid sequence LRRGVVQRRGGPYEVDT (SEQ ID NO: 1065). The antigen binding domain capable of selectively binding to the IL2Rγ polypeptide contains a CDR1 containing the amino acid sequence RRTSSYY (SEQ ID NO: 1066), a CDR2 containing the amino acid sequence TWGVGD (SEQ ID NO: 1067), and a CDR3 containing the amino acid sequence ADVWPSALSYDYTY (SEQ ID NO: 1068). The method results in selectively activating and / or expanding the immune effector cell.

[0046] In another aspect, the present disclosure features a method for treating a neoplasia in a subject in need thereof. The method involves administering to a subject containing an immune effector cell engineered to express an IL2RP polypeptide variant containing the amino acid alteration R107G a bispecific antibody. The bispecific antibody contains an antigen binding domain capable of selectively binding to the IL2RP polypeptide variant and an antigen binding domain capable of specifically binding to an IL2RY polypeptide expressed by the cell. The bispecific antibody contains an amino acid sequence with at least 90% identity to the following sequence:

[0047] Q VQL VE S GGGL VQAGGS LRLS CAAS RRTS S Y YVMGWFRQAPGKERE F VAG I TWGVGDT Y YKDGV KGRFTISRDNAKNTVYLQMSSLKPEDTAVYYCATADVWPSALSYDYTYWGQGTQVTVSSGGGGS QVQLVESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSV KGRFTISRDNAKNTVSLQMNSLKPEDTAVYYCAALRRGVVQRRGGPYEVDTWGQGTQVTVSSPK SCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP QVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 1062). The antigen binding domain capable of selectively binding to the IL2RP polypeptide variant contains a cluster of differentiation 1 (CDR) 1 containing the amino acid sequence TQTFTSY (SEQ ID NO: 1063), a CDR2 containing the amino acid sequence NWSGS (SEQ ID NO: 1064), and a CDR3 containing the amino acid sequence LRRGVVQRRGGPYEVDT (SEQ ID NO: 1065). The antigen binding domain capable of selectively binding to the IL2Ry polypeptide contains a CDR1 containing the amino acid sequence RRTSSYY (SEQ ID NO: 1066), a CDR2 containing theATTORNEY DOCKET NO. 180802-049202 / PCT

[0048] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0049] amino acid sequence TWGVGD (SEQ ID NO: 1067), and a CDR3 containing the amino acid sequence ADVWPSALSYDYTY (SEQ ID NO: 1068).

[0050] In any aspect of the disclosure, or embodiments thereof, the immune effector cell is an NK cell or a T cell. In any aspect of the disclosure, or embodiments thereof, the immune effector cell is a tumor infiltrating lymphocyte.

[0051] In any aspect of the disclosure, or embodiments thereof, the immune effector cell expresses the IL2RP polypeptide variant containing the epitope tag. In any aspect of the disclosure, or embodiments thereof, the immune effector cell expresses the IL2RP polypeptide variant containing the amino acid alteration selected from one or more of R107G, W48R, Q50R, Q60R, H62R, W64R, D66G, R67G, D102G, I103V, W116R, N129S, and F217S.

[0052] In any aspect of the disclosure, or embodiments thereof, the method further involves preparing the engineered immune effector cell by contacting an immune effector cell with a polynucleotide expressing the IL2RP polypeptide variant. In any aspect of the disclosure, or embodiments thereof, the polynucleotide is present in a lentiviral vector. In any aspect of the disclosure, or embodiments thereof, preparing the engineered immune effector cell involves incorporating the polynucleotide into the genome of the immune effector cell.

[0053] In any aspect of the disclosure, or embodiments thereof, the epitope tag contains the amino acid sequence PDRKAAVSHWQQ (SEQ ID NO: 690).

[0054] In any aspect of the disclosure, or embodiments thereof, the cell is a mammalian cell. In any aspect of the disclosure, or embodiments thereof, the method further involves preparing the engineered immune effector cells by contacting an immune effector cell with a base editor system containing a base editor containing an adenosine deaminase domain and a nucleic acid programmable DNA binding (napDNAbp) domain, and a guide RNA, or one or more polynucleotides encoding the base editor system or a component thereof, where the guide RNA directs the base editor to effect a nucleotide alteration in an IL2RP polynucleotide to yield an IL2RP polynucleotide encoding the IL2RP polypeptide variant. In any aspect of the disclosure, or embodiments thereof, the adenosine deaminase domain is a TadA*8e, TadA*8.20, TadA*9.1, or TadA*9.52. In any aspect of the disclosure, or embodiments thereof, the guide RNA contains a spacer containing at least 10 contiguous nucleotides of a spacer sequence listed in Table 1. In any aspect of the disclosure, or embodiments thereof, the spacer contains the nucleic acid sequence CCUGAGGGUGCUGUGCCGUG (SEQ ID NO: 1046; sgRNA123). In any aspect of the disclosure, or embodiments thereof, the napDNAbp domain is an SpCas9 nickase. In any aspect of the disclosure, or embodiments thereof, the SpCas9 nickase contains the alteration D10A referenced to SEQ ID NO: 197. In any aspect of the disclosure, or embodimentsATTORNEY DOCKET NO. 180802-049202 / PCT

[0055] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0056] thereof, the base editor is a fusion protein containing a peptide linker connecting the adenosine deaminase domain to the napDNAbp domain. In any aspect of the disclosure, or embodiments thereof, the peptide linker contains a sequence selected from one or more of: EGGSEEEEESGS (SEQ ID NO: 675), SKSQQFVTYE (SEQ ID NO: 677), and SGGSSGGSSGSETPGTSESATPESSGGSSGGS (SEQ ID NO: 357). In any aspect of the disclosure, or embodiments thereof, the base editor contains a nuclear localization signal. In any aspect of the disclosure, or embodiments thereof, the base editor contains an amino acid sequence with at least 85% identity to a sequence selected from the amino acid sequences listed in Table 2.

[0057] In any aspect of the disclosure, or embodiments thereof, contacting the immune effector cell with the base editor system involves contacting the immune effector cell with a lipid nanoparticle containing mRNA encoding the base editor and the guide RNA. In any aspect of the disclosure, or embodiments thereof, the lipid nanoparticle contains or further contains the ionizable lipid IZ4.

[0058] In any aspect of the disclosure, or embodiments thereof, the antigen binding domains are VHH domains. In any aspect of the disclosure, or embodiments thereof, the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant contains cluster of differentiation (CDR) 1, CDR2, and CDR3 amino acid sequences of an IL-2RP VHH domain amino acid sequence listed in Table A corresponding to CDR1, CDR2, or CDR3 sequences listed in Table B and calculated using a numbering method selected from Chothia, AbM, Kabat, Contact, and IMGT. In any aspect of the disclosure, or embodiments thereof, the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant contains an amino acid sequence with at least 85% identity to an IL-2RP VHH domain amino acid sequence listed in Table A. In any aspect of the disclosure, or embodiments thereof, the antigen binding domain capable of selectively binding to the IL2Ry polypeptide contains cluster of differentiation (CDR) 1, CDR2, and CDR3 amino acid sequences of an IL-2Ry VHH domain amino acid sequence listed in Table A corresponding to CDR1, CDR2, or CDR3 sequences listed in Table C and calculated using a numbering method selected from Chothia, AbM, Kabat, Contact, and IMGT. In any aspect of the disclosure, or embodiments thereof, the antigen binding domain capable of selectively binding to the IL2Rγ polypeptide contains an amino acid sequence with at least 85% identity to an IL-2Rγ VHH domain amino acid sequence listed in Table A. In any aspect of the disclosure, or embodiments thereof, the bispecific antibody contains from N-terminus to C-terminus: A) [A]-[B]-[Fc]; or B) [B]-[ A]-[Fc]; where i) A contains the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant; ii) B contains the antigenATTORNEY DOCKET NO. 180802-049202 / PCT

[0059] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0060] binding domain capable of specifically binding to the IL2Ry polypeptide; and iii) Fc contains a human Fc domain or an hIgG4 Fc domain. In any aspect of the disclosure or embodiments thereof, the bispecific antibody has a structure described in FIG. 10 and / or corresponding to a sequence listed in Table E. In any aspect of the disclosure, or embodiments thereof, the bispecific antibody contains an amino acid sequence with at least 85% identity to a sequence listed in Table E. In any aspect of the disclosure, or embodiments thereof, the bispecific antibody contains an amino acid sequence with at least 85% identity to an amino acid sequence selected from one or more of:

[0061] QVQLVESGGGLVQAGGSLRLSCAASRRTSSYYVMGWFRQAPGKEREFVAGITWGVGDTYYKDGVKGRFTISRDNAKNTVYLQMSSLKPEDTAVYYCATADVWPSALSYDYTYWGQGTQVTVSSGGGGS QVQLVESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSVKGRFTISRDNAKNTVSLQMNSLKPEDTAVYYCAALRRGVVQRRGGPYEVDTWGQGTQVTVSSPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 1062; ABTx698);

[0062] QVQLVESGGGLVQAGGSLRLSCAASGSLGRTTFMGWYRQAPGNEREFVAQFGSGGSTNYVDTVK GRFTISSDNAKNRVYLQMNSLKPEDTAVYYCYALTYDSGDFRNYWGQGTQVTVSSGGGGSQVQL VESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSVKGRF T I SRDNAKNTVS LQMNS LKPEDTAVYYCAALRRGVVQRRGGP YE VDTWGQGTQVTVS S PKS CDK THTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT LPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO: 988; ABTx619);

[0063] QVQLVESGGGLVQAGGSLRLSCAASGSLGRTTFMGWYRQAPGNEREFVAQFGSGGSTNYVDTVK GRFTISSDNAKNRVYLQMNSLKPEDTAVYYCYALTYDSGDFRNYWGQGTQVTVSSGGGGSQLQL VESGGGLVQPGGSLRLTCAASGFTFSRYPMSWARQAPGKGLEWVSTLSQDGGTTAYEPSVKGRF TISRDNAKNTLYLQMNNLEPEDTAVYFCAKGPPPFGPETTWGQGTQVTVSSPKSCDKTHTCPPC PAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO: 999; ABTx630); and QVQLVESGGGLVQAGGSLRLSCAASGSLGRTTFMGWYRQAPGNEREFVAQFGSGGSTNYVDTVK GRFTISSDNAKNRVYLQMNSLKPEDTAVYYCYALTYDSGDFRNYWGQGTQVTVSSGGGGSQVQLATTORNEY DOCKET NO. 180802-049202 / PCT

[0064] ELECTRONIC DEPOSIT DATE: January 14, 2026 VESGGGLVQAGGSLRLSCAASGIIFGINAWAWAWYRQAPGKQRELVAVITSGGITNYTDFVKGR FTISRDNALKAVYLQMNSPKPEDTGVYFCNIRAYTGHNGFWGQGIQVTVSSPKSCDKTHTCPPC PAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 1000; ABTx631).

[0065] In any aspect of the disclosure, or embodiments thereof, the immune effector cell is in vivo or in vitro.

[0066] In any aspect of the disclosure, or embodiments thereof, the method further involves engineering the immune effector cell to express a chimeric antigen receptor containing an antigen binding domain capable of binding an antigen associated with a disease or disorder.

[0067] In any aspect of the disclosure, or embodiments thereof, the disease or disorder is a neoplasia.

[0068] In any aspect of the disclosure, or embodiments thereof, the IL2RP polypeptide variant contains the R107G amino acid alteration.

[0069] In any aspect of the disclosure, or embodiments thereof, the method involves intratumorally administering to the subject the lipid nanoparticle defined in any aspect of the disclosure, or embodiments thereof.

[0070] In any aspect of the disclosure, or embodiments thereof, the method further involves engineering the immune effector cell ex vivo to express the IL2RP polypeptide variant and subsequently administering the immune effector cells to the subject.

[0071] In any aspect of the disclosure, or embodiments thereof, the immune effector cell is a tumor infiltrating lymphocyte isolated from a tumor of the subject.

[0072] In any aspect of the disclosure, or embodiments thereof, the lipid nanoparticle contains or further contains mRNA encoding the base editor, and the guide RNA.

[0073] In any aspect of the disclosure, or embodiments thereof, the method further involves engineering the immune effector cell to express a chimeric antigen receptor containing an antigen binding domain capable of binding an antigen associated with the neoplasia.

[0074] In any aspect of the disclosure, or embodiments thereof, the VHH domain contains a VHH domain listed in Table A. In any aspect of the disclosure, or embodiments thereof, the VHH domain contains a VHH domain listed in Table A.

[0075] In any aspect of the disclosure, or embodiments thereof, the polynucleotide encoding the base editor is an mRNA. In any aspect of the disclosure, or embodiments thereof, theATTORNEY DOCKET NO. 180802-049202 / PCT

[0076] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0077] composition is formulated in a lipid nanoparticle (LNP). In any aspect of the disclosure, or embodiments thereof, the LNP contains the ionizable lipid IZ4.

[0078] In any aspect of the disclosure, or embodiments thereof, the spacer sequence is CCUGAGGGUGCUGUGCCGUG (SEQ ID NO: 1046; sgRNA123).

[0079] In any aspect of the disclosure, or embodiments thereof, the method further involves administering to the subject a bispecific antibody after administration of the lipid nanoparticle, where the bispecific antibody contains an amino acid sequence with at least 95% identity to a sequence listed in Table E.

[0080] In any aspect of the disclosure, or embodiments thereof, the method results in a reduction in size of a tumor in the subject that is distinct from the tumor into which the lipid nanoparticle was intratumorally administered.

[0081] In any aspect provided herein, or embodiments thereof, the method is not a process for modifying the germline genetic identity of human beings.

[0082] In any aspect provided herein, or embodiments thereof, the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant contains a CDR1 containing the amino acid sequence TQTFTSY (SEQ ID NO: 1063), a CDR2 containing the amino acid sequence NWSGS (SEQ ID NO: 1064), and a CDR3 containing the amino acid sequence LRRGVVQRRGGPYEVDT (SEQ ID NO: 1065). In any aspect provided herein, or embodiments thereof, the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant contains an amino acid sequence with at least about 90% identity to the following amino acid sequence:

[0083] QVQLVESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSV KGRFT I SRDNAKNTVS LQMNS LKPEDTAVYYCAALRRGVVQRRGGP YE VDTWGQGTQVTVS S

[0084] (SEQ ID NO: 1069). In any aspect provided herein, or embodiments thereof, the antigen binding domain capable of selectively binding to the IL2RY polypeptide contains a CDR1 containing the amino acid sequence RRTSSYY (SEQ ID NO: 1066), a CDR2 containing the amino acid sequence TWGVGD (SEQ ID NO: 1067), and a CDR3 containing the amino acid sequence ADVWPSALSYDYTY (SEQ ID NO: 1068). In any aspect provided herein, or embodiments thereof, the antigen binding domain capable of selectively binding to the IL2Ry polypeptide variant contains an amino acid sequence with at least about 90% identity to the following amino acid sequence:

[0085] Q VQL VE S GGGL VQAGGS LRLS CAAS RRTS S Y YVMGWFRQAPGKERE F VAG I TWGVGDT Y YKDGV KGRFTISRDNAKNTVYLQMSSLKPEDTAVYYCATADVWPSALSYDYTYWGQGTQVTVSS (SEQ ID NO: 1070).ATTORNEY DOCKET NO. 180802-049202 / PCT

[0086] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0087] Definitions

[0088] Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art to which this disclosure belongs. The following references provide one of skill with a general definition of many of the terms used in this disclosure: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). As used herein, the following terms have the meanings ascribed to them below, unless specified otherwise.

[0089] By “adenine” or “ 9Z7-Purin-6-amine” is meant a purine nucleobase with the molecular

[0090]

[0091] formula C5H5N5, having the structure, and corresponding to CAS No. 73-24-5.

[0092] By “adenosine” or “ 4-Amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2(1H)-one” is meant an adenine molecule attached to a NH2

[0093] ribose sugar via a glycosidic bond, having the structure

[0094]

[0095] corresponding to CAS No. 65-46-3. Its molecular formula is C10H13N5O4.

[0096] By “adenosine deaminase” or “adenine deaminase” is meant a polypeptide or fragment thereof capable of catalyzing the hydrolytic deamination of adenine or adenosine. In some embodiments, the deaminase or deaminase domain is an adenosine deaminase catalyzing the hydrolytic deamination of adenosine to inosine or deoxy adenosine to deoxyinosine. In some embodiments, the adenosine deaminase catalyzes the hydrolytic deamination of adenine or adenosine in deoxyribonucleic acid (DNA). The adenosine deaminases (e.g., engineered adenosine deaminases, evolved adenosine deaminases) provided herein may be from anyATTORNEY DOCKET NO. 180802-049202 / PCT

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[0098] organism (e.g., eukaryotic, prokaryotic), including but not limited to algae, bacteria, fungi, plants, invertebrates (e.g., insects), and vertebrates (e.g., amphibians, mammals). In some embodiments, the adenosine deaminase is an adenosine deaminase variant with one or more alterations and is capable of deaminating both adenine and cytosine in a target polynucleotide e.g., DNA, RNA) and may be referred to as a “dual deaminase”. Non-limiting examples of dual deaminases include those described in PCT / US22 / 22050. In some embodiments, the target polynucleotide is single or double stranded. In some embodiments, the adenosine deaminase variant is capable of deaminating both adenine and cytosine in DNA. In some embodiments, the adenosine deaminase variant is capable of deaminating both adenine and cytosine in singlestranded DNA. In some embodiments, the adenosine deaminase variant is capable of deaminating both adenine and cytosine in RNA. In embodiments, the adenosine deaminase variant is selected from those described in PCT / US2020 / 018192, PCT / US2020 / 049975, PCT / US2017 / 045381, PCT / US2021 / 016827, PCT / US2022 / 073781, PCT / US24 / 34189, or PCT / US2020 / 028568, the full contents of which are each incorporated herein by reference in their entireties for all purposes. Further non-limiting examples of adenosine deaminases include those disclosed or referenced in Rufflow, etal., “Design of highly functional genome editors by modeling of the universe of CRISPR-Cas Sequences,” bioRxiv, posted April 22, 2024, doi: 10.1101 / 2024.04.22.590591, the disclosure of which is incorporated herein by reference in its entirety for all purposes, which were designed using artificial intelligence. Further exemplary adenosine deaminase amino acid sequenes include: TadA-8e (SEQ ID NO: 470), Tadl (SEQ ID NO: 471), Tad2 (SEQ ID NO: 472), Tad3 (SEQ ID NO: 473), Tad4 (SEQ ID NO: 474), Tad6 (SEQ ID NO: 475), Tad6-SR (SEQ ID NO: 476), TadA9 (SEQ ID NO: 477), TadA20 (SEQ ID NO: 478), Staphylococcus aureus TadA (SEQ ID NO: 479), Bacillus subtilis TadA (SEQ ID NO: 480), Salmonella typhimurium TadA (SEQ ID NO: 481), Shewanella putrefaciens (SEQ ID NO: 482), Haemophilus influenzae F3031 ’TadA (SEQ ID NO: 483), Caulobacter crescentus TadA (SEQ ID NO: 484), Geobacter sulfurreducens TadA (SEQ ID NO: 485), Streptococcus pyogenes TadA (SEQ ID NO: 486), Aquifex aeolicus TadA (SEQ ID NO: 487), and E. coli TadA deaminase (ecTadA) (SEQ ID NO: 488).

[0099] By “adenosine deaminase activity” is meant catalyzing the deamination of adenine or adenosine to guanine in a polynucleotide.

[0100] By “Adenosine Base Editor (ABE)” is meant a base editor comprising an adenosine deaminase.

[0101] By “Adenosine Base Editor (ABE) polynucleotide” is meant a polynucleotide encoding an ABE.ATTORNEY DOCKET NO. 180802-049202 / PCT

[0102] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0103] By “Adenosine Base Editor 8 (ABE8) polypeptide” or “ABE8” is meant a base editor as defined herein comprising an adenosine deaminase or adenosine deaminase variant comprising one or more of the alterations listed in Table 5B, one of the combinations of alterations listed in Table 5B, or an alteration at one or more of the amino acid positions listed in Table 5B, where such alterations are relative to the following reference sequence:

[0104] MSEVEFSHEYWMRHALTLAKRARDEREVPVGAVLVLNNRVIGEGWNRAIGLHDPTAHAEIMALR QGGLVMQNYRLIDATLYVTFEPCVMCAGAMIHSRIGRVVFGVRNAKTGAAGSLMDVLHYPGMNH RVEITEGILADECAALLCYFFRMPRQVFNAQKKAQSSTD (SEQ ID NO: 1), or a corresponding position in another adenosine deaminase. In embodiments, ABE8 comprises alterations at amino acids 82 and / or 166 of SEQ ID NO: 1. In some embodiments, ABE8 comprises further alterations, as described herein, relative to the reference sequence.

[0105] By “Adenosine Base Editor 8 (ABE8) polynucleotide” is meant a polynucleotide encoding an ABE8 polypeptide.

[0106] “Administering” is referred to herein as providing one or more compositions described herein to a patient or a subject. By way of example and without limitation, composition administration (e.g., injection) can be performed by intravenous (i.v.) injection, sub-cutaneous (s.c.) injection, intradermal (i.d.) injection, intraperitoneal (i.p.) injection, or intramuscular (i.m.) injection. One or more such routes can be employed. Parenteral administration can be, for example, by bolus injection or by gradual perfusion over time. In some embodiments, parenteral administration includes infusing or injecting intravascularly, intravenously, intramuscularly, intraarterially, intrathecally, intratumorally, intradermally, intraperitoneally, transtracheally, subcutaneously, subcuticularly, intraarticularly, subcapsularly, subarachnoidly and intrasternally. Alternatively, or concurrently, administration can be by the oral route. An agent of the disclosure may be administered to a subject intratumorally.

[0107] By “agent” is meant any small molecule chemical compound, antibody, nucleic acid molecule, polypeptide, or functional fragments thereof. In some embodiments, an agent is a lipid nanoparticle. In some cases, an agent may be a base editor system or a component thereof (e.g, a guide RNA molecule, mRNA encoding a base editor, a base editor polynucleotide) a guide RNA). An agent may be a modified cell, such as a cell modified to express a modified IL2RP polypeptide (e.g., an IL2RP (R107G) polypeptide). An further non-limiting example of an agent includes an antibody, functional fragment thereof (e.g., a VHH domain), or bispecific antibody, such as a bispecific antibody provided herein capable of selectively binding to a modified IL2RP polypeptide.ATTORNEY DOCKET NO. 180802-049202 / PCT

[0108] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0109] By “alteration” is meant a change in the level, structure, or activity of an analyte, gene or polypeptide as detected by standard art known methods such as those described herein. As used herein, an alteration includes a change (e.g., increase or reduction) in expression levels. In embodiments, the increase or reduction in expression levels is by 10%, 25%, 40%, 50% or greater. In some embodiments, an alteration includes an insertion, deletion, or substitution of a nucleobase or amino acid (by, e.g., genetic engineering).

[0110] By “ameliorate” is meant reduce, suppress, attenuate, diminish, arrest, or stabilize the development or progression of a disease.

[0111] By “analog” is meant a molecule that is not identical but has analogous functional or structural features. For example, a polypeptide analog retains the biological activity of a corresponding naturally-occurring polypeptide, while having certain biochemical modifications that enhance the analog’s function relative to a naturally occurring polypeptide. Such biochemical modifications could increase the analog’s protease resistance, membrane permeability, or half-life, without altering, for example, ligand binding. An analog may include an unnatural amino acid.

[0112] As used herein, the term “antibody” refers to a polypeptide that specifically binds to, or is immunologically reactive with, a particular antigen, and includes polyclonal, monoclonal, genetically engineered, VHH, and otherwise modified forms of antibodies, including but not limited to chimeric antibodies, humanized antibodies, heteroconjugate antibodies e.g., bi- tri-and quad-specific antibodies, diabodies, triabodies, and tetrabodies), and antigen binding fragments of antibodies, including, for example, Fab’, F(ab’)2, Fab, Fv, rlgG, and scFv fragments. VHH domains are a non-limiting example of antibodies. Unless otherwise indicated, the term “monoclonal antibody” (mAb) is meant to include both intact molecules, as well as antibody fragments (including, for example, Fab and F(ab’)2 fragments) that are capable of specifically binding to a target protein. As used herein, the Fab and F(ab’)2 fragments refer to antibody fragments that lack the Fc fragment of an intact antibody.

[0113] Antibodies (immunoglobulins) may comprise two heavy chains linked together by disulfide bonds, and two light chains, with each light chain being linked to a respective heavy chain by disulfide bonds in a " Y" shaped configuration. Each heavy chain has at one end a variable domain (VH) followed by a number of constant domains (CH). Each light chain has a variable domain (VL) at one end and a constant domain (CL) at its other end. The variable domain of the light chain (VL) is aligned with the variable domain of the heavy chain (VL), and the light chain constant domain (CL) is aligned with the first constant domain of the heavy chain (CHI). The variable domains of each pair of light and heavy chains form the antigen bindingATTORNEY DOCKET NO. 180802-049202 / PCT

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[0115] site. The isotype of the heavy chain (gamma, alpha, delta, epsilon or mu) determines the immunoglobulin class (IgG, IgA, IgD, IgE or IgM, respectively). The light chain is either of two isotypes (kappa (K) or lambda (1)) found in all antibody classes. The terms "antibody" or "antibodies" include intact antibodies, such as polyclonal antibodies or monoclonal antibodies (mAbs), as well as proteolytic portions or fragments thereof, such as the Fab or F(ab')2 fragments, that are capable of specifically binding to a target protein. Antibodies may include chimeric antibodies; recombinant and engineered antibodies, and antigen binding fragments thereof. Exemplary functional antibody fragments comprising whole or essentially whole variable regions of both the light and heavy chains are defined as follows: (i) Fv, defined as a genetically engineered fragment consisting of the variable region of the light chain and the variable region of the heavy chain expressed as two chains; (ii) single-chain Fv (“scFv”), a genetically engineered single-chain molecule including the variable region of the light chain and the variable region of the heavy chain, linked by a suitable polypeptide linker; (iii) Fab, a fragment of an antibody molecule containing a monovalent antigen-binding portion of an antibody molecule, obtained by treating an intact antibody with the enzyme papain to yield the intact light chain and the Fd fragment of the heavy chain, which consists of the variable and CHI, CH2, and / or CH3 domains thereof; (iv) Fab', a fragment of an antibody molecule containing a monovalent antigen-binding portion of an antibody molecule, obtained by treating an intact antibody with the enzyme pepsin, followed by reduction (two Fab' fragments are generated per antibody molecule); and (v) F(ab')2, a fragment of an antibody molecule containing a monovalent antigen-binding portion of an antibody molecule, obtained by treating an intact antibody with the enzyme pepsin (i.e., a dimer of Fab' fragments held together by two disulfide bonds).

[0116] The term “antigen-binding fragment,” as used herein, refers to one or more portions or fragments of an antibody that retain the ability to specifically bind to a target antigen. The antigen-binding function of an antibody can be performed by fragments of a full-length antibody. The antibody fragments can be a Fab, F(ab')2, scFv, SMIP, diabody, a triabody, an affibody, a VHH domain, an aptamer, or a domain antibody. Examples of binding fragments encompassed by the term "antigen-binding fragment" of an antibody include, but are not limited to: (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL, and CH1 domains; (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CH1 domains; (iv) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (v) a dAb including VH and VL domains; (vi) a dAb fragment (Ward et al., Nature 341:544-546, 1989), which consists of aATTORNEY DOCKET NO. 180802-049202 / PCT

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[0118] VH domain; (vii) a dAb which consists of a VH or a VL domain; (viii) an isolated complementarity determining region (CDR); and (ix) a combination of two or more isolated CDRs which may optionally be joined by a synthetic linker. Furthermore, although the two domains of the Fv fragment, VL and VH, are coded for by separate genes, they can be joined, using recombinant methods, by a linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single-chain Fv (scFv); see, e.g., Bird et al., Science 242:423-426, 1988, and Huston et al., Proc. Natl. Acad. Sci. USA 85:5879-5883, 1988). Such antibody fragments can be obtained using conventional techniques known to those of skill in the art, and the fragments can be screened for utility in the same manner as intact antibodies. Antigen-binding fragments can be produced by recombinant DNA techniques, enzymatic or chemical cleavage of intact immunoglobulins, or, in some cases, by chemical peptide synthesis procedures known in the art. In some embodiments, antigenbinding fragments (e.g.,.g., Fab', F(ab')2, Fab, scFab, Fv, rlgG, and scFv fragments) of an antibody, which are joined by a synthetic linker, are encompassed herein.

[0119] By “base editor (BE),” or “nucleobase editor polypeptide (NBE)” is meant an agent that binds a polynucleotide and has nucleobase modifying activity. In various embodiments, the base editor comprises a nucleobase modifying polypeptide (e.g., a deaminase) and a polynucleotide programmable nucleotide binding domain (e.g., Cas9 or Cpfl). Representative nucleic acid and protein sequences of base editors include those sequences having about or at least about 85% sequence identity to any base editor sequence provided in the sequence listing, such as those corresponding to SEQ ID NOs: 2-11.

[0120] By “BE4 cytidine deaminase (BE4) polypeptide,” is meant a base editor comprising a nucleic acid programmable DNA binding protein (napDNAbp) domain, a cytidine deaminase domain, and two uracil glycosylase inhibitor domains (UGIs). In embodiments, the napDNAbp is a Cas9n (D10A) polypeptide. Non-limiting examples of cytidine deaminase domains include rAPOBEC, ppAPOBEC, RrA3F, AmAPOBECl, and SsAPOBEC3B.

[0121] By “BE4 cytidine deaminase (BE4) polynucleotide,” is meant a polynucleotide encoding a BE4 polypeptide.

[0122] By “base editing activity” is meant acting to chemically alter a base within a polynucleotide. In one embodiment, a first base is converted to a second base. In one embodiment, the base editing activity is cytidine deaminase activity, e.g., converting target C•G to T•A. In another embodiment, the base editing activity is adenosine or adenine deaminase activity, e.g., converting A•T to G•C.ATTORNEY DOCKET NO. 180802-049202 / PCT

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[0124] By “base editing efficiency” is meant the total percent of one or more target bases in a sample that have been modified using a base editor. In some cases, the base editing efficiency is calculated as the total percent of target polynucleotides in a sample containing a modified target base. In some instances, the base editing efficiency is calculated as the total percent of target polynucleotides in a sample containing a modification to one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9 or 10) of 2, 3, 4, 5, 6, 7, 8, 9, or 10 target bases. Methods for measuring base editing efficiency for a base editor are known in the art (see, e.g., Gaudelli, etal. Nature 551:464-471 (2017), the disclosure of which is incorporated herein in its entirety for all purposes). In some cases a base editing efficiency is a median base editing efficiency calculated across 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100 or more target sites.

[0125] By “base editing window” for a base editor is meant bases within a target polynucleotide sequence that can be modified using the base editor. In some embodiments, the position of the nucleobases in the target polynucleotide sequence are numbered relative to a protospacer adjacent motif (PAM) for which a nucleic acid programmable DNA binding protein (napDNAbp) domain of the base editor has specificity, where base 1 corresponds to the base immediately adjacent to the PAM. In some embodiments, the position of the nucleobases in the target polynucleotide sequence are numbered relative to the 5' or 3' end of a spacer of a guide polynucleotide used to guide a nucleic acid programmable DNA binding protein (napDNAbp) domain of the base editor to a target site, where base 1 corresponds to the 5' or 3' terminal base of the spacer.

[0126] The term “base editor system” refers to an intermolecular complex for editing a nucleobase of a target nucleotide sequence. In various embodiments, the base editor (BE) system comprises (1) a polynucleotide programmable nucleotide binding domain, a deaminase domain (e.g., cytidine deaminase or adenosine deaminase) for deaminating nucleobases in the target nucleotide sequence; and (2) one or more guide polynucleotides (e.g., guide RNA) in conjunction with the polynucleotide programmable nucleotide binding domain. In various embodiments, the base editor (BE) system comprises a nucleobase editor domain selected from an adenosine deaminase or a cytidine deaminase, and a domain having nucleic acid sequence specific binding activity. In some embodiments, the base editor system comprises (1) a base editor (BE) comprising a polynucleotide programmable DNA binding domain and a deaminase domain for deaminating one or more nucleobases in a target nucleotide sequence; and (2) one or more guide RNAs in conjunction with the polynucleotide programmable DNA binding domain. In some embodiments, the polynucleotide programmable nucleotide binding domain is a polynucleotide programmable DNA binding domain. In some embodiments, the base editor is aATTORNEY DOCKET NO. 180802-049202 / PCT

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[0128] cytidine base editor (CBE). In some embodiments, the base editor is an adenine or adenosine base editor (ABE). In some embodiments, the base editor is an adenine or adenosine base editor (ABE) or a cytidine or cytosine base editor (CBE). In some embodiments, the base editor system (e.g., a base editor system comprising a cytidine deaminase) comprises a uracil glycosylase inhibitor or other agent or peptide (e.g., a uracil stabilizing protein such as provided in WO2022015969, the disclosure of which is incorporated herein by reference in its entirety for all purposes) that inhibits the inosine base excision repair system.

[0129] The term “Cas9” or “Cas9 domain” refers to an RNA guided nuclease comprising a Cas9 protein, or a fragment thereof e.g., a protein comprising an active, inactive, or partially active DNA cleavage domain of Cas9, and / or the gRNA binding domain of Cas9). A Cas9 nuclease is also referred to sometimes as a casnl nuclease or a CRISPR (clustered regularly interspaced short palindromic repeat) associated nuclease.

[0130] As used herein, the term “complementarity determining region (CDR)” refers to noncontiguous antigen-binding sites within an antibody. In various embodiments, amino acids in a CDR are identified using sequence or structure based methods. These particular regions have been described by Kabat et al., J. Biol. Chem. 252:6609-6616, 1977 and Kabat, et al., Sequences of Proteins of Immunological Interest, Fifth Edition, U. S. Department of Health and Human Services, NIH Publication No. 91-3242, 1991; by Chothia et al., (J. Mol. Biol. 196:901-917, 1987), and by MacCallum et al., (J. Mol. Biol. 262:732-745, 1996) where the definitions include overlapping or subsets of amino acid residues when compared against each other. As used herein, numbering of immunoglobulin amino acid residues is done according to the immunoglobulin amino acid residue numbering system of Kabat, unless otherwise indicated. In certain embodiments, the term “CDR” is a CDR as defined by Kabat based on sequence comparisons. Highly conserved portions of antibody variable regions are called the framework regions (FRs). As is appreciated in the art, the amino acid positions that delineate a hypervariable region of an antibody (i.e., CDRs) can vary, depending on the context and the various definitions known in the art. Some positions within a variable domain may be viewed as hybrid hypervariable positions in that these positions can be deemed to be within a hypervariable region under one set of criteria while being deemed to be outside a hypervariable region under a different set of criteria. One or more of these positions can also be found in extended hypervariable regions. The variable regions of native heavy and light chains each comprise four framework regions (FR1, FR2, FR3, FR4) that primarily adopt a beta-sheet configuration, connected by three CDRs (CDR1, CDR2, CDR3), which form loops that connect, and in some cases form part of, the beta-sheet structure. The CDRs in each chain are held together in closeATTORNEY DOCKET NO. 180802-049202 / PCT

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[0132] proximity by the FR regions in the order FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. and the CDRs in each antibody chain contribute to the formation of the target binding site of antibodies (see Kabat et al, Sequences of Proteins of Immunological Interest (National Institute of Health, Bethesda, Md. 1987; incorporated herein by reference). In various embodiments, complementarity determining regions are identified using any of the methodologies available to one of skill in the art such as those methods described in “Antibody Structure-Function Relationships.” Therapeutic Antibody Engineering, edited by William R. Strohl and Lilia M. Strohl, Woodhead Publishing Series in Biomedicine, 2012, 37-56, 459-595, the entirety of which is incorporated herein in its entirety for all purposes, where such methods include, as nonlimiting examples, those of Kabat, Chothia, Lefranc, Honegger, Martin, MacCallum, and Zhao. CDRs can be identified using sequence or structure based methods. Various software programs are available to one of skill in the art to identify CDRs for an antibody amino acid sequence. In various embodiments, a CDR as provided herein may be modified to include 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 additional amino acids and / or to exclude 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acids at the N-terminal and / or C-terminal end. The present disclosure contemplates that the CDRs identified for a particular antibody can vary in location or length depending upon the method by which they are determined.

[0133] By “chimeric antigen receptor” or “CAR” is meant a synthetic or engineered receptor comprising an extracellular antigen binding domain operationally joined to one or more intracellular signaling domains where the CAR confers specificity for an antigen bound by the extracellular antigen binding domain onto an immune effector cell. In some cases, the intracellular signaling domain is a T cell signaling domain. In embodiments, the immune effector cell is a T cell, an NK cell, or a macrophage. In embodiments, the CAR is a SUPRA CAR, an anti-tag CAR, a TCR-CAR, or a TCR-like CAR (see, e.g., Guedan, etal. “Engineering and Design of Chimeric Antigen Receptors,” Methods and Clinical Development, 12: 145-156 (2019); Poorebrahim, etal., “TCR-like CARs and TCR-CARs targeting neoepitopes: an emerging potential,” Cancer Gene Therapy, 28:581-589 (2021); and Minutolo, et al. “The Emergence of Universal Immune Receptor T Cell Therapy for Cancer,” Front Oncol., 9:176 (2019), the disclosures of which are incorporated herein by reference in their entireties for all purposes).

[0134] By “chimeric antigen receptor (CAR) T cell” or “CAR-T cell” is meant a T cell expressing a CAR that has antigen specificity determined by the antibody-derived targeting domain of the CAR. As used herein, “CAR-T cells” include T cells, regulatory T cells (TREG), macrophages, or NK cells. As used herein, the term “CAR-T cells” includes cells engineered toATTORNEY DOCKET NO. 180802-049202 / PCT

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[0136] express a CAR or a T cell receptor (TCR, sometimes referred to as TCR-CARs or TCR-like CARs). Methods of making CARs (e.g., for treatment of cancer) are publicly available (see, e.g., Park et al., Trends Biotechnol., 29:550-557, 2011; Grupp et al., N Engl J Med., 368:1509-1518, 2013; Han et al., J. Hematol Oncol. 6:47, 2013; Haso et al., (2013) Blood, 121, 1165-1174; Mohseni, et al., (2020) Front. Immunol., 11, art. 1608, doi: 10.3389 / fimmu.2020.01608;

[0137] Eggenhuizen, et al. Int. J. Mol. Sci. (2020), 21:7015, doi: 10.3390 / ijms21197015; Poorebrahim, et al., Cancer Gene Ther 28, 581-589 (2021), doi.org / 10.1038 / s41417-021-00307-7, PCT Pubs. W02012 / 079000, WO2013 / 059593; and U. S. Pub. 2012 / 0213783, the disclosure of each of which is incorporated herein by reference herein in its entirety).

[0138] The term “conservative amino acid substitution” or “conservative mutation” refers to the replacement of one amino acid by another amino acid with a common property. A functional way to define common properties between individual amino acids is to analyze the normalized frequencies of amino acid changes between corresponding proteins of homologous organisms (Schulz, G. E. and Schirmer, R. H., Principles of Protein Structure, Springer-Verlag, New York (1979)). According to such analyses, groups of amino acids can be defined where amino acids within a group exchange preferentially with each other, and therefore resemble each other most in their impact on the overall protein structure (Schulz, G. E. and Schirmer, R. H., supra). Nonlimiting examples of conservative mutations include amino acid substitutions of amino acids, for example, lysine for arginine and vice versa such that a positive charge can be maintained; glutamic acid for aspartic acid and vice versa such that a negative charge can be maintained; serine for threonine such that a free -OH can be maintained; and glutamine for asparagine such that a free –NH2can be maintained.

[0139] Amino acids generally can be grouped into classes according to the following common side- chain properties:

[0140] (1) hydrophobic: Norleucine, Met, Ala, Vai, Leu, He;

[0141] (2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gin;

[0142] (3) acidic: Asp, Glu;

[0143] (4) basic: His, Lys, Arg;

[0144] (5) residues that influence chain orientation: Gly, Pro;

[0145] (6) aromatic: Trp, Tyr, Phe. In some embodiments, conservative substitutions can involve the exchange of a member of one of these classes for another member of the same class. In some embodiments, non-conservative amino acid substitutions can involve exchanging a member of one of these classes with a member of another class.ATTORNEY DOCKET NO. 180802-049202 / PCT

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[0147] The term “coding sequence” or “protein coding sequence” as used interchangeably herein refers to a segment of a polynucleotide that codes for a protein. Coding sequences can also be referred to as open reading frames. The region or sequence is bounded nearer the 5' end by a start codon and nearer the 3' end with a stop codon. Stop codons useful with the base editors described herein include the following: TAG, TAA, and TGA.

[0148] By “complex” is meant a combination of two or more molecules whose interaction relies on inter-molecular forces. Non-limiting examples of inter-molecular forces include covalent and non-covalent interactions. Non-limiting examples of non-covalent interactions include hydrogen bonding, ionic bonding, halogen bonding, hydrophobic bonding, van der Waals interactions (e.g., dipole-dipole interactions, dipole-induced dipole interactions, and London dispersion forces), and 7t-effects. In an embodiment, a complex comprises polypeptides, polynucleotides, or a combination of one or more polypeptides and one or more polynucleotides. In one embodiment, a complex comprises one or more polypeptides that associate to form a base editor (e.g., base editor comprising a nucleic acid programmable DNA binding protein, such as Cas9, and a deaminase) and a polynucleotide (e.g., a guide RNA). In an embodiment, the complex is held together by hydrogen bonds. It should be appreciated that one or more components of a base editor (e.g., a deaminase, or a nucleic acid programmable DNA binding protein) may associate covalently or non-covalently. As one example, a base editor may include a deaminase covalently linked to a nucleic acid programmable DNA binding protein (e.g., by a peptide bond).

[0149] Alternatively, a base editor may include a deaminase and a nucleic acid programmable DNA binding protein that associate noncovalently (e.g., where one or more components of the base editor are supplied in trans and associate directly or via another molecule such as a protein or nucleic acid). In an embodiment, one or more components of the complex are held together by hydrogen bonds.

[0150] By “cytosine” or “4-Aminopyrimidin-2(1H)-one” is meant a purine nucleobase with the o

[0151] N^NH ANH

[0152] molecular formula C4H5N3O, having the structure

[0153]

[0154] 2anc[ corresponding to CAS No. 71-30-7.ATTORNEY DOCKET NO. 180802-049202 / PCT

[0155] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0156] By “cytidine” is meant a cytosine molecule attached to a ribose sugar via a glycosidic

[0157]

[0158] bond, having the structure, and corresponding to CAS No. 65-46-3. Its molecular formula is C9H13N3O5.

[0159] By “Cytidine Base Editor (CBE)” is meant a base editor comprising a cytidine deaminase. Non-limiting examples of cytidine deaminase base editor amino acid sequences include amino acid sequences for BE4max (SEQ ID NO: 553), YE1-BE4 (SEQ ID NO: 554), YE2-BE4 (SEQ ID NO: 555), YEE-BE4 (SEQ ID NO: 556), EE-BE4 (SEQ ID NO: 557), R33A-BE4 (SEQ ID NO: 558), R33A+K34A-BE4 (SEQ ID NO: 559), APOBEC3A (A3A)-BE4 (SEQ ID NO: 560), APOBEC3B (A3B)-BE4 (SEQ ID NO: 561), APOBEC3G (A3G)-BE4 (SEQ ID NO: 562), AID-BE4 (SEQ ID NO: 563), CDA-BE4 (SEQ ID NO: 564), FERNY-BE4 (SEQ ID NO: 565), evolved APOBEC3A (eA3A)-BE4 (SEQ ID NO: 566), AALN-BE4 (SEQ ID NO: 567), BE4max modified with SpCas9-NG (SEQ ID NO: 568), YEl-SpCas9-NG (YE1-NG) (SEQ ID NO: 569), YE2-SpCas9-NG (SEQ ID NO: 570), YEE-SpCas9-NG (SEQ ID NO: 571), EE-SpCas9-NG (SEQ ID NO: 572), R33A+K34A-SpCas9-NG (SEQ ID NO: 573), YE1-CP1028 (YE1-BE4-CP1028, or YE1-CP) (SEQ ID NO: 574), YE2-CP1028 (YE2-BE4-CP1028) (SEQ ID NO: 575), YEE-CP1028 (YEE-BE4-CP1028) (SEQ ID NO: 576), EE-CP1028 (EE-BE4-CP1028) (SEQ ID NO: 577), R33A+K34A-CP1028 (R33A+K34A-BE4-CP1028) (SEQ ID NO: 578), BE4max (with nickase) (SEQ ID NO: 597), BE4 (SEQ ID NO: 598), BE4 with His tag (SEQ ID NO: 599), BE4max (SEQ ID NO: 600), AncBE4max 689 (SEQ ID NO: 601), and AncBE4max 687 (SEQ ID NO: 602). Details of cytidine base editor polypeptides are described in International PCT Application No. PCT / US2016 / 058344 (WO2017 / 070632) and Komor, A. C., et al., “Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage” Nature 533, 420-424 (2016), the entire contents of which are hereby incorporated by reference. Further non-limiting examples of C to T nucleobase editing proteins are described in PCT Applications No. PCT / US2020 / 062428 and PCT / US2019 / 033848, the entire contents of which are hereby incorporated by reference.

[0160] By “Cytidine Base Editor (CBE) polynucleotide” is meant a polynucleotide encoding a CBE. Non-limiting examples of polynucleotide sequences encoding cytidine deaminase baseATTORNEY DOCKET NO. 180802-049202 / PCT

[0161] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0162] editors include those encoding BE4max (SEQ ID NO: 616), AncBE4max689 (SEQ ID NO: 617), and AncBE4max687 (SEQ ID NO: 618).

[0163] By “cytidine deaminase” or “cytosine deaminase” is meant a polypeptide or fragment thereof capable of deaminating cytidine or cytosine. In embodiments, the cytidine or cytosine is present in a polynucleotide. In one embodiment, the cytidine deaminase converts cytosine to uracil or 5-methylcytosine to thymine. The terms “cytidine deaminase” and “cytosine deaminase” are used interchangeably throughout the application. Petromyzon marinus cytosine deaminase 1 (PmCDAl) (SEQ ID NO: 12-13), Activation-induced cytidine deaminase (AICDA) (SEQ ID NOs: 14-20), and APOBEC (SEQ ID NOs: 21-61) are exemplary cytidine deaminases. Further exemplary cytidine deaminase (CD A) sequences are provided in the Sequence Listing as SEQ ID NOs: 62-66 and SEQ ID NOs: 67-189. Non-limiting examples of cytidine deaminases include those described in PCT / US20 / 16288, PCT / US2018 / 021878, 180802-021804 / PCT, PCT / US2018 / 048969, PCT / US2016 / 058344, PCT / US2020 / 062428, and PCT / US2019 / 033848, the disclosures of which are incorporated herein by reference in their entireties for all purposes. Non-limiting examples of cytidine deaminase amino acid sequences include amino acid sequences for Rat APOBEC1 (SEQ ID NO: 579), Human APOBEC1 (SEQ ID NO: 580), Human APOBEC3 (SEQ ID NO: 581), Human APOBEC3B (SEQ ID NO: 582), Human APOBEC3G (SEQ ID NO: 583), evoAPOBEC3A(eA3A) (SEQ ID NO: 584), evoCDA (SEQ ID NO: 585), evoAPOBECl (SEQ ID NO: 586), YE1 (SEQ ID NO: 587), YE2 (SEQ ID NO: 588), YEE (SEQ ID NO: 589), EE (SEQ ID NO: 590), R33A (SEQ ID NO: 591), R33A+K34A (SEQ ID NO: 592), AALN (SEQ ID NO: 593), FERNY (SEQ ID NO: 594), evoFERNY (SEQ ID NO: 595), APOBEC (SEQ ID NO: 619), Anc686 APOBEC (SEQ ID NO: 620), Human APOBEC-3G D316R D317R (SEQ ID NO: 621), Human APOBEC-3G chain A (SEQ ID NO: 622), Human APOBEC3-G chain A D120R D121R (SEQ ID NO: 623), Mouse APOBEC3 (SEQ ID NO: 624), Rat APOBEC3 (SEQ ID NO: 625), Rhesus macaque APOBEC-3G (SEQ ID NO: 626), Chimpanzee APOBEC-3G (SEQ ID NO: 627), Green Monkey APOBEC-3G (SEQ ID NO: 628), Human APOBEC-3G (SEQ ID NO: 629), Human APOBEC-3F (SEQ ID NO: 630), Human APOBEC-3B (SEQ ID NO: 631), Rat APOBEC-3B (SEQ ID NO: 632), Bovine APOBEC-3B (SEQ ID NO: 633), Chimpanzee APOBEC-3B (SEQ ID NO: 634), Gorilla APOBEC-3C (SEQ ID NO: 635), Human APOBEC-3A (SEQ ID NO: 636), Rhesus macaque APOBEC-3A (SEQ ID NO: 637), Bovine APOBEC-3A (SEQ ID NO: 638), Human APOBEC-3H (SEQ ID NO: 639), Human APOBEC-3D (SEQ ID NO: 640), Rat ABOPEC1 (SEQ ID NO: 641), Anc689 APOBEC (SEQ ID NO: 642), Anc687 APOBEC (SEQ ID NO: 643), Anc686ATTORNEY DOCKET NO. 180802-049202 / PCT

[0164] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0165] APOBEC (SEQ ID NO: 644), Anc655 APOBEC (SEQ ID NO: 645), and Anc733 APOBEC (SEQ IDNO: 646).

[0166] By “cytidine deaminase polynucleotide” is meant a polynucleotide encoding a cytidine deaminase. Non-limiting examples of polynucleotide sequences encoding cytidine deaminase domains include those encoding Rat APOBEC 1 (SEQ ID NO: 604), Anc689 APOBEC (SEQ ID NO: 605), Anc687 APOBEC (SEQ ID NO: 606), Anc686 APOBEC (SEQ ID NO: 607), Anc655 APOBEC (SEQ ID NO: 608), Anc733 APOBEC (SEQ ID NO: 609), Rat APOBEC 1 (SEQ ID NO: 610), Anc689 APOBEC (SEQ ID NO: 611), Anc687 APOBEC (SEQ ID NO: 612), Anc686 APOBEC (SEQ ID NO: 613), Anc655 APOBEC (SEQ ID NO: 614), and Anc733 APOBEC (SEQ IDNO: 615).

[0167] By “cytosine deaminase activity” is meant catalyzing the deamination of cytosine or cytidine. In one embodiment, a polypeptide having cytosine deaminase activity converts an amino group to a carbonyl group. In an embodiment, a cytosine deaminase converts cytosine to uracil (i.e., C to U) or 5-methylcytosine to thymine (i.e., 5mC to T). In some embodiments, a cytosine deaminase as provided herein has increased cytosine deaminase activity (e.g., at least 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold or more) relative to a reference cytosine deaminase.

[0168] The term “deaminase” or “deaminase domain,” as used herein, refers to a protein or fragment thereof that catalyzes a deamination reaction.

[0169] The term, “detect” refers to identifying the presence, absence or amount of the analyte to be detected. In one embodiment, a sequence alteration in a polynucleotide or polypeptide is detected. In another embodiment, the presence of indels is detected.

[0170] By “detectable label” is meant a composition that when linked to a molecule of interest renders the latter detectable, via spectroscopic, photochemical, biochemical, immunochemical, or chemical means. For example, useful labels include radioactive isotopes, magnetic beads, metallic beads, colloidal particles, fluorescent dyes, electron-dense reagents, enzymes (for example, as commonly used in an enzyme linked immunosorbent assay (ELISA)), biotin, digoxigenin, or haptens.

[0171] By “disease” is meant any condition or disorder that damages or interferes with the normal function of a cell, tissue, or organ. Non-limiting examples of diseases include neoplasias. In some embodiments the neoplasia is a tumor (e.g., a solid tumor) or a cancer. Non-limiting examples of cancers include melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), breast cancer, ovarian cancer, cervical cancer, endometrial cancer, and renal cell carcinoma (RCC). In various embodiments, a disease is any diseaseATTORNEY DOCKET NO. 180802-049202 / PCT

[0172] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0173] amenable to treatment using tumor infiltrating lymphocytes (TILs), such as TILs modified according to the methods of the present disclosure.

[0174] By “dual editing activity” or “dual deaminase activity” is meant having adenosine deaminase and cytidine deaminase activity. In one embodiment, a base editor having dual editing activity has both A~> G and C~ T activity, wherein the two activities are approximately equal or are within about 10% or 20% of each other. In another embodiment, a dual editor has A→G activity that no more than about 10% or 20% greater than C→T activity. In another embodiment, a dual editor has A-> G activity that is no more than about 10% or 20% less than C~ T activity. In some embodiments, the adenosine deaminase variant has predominantly cytosine deaminase activity, and little, if any, adenosine deaminase activity. In some embodiments, the adenosine deaminase variant has cytosine deaminase activity, and no significant or no detectable adenosine deaminase activity. Non-limiting examples of proteins having dual deaminase activity include those described in International Patent Application Publications No. WO 2024 / 040083 and WO 2022 / 204574, the disclosures of which are hereby incorporated by reference in their entireties for all purposes.

[0175] By “effective amount” is meant the amount of an agent (e.g., a base editor, cell) as described herein, that is required to ameliorate the symptoms of a disease relative to an untreated patient or an individual without disease, i.e., a healthy individual, or is the amount of the agent sufficient to elicit a desired biological response. The effective amount of active compound(s) used to practice embodiments of the present disclosure for therapeutic treatment of a disease varies depending upon the manner of administration, the age, body weight, and general health of the subject. Ultimately, the attending physician or veterinarian will decide the appropriate amount and dosage regimen. Such amount is referred to as an “effective” amount. In one embodiment, an effective amount is the amount of a base editor of the disclosure sufficient to introduce an alteration in a gene of interest in a cell (e.g., a cell in vitro or in vivo). In one embodiment, an effective amount is the amount of a base editor required to achieve a therapeutic effect. Such therapeutic effect need not be sufficient to alter a gene in all cells of a subject, tissue or organ, but only to alter the gene in about 1%, 5%, 10%, 25%, 50%, 75% or more of the cells present in a subject, tissue or organ. In one embodiment, an effective amount is the amount of an antibody polypeptide as disclosed herein required to achieve a therapeutic effect (e.g., selective stimulation of cells having a variant IL-2 receptor chain). In one embodiment, an effective amount is sufficient to ameliorate one or more symptoms of a disease.

[0176] An “epitope tag” refers to a peptide or amino acid sequence (e.g., an epitope) that is fused, linked, or coupled to a protein, such as a recombinant protein produced by recombinantATTORNEY DOCKET NO. 180802-049202 / PCT

[0177] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0178] techniques, and that can be specifically bound by an antibody, e.g., an anti-tag monoclonal antibody or binding molecule that is directed to or generated against the tag peptide or amino acid sequence. In an embodiment, the protein to which an epitope tag is fused, linked, or coupled is an antibody or VHH protein, e.g., a recombinantly produced antibody or VHH protein. In an embodiment, the tag can be specifically bound by an antibody, e.g., an anti -tag monoclonal antibody or binding molecule that is directed to or generated against the tag peptide or amino acid sequence. Examples of tags include, without limitation, FLAG tags (peptide sequence DYKDDDDK (SEQ ID NO: 687) recognized by an anti-FLAG antibody), polyHistidine (His) tags (5-10 histidine residues (HHHHHH (SEQ ID NO: 688)) bound by a nickel or cobalt chelate), E-tag, a peptide comprising amino acid sequence GAPVPYPDPLEPR (SEQ ID NO: 689) recognized by an antibody, an immunoglobulin Fc region or portion thereof, e.g., having effector or modulator function (Fc tag), and a BC2 tag (peptide sequence PDRKAAVSHWQQ (SEQ ID NO: 690)).

[0179] By “fragment” is meant a portion of a polypeptide or nucleic acid molecule. This portion contains, at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the entire length of the reference nucleic acid molecule or polypeptide. A fragment may contain 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 nucleotides or amino acids. In some embodiments, the fragment is a functional fragment.

[0180] As used herein, the term “framework region” or “FR region” includes amino acid residues that are adjacent to the CDRs. FR region residues may be present in, for example, human antibodies, rodent-derived antibodies (e.g., murine antibodies), humanized antibodies, primatized antibodies, chimeric antibodies, antibody fragments (e.g., Fab fragments), singlechain antibody fragments (e.g., scFv fragments), antibody domains, and bispecific antibodies, among others.

[0181] A “camelid VHH framework region (FR)” refers to the structural FR portions or components of a camelid VHH antibody or binding molecule, namely, FR1, FR2, FR4 and FR4, that positionally and structurally support the three CDR components, namely, CDR1, CDR2 and CDR3 of a VHH polypeptide, as described above. Similar to the FRs in conventional antibody polypeptides, the respective FR regions (FR1, FR2, FR3 and FR4) of the VHH polypeptides described herein are highly similar in sequence those of other camelid VHH polypeptides that bind to other antigens, e.g., unrelated VHH polypeptides. See, e.g., L. S. Mitchell and L. J. Colwell, 2018, Proteins, 86(7): 697-706 and A. M. Vattekatte et al., March, 2020, PeerJ, 6(8):e8408. DOI: 10.7717 / peerj.8408). Accordingly, the FR regions FR1, FR2, FR3 and FR4 of different VHHs do not vary significantly in sequence. By way of example, the below FRATTORNEY DOCKET NO. 180802-049202 / PCT

[0182] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0183] sequences of the VHH in the above-mentioned publication of Mitchell and Colwell are similar to the FR sequences of other VHHs, including the VHH polypeptides described herein.

[0184] FR1 (SEQ ID NO: 691):

[0185] Position 1 2 3 4 5 6 7 8 9 10 11 12 13

[0186] #

[0187] AA Q V Q L Q E S G G G L V Q

[0188] or or

[0189] V S

[0190]

[0191] FR1 (continued):

[0192] Position 14 15 16 17 18 19 20 21 22 23 24 25

[0193] #

[0194] AA A G G S L R L S C A A S

[0195] or

[0196] P

[0197]

[0198] FR2 (SEQ ID NO: 692):

[0199] Position 36 37 38 39 40 41 42 43 44 45 46 47 48 49

[0200] #

[0201] AA W F, R Q A P G K E, R E F, V A,

[0202] Y, c, or G, s,

[0203] or or L L, or

[0204] V G or T

[0205] W

[0206]

[0207] FR3 (SEQ ID NO: 693):

[0208] Positio 6 61 62 6 64 6 6 6 6 69 70 7 72 7 74 7 76 7 7 n # 0 3 5 6 7 8 1 3 5 7 8 AA Y A D S V K G R F T I S R D N A K N T

[0209] O o O o o O O

[0210] Q r r r r r r r

[0211] E A A V Q K A

[0212] T

[0213] r

[0214] o

[0215] r

[0216]

[0217] VATTORNEY DOCKET NO. 180802-049202 / PCT

[0218] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0219] FR3 (continued):

[0220] Position 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 #

[0221] AA V, Y L Q M N S L K P E D T A V, Y Y C L, or or or or or I,

[0222] or D N R D G T,

[0223] M or

[0224] M

[0225]

[0226] FR4 (SEQ ID NO: 694):

[0227] Position 117 118 119 120 121 122 123 124 125 126 127

[0228] #

[0229] AA W G Q G T Q V T V S S

[0230]

[0231] It will be appreciated that the amino acid position numbers of the VHH FRs shown above are approximate and may vary to some degree in length or amino acid sequence depending on VHH length and on the start and termination amino acid positions of the VHH CDRs. Thus, substantial similarities exist among the structural FRs of camelid VHHs, independent of antigen binding specificity.

[0232] The term “expansion” in reference to a cell refers to the proliferation of the cell through cell division into increasing numbers of cells.

[0233] By “guide polynucleotide” is meant a polynucleotide or polynucleotide complex which is specific for a target sequence and can form a complex with a polynucleotide programmable nucleotide binding domain protein (e.g., Cas9 or Cpfl). In an embodiment, the guide polynucleotide is a guide RNA (gRNA). gRNAs can exist as a complex of two or more RNAs, or as a single RNA molecule.

[0234] As used herein, the term “human antibody” refers to an antibody in which substantially every part of the protein (e.g., CDR, framework, CL, CH domains (e.g., CH1, CH2, CH3), hinge, (VL, VH)) is substantially non-immunogenic in humans, with only minor sequence changes or variations. A human antibody can be produced in a human cell (e.g., by recombinant expression), or by a non-human animal or a prokaryotic or eukaryotic cell (e.g., yeast) that is capable of expressing functionally rearranged human immunoglobulin (e.g., heavy chain and / or light chain) genes. Further, when a human antibody is a single-chain antibody, it can include a linker peptide that is not found in native human antibodies. For example, an Fv can comprise a linker peptide, such as two to about eight glycine or other amino acid residues, which connects the variable region of the heavy chain and the variable region of the light chain. Such linker peptides are considered to be of human origin. Human antibodies can be made by a variety ofATTORNEY DOCKET NO. 180802-049202 / PCT

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[0236] methods known in the art including phage display methods using antibody libraries derived from human immunoglobulin sequences. See U. S. Pat. Nos. 4,444,887 and 4,716,111; and PCT publications WO 1998 / 46645; WO 1998 / 50433; WO 1998 / 24893; WO 1998 / 16654; WO 1996 / 34096; WO 1996 / 33735; and WO 1991 / 10741; incorporated herein by reference. Human antibodies can also be produced using transgenic mice that are incapable of expressing functional endogenous immunoglobulins, but which can express human immunoglobulin genes. See, e.g., PCT publications WO 98 / 24893; WO 92 / 01047; WO 96 / 34096; WO 96 / 33735; U. S. Pat. Nos.

[0237] 5,413,923; 5,625,126; 5,633,425; 5,569,825; 5,661,016; 5,545,806; 5,814,318; 5,885,793;

[0238] 5,916,771; and 5,939,598; incorporated by reference herein.

[0239] By “human Fc domain (hFc) polypeptide” is meant a polypeptide, or a functional fragment thereof, having at least 85% sequence identity to the following amino acid sequence: PKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVD GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR EPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 695). In various embodiments, an hFc polypeptide is capable of mediating an immune response. In some instances, an hFc polypeptide facilitates an increase in serum half-life of a VHH domain(s) fused thereto.

[0240] By “human Fc domain (hFc) polynucleotide” is meant a polynucleotide encoding an hFc polypeptide.

[0241] By “human IgG4 domain (hIgG4 Fc) polypeptide” is meant a polypeptide, or a functional fragment thereof, having at least 85% sequence identity to the following amino acid sequence: ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGV EVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREP QVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRL TVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 696). In various embodiments, an hIgG4 Fc polypeptide is capable of mediating an immune response. In some instances, an hIgG4 Fc polypeptide facilitates an increase in serum half-life of a VHH domain(s) fused thereto.

[0242] By “human IgG4 domain (hIgG4 Fc) polynucleotide” is meant a polynucleotide encoding an hIgG4 Fc polypeptide.

[0243] As used herein, the term “humanized” antibodies refers to forms of non-human (e.g., murine) antibodies that are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')2or other target-binding subdomains of antibodies) whichATTORNEY DOCKET NO. 180802-049202 / PCT

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[0245] contain minimal sequences derived from non-human immunoglobulin. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable regions, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin. All or substantially all of the FR regions may also be those of a human immunoglobulin sequence. The humanized antibody can also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin consensus sequence. Methods of antibody humanization are known in the art. See, e.g., Riechmann et al., Nature 332:323-7, 1988; U. S. Pat. Nos. 5,530,101; 5,585,089; 5,693,761; 5,693,762; and U. S. Pat. No. 6,180,370 to Queen et al; EP239400; PCT publication WO 91 / 09967; U. S. Pat. No. 5,225,539; EP592106; and EP519596; incorporated herein by reference.

[0246] “Hybridization” means hydrogen bonding, which may be Watson-Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding, between complementary nucleobases. For example, adenine and thymine are complementary nucleobases that pair through the formation of hydrogen bonds.

[0247] By “immune cell” is meant a cell of the immune system capable of generating an immune response. Exemplary immune cells include, but are not limited to, T cells, NK cells, B cells, macrophages, hematopoietic stem cells, or precursors thereof. In embodiments, an immune cell is allogeneic to a subject to whom the cell is to be administered. In embodiments, an immune cell is from a donor and is allogeneic to a subject to which the immune cell will be administered after being modified according to the methods provided herein. In some embodiments, the T cells are tumor infiltrating lymphocytes (TILs).

[0248] By “immune effector cell” is meant a lymphocyte, once activated, capable of effecting an immune response upon a target cell. In some embodiments, immune effector cells are effector T cells. In some embodiments, the effector T cell is a naive CD8+T cell, a cytotoxic T cell, a natural killer T (NKT) cell, a natural killer (NK) cell, or a regulatory T (Treg) cell. In some embodiments, immune effector cells are effector NK cells. In some embodiments, the effector T cells are thymocytes, immature T lymphocytes, mature T lymphocytes, resting T lymphocytes, or activated T lymphocytes. In some embodiments the immune effector cell is a CD4+CD8+T cell or a CD4-CD8-T cell. In some embodiments the immune effector cell is a T helper cell. In some embodiments the T helper cell is a T helper 1 (Th1), a T helper 2 (Th2) cell, or a helper T cell expressing CD4 (CD4+ T cell).

[0249] By “increases” is meant a positive alteration of at least 10%, 25%, 50%, 75%, or 100%, or about 1.5 fold, about 2 fold, about 3-fold, about 4-fold, about 5-fold, about 6-fold, about 7-ATTORNEY DOCKET NO. 180802-049202 / PCT

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[0251] fold, about 8-fold, about 9-fold, about 10-fold, about 15-fold, about 20-fold, about 25-fold, about 30-fold, about 35-fold, about 40-fold, about 45-fold, about 50-fold, or about 100-fold.

[0252] The terms “inhibitor of base repair”, “base repair inhibitor”, “IBR” or their grammatical equivalents refer to a protein that is capable in inhibiting the activity of a nucleic acid repair enzyme, for example a base excision repair enzyme.

[0253] By “interleukin 2 receptor, beta (IL2RP; IL-2RP) polypeptide” is meant an IL2RP protein with at least about 85% amino acid sequence identity to GenBank Accession No. AAH25691.1, which is provided below, or a fragment thereof capable of functioning in IL-2 signaling. In some embodiments, an IL2RP polypeptide contains an R107G amino acid alteration, where the amino acid position corresponding to position 107 is shown in bold in the below amino acid sequence. Further embodiments of IL2Ry polypeptide sequences are provided at SEQ ID NOs: 821, 822, 855, and 856.

[0254] > AAH25691.1 Interleukin 2 receptor, beta [Homo sapiens] MAAPALSWRLPLLILLLPLATSWASAAVNGTSQFTCFYNSRANISCVWSQDGALQDTSCQVHAW PDRRRWNQTCELLPVSQASWACNLILGAPDSQKLTTVDIVTLRVLCREGVRWRVMAIQDFKPFE NLRLMAP I S LQVVHVETHRCNI S WE I SQASHYFERHLE FEARTLS PGHTWEEAPLLTLKQKQEW ICLETLTPDTQYEFQVRVKPLQGEFTTWSPWSQPLAFRTKPAALGKDTIPWLGHLLVGLSGAFG FI ILVYLLINCRNTGPWLKKVLKCNTPDPSKFFSQLSSEHGGDVQKWLSSPFPSSSFSPGGLAP EISPLEVLERDKVTQLLLQQDKVPEPASLSSNHSLTSCFTNQGYFFFHLPDALEIEACQVYFTY DPYSEEDPDEGVAGAPTGSSPQPLQPLSGEDDAYCTFPSRDDLLLFSPSLLGGPSPPSTAPGGS GAGEERMPPSLQERVPRDWDPQPLGPPTPGVPDLVDFQPPPELVLREAGEEVPDAGPREGVSFP WSRPPGQGEFRALNARLPLNTDAYLSLQELQGQDPTHLV (SEQ ID NO: 697)

[0255] By “interleukin 2 receptor, gamma (IL2RP; IL-2RP) polynucleotide” is meant a nucleic acid molecule encoding an IL2RP polypeptide, as well as the introns, exons, 3' untranslated regions, 5' untranslated regions, and regulatory sequences associated with its expression, or fragments thereof. In embodiments, an IL2RP polynucleotide is the genomic sequence, cDNA, mRNA, or gene associated with and / or required for IL2RP expression. An exemplary IL2RP nucleotide sequence from Homo Sapiens is provided below (GenBank Accession No.

[0256] BC025691.1: 115-1770) and at Ensembl Accession No. ENSG00000100385.

[0257] > BC025691.1: 115- 1770 Homo sapiens interleukin 2 receptor, beta, mRNA (cDNA clone MGC:34584 IMAGE:5207833), complete cds ATGGCGGCCCCTGCTCTGTCCTGGCGTCTGCCCCTCCTCATCCTCCTCCTGCCCCTGGCTACCT CTTGGGCATCTGCAGCGGTGAATGGCACTTCCCAGTTCACATGCTTCTACAACTCGAGAGCCAA CATCTCCTGTGTCTGGAGCCAAGATGGGGCTCTGCAGGACACTTCCTGCCAAGTCCATGCCTGGATTORNEY DOCKET NO. 180802-049202 / PCT

[0258] ELECTRONIC DEPOSIT DATE: January 14, 2026 CCGGACAGACGGCGGTGGAACCAAACCTGTGAGCTGCTCCCCGTGAGTCAAGCATCCTGGGCCT GCAACCTGATCCTCGGAGCCCCAGATTCTCAGAAACTGACCACAGTTGACATCGTCACCCTGAG GGTGCTGTGCCGTGAGGGGGTGCGATGGAGGGTGATGGCCATCCAGGACTTCAAGCCCTTTGAG AACCTTCGCCTGATGGCCCCCATCTCCCTCCAAGTTGTCCACGTGGAGACCCACAGATGCAACA TAAGCTGGGAAATCTCCCAAGCCTCCCACTACTTTGAAAGACACCTGGAGTTCGAGGCCCGGAC GCTGTCCCCAGGCCACACCTGGGAGGAGGCCCCCCTGCTGACTCTCAAGCAGAAGCAGGAATGG ATCTGCCTGGAGACGCTCACCCCAGACACCCAGTATGAGTTTCAGGTGCGGGTCAAGCCTCTGC AAGGCGAGTTCACGACCTGGAGCCCCTGGAGCCAGCCCCTGGCCTTCAGGACAAAGCCTGCAGC CCTTGGGAAGGACACCATTCCGTGGCTCGGCCACCTCCTCGTGGGTCTCAGCGGGGCTTTTGGC TTCATCATCTTAGTGTACTTGCTGATCAACTGCAGGAACACCGGGCCATGGCTGAAGAAGGTCC TGAAGTGTAACACCCCAGACCCCTCGAAGTTCTTTTCCCAGCTGAGCTCAGAGCATGGAGGAGA CGTCCAGAAGTGGCTCTCTTCGCCCTTCCCCTCATCGTCCTTCAGCCCTGGCGGCCTGGCACCT GAGATCTCGCCACTAGAAGTGCTGGAGAGGGACAAGGTGACGCAGCTGCTCCTGCAGCAGGACA AGGTGCCTGAGCCCGCATCCTTAAGCAGCAACCACTCGCTGACCAGCTGCTTCACCAACCAGGG TTACTTCTTCTTCCACCTCCCGGATGCCTTGGAGATAGAGGCCTGCCAGGTGTACTTTACTTAC GACCCCTACTCAGAGGAAGACCCTGATGAGGGTGTGGCCGGGGCACCCACAGGGTCTTCCCCCC AACCCCTGCAGCCTCTGTCAGGGGAGGACGACGCCTACTGCACCTTCCCCTCCAGGGATGACCT GCTGCTCTTCTCCCCCAGTCTCCTCGGTGGCCCCAGCCCCCCAAGCACTGCCCCTGGGGGCAGT GGGGCCGGTGAAGAGAGGATGCCCCCTTCTTTGCAAGAAAGAGTCCCCAGAGACTGGGACCCCC AGCCCCTGGGGCCTCCCACCCCAGGAGTCCCAGACCTGGTGGATTTTCAGCCACCCCCTGAGCT GGTGCTGCGAGAGGCTGGGGAGGAGGTCCCTGACGCTGGCCCCAGGGAGGGAGTCAGTTTCCCC TGGTCCAGGCCTCCTGGGCAGGGGGAGTTCAGGGCCCTTAATGCTCGCCTGCCCCTGAACACTG ATGCCTACTTGTCCCTCCAAGAACTCCAGGGTCAGGACCCAACTCACTTGGTGTAG (SEQ ID NO: 698)

[0259] By “interleukin 2 receptor, gamma (IL2Ry; IL-2Ry) polypeptide” is meant an IL2Ry protein with at least about 85% amino acid sequence identity to GenBank Accession

[0260] No. BAA01857.1, which is provided below, or a fragment thereof capable of functioning in IL-2 signaling.

[0261] > BAA01857.1 interleukin 2 receptor gamma chain [Homo sapiens] MLKPSLPFTSLLFLQLPLLGVGLNTTILTPNGNEDTTADFFLTTMPTDSLSVSTLPLPEVQCFV FNVEYMNCTWNSSSEPQPTNLTLHYWYKNSDNDKVQKCSHYLFSEEITSGCQLQKKEIHLYQTF VVQLQDPREPRRQATQMLKLQNLVIPWAPENLTLHKLSESQLELNWNNRFLNHCLEHLVQYRTD WDHSWTEQSVDYRHKFSLPSVDGQKRYTFRVRSRFNPLCGSAQHWSEWSHPIHWGSNTSKENPF LFALEAVVISVGSMGLI ISLLCVYFWLERTMPRIPTLKNLEDLVTEYHGNFSAWSGVSKGLAES LQPDYSERLCLVSEIPPKGGALGEGPGASPCNQHSPYWAPPCYTLKPET (SEQ ID NO: 699)ATTORNEY DOCKET NO. 180802-049202 / PCT

[0262] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0263] By “interleukin 2 receptor, gamma (IL2Ry; IL-2Ry) polynucleotide” is meant a nucleic acid molecule encoding an IL2Ry polypeptide, as well as the introns, exons, 3' untranslated regions, 5' untranslated regions, and regulatory sequences associated with its expression, or fragments thereof. In embodiments, an IL2Ry polynucleotide is the genomic sequence, cDNA, mRNA, or gene associated with and / or required for fL2Ry expression. An exemplary fL2Ry nucleotide sequence from Homo Sapiens is provided below (GenBank Accession No.

[0264] D11086.1:15-1124) and at Ensembl Accession No. ENSG00000147168.

[0265] > D11086.1:15-1124 Homo sapiens hIL-2Rg mRNA for interleukin 2 receptor gamma chain, complete cds ATGTTGAAGCCATCATTACCATTCACATCCCTCTTATTCCTGCAGCTGCCCCTGCTGGGAGTGG GGCTGAACACGACAATTCTGACGCCCAATGGGAATGAAGACACCACAGCTGATTTCTTCCTGAC CACTATGCCCACTGACTCCCTCAGTGTTTCCACTCTGCCCCTCCCAGAGGTTCAGTGTTTTGTG TTCAATGTCGAGTACATGAATTGCACTTGGAACAGCAGCTCTGAGCCCCAGCCTACCAACCTCA CTCTGCATTATTGGTACAAGAACTCGGATAATGATAAAGTCCAGAAGTGCAGCCACTATCTATT CTCTGAAGAAATCACTTCTGGCTGTCAGTTGCAAAAAAAGGAGATCCACCTCTACCAAACATTT GTTGTTCAGCTCCAGGACCCACGGGAACCCAGGAGACAGGCCACACAGATGCTAAAACTGCAGA ATCTGGTGATCCCCTGGGCTCCAGAGAACCTAACACTTCACAAACTGAGTGAATCCCAGCTAGA ACTGAACTGGAACAACAGATTCTTGAACCACTGTTTGGAGCACTTGGTGCAGTACCGGACTGAC TGGGACCACAGCTGGACTGAACAATCAGTGGATTATAGACATAAGTTCTCCTTGCCTAGTGTGG ATGGGCAGAAACGCTACACGTTTCGTGTTCGGAGCCGCTTTAACCCACTCTGTGGAAGTGCTCA GCATTGGAGTGAATGGAGCCACCCAATCCACTGGGGGAGCAATACTTCAAAAGAGAATCCTTTC CTGTTTGCATTGGAAGCCGTGGTTATCTCTGTTGGCTCCATGGGATTGATTATCAGCCTTCTCT GTGTGTATTTCTGGCTGGAACGGACGATGCCCCGAATTCCCACCCTGAAGAACCTAGAGGATCT TGTTACTGAATACCACGGGAACTTTTCGGCCTGGAGTGGTGTGTCTAAGGGACTGGCTGAGAGT CTGCAGCCAGACTACAGTGAACGACTCTGCCTCGTCAGTGAGATTCCCCCAAAAGGAGGGGCCC TTGGGG GGGGCCTGGGGCCTCCCC TGC CC GC T GCCCCT CTGGGCCCCCCC TGTT CACCCTAAAGCCTGAAACCTGA (SEQ ID NO: 700)

[0266] The terms “isolated,” “purified,” or “biologically pure” refer to material that is free to varying degrees from components which normally accompany it as found in its native state. “Isolate” denotes a degree of separation from original source or surroundings. “Purify” denotes a degree of separation that is higher than isolation. A “purified” or “biologically pure” protein is sufficiently free of other materials such that any impurities do not materially affect the biological properties of the protein or cause other adverse consequences. That is, a nucleic acid or peptide of this disclosure is purified if it is substantially free of cellular material, viral material, or cultureATTORNEY DOCKET NO. 180802-049202 / PCT

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[0268] medium when produced by recombinant DNA techniques, or chemical precursors or other chemicals when chemically synthesized. Purity and homogeneity are typically determined using analytical chemistry techniques, for example, polyacrylamide gel electrophoresis or high performance liquid chromatography. The term “purified” can denote that a nucleic acid or protein gives rise to essentially one band in an electrophoretic gel. For a protein that can be subjected to modifications, for example, phosphorylation or glycosylation, different modifications may give rise to different isolated proteins, which can be separately purified.

[0269] By “isolated polynucleotide” is meant a nucleic acid molecule that is free of the genes which, in the naturally-occurring genome of the organism from which the nucleic acid molecule of the disclosure is derived, flank the gene. The term therefore includes, for example, a recombinant DNA that is incorporated into a vector; into an autonomously replicating plasmid or virus; or into the genomic DNA of a prokaryote or eukaryote; or that exists as a separate molecule (for example, a cDNA or a genomic or cDNA fragment produced by PCR or restriction endonuclease digestion) independent of other sequences. In addition, the term includes an RNA molecule that is transcribed from a DNA molecule, as well as a recombinant DNA that is part of a hybrid gene encoding additional polypeptide sequence.

[0270] By an “isolated polypeptide” is meant a polypeptide of the disclosure that has been separated from components that naturally accompany it. Typically, the polypeptide is isolated when it is at least 60%, by weight, free from the proteins and naturally-occurring organic molecules with which it is naturally associated. In embodiments, the preparation is at least 75%, at least 90%, or at least 99%, by weight, a polypeptide of the disclosure. An isolated polypeptide of the disclosure may be obtained, for example, by extraction from a natural source, by expression of a recombinant nucleic acid encoding such a polypeptide; or by chemically synthesizing the protein. Purity can be measured by any appropriate method, for example, column chromatography, polyacrylamide gel electrophoresis, or by HPLC analysis.

[0271] By “IZ4” is meant the ionizable lipid 3-((4,4-bis(((Z)-oct-5-en-1-yl)oxy)butanoyl)oxy)-2-(((7-((2- butyloctanoyl)oxy)heptanoyl)oxy)methyl)propyl 4-(((2-(pyrrolidin-l-yl)ethyl)carbamoyl)oxy)decanoate or a pharmaceutically acceptable salt thereof. IZ4 is described as Example 7-7 in International Patent Application No. PCT / US23 / 27741, the disclosure of which is hereby incorporated by reference in its entirety for all purposes

[0272] The term “linker”, as used herein, refers to a molecule that links two moieties. In one embodiment, the term “linker” refers to a covalent linker (e.g., covalent bond) or a non-covalent linker.ATTORNEY DOCKET NO. 180802-049202 / PCT

[0273] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0274] By “marker” is meant any protein or polynucleotide having an alteration in expression, level, structure, or activity compared to a reference. In some cases, a marker is a modified IL2RP polypeptide, such as an IL2RP polypeptide containing an R107G amino acid alteration. In embodiments, the marker is associated with a disease or disorder. In some instances, the disease or disorder is a neoplasia. Non-limiting examples of markers include B2M, CD2, CD5, CD45, CIITA, HLA-DR, IFNg, PD1, and TCRap.

[0275] The term “mutation,” as used herein, refers to a substitution of a residue within a sequence, e.g., a nucleic acid or amino acid sequence, with another residue, or a deletion or insertion of one or more residues within a sequence. Mutations are typically described herein by identifying the original residue followed by the position of the residue within the sequence and by the identity of the newly substituted residue. Various methods for making the amino acid substitutions (mutations) provided herein are well known in the art, and are provided by, for example, Green and Sambrook, Molecular Cloning: A Laboratory Manual (4thed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y. (2012)).

[0276] The terms “nucleic acid” and “nucleic acid molecule,” as used herein, refer to a compound comprising a nucleobase and an acidic moiety, e.g., a nucleoside, a nucleotide, or a polymer of nucleotides. Typically, polymeric nucleic acids, e.g., nucleic acid molecules comprising three or more nucleotides are linear molecules, in which adjacent nucleotides are linked to each other via a phosphodiester linkage. In some embodiments, “nucleic acid” refers to individual nucleic acid residues (e.g., nucleotides and / or nucleosides). In some embodiments, “nucleic acid” refers to an oligonucleotide chain comprising three or more individual nucleotide residues. As used herein, the terms “oligonucleotide” and “polynucleotide” can be used interchangeably to refer to a polymer of nucleotides (e.g., a string of at least three nucleotides). In some embodiments, “nucleic acid” encompasses RNA as well as single and / or doublestranded DNA. Nucleic acids may be naturally occurring, for example, in the context of a genome, a transcript, an mRNA, tRNA, rRNA, siRNA, snRNA, a plasmid, cosmid, chromosome, chromatid, or other naturally occurring nucleic acid molecule. On the other hand, a nucleic acid molecule may be a non-naturally occurring molecule, e.g., a recombinant DNA or RNA, an artificial chromosome, an engineered genome, or fragment thereof, or a synthetic DNA, RNA, DNA / RNA hybrid, or including non-naturally occurring nucleotides or nucleosides.

[0277] Furthermore, the terms “nucleic acid,” “DNA,” “RNA,” and / or similar terms include nucleic acid analogs, e.g., analogs having other than a phosphodiester backbone. Nucleic acids can be purified from natural sources, produced using recombinant expression systems and optionally purified, chemically synthesized, etc. Where appropriate, e.g, in the case of chemicallyATTORNEY DOCKET NO. 180802-049202 / PCT

[0278] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0279] synthesized molecules, nucleic acids comprise nucleoside analogs such as analogs having chemically modified bases or sugars, and backbone modifications. A nucleic acid sequence is presented in the 5' to 3' direction unless otherwise indicated. In some embodiments, a nucleic acid is or comprises natural nucleosides (e.g. adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine, deoxythymidine, deoxyguanosine, and deoxycytidine); nucleoside analogs (e.g., 2-aminoadenosine, 2-thiothymidine, inosine, pyrrolo-pyrimidine, 3-methyl adenosine, 5-methylcytidine, 2-aminoadenosine, C5-bromouridine, C5-fluorouridine, C5-iodouridine, C5-propynyl-uridine, C5-propynyl-cytidine, C5-methylcytidine, 2-aminoadenosine, 7-deazaadenosine, 7-deazaguanosine, 8-oxoadenosine, 8-oxoguanosine, O(6)-methylguanine, and 2 -thiocytidine); chemically modified bases; biologically modified bases (e.g., methylated bases); intercalated bases; modified sugars (e.g., 2'-fluororibose, ribose, 2'-deoxyribose, arabinose, and hexose); and / or modified phosphate groups (e.g., phosphorothioates and 5'-7V-phosphoramidite linkages).

[0280] The term “nuclear localization sequence,” “nuclear localization signal,” or “NLS” refers to an amino acid sequence that promotes import of a protein into the cell nucleus. Nuclear localization sequences are known in the art and described, for example, in Plank et al., International PCT application, PCT / EP2000 / 011690, filed November 23, 2000, published as W 0 / 2001 / 038547 on May 31, 2001, the contents of which are incorporated herein by reference for their disclosure of exemplary nuclear localization sequences. In other embodiments, the NLS is an optimized NLS described, for example, by Koblan etal., Nature Biotech. 2018 doi:10.1038 / nbt.4172. In some embodiments, an NLS comprises the amino acid sequence KRTADGSEFESPKKKRKV (SEQ ID NO: 190), KRPAATKKAGQAKKKK (SEQ ID NO: 191), KKTELQTTNAENKTKKL (SEQ ID NO: 192), KRGINDRNFWRGENGRKTR (SEQ ID NO: 193), RKSGKIAAIVVKRPRK (SEQ ID NO: 194), PKKKRKV (SEQ ID NO: 195), MDSLLMNRRKFLYQFKNVRWAKGRRETYLC (SEQ ID NO: 196), PKKKRKVEGADKRTADGSEFESPKKKRKV (SEQ ID NO: 328), or RKSGKIAAIVVKRPRKPKKKRKV (SEQ ID NO: 329).

[0281] The term “nucleobase,” “nitrogenous base,” or “base,” used interchangeably herein, refers to a nitrogen-containing biological compound that forms a nucleoside, which in turn is a component of a nucleotide. The ability of nucleobases to form base pairs and to stack one upon another leads directly to long-chain helical structures such as ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). Five nucleobases - adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U) - are called primary or canonical. Adenine and guanine are derived from purine, and cytosine, uracil, and thymine are derived from pyrimidine. DNA and RNA canATTORNEY DOCKET NO. 180802-049202 / PCT

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[0283] also contain other (non-primary) bases that are modified. Non-limiting exemplary modified nucleobases can include hypoxanthine, xanthine, 7-methylguanine, 5,6-dihydrouracil, 5-methylcytosine (m5C), and 5-hydromethylcytosine. Hypoxanthine and xanthine can be created through mutagen presence, both of them through deamination (replacement of the amine group with a carbonyl group). Hypoxanthine can be modified from adenine. Xanthine can be modified from guanine. Uracil can result from deamination of cytosine. A “nucleoside” consists of a nucleobase and a five carbon sugar (either ribose or deoxyribose). Examples of a nucleoside include adenosine, guanosine, uridine, cytidine, 5-methyluridine (m5U), deoxyadenosine, deoxyguanosine, thymidine, deoxyuridine, and deoxycytidine. Examples of a nucleoside with a modified nucleobase includes inosine (I), xanthosine (X), 7-methylguanosine (m7G), dihydrouridine (D), 5-methylcytidine (m5C), and pseudouridine (T). A “nucleotide” consists of a nucleobase, a five carbon sugar (either ribose or deoxyribose), and at least one phosphate group. Non-limiting examples of modified nucleobases and / or chemical modifications that a modified nucleobase may include are the following: pseudo-uridine, 5-Methyl-cytosine, 2'-O-methyl-3'-phosphonoacetate, 2'-O-methyl thioPACE (MSP), 2'-O-methyl-PACE (MP), 2'-fluoro RNA (2'-F-RNA), constrained ethyl (S-cEt), 2'-O-methyl (‘M’), 2'-O-methyl-3'-phosphorothioate (‘MS’), 2'-O-methyl-3'-thiophosphonoacetate (‘MSP’), 5-methoxyuridine, phosphorothioate, and N1 -Methylpseudouridine.

[0284] The term “nucleic acid programmable DNA binding protein” or “napDNAbp” may be used interchangeably with “polynucleotide programmable nucleotide binding domain” to refer to a protein that associates with a nucleic acid (e.g., DNA or RNA), such as a guide nucleic acid or guide polynucleotide (e.g., gRNA), that guides the napDNAbp to a specific nucleic acid sequence. In some embodiments, the polynucleotide programmable nucleotide binding domain is a polynucleotide programmable DNA binding domain. In some embodiments, the polynucleotide programmable nucleotide binding domain is a polynucleotide programmable RNA binding domain. In some embodiments, the polynucleotide programmable nucleotide binding domain is a Cas9 protein. A Cas9 protein can associate with a guide RNA that guides the Cas9 protein to a specific DNA sequence that is complementary to the guide RNA. In some embodiments, the napDNAbp is a Cas9 domain, for example a nuclease active Cas9, a Cas9 nickase (nCas9), or a nuclease inactive Cas9 (dCas9). Non-limiting examples of nucleic acid programmable DNA binding proteins include, Cas9 (e.g., dCas9 and nCas9), Casl2a / Cpfl, Cas12b / C2c1, Casl2c / C2c3, Casl2d / CasY, Casl2e / CasX, Casl2g, Casl2h, Casl2i, and Cas12j / CasΦ (Casl2j / Casphi). Non-limiting examples of Cas enzymes include Casl, CaslB, Cas2, Cas3, Cas4, Cas5, Cas5d, Cas5t, Cas5h, Cas5a, Cas6, Cas7, Cas8, Cas8a, Cas8b, Cas8c, Cas9 (alsoATTORNEY DOCKET NO. 180802-049202 / PCT

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[0286] known as Csnl or Csxl2), CaslO, CaslOd, Casl2a / Cpfl, Cas12b / C2c1, Casl2c / C2c3, Casl2d / CasY, Casl2e / CasX, Casl2g, Casl2h, Casl2i, Cas12j / CasΦ, Cpfl, Csyl, Csy2, Csy3, Csy4, Csel, Cse2, Cse3, Cse4, Cse5e, Cscl, Csc2, Csa5, Csnl, Csn2, Csml, Csm2, Csm3, Csm4, Csm5, Csm6, Cmrl, Cmr3, Cmr4, Cmr5, Cmr6, Csbl, Csb2, Csb3, Csxl7, Csxl4, CsxlO, Csxl6, CsaX, Csx3, Csxl, CsxlS, Csxll, Csfl, Csf2, CsO, Csf4, Csdl, Csd2, Cstl, Cst2, Cshl, Csh2, Csal, Csa2, Csa3, Csa4, Csa5, Type II Cas effector proteins, Type V Cas effector proteins, Type VI Cas effector proteins, CARF, DinG, homologues thereof, or modified or engineered versions thereof. Other nucleic acid programmable DNA binding proteins are also within the scope of this disclosure, although they may not be specifically listed in this disclosure. See, e.g., Makarova et al. “Classification and Nomenclature of CRISPR-Cas Systems: Where from Here?” CRISPRJ. 2018 Oct; 1:325-336. doi: 10.1089 / crispr.2018.0033; Yan eta / ., “Functionally diverse type V CRISPR-Cas systems” Science. 2019 Jan 4;363(6422):88-91. doi: 10.1126 / science.aav7271, the entire contents of each are hereby incorporated by reference.

[0287] Exemplary nucleic acid programmable DNA binding proteins and nucleic acid sequences encoding nucleic acid programmable DNA binding proteins are provided in the Sequence Listing as SEQ ID NOs: 197-231, 232-245, 254-257, 260, and 378. In some embodiments, the napDNAbp is a (CRISPR-associated system) Cas9 endonuclease, for example, Cas9 (Csnl) from Streptococcus pyogenes (e.g., SEQ ID NO: 197), Cas9 from Neisseria meningitidis (NmeCas9; SEQ ID NO: 208), Nme2Cas9 (SEQ ID NO: 209), Streptococcus constellatus (ScoCas9), or derivatives thereof (e.g., a sequence with at least about 85% sequence identity to a Cas9, such as Nme2Cas9 or spCas9). Further non-limiting examples of nucleic acid programmable DNA binding proteins include those disclosed or referenced in Rufflow, et al., “Design of highly functional genome editors by modeling of the universe of CRISPR-Cas Sequences,” bioRxiv, posted April 22, 2024, doi: 10.1101 / 2024.04.22.590591, the disclosure of which is incorporated herein by reference in its entirety for all purposes, which were designed using artificial intelligence. In some embodiments, the napDNAbp is OpenCRISPR-1, or a variant thereof (e.g., a variant comprising a D10A amino acid alteration and / or lacking an N-terminal methionine). Further non-limiting examples of nucleic acid programmable DNA binding proteins include those disclosed in International Patent Application No. PCT / US2019 / 047996.

[0288] The terms “nucleobase editing domain” or “nucleobase editing protein,” as used herein, refers to a protein or enzyme that can catalyze a nucleobase modification in RNA or DNA, such as cytosine (or cytidine) to uracil (or uridine) or thymine (or thymidine), and adenine (or adenosine) to hypoxanthine (or inosine) deaminations, as well as non-templated nucleotide additions and insertions. In some embodiments, the nucleobase editing domain is a deaminaseATTORNEY DOCKET NO. 180802-049202 / PCT

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[0290] domain (e.g., an adenine deaminase or an adenosine deaminase; or a cytidine deaminase or a cytosine deaminase).

[0291] As used herein, “obtaining” as in “obtaining an agent” includes synthesizing, purchasing, or otherwise acquiring the agent.

[0292] By “subject” or “patient” is meant a mammal, including, but not limited to, a human or non-human mammal. In embodiments, the mammal is a bovine, equine, canine, ovine, rabbit, rodent, nonhuman primate, or feline. In an embodiment, “patient” refers to a mammalian subject with a higher than average likelihood of developing a disease or a disorder. Exemplary patients can be humans, non-human primates, cats, dogs, pigs, cattle, cats, horses, camels, llamas, goats, sheep, rodents (e.g., mice, rabbits, rats, or guinea pigs) and other mammalians that can benefit from the therapies disclosed herein. Exemplary human patients can be male and / or female.

[0293] “Patient in need thereof’ or “subject in need thereof’ is referred to herein as a patient diagnosed with, at risk or having, predetermined to have, or suspected of having a disease or disorder.

[0294] The terms “protein”, “peptide”, “polypeptide”, and their grammatical equivalents are used interchangeably herein, and refer to a polymer of amino acid residues linked together by peptide (amide) bonds. A protein, peptide, or polypeptide can be naturally occurring, recombinant, or synthetic, or any combination thereof.

[0295] The term “fusion protein” as used herein refers to a hybrid polypeptide which comprises protein domains from at least two different proteins.

[0296] The term “recombinant” as used herein in the context of proteins or nucleic acids refers to proteins or nucleic acids that do not occur in nature but are the product of human engineering. For example, in some embodiments, a recombinant protein or nucleic acid molecule comprises an amino acid or nucleotide sequence that comprises at least one, at least two, at least three, at least four, at least five, at least six, or at least seven mutations as compared to any naturally occurring sequence.

[0297] By “reduces” is meant a negative alteration of at least 5%, 10%, 25%, 50%, 75%, or 100%.

[0298] By “reference” is meant a standard or control condition. In one embodiment, the reference is a wild-type or healthy cell. In other embodiments and without limitation, a reference is an untreated cell that is not subjected to a test condition, or is subjected to placebo or normal saline, medium, buffer, and / or a control vector that does not harbor a polynucleotide of interest. A reference may be a cell expressing only a wild-type IL2RP polypeptide. A reference may be a subject that has not been subjected to a treatment or administered an agent, such as a base editorATTORNEY DOCKET NO. 180802-049202 / PCT

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[0300] system or a bispecific antibody of the disclosure. A reference may be a cell that has not been base edited according to the methods of the disclosure, or that has not been contacted with a bispecific antibody.

[0301] A “reference sequence” is a defined sequence used as a basis for sequence comparison. A reference sequence may be a subset of or the entirety of a specified sequence; for example, a segment of a full-length cDNA or gene sequence, or the complete cDNA or gene sequence. For polypeptides, the length of the reference polypeptide sequence will generally be at least about 16 amino acids, at least about 20 amino acids, at least about 25 amino acids, about 35 amino acids, about 50 amino acids, or about 100 amino acids. For nucleic acids, the length of the reference nucleic acid sequence will generally be at least about 50 nucleotides, at least about 60 nucleotides, at least about 75 nucleotides, about 100 nucleotides or about 300 nucleotides or any integer thereabout or therebetween. In some embodiments, a reference sequence is a wild-type sequence of a protein of interest. In other embodiments, a reference sequence is a polynucleotide sequence encoding a wild-type protein.

[0302] The terms “RNA-programmable nuclease,” and “RNA-guided nuclease” refer to a nuclease that forms a complex with (e.g., binds or associates with) one or more RNA(s) that is not a target for cleavage. In some embodiments, an RNA-programmable nuclease, when in a complex with an RNA, may be referred to as a nuclease-RNA complex. Typically, the bound RNA(s) is referred to as a guide RNA (gRNA).

[0303] As used herein, the term “scFv” refers to a single chain Fv antibody in which the variable domains of the heavy chain and the light chain from an antibody have been joined to form one chain. scFv fragments contain a single polypeptide chain that includes the variable region of an antibody light chain (VL) (e.g, CDR-L1, CDR- L2, and / or CDR-L3) and the variable region of an antibody heavy chain (VH) (e.g, CDR-H1, CDR-H2, and / or CDR-H3) separated by a linker. The linker that joins the VL and VH regions of a scFv fragment can be a peptide linker composed of proteinogenic amino acids. Alternative linkers can be used to so as to increase the resistance of the scFv fragment to proteolytic degradation (for example, linkers containing D-amino acids), in order to enhance the solubility of the scFv fragment (for example, hydrophilic linkers such as polyethylene glycol-containing linkers or polypeptides containing repeating glycine and serine residues), to improve the biophysical stability of the molecule (for example, a linker containing cysteine residues that form intramolecular or intermolecular disulfide bonds), or to attenuate the immunogenicity of the scFv fragment (for example, linkers containing glycosylation sites). It will also be understood by one of ordinary skill in the art that the variable regions of the scFv molecules described herein can be modified such that they vary in aminoATTORNEY DOCKET NO. 180802-049202 / PCT

[0304] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0305] acid sequence from the antibody molecule from which they were derived. For example, nucleotide or amino acid substitutions leading to conservative substitutions or changes at amino acid residues can be made (e.g., in CDR and / or framework residues) so as to preserve or enhance the ability of the scFv to bind to the antigen recognized by the corresponding antibody.

[0306] By “selectively binds” is meant specifically binds an altered version of a polypeptide but exhibits reduced binding or fails to bind to a wild-type version of the polypeptide. In some embodiments, a VHH domain of the disclosure is capable of selectively binding to an IL2RP polypeptide with an R107G amino acid alteration. In some embodiments, a bispecific antibody provided herein is capable of both specifically binding to a wild type IL2Ry polypeptide and selectively binding a IL2RP polypeptide having an R107G amino acid alteration.

[0307] By “ Streptococcus pyogenes Cas9 (SpCas9) polypeptide” is meant a nucleic acid programmable DNA binding domain comprising an amino acid sequence with at least 85% identity to the following amino acid sequence:

[0308] MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAEATRL KRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAY HEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTY NQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSAS MIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMD GTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRI PYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHS LLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFD SVEISGVEDRFNASLGTYHDLLKI IKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYA HLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTF KEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQ TTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINR LSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRK FDNLTKAERGGLS ELDKAGF I KRQLVETRQ I TKHVAQ I LDSRMNTKYDENDKL I RE VKVI TLKS KLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAK SEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLS MPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKG KSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLI IKLPKYSLFELENGRKRMLAS AGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEI IEQISEFSKRV ILADANLDKVLSAYNKHRDKPIREQAENI IHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLDATTORNEY DOCKET NO. 180802-049202 / PCT

[0309] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0310] ATLIHQSITGLYETRIDLSQLGGD (SEQ ID NO: 197), or a functional fragment thereof. In some embodiments, the SpCas9 polypeptide lacks an N-terminal methionine. In some embodiments, SpCas9 polypeptide comprises alterations, as described herein, such as a D10A amino acid alteration.

[0311] By “SpCas9 polynucleotide” is meant a polynucleotide encoding an SpCas9 polypeptide. By “nSpCas9 polypeptide” is meant an SpCas9 polypeptide that is a nickase. In various embodiments, an nSpCas9 polypeptide is an nSpCas9 polypeptide comprising a D10A amino acid alteration.

[0312] By “nSpCas9 polynucleotide” is meant a polynucleotide encoding an nSpCas9 polypeptide.

[0313] By “specifically binds” is meant a nucleic acid molecule, polypeptide, polypeptide / polynucleotide complex, compound, or molecule that recognizes and binds a polypeptide and / or nucleic acid molecule of the disclosure, but which does not substantially recognize and bind other molecules in a sample, for example, a biological sample.

[0314] By “substantially identical” is meant a polypeptide or nucleic acid molecule exhibiting at least 50% identity to a reference amino acid sequence. In one embodiment, a reference sequence is a wild-type amino acid or nucleic acid sequence. In another embodiment, a reference sequence is any one of the amino acid or nucleic acid sequences described herein. In one embodiment, such a sequence is at least about 60%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.9%, or even 99.99%, identical at the amino acid level or nucleic acid level to the sequence used for comparison.

[0315] Sequence identity is typically measured using sequence analysis software (for example, Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis. 53705, BLAST, BESTFIT, GAP, or PILEUP / PRETTYBOX programs). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine.

[0316] Nucleic acid molecules useful in the methods of the disclosure include any nucleic acid molecule that encodes a polypeptide of the disclosure or a functional fragment thereof. Such nucleic acid molecules need not be 100% identical with an endogenous nucleic acid sequence but will typically exhibit substantial identity. Polynucleotides having “substantial identity” to an endogenous sequence are typically capable of hybridizing with at least one strand of a double-ATTORNEY DOCKET NO. 180802-049202 / PCT

[0317] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0318] stranded nucleic acid molecule. Nucleic acid molecules useful in the methods of the disclosure include any nucleic acid molecule that encodes a polypeptide of the disclosure or a functional fragment thereof. Such nucleic acid molecules need not be 100% identical with an endogenous nucleic acid sequence but will typically exhibit substantial identity. Polynucleotides having “substantial identity” to an endogenous sequence are typically capable of hybridizing with at least one strand of a double-stranded nucleic acid molecule. By “hybridize” is meant pair to form a double-stranded molecule between complementary polynucleotide sequences (e.g., a gene described herein), or portions thereof, under various conditions of stringency. (See, e.g., Wahl, G. M. and S. L. Berger (1987) Methods Enzymol. 152:399; Kimmel, A. R. (1987) Methods Enzymol. 152:507).

[0319] By “TadA*8e polypeptide” is meant an adenosine deaminase comprising an amino acid sequence with at least 85% identity to the following amino acid sequence MSEVEFSHEYWMRHALTLAKRARDEREVPVGAVLVLNNRVIGEGWNRAIGLHDPTAHAEIMALR QGGLVMQNYRLIDATLYVTFEPCVMCAGAMIHSRIGRVVFGVRNAKTGAAGSLMDVLHYPGMNH RVEITEGILADECAALLCYFFRMPRQVFNAQKKAQSSTD (SEQ ID NO: 1) and comprising the following amino acid alterations referenced to SEQ ID NO: 1: A109S, Til 1R, DI 19N, H122N, Y147D, F149Y, T166I, and D167N, or a functional fragment thereof. In some embodiments, the TadA*8e polypeptide lacks an N-terminal methionine. In some embodiments, the TadA*8e polypeptide comprises alterations, as described herein. By “ABE8e” is meant a base editor as defined herein comprising a TadA*8e polypeptide.

[0320] By “TadA*8e polynucleotide” is meant a polynucleotide encoding a TadA*8e polypeptide.

[0321] By “TadA*8.20 polypeptide” is meant an adenosine deaminase comprising an amino acid sequence with at least 85% identity to the following amino acid sequence MSEVEFSHEYWMRHALTLAKRARDEREVPVGAVLVLNNRVIGEGWNRAIGLHDPTAHAEIMALR QGGLVMQNYRLIDATLYVTFEPCVMCAGAMIHSRIGRVVFGVRNAKTGAAGSLMDVLHYPGMNH RVEITEGILADECAALLCYFFRMPRQVFNAQKKAQSSTD (SEQ ID NO: 1) and comprising the following amino acid alterations referenced to SEQ ID NO: 1: I76Y, V82S, Y123H, Y147R, and Q154R, or a functional fragment thereof. In some embodiments, the TadA*8.20 polypeptide lacks an N-terminal methionine. In some embodiments, the TadA*8.20 polypeptide comprises alterations, as described herein. By “ABE8.20” is meant a base editor as defined herein comprising a TadA*8.20 polypeptide.

[0322] By “TadA*8.20 polynucleotide” is meant a polynucleotide encoding a TadA*8.20 polypeptide.ATTORNEY DOCKET NO. 180802-049202 / PCT

[0323] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0324] By “TadA*9.1 polypeptide” is meant an adenosine deaminase comprising an amino acid sequence with at least 85% identity to the following amino acid sequence MSEVEFSHEYWMRHALTLAKRARDEREVPVGAVLVLNNRVIGEGWNRAIGLHDPTAHAEIMALR QGGLVMQNYRLIDATLYVTFEPCVMCAGAMIHSRIGRVVFGVRNAKTGAAGSLMDVLHYPGMNH RVEITEGILADECAALLCYFFRMPRQVFNAQKKAQSSTD (SEQ ID NO: 1) and comprising the following amino acid alterations referenced to SEQ ID NO: 1: I76Y, V82T, Y123H, Y147R, F149Y, and Q154R, or a functional fragment thereof. In some embodiments, the TadA*9.1 polypeptide lacks anN-terminal methionine. In some embodiments, the TadA*9.1 polypeptide comprises alterations, as described herein. By “ABE9.1” is meant a base editor as defined herein comprising a TadA*9.1 polypeptide.

[0325] By “TadA*9.1 polynucleotide” is meant a polynucleotide encoding a TadA*9.1 polypeptide.

[0326] By “TadA*9.52 polypeptide” is meant an adenosine deaminase comprising an amino acid sequence with at least 85% identity to the following amino acid sequence MSEVEFSHEYWMRHALTLAKRARDEREVPVGAVLVLNNRVIGEGWNRAIGLHDPTAHAEIMALR QGGLVMQNYRLIDATLYVTFEPCVMCAGAMIHSRIGRVVFGVRNAKTGAAGSLMDVLHYPGMNH RVEITEGILADECAALLCYFFRMPRQVFNAQKKAQSSTD (SEQ ID NO: 1) and comprising the following amino acid alterations referenced to SEQ ID NO: 1: I76Y, V82T, Y123H, Y147T, and Q154S, or a functional fragment thereof. In some embodiments, the TadA*9.52 polypeptide lacks anN-terminal methionine. In some embodiments, the TadA*9.52 polypeptide comprises alterations, as described herein. By “ABE9.52” is meant a base editor as defined herein comprising a TadA*9.52 polypeptide.

[0327] By “TadA*9.52 polynucleotide” is meant a polynucleotide encoding a TadA*9.52 polypeptide.

[0328] The term “target site” refers to a nucleotide sequence or nucleobase of interest within a nucleic acid molecule that is modified. In embodiments, the modification is deamination of a base.

[0329] As used herein, the terms “treat,” treating,” “treatment,” and the like refer to reducing or ameliorating a disorder and / or symptoms associated therewith or obtaining a desired pharmacologic and / or physiologic effect. It will be appreciated that, although not precluded, treating a disorder or condition does not require that the disorder, condition or symptoms associated therewith be completely eliminated. In some embodiments, the effect is therapeutic, i.e., without limitation, the effect partially or completely reduces, diminishes, abrogates, abates, alleviates, reduces the intensity of, or cures a disease and / or adverse symptom attributable to theATTORNEY DOCKET NO. 180802-049202 / PCT

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[0331] disease. In some embodiments, the effect is preventative, i.e., the effect protects or prevents an occurrence or reoccurrence of a disease or condition. To this end, the presently disclosed methods comprise administering a therapeutically effective amount of a composition as described herein.

[0332] By “uracil glycosylase inhibitor” or “UGI” is meant an agent that inhibits the uracil-excision repair system. Base editors comprising a cytidine deaminase convert cytosine to uracil, which is then converted to thymine through DNA replication or repair. In various embodiments, a uracil DNA glycosylase (UGI) prevent base excision repair which changes the U back to a C. In some instances, contacting a cell and / or polynucleotide with a UGI and a base editor prevents base excision repair which changes the U back to a C. An exemplary UGI comprises an amino acid sequence as follows:

[0333] >splP14739IUNGI_BPPB2 Uracil-DNA glycosylase inhibitor MTNLSDIIEKETGKQLVIQESILMLPEEVEEVIGNKPESDILVHTAYDESTDENVMLLTSDAPE YKPWALVIQDSNGENKIKML (SEQ ID NO: 231).

[0334] In some embodiments, the agent inhibiting the uracil-excision repair system is a uracil stabilizing protein (USP). See, e.g., WO 2022015969 Al, incorporated herein by reference.

[0335] As used herein, the term “vector” refers to a means of introducing a nucleic acid molecule into a cell, resulting in a transformed cell. Vectors include plasmids, transposons, phages, viruses, liposomes, lipid nanoparticles, and episomes.

[0336] Ranges provided herein are understood to be shorthand for all of the values within the range. For example, a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50.

[0337] As used herein, the term “VH” refers to the variable region of an immunoglobulin heavy chain of an antibody, including the heavy chain of an Fv, scFv, or Fab. References to “VL” refer to the variable region of an immunoglobulin light chain, including the light chain of an Fv, scFv, dsFv or Fab. Antibodies (Abs) and immunoglobulins (Igs) are glycoproteins having the same structural characteristics. While antibodies exhibit binding specificity to a specific target, immunoglobulins include both antibodies and other antibody-like molecules which lack target specificity. Native antibodies and immunoglobulins are usually heterotetrameric glycoproteins of about 150,000 Daltons, composed of two identical light (L) chains and two identical heavy (H) chains. Each heavy chain of a native antibody has at the amino terminus a variable domain (VH)ATTORNEY DOCKET NO. 180802-049202 / PCT

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[0339] followed by a number of constant domains. Each light chain of a native antibody has a variable domain at the amino terminus (VL) and a constant domain at the carboxy terminus.

[0340] By “VHH domain” is meant an antigen binding domain of a heavy chain only antibody or an antigen binding fragment thereof.

[0341] A “VHH binding molecule” or “VHH antibody,” or simply “VHH,” as referred to herein is, in general, a single domain immunoglobulin molecule (antibody). A VHH (or VHH antibody) corresponds to the heavy chain of a VHH antibody having a single variable domain (or single variable region), e.g., a camelid-derived single variable H (VH) domain antibody. A VHH typically has a molecular weight (MW) of about 12-15 kDa. VHH antibodies lack light chains. These heavy-chain antibody molecules contain a single variable domain (VHH) and, typically, two constant domains (CH2and CH3). See, e.g., Methods in Molecular Biology, “Single Domain Antibodies - Methods and Protocols,” Eds. D. Saerens and S. Muyldermans, Humana Press (Springer), 2012. A cloned (recombinantly produced) and isolated VHH domain is a stable polypeptide harboring the antigen-binding capacity of the original heavy-chain antibody. See, e.g., U. S. Patent No. 5,840,526 and U. S. Patent No. 6,015,695, each of which is incorporated by reference herein in its entirety.

[0342] VHHs are efficiently expressed in E. coli, coupled to detection markers, such as a fluorescent marker, or conjugated with enzymes. The small size of VHHs permits their binding to epitopes (antigenic determinants in antigen proteins), e.g., “hidden epitopes” that are not accessible to whole antibodies of much larger size. As a therapeutic, a VHH is capable of efficient penetration and rapid clearance. Its single domain nature allows a VHH to be expressed in a cell without a requirement for supramolecular assembly, as is needed for whole antibodies which are typically tetrameric (two heavy chains and two light chains, having a MW of about 150 kDa). VHHs are also exhibit stability over time and have a longer half-life versus non- VHH antibody molecules, which comprise disulfide bonds that are susceptible to chemical reduction or enzymatic cleavage. Similar to immunoglobulins, VHHs may be modified post-translationally, e.g., to add chemical linkers, detectable moieties, such as fluorescent dyes, enzymes, substrates, chemiluminescent moieties, etc., or specific binding moieties, such as streptavidin, avidin, or biotin, etc., for use in the compositions and methods described herein.

[0343] The recitation of a listing of chemical groups in any definition of a variable herein includes definitions of that variable as any single group or combination of listed groups. The recitation of an embodiment for a variable or aspect herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof.ATTORNEY DOCKET NO. 180802-049202 / PCT

[0344] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0345] All terms are intended to be understood as they would be understood by a person skilled in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure pertains

[0346] In this application, the use of the singular includes the plural unless specifically stated otherwise. It must be noted that, as used in the specification, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. In this application, the use of “or” means “and / or” unless stated otherwise. Furthermore, use of the term “including” as well as other forms, such as “include”, “includes,” and “included,” is not limiting.

[0347] As used in this specification and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended. This wording indicates that specified elements, features, components, and / or method steps are present, but does not exclude the presence of other elements, features, components, and / or method steps. Any embodiments specified as “comprising” a particular component(s) or element(s) are also contemplated as “consisting of’ or “consisting essentially of’ the particular component(s) or element(s) in some embodiments. It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method or composition of the present disclosure, and vice versa. Furthermore, compositions of the present disclosure can be used to achieve methods of the present disclosure.

[0348] The term “about” or “approximately” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, z.e., the limitations of the measurement system.

[0349] Reference in the specification to “some embodiments,” “an embodiment,” “one embodiment” or “other embodiments” means that a particular feature, structure, or characteristic described in connection with the embodiments is included in at least some embodiments, but not necessarily all embodiments, of the present disclosures.

[0350] BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 provides a schematic diagram providing a description of an Expansion by Paired ANtibody Dimerization (EXPAND) system for the selective expansion of cell therapies. The cells are modified (e.g., through base editing) to express an IL2RP polypeptide variant selectively bound by a bispecific antibody.ATTORNEY DOCKET NO. 180802-049202 / PCT

[0351] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0352] FIG. 2 provides a schematic diagram depicting a method for using an embodiment of the EXPAND system of FIG. 1 to treat a solid tumor. Tumor infiltrating lymphocytes (TILs) are base edited in situ by injecting into a tumor (i.e., intratumoral injection) of a subject lipid nanoparticles (LNPs) containing a base editor system containing a guide RNA (gRNA) and mRNA encoding a base editor (base editor mRNA). Following base editing, the subject is administered a bispecific antibody capable of selectively mediating the expansion and activation of the base edited cells.

[0353] FIGs. 3A to 3C provide a schematic diagram and plots showing that bispecific antibodies induced T cell activation and expansion in vitro in an embodiment of the EXPAND system of FIG. 1 referred to as a “BC2 system”. FIG. 3A provides a schematic diagram showing the BC2 system where target cells were modified to express an IL2RP polypeptide containing an N-terminal BC2 tag (a 12 amino acid peptide) (IL2RpBC2polypeptide) functioning as a “specificity anchor” allowing for the selective binding of a bispecific antibody to the IL2RpBC2polypeptide, where the bispecific antibody was also capable of binding to a wild-type IL2Ry polypeptide (fL2RyWT). FIG. 3B provides a plot showing that cells expressing the IL2RpBC2polypeptide were selectively activated by a bispecific antibody capable of binding the IL2RpBC2polypeptide and the wild-type IL2Rγ polypeptide. The x-axis of FIG. 3B represents different nM concentrations of the bispecific antibody, and the y-axis indicates the percent of cells in the culture that contained phosphorylated STAT5, which is an indicator of T cell activation. FIG.

[0354] 3C provides a plot showing that T cells expressing the IL2RpBC2polypeptide were expanded from low frequencies when co-cultured in the presence of different amounts of T cells expressing a wild-type IL2RP polypeptide and not the IL2RpBC2polypeptide and contacted with the bispecific antibody. The y-axis of FIG. 3C indicates the percent of T cells in the culture that expressed the IL2RpBC2polypeptide. The arrows along the x-axis of FIG. 3C indicate times at which the bispecific antibody (BC2 bispecific antibody) was administered to the cell cultures.

[0355] FIGs. 4A to 4C provide a schematic diagram, a bar graph, and bioluminescence images showing that the BC2 system described in FIG. 3A mediated in vivo expansion of engineered T cells in NSG background mice. FIG. 4A provides a schematic diagram showing that the engineered T cells administered to the mice expressed luciferase and the IL2RpBC2polypeptide.

[0356] FIG. 4B provides a bar graph showing that T cells expressing the IL2RpBC2polypeptide proliferated in mice systemically administered 2 mg / kg (mpk) of the BC2 bispecific antibody, whereas the T cells expressing the IL2RpBC2polypeptide did not proliferate in mice that were administered phosphate buffered saline (PBS) rather than the BC2 bispecific antibody. CellATTORNEY DOCKET NO. 180802-049202 / PCT

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[0358] proliferation was measured as increase in total flux expressed as photons per second (p / s). FIG.

[0359] 4C provides bioluminescence images corresponding to the data presented in FIG. 4B.

[0360] FIGs. 5A and 5B provide flow cytometry histograms and a bar graph showing that tumor infiltrating lymphocytes (TILs) engineered in situ to express the IL2RpBC2polypeptide selectively proliferated in an NSG background mouse A549 (lung) subcutaneous tumor model when the mice were administered a BC2 bispecific antibody treatment. The mice were intravenously administered human T cells and the human T cells were then engineered intratum orally by injecting into the A549 tumors of the mice Lenti Viral constructs encoding EGFR. IL2RpBC2or EGFR. IL2RpWT(control), where EGFR was used as an detectable tag.

[0361] Following intratumoral injection of the LentiViral constructs, the mice were administered a systemic infusion of the BC2 bispecific antibody (x2). FIG. 5A provides stacked flow cytometry histograms demonstrating that TILs were successfully engineered via the intratumoral injection to express IL2RpBC2or IL2RpWT, and that non-TILs (e.g., splendic T cells) were not altered. FIG. 5B provides a bar graph demonstrating that the engineered TILs expressing the IL2RpBC2polypeptide selectively expanded with BC2 bispecific antibody (Bisp) treatment. In FIG. 5B, “mpk” indicates a mg / kg dose of the bispecific antibody and “IL2RP” indicates wild-type IL2Rp.

[0362] FIGs. 6A and 6B provide a schematic diagram, flow cytometry contour plots, a plot, and bioluminescence images demonstrating that that tumor infiltrating lymphocytes (TILs) engineered in situ to express the IL2RpBC2polypeptide migrated to distal tumors in an NSG background mouse A549 (lung) subcutaneous dual flank tumor model when the mice were administered a BC2 bispecific antibody treatment. The mice were intravenously administered human T cells expressing a chimeric antigen receptor (CAR) and luciferase, and the human T cells were then engineered intratumorally by injecting into one of the A549 tumors of each mouse (see schematic diagram of FIG. 6A) a LentiViral construct encoding EGFR. IL2RpBC2or EGFR. IL2RpWT(control), where EGFR was used as an detectable tag. Following intratumoral injection of the LentiViral constructs, the mice were administered a systemic infusion of the BC2 bispecific antibody (x2). FIG. 6A provides flow cytometry contour plots showing that the engineered T cells migrated to the distal tumor. In FIG. 6A, “distal tumor” indicates the tumor that was not injected with the LentiViral constructs, “did not leak” indicates that LentiViral constructs administered to one tumor (LV-treated tumor) did not reach the other tumor (distal tumor), and “control” refers to mice that were not administered any LentiViral construct. FIG.

[0363] 6B provides a plot and bioluminescent images demonstrating that the T cells engineered to express the IL2RpBC2polypeptide migrated to the distal tumor. In FIG. 6B, “ROI” indicates aATTORNEY DOCKET NO. 180802-049202 / PCT

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[0365] region of interest corresponding to a tumor, and the amount of engineered T cells present in each tumor of the mice was measured as total flux expressed in photons per second (p / s).

[0366] FIGs. 7A and 7B provide bar graphs demonstrating successful base editing of a IL2Rβ polynucleotide in TILs in situ or in T cells in vitro to express an IL2Rβ polypeptide having an R107G alteration. For in situ base editing of TILs, an NSG background mouse A549 (lung) subcutaneous tumor model was administered human T cells. The mice were then intratumorally (i.t.) administered a base editor system capable of editing the IL2Rβ polynucleotide to express an IL2RP polypeptide having the R107G alteration. As a negative control, mice were administered phosphate buffered saline (PBS). The base editor systems were administered in situ or in vitro using lipid nanoparticles (LNPs) containing the ionizable lipid BL4 or IZ4. Lipid nanoparticles containing the lipid BL4 were used as an LNP control. The mice were administered 1 mg / kg (mpk) of the bispecific antibody ABTx630 intraperitoneally (i.p.) following administration of the base editor system. BL4 corresponds to TT3 described in United States Patent No. 10,369,122 (e.g., at claim 9; at column 64, lines 10-30; and at column 68, lines 16-22) and having the following structure:

[0367]

[0368] v v. The IZ4 lipid nanoparticles contained the ionizable lipid presented as Example 7-7 (3-((4,4-bis(((Z)-oct-5-en-1-yl)oxy)butanoyl)oxy)-2-(((7-((2- butyloctanoyl)oxy)heptanoyl)oxy)methyl)propyl 4-(((2-(pyrrolidin-1- yl)ethyl)carbamoyl)oxy)decanoate) in International Patent Application No.

[0369] PCT / US23 / 27741, the disclosure of which is hereby incorporated by reference in its entirety for all purposes. FIG. 7A provides a bar graph showing that TILs were successfully base edited in the mice, as were A549 tumor cells. FIG. 7B provides a bar graph showing that base editing of T cells in vitro increased in proportion to the dose of the base editor systems administered to the T cells using lipid nanoparticles containing the BL4 ionizable lipid. Doses are expressed in FIG.

[0370] 7B as total micrograms (ug) of RNA (guide RNA and mRNA encoding the base editor) administered to the cells. In FIG. 7B, each set of 6 bars (the rightmost bar represents a base editing rate of 0%, so it is not visible) corresponds, from left-to-right, to doses of 10 pg, 9 pg, 4.5 pg, 2.25 pg, 1.125 pg, and 0 pg gRNA. The y-axis of FIGs. 7A and 7B represents the total number of cells edited to contain a polynucleotide encoding the IL2RP polypeptide having the R107G alteration.ATTORNEY DOCKET NO. 180802-049202 / PCT

[0371] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0372] FIGs. 8A-8C provide bar graphs and a schematic diagram. FIG. 8A provides a schematic diagram showing the structural location of target amino acid alterations in IL2Rp. FIG. 8B provides a bar graph showing base editing rates for cells administered base editor systems containing mRNA encoding an ABE8.20 base editor and a guide RNA targeting the base editor to effect an alteration of a nucleobase in an IL2RP polynucleotide such that the polynucleotide encodes an IL2RP polypeptide with one of the alterations indicated along the x-axis. FIG. 8C provides a graph showing rates of on-target editing in T cells contacted with base editor systems containing mRNA encoding one of the base editors listed along the x-axis and a guide RNA molecule guiding the base editor to alter an IL2Rβ polynucleotide to encode an IL2Rβ polypeptide having an R107G alteration. Base editor and guide RNA sequences are provided in Tables 1 and 2.

[0373] FIGs. 9A and 9B provide plots and schematic diagrams showing binding of an IL-2RP R107G-specific VHH polypeptide (where IL-2R2RP R107G refers to an IL2RP polypeptide having an R107G alteration, and IL-2R2RP R107G refers to a wild-type IL2RP polypeptide) (FIG. 9A) and representative IL-2Ry-specific VHH polypeptides (where IL-2Ry refers to wildtype IL2Ry) (FIG. 9B) to their respective antigens. Binding was measured using a Octet™ biolayer interferometry (BLI) assay. FIG. 9A provides plots demonstrating that the antibody VHH9 selectively bound IL-2R2RP R107G. In each of FIGs. 9A and 9B, the zero timepoint indicates the time at which a biosensor containing a VHH antibody was contacted with a solution containing the antigen and the dashed vertical lines represent the time at which the biosensor containing the VHH antibody was contacted with a solution not containing the antigen. The schematic diagrams presented in FIGs. 9A and 9B provide a description of the structure of the antibodies evaluated in the plots. In FIGs. 9A and 9B, the terms “CH3” and “CH2” refer to constant chain regions of an IgGFc region. The plots of FIG. 9B correspond, from left-to-right, to VHH antibodies having strong, medium, or weak binding to a wild-type IL2Ry antigen.

[0374] FIG. 10 provides schematic representations of embodiments of designs of bispecific polypeptides containing one VHH domain capable of binding to an IL2RP polypeptide having an R107G alteration (P VHH) and one VHH domain capable of binding to a wild-type IL2Ry polypeptide (y VHH). In FIG. 10, the terms “CH3” and “CH2” refer to constant chain regions of an IgG Fc region, the horizontal lines represent disulfide bridges, and the thin lines represent linkers.

[0375] FIGs. 11A and 11B provide a schematic diagram and a plot showing that structural modeling suggests that the R107G alteration in IL2RP may lead to a conformational change and that signaling mediated by an IL2RP polypeptide containing the R107G alteration is equivalentATTORNEY DOCKET NO. 180802-049202 / PCT

[0376] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0377] to signaling mediated by a wild-type IL2RP polypeptide. FIG. 11A provides ribbon structural diagrams showing that, according to the structure of wild-type IL-2RP (PDB accession no.

[0378] 7S2S), the R107G alteration in IL2RP may lead to a conformation change (e.g., reduced P-strand content). The F217S alteration in IL2RP was not predicted to result in such a conformational change. FIG. 11B provides a plot showing that cells expressing a wild-type IL2RP polypeptide or an IL2RP polypeptide containing an R107G alteration each showed similar levels of signaling when contacted with different concentrations of IL-2 (x-axis). Signaling levels were measured using flow cytometry as geometric mean fluorescence intensity (gMFI) levels of immunolabeled phosphorylated STAT5.

[0379] FIGs. 12A to 12C provide schematic diagrams and a bar graph showing binding of the VHH antigen-binding domains indicated along the x-axis to HEK cells overexpressing a wildtype (WT) IL2RP or IL2RP containing the R107G amino acid alteration (R107G IL2RP). FIG.

[0380] 12A provides a schematic diagram showing how cells were immunostained to collect the data depicted in FIG. 12C. The schematic diagram shows binding of an IL2RP-binding polypeptide binding to an IL2RP polypeptide expressed on the surface of an HEK cell and an anti-human Fc secondary antibody (anti-hFc 2°) used to detectably label the IL2RP-binding polypeptide. FIG.

[0381] 12B provides a schematic diagram showing the structure of the IL2RP-binding polypeptides evaluated in FIG. 12C. In FIG. 12B, the terms “CH3” and “CH2” refer to constant chain regions of an IgG Fc region, the horizontal lines represent disulfide bridges, and the thin lines represent linkers. FIG. 12C provides a bar graph showing binding of VHH antigen-binding domains indicated along the x-axis to HEK cells overexpressing a wild-type (WT) IL2RP or IL2RP containing the R107G amino acid alteration (R107G IL2RP). In FIG. 12C, the term “anti-Fc gMFI” refers to the geometric mean of the fluorescent intensity of the cells labeled with the anti-hFc 2° (secondary) antibody.

[0382] FIGs. 13A to 13D provide plots showing activation of T cells expressing a wild-type IL2RP polypeptide (WT) or IL-2RP polypeptide containing the R107G amino acid alteration (R107G) when exposed to the concentrations indicated along the x-axis of the indicated representative bispecific antibodies (541, 618, 631, 630, 619, 634, 635, or 636) having structures corresponding to the yP VHH-Fc structure depicted in FIG. 10 and containing the indicated VHH domains (e.g., PVHHI). The bispecific antibodies mediated either unbiased / non-specific activation (FIG. 13A), weak activation (FIG. 13B), strong activation with low selectivity (FIG.

[0383] 13C), or activation with high selectivity (FIG. 13D). T cell activation was measured as geometric mean fluorescence intensity (gMFI) of immunolabeled phosphorylated STAT5, as quantified using flow cytometry.ATTORNEY DOCKET NO. 180802-049202 / PCT

[0384] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0385] FIGs. 14A and 14B provide a plot and a bar graph showing potency and selective binding to a IL2RP polypeptide containing the R107G amino acid alteration for representative bispecific antibodies containing VHH antigen-binding domains capable of binding to a wild-type IL2Ry polypeptide and an IL2RP polypeptide containing the R107G amino acid alteration. FIG.

[0386] 14A provides a plot showing EC50 (nM) values for activation of T cells expressing either a wildtype IL2RP polypeptide (WT) or an IL2RP polypeptide containing the R107G amino acid alteration (R107G) using the bispecific antibodies (ABTx) indicated along the x-axis, where the bispecific antibodies contained one of the anti-IL2Rp VHH antigen-binding domains (PVHH) indicated along the x-axis. FIG. 14B provides a bar graph showing the ratio of EC50 for activation of T cells expressing WT to T cells expressing R107G (WT: R107G) for each of the bispecific antibodies listed along the x-axis in FIG. 14A. In FIGs. 13A to 13D, the boxed number in bold refers to the bispecific antibody identifier with the term “ABTx” removed (e.g., 541 refers to ABTx541) and the term PVHHI and the like refer to the VHH domain of the bispecific antibody capable of binding to IL2RP (see Tables A and D). FIG. 14A does not include wild-type (WT) data points for ABTx618 or ABTx635 because there was no dose response signal that would allow for an EC50 value to be calculated.

[0387] FIGs. 15A to 15C provide plots showing selective expansion of T cells expressing an IL2RP polypeptide containing the R107G amino acid alteration when contacted with the indicated bispecific antibodies (Bisp 630, Bisp 631, Bisp 619, Bisp 618, Bisp 634, or Bisp 636) containing the indicated VHH domains (e.g., PVHH87) at the concentrations indicated along the x-axis. The plots of FIGs. 15A to 15C show expansion of T cells expressing either a wild-type IL2RP polypeptide or an IL2RP polypeptide containing the R107G amino acid alteration, and expansion levels are expressed as a percent of growth relative to the cells when expanded in the presence of IL-2. The antibodies mediated either strong expansion with comparatively reduced selectivity (FIG. 15A), high selectivity (FIG. 15B), or mediated low expansion levels (FIG. 15C). In FIGs. 15A to 15C, the terms beginning “Bisp ” indicate the bispecific antibody identifier with the term “ABTx” replaced with “Bisp “ (e.g., Bisp 630 refers to ABTx630) and the term PVHH87 and the like refer to the VHH domain of the bispecific antibody capable of binding to IL2RP (see Tables A and D).

[0388] FIG. 16 provides plots showing selective activation of T cells expressing an IL2RP polypeptide containing the R107G amino acid alteration (R107G IL2RP) when exposed to the indicated representative bispecific antibodies (Bisp 619, Bisp 630, or Bisp 631) containing the indicated VHH domains (PVHH9, PVHH87, or PVHH88) at the concentrations indicated along the x-axis. T cell activation was measured using flow cytometry and expressed as percentATTORNEY DOCKET NO. 180802-049202 / PCT

[0389] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0390] geometric mean fluorescence intensity (gMFI) of immunolabeled phosphorylated STAT5 relative to cells activated using IL-2. In FIG. 16, T cells expressing a wild-type IL2RP polypeptide are referred to as “WT IL2RP”.

[0391] FIGs. 17A to 17F provide plots showing expansion (alternatively “growth”) of T cells expressing an IL2RP polypeptide containing the R107G amino acid alteration (R107G) when contacted with the indicated bispecific antibodies, namely 541 (FIGs. 17A to 17F), 618 (FIG.

[0392] 17A), 619 (FIG. 17B), 630 (FIG. 17C), 631 (FIG. 17D), 634 (FIG. 17E), or 636 (FIG. 17F), at the concentrations indicated along the x-axis. The plots of FIGs. 17A to 17F show expansion of T cells expressing either a wild-type IL2RP polypeptide (WT) or R107G, and expansion levels are expressed as a percent of growth relative to the cells when expanded in the presence of IL-2.

[0393] FIG. 18 provides a plot showing activation of T cells contacted with the indicated concentrations (0.001 to 1000 nM) of the bi specific antibody ABTx698 (“698”). The T cells expressed a wild type IL2Ry polypeptide and either wild type IL2RP (“WT”) or an IL2RP variant containing an R107G amino acid alteration. The T cells were contacted with the bispecific antibody ABTx698 for 24-48 hours and activation was then through phosphor-STAT5 (pSTAT5) detection by intracellular flow cytometry using phosphor-specific antibodies. In FIG.

[0394] 18, “gMFI” indicates “geometric mean fluorescence intensity.”

[0395] FIGs. 19A and 19B provide plots showing activation of T cells contacted with the indicated concentrations (0.001 to 100 nM) of a bispecific antibody selected from ABTx698, ABTx1134, ABTx541, and ABTx1201. The T cells expressed a wild type IL2Rγ polypeptide and either wild type IL2Rβ (“WT”) or an IL2RP variant containing an R107G amino acid alteration. The T cells were incubated with the bispecific antibodies for 4-6 hours at 37°C, and activation was then measured through phosphor-STAT5 (pSTAT5) detection. Phospho-STAT5 was labeled using the AF647-conjugated anti-phospho-STAT5 antibody (Clone 47) and levels of pSTAT5 were then measured using flow cytometry carried out using a BD LSRFortessa™ flow cytometer instrument. EC50 values were calculated using four-parameter logistic regression analysis in GraphPad Prism™ data analysis software. FIG. 19A provides a plot presenting data gathered using T cells prepared using lentiviral transduction to overexpress an IL2RP variant containing the R107G amino acid alteration. FIG. 19B provides a plot presenting gathered using T cells altered through base editing to overexpress a IL2RP variant containing the R107G amino acid alteration.

[0396] FIG. 20 provides bar graphs showing expansion (% cell growth) of T cells contacted with the indicated antibodies (see Table E for a description of the antibodies) at a concentration of from about 1 nM to about 10 nM every other day for a total of five treatments over an 8-dayATTORNEY DOCKET NO. 180802-049202 / PCT

[0397] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0398] culture period. The T cells expressed a wild type IL2Ry polypeptide and either wild type IL2RP (“WT”) or an IL2RP variant containing an R107G amino acid alteration. The T cells expressing the IL2RP variant containing the R107G amino acid alteration were prepared by base editing the cells to express the variant. Cell expansion was monitored using automated cell counting (Vi-CELL™ XR cell viability analyzer) with trypan blue exclusion for viability assessment. Growth measurements were normalized to IL- 15 control conditions (10 ng / mL recombinant human IL-15) to account for baseline proliferation.

[0399] FIGs. 21A and 21B provide plots demonstrating that the EXPAND system of the present disclosure enhanced chimeric antigen receptor (CAR) T cell therapy. The CAR-T cells (“EXPAND-CAR T”) were engineered to express an IL2RP variant containing an R107G amino acid alteration. FIG. 21A provides a plot showing results from enrichment assays, which were initiated in vitro with EXPAND-CAR T cell populations containing 1-10% CAR-positive cells and 99-90% CAR-negative cells, as determined by flow cytometry using CAR-specific detection reagents. At day 2 of cell culture, the cells were contacted with the bispecific antibody ABTx698 (10 pL of a 1 pM ABTx698 stock solution). FIG. 21B provides a plot showing results from an in vitro anti-tumor efficacy assessment carried out by co-culturing the EXPAND-CAR T cells with a target tumor cell line expressing an antigen targeted by the CAR and green fluorescent protein (GFP). The cytotoxicity data of FIG. 21B was measured by monitoring total integrated intensity of GRP (green channel) every 4 hours using an IncuCyte™ (Sartorius) automated livecell imaging system. The co-cultures were administered either phosphate buffered saline (PBS) or the bispecific antibody ABTx619 (administered 2 pL of a 5 pM ABTx698 stock solution to yield a 50 nM concentration on day 0; administered 2 pL of a 5 pM ABTx698 stock solution on day 3). Cultures containing only tumor cells (“Tumor cells only”) were analyzed as a control. In FIG. 21B, “GCU” indicates “green calibrated unit.”

[0400] FIGs. 22A to 22C provide bar graphs showing counts of CD3+and CD3+CAR-T cells in a tumor (FIG. 22A), blood (FIG. 22B), and spleen (FIG. 22C) of mice implanted with A549 cells on day -15, administered on day 0 le6 anti-RORl chimeric antigen receptor (CAR)-T cells expressing an IL2RP variant containing an R107G amino acid alteration, and administered on day 3 a 1 mg / kg (mpk) dose of the bispecific antibody ABTx698 (Group 3 (Gr3) mice). As controls, mice were administered only the A549 cells and no CAR-T cells (Group 1 (Grl);

[0401] “tumor only”) or were administered A549 cells, CAR-T cells, and no bispecific antibody (Group 2 (Gr2); “le6 CAR-T”). The Group 3 mice were administered the bispecific antibody at a dose of 1 mpk twice a week, and mice were terminally taken down at day 28, at which point the measurements shown in FIGs. 22A to 22C were collected. In FIGs. 22A to 22C, grey symbolsATTORNEY DOCKET NO. 180802-049202 / PCT

[0402] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0403] denote mice that came down from study early due to high tumor burden or rapidly decreasing body weights.

[0404] DETAILED DESCRIPTION

[0405] It has been surprisingly found that cell surface proteins on cells, including immune cells can be genetically modified in vivo or in vitro to enable selective targeting of the cells with an agent such as an antibody. Accordingly, the disclosure feature compositions and methods for the selective activation and / or proliferation of cells (e.g., immune cells). The methods involve modifying a surface protein (e.g., an IL receptor, G protein-coupled receptor (GPCRs), ion channel receptor, enzyme-linked receptors, IL-2, or any other protein displayed on the surface of a cell) on a cell (e.g., an immune cell, a t-cell, Treg cell, an NK cell, a macrophage, CAR-T, CAR-Macrophage, CAR-NK, or any other cell type that may or may not be an immune cell) so that the cell can be selectively targeted by an agent (e.g., an antibody, small molecule, peptide) either in vivo or ex vivo. The present disclosure also provides base editor systems for use in preparing engineered immune cells capable of being selectively activated and / or expanded. The present disclosure further provides bispecific antibodies and VHH domains capable of selectively binding the IL2RP polypeptide and specifically binding a wild-type fL2Ry.

[0406] The various aspects and embodiments of the disclosure are based, at least in part, on the development outlined in the Examples provided herein of a system for expanding immune cells referred to as “expansion by paired antibody dimerization (EXPAND)” in vitro and in vivo (see, e.g., FIGs. 1 and 2). The system contains immune effector cells engineered to express a modified interleukin-2 receptor p (IL-2RP) polypeptide and a bispecific antibody capable of selectively binding to the modified IL-2RP polypeptide and specifically binding a wild-type IL-2Ry polypeptide. Methods for using EXPAND system involve engineering immune cells (e.g., through base editing) to express an interleukin 2 receptor, beta (IL2RP) polypeptide variant (e.g., a variant containing an amino acid alteration listed in Table 1 or an epitope tag, such as a BC2 tag) capable of being selectively bound by a bispecific antibody containing an antigen-binding domain capable of selectively binding the IL2RP polypeptide and an antigen-binding domain capable of specifically binding a wild-type IL2Ry polypeptide. The cells are subsequently contacted with the bispecific antibody. The various aspects and embodiments of the disclosure are also based, at least in part, upon the development outlined in the Examples provided herein of the bispecific antibodies and the discovery of VHH antibodies suitable for use in the bispecific antibodies. The EXPAND system allowed for the selective in vivo expansion and activation of TILs engineered in situ to express the modified IL-2RP polypeptide.ATTORNEY DOCKET NO. 180802-049202 / PCT

[0407] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0408] IL-2 RECEPTOR

[0409] The interleukin-2 receptor (IL-2R) is a protein that binds to the cytokine IL-2 and is found on the surface of certain immune cells (e.g., NK cells, Naive / resting CD8+ T cells, and Treg cells), such as lymphocytes. IL-2R signaling regulates immunity and tolerance and plays a role in the development of regulatory T (Treg) cells. The IL-2R is made up of three subunits: alpha, beta, and gamma (see, e.g., FIG. 1). The a chain binds IL-2 with low affinity, the combination of P and y together form a complex that binds IL-2 with intermediate affinity, primarily on memory T cells and NK cells; and all three receptor chains form a complex that binds IL-2 with high affinity (Kd ~ 10-11M) on activated T cells and regulatory T cells. The intermediate and high affinity receptor forms are functional and cause changes in the cell when IL-2 binds to them.

[0410] The three IL-2 receptor chains span the cell membrane and extend into the cell, thereby delivering biochemical signals to the cell interior. The alpha chain does not participate in signaling, but the beta chain is complexed with an enzyme called Janus kinase 1 (JAK1), that is capable of adding phosphate groups to molecules. Similarly, the gamma chain complexes with another tyrosine kinase called JAK3. These enzymes are typically activated by IL-2 binding to the external domains of the IL-2R. As a consequence, three intracellular signaling pathways are initiated: the MAP kinase pathway, the Phosphoinositide 3-kinase (PI3K) pathway, and the JAK-STAT pathway.

[0411] METHODS FOR EXPANSION BY PAIRED ANTIBODY DIMERIZATION (EXPAND) In various aspects the present disclosure features methods for the selective expansion of immune effector cells. One of skill in the art will understand that, when used in reference to cells, “expansion” indicates cell proliferation. The immune effector cells may be in vivo or ex vivo. The methods involve engineering immune cells (e.g., through base editing or through transduction) to express an interleukin 2 receptor, beta (IL2RP) polypeptide variant (e.g., a variant containing an amino acid alteration listed in Table 1 or an epitope tag, such as a BC2 tag) capable of being selectively bound by a bispecific antibody containing an antigen-binding domain capable of selectively binding the IL2RP polypeptide variant and an antigen-binding domain capable of specifically binding a wild-type IL2Ry polypeptide. The methods further involve contacting the engineered immune cells with the bispecific antibody, such as those bispecific antibodies provided herein (e.g., those having sequences at least 85% identical to an amino acid sequence listed in Table E). In some embodiments, the immune effector cells areATTORNEY DOCKET NO. 180802-049202 / PCT

[0412] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0413] tumor infiltrating lymphocytes (TILs). In some instances, the immune effector cells are allogeneic (i.e., from a donor genetically dissimilar to a subject to which the cells are to be administered) to a subject to be administered the cells.

[0414] In some embodiments, the methods involve altering immune effector cells in vivo (e.g., intratumorally) to express the IL2RP variant and / or a chimeric antigen receptor. In some cases, the methods involve altering immune effector cells in vitro to express the IL2RP variant and / or a chimeric antigen receptor. In one case, the immune cells may be altered by introducing into the cells a polynucleotide sequence encoding an IL2RP variant (e.g., using a viral vector or a lipid nanoparticle), such as an IL2RP variant containing one of the amino acid alterations listed in Table 1, e g, an R107G alteration, or an IL2RP variant containing an epitope tag (e.g., at the N-terminus or C-terminus), such as a BC2 tag. In some cases, the immune cells may be altered through base editing to express the IL2RP variant through editing of an IL2RP polynucleotide in the cells. If the cells are altered in vitro, the methods of the disclosure may further involve administering the altered cells to a subject in need thereof to treat a disease or disorder. In some embodiments, the methods of the disclosure involve incorporating the polynucleotide(s) encoding the CAR and / or IL2RP variant into the genomes of the cells. Altering the cells in vitro may involve isolating TILs from a tumor of a subject and subsequently altering the cells.

[0415] Altering the cells in vitro may involve isolating circulating TILs and / or a subset of peripheral lymphocytes sharing clonotypes with TILs referred to as “circulating tumor-reactive lymphocytes (CTRLs)” from the blood of a patient (see, e.g., Kelley S, Wang Z 17 Isolation and expansion of circulating tumor-reactive lymphocytes for adoptive cell therapy. Journal for ImmunoTherapy of Cancer 2022;10: doi: 10.1136 / jitc-2022-SITC2022.0017). Isolating circulating TILs from the blood of a patient may involve microfluidic immunomagnetic cell sorting (MICS).

[0416] Base editing may involve contacting the cells with a base editor and a guide RNA. The guide RNA directs the base editor to effect an alteration in an IL2RP polynucleotide such that the IL2RP polynucleotide encodes one of the IL2RP amino acid alterations (e.g., R107G) listed in Table 1. The guide RNA may contain a spacer sequence containing at least 10 contiguous nucleotides of a spacer sequence listed in Table 1. The base editor contains in various cases an adenosine deaminase domain and a nucleic acid programmable DNA binding protein (napDNAbp) domain. The adenosine deaminase domain may be a TadA*9.52, TadA*9.1, TadA*8e, or TadA*8.20 polypeptide. The napDNAbp may be an SpCas9 nickase polypeptide containing a D10A alteration. The base editor systems may be administered to a subject and / or to a cell according to any of the methods provided herein. In some embodiments, the base editorATTORNEY DOCKET NO. 180802-049202 / PCT

[0417] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0418] system is administered to a subject using a lipid nanoparticle containing the ionizable lipid IZ4, mRNA encoding the base editor, and a guide RNA molecule.

[0419] The methods further involve contacting the cells with the bispecific antibody containing an antigen-binding domain capable of selectively binding the IL2RP variant polypeptide and an antigen-binding domain capable of specifically binding a wild-type IL2Rγ polypeptide.

[0420] Contacting the cells with the bispecific antibody may involve systemically administering the bispecific antibody to a subject in which the cells have been altered or to which the altered cells have been administered. Contacting the cells with the bispecific antibody leads to selective activation and expansion of the altered cells and lower or undetectable levels of activation of wild-type cells or cells that do not express the IL2RP polypeptide variant. In some cases, administration of the bispecific antibody facilitates the migration of cells altered in situ within one tumor in a subject to other tumors within a subject.

[0421] In various embodiments, when the methods of the disclosure involve altering immune effectors intratumorally in a first tumor, administration of the bispecific antibody results in expansion of the altered cells both within the first tumor and within a second tumor in the subject that is distinct from the first tumor. In some embodiments, when the methods of the disclosure involve altering immune effectors intratumorally in a first tumor, administration of the bispecific antibody results in a reduction in tumor size (e.g., mass and / or volume) of the first tumor as well as a reduction in tumor size of a second tumor distinct from the first tumor (i.e., an abscopal effect). In various embodiments, the methods of the disclosure are associated with an abscopal effect.

[0422] VHH ANTIBODIES

[0423] In various aspects, the disclosure provides VHH antibodies, also known as “singledomain antibodies (sdAbs),” capable of selectively binding a IL2RP variant (e.g., a variant containing an amino acid alteration listed in Table 1) or specifically binding a wild-type IL2Ry antigen, as well as polypeptides containing VHH domains (e.g., the bispecific antibodies provided herein) or polynucleotides encoding the same.

[0424] VHH domains are derived from sdAbs. Single-domain antibodies are antibody-derived therapeutic proteins that contain the unique structural and functional properties of naturally-occurring heavy-chain antibodies. These heavy-chain antibodies contain a single variable domain (VHH) and two constant domains (CH2and CH3). Importantly, a cloned and isolated VHH domain is a stable polypeptide harboring the full antigen-binding capacity of the original heavychain antibody. Single-domain antibodies have a high homology with the VH domains of humanATTORNEY DOCKET NO. 180802-049202 / PCT

[0425] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0426] antibodies and can be further humanized without any loss of activity. Importantly, Singledomain antibodies have a low immunogenic potential, which has been confirmed in primate studies with sdAb lead compounds.

[0427] Single-domain antibodies combine the advantages of conventional antibodies with important features of small molecule drugs. Like conventional antibodies, sdAbs show high target specificity, high affinity for their target, and low inherent toxicity. However, like small molecule drugs they can inhibit enzymes and readily access receptor clefts. Furthermore, sdAbs are stable, can be administered by means other than injection (see, e.g., W02004041867A2, which is herein incorporated by reference in its entirety) and are easy to manufacture. Other advantages of sdAbs include recognizing uncommon or hidden epitopes as a result of their small size, binding into cavities or active sites of protein targets with high affinity and selectivity due to their unique 3 -dimensional, drug format flexibility, tailoring of half-life and ease and speed of drug discovery.

[0428] Single-domain antibodies are encoded by single genes and are efficiently produced in almost all prokaryotic and eukaryotic hosts, e.g., E. coli (see, e.g., U. S. Pat. No. 6,765,087, which is herein incorporated by reference in its entirety), molds (for example Aspergillus or Trichoderma) and yeast (for example Saccharomyces, Kluyveromyces, Hansenula, or Pichia) (see, e.g., U. S. Pat. No. 6,838,254, which is herein incorporated by reference in its entirety).

[0429] VHH antibodies, such as the anti-IL2Rp and anti-IL2Ry VHH antibodies described herein, have a number of advantages over conventional antibodies and recombinant antibody domains, including (i) they are small monomeric proteins (14 kDa) that express and fold efficiently in recombinant hosts; (ii) they are more stable to extremes of pH and temperature compared with conventional antibodies; (iii) they typically bind conformational epitopes; and (iv) they are amenable to designed multimerization which often leads to higher potencies; and (v) they offer more therapeutic versatility, such as multi specificity, thus supporting their beneficial utility.

[0430] The amino acid sequences of representative anti-IL2Rp and anti-fL2Ry VHH antibodies described herein are provided in Table A below. The VHH domain regions of the VHH antibodies in Table A are shown as plain text. The CDR binding regions of the VHH antibodies are positioned within framework (FR) regions of the VHH antibodies, which do not vary substantially in sequence between discrete anti-IL2Rp or anti-fL2Ry VHHs and which provide a “structural scaffold” for the CDRs, which bind to IL2RP or IL2Ry. By way of non-limiting example, the binding of CDRs within FRs to a target protein (antigen), e.g., IL2RP or IL2Ry, may be via conformational binding or interaction, electrostatic binding interaction, hydrogenATTORNEY DOCKET NO. 180802-049202 / PCT

[0431] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0432] bonding, Van der Waals forces, or hydrophobic bonding, or combinations thereof, as would be appreciated by those having skill in the art.

[0433] Table A. Representative VHH antibody amino acid sequences.1In various embodiments, a VHH domain, or a functional fragment thereof, contains an amino acid sequence with at least 85% identity to a full-length sequence shown as plain all caps text in Table A, or to a portion thereof.

[0434] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0435] 457 IL2RP QVQLVESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKERE 784

[0436] VHH9-2 YVAWNWSGSTTDYLDSVKGRFTISRDNAKNTVSLQMNSLKPEDTA VY YCAALRRG WQRRGGP YE VDTWGQGTQVTVS S PKS CDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0437] 318 IL-2Ry QVQLVESGGGLVQAGGSLRLSCAASRRTSSYYVMGWFRQAPGKERE 744

[0438] VHH 13 FVAGITWGVGDTYYKDGVKGRFTISRDNAKNTVYLQMSSLKPEDTA

[0439]

[0440] VYYCATADVWPSALSYDYTYWGQGTQVTVSSPKSCDKTHTCPPCPA

[0441] 1In Table A, amino acid sequences corresponding to a human Fc (hFc) domain are shown in bold, linkers are shown in italics, and corresponding to CL1 Kappa are underlined, His tags are shown in lowercase text, and antigen-binding domains are shown in PLAIN ALL CAPS TEXT.

[0442] 2The term IL-2Ry indicates that the VHH antibody binds IL-2Ry, and the term IL-2RP indicates that the VHH antibody binds IL-2RP or the indicated IL-2RP variant. The amino acid alterations listed in this column refer to alterations in the Fc domain referenced to the following amino acid sequence:

[0443] SGAAVKKPGESLKISCKGSGYRFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNGYEGAFDIWGQGTMVTVSSASTKGPSVFPL APSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS LGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

[0444] (SEQ IDNO: 701).

[0445] 3In some embodiments, any of the amino acid sequences listed in the table further contain the following signal peptide sequence at the N-terminus: MGWSCIILFLVATATGVHS (SEQ ID NO: 702).ATTORNEY DOCKET NO. 180802-049202 / PCT

[0446] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0447] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0448] PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0449] 110 IL-2Ry QVQLQESGGGSVQAGGSLRLSCAASGYTYRDYYMGWFRQAPGRERE 703

[0450] VHH6 GVASIYTRGSREGSTRYSSSVEGRFTITLDTAKNTLYLQMNSLKPE control hFc DTAMYYCAADDRTWLPRVQLGGPRENEYNYWGQGTQVTVSSPKSCD tag KTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVS HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDW LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0451] 278 IL-2R0 EVQLVESGGGPVQAGGSLRLSCAASGRTFTFSRHDMGWFRQSPGKE 704

[0452] VHH 36 REFVAGITWSSSSTLYEDSVEGRFTISRDNAKNMVYLQMTSLNVED TAVYYCAAGRSYVDRSSAWVNYWGKGTLVTVSSPKSCDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKF NWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKC KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0453] 279 IL-2R0 QVQLVESGGGLVQAGGSLRLSCAASGRTFSGYAMAWFRQAPGKERE 705

[0454] VHH 94 FVAGITSISGTTLYGDSVKGRFTISRDNAKNTSYLRMNSLKPEDTA VY YCAANRRG WTRTATNFE S WGQGTQVTVS S PKS CDKTHTCPP CP APELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK VSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0455] 280 IL-2R0 QVQLVESGGGSVQAGGSLRLSCAASIRTFSSDSMAWFRQAPGKERE 706

[0456] VHH 158 FVGGVTWSGGNTLYGDSVKGRFTISRDNAKNTVYLQMNSLKFEDTA VYYCAAARYYRALTSNQRNYDTWGQGTQVTVSSPKSCDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKF NWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKC KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0457] 281 IL-2R0 QVQLVESGGGLVQAGGSLRLSCAASGRTFSDINMAWFRQAPGKERD 707

[0458] VHH 92 FVAGITWSSRSTLYADSVGGRFTISRDNAKSTVYLQMNSLKPEDTA VYYCAATRNALTRVNTPYDYWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0459] 282 IL-2R0 QVQLVESGGGWVQPGGSLRLSCVASGSIGSIGAMGWYRQAPGKERE 708

[0460] VHH MVAEI SRDGI TNYADS VKGRFTI SRDNPQNTI YLQMNS LKPEDTAV YSCNADVLYKRSNFYYREDFWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV

[0461]

[0462] SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVATTORNEY DOCKET NO. 180802-049202 / PCT

[0463] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0464] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0465] KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0466] 283 IL-2R0 QVQLVESGGGWVQPGGSLRLSCVASGSIGSIGAMGWYRQAPGKERE 709

[0467] VHH MVAEI TRDGI TNYADS VKGRFTI SRDNPQNTI YLQMNS LKPEDTAV YSCNADVLYKRSNFYYREDFWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0468] 284 IL-2R0 QVHLVQSGGGWVHPGGSLRLSCVASGTIGSIGAMGWYRQAPGKERE 710

[0469] VHH MVAEI SRDGI TNYADS VKGRFTI SRDNPQNTI YLQMNS LKPEDTAV YSCNANVLYKRINFYYPEYFWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0470] 285 IL-2R0 EVQLVESGGGLVQAGGSLRLSCAASGRTFNSNAMGWFREAPGKERE 711

[0471] VHH 6 FVAAI RTGGRTYYADS VKGRFTI SRGNAKNTVYLQMNS LKPEDTAV YYCAADTSGSYDSSRSDFTSWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0472] 286 IL-2R0 EVQLVESGGGLVQAGGSLRLSCVASGRTFSRYDMAWFRQAPGKEEP 712

[0473] VHH 15 ELAAAILSGGISYYGDSVKGRFTISRDNAKNTVYLQMNSLKPEDTA VYYCAADRSPDGRSRSQFDIWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0474] 287 IL-2R0 EVQLVESGGGLVQAGGSLRLSCWSGYTFNNYNMAWFRQAPGKEHE 713

[0475] VHH 16 LEREFVASITWSGSHTYYADSMKGRFTISRDNAKNTVTLQMNSLKP EDSAVYLCAMPPYAYGPAYGSGTRYDYWGQGTQVTVSSPKSCDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNG KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0476] 288 IL-2R0 QLQLVESGGGLVQPGGSLRLSCAASGFNLDYHAIGWFRQAPGKERE 714

[0477] VHH 44 GVSCISSGDGSTYSADSVKGRFTISRDNAKNTVYLQMNSLKPEDTA VYYCATVPYGCIAGSSGGGADYRSLEVWGQGTLVTVSSPKSCDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHED PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNG KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0478] 289 IL-2R0 QLQLVESGGGLVQPGGSLRLSCAASGFTFSRYAMSWVRQVPGKGLE 715

[0479]

[0480] VHH 46 WVSGISASSESTEYADAVKGRFTISRDNARNALYLQLNSLKPEDTAATTORNEY DOCKET NO. 180802-049202 / PCT

[0481] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0482] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0483] VY YCAKHAGS E I NTTS TGGGGRGTQVTVS S PKS CDKTHTCPP CP AP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0484] 290 IL-2R0 QLQLVESGGGLVQPGGSLRLSCAASGFTFSRYAMSWVRQVPGKGLE 716

[0485] VHH48 WVSGISASSGTTEYADAVKGRFTISRDNARNTLYLHLNSLKPEDTA VY YCAKHAGS E I NTTS TGGGGQGTQVTVS S PKS CDKTHTCPP CP AP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0486] 291 IL-2R0 QLQLVESGGGLVQPGGSLRLSCAASGFTFSRYAMSWVRQVPGKGLE 717

[0487] VHH49 WVSGISSSSSSTEYADAVKGRFTISRDNARNTLYLQLNSLKPEDTA VY YCAKHEGS Y I NS TS HGGGGQGTQVTVS S PKS CDKTHTCPP CP AP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0488] 292 IL-2R0 QLQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLE 718

[0489] VHH 50 WVSAINSAGGSTMYADSVKGRFTISRDNAKNTLYLQMSSLKPEDTA VYYCAKHDTYTYESRSQGRGQGTQVLVSSPKSCDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0490] 293 IL-2R0 QVQLQESGGGLVQAGGSLRLSCLASGITFSFNYMGWYRQAPGKERE 719

[0491] VHH 61 LVAYITSSGRTDYGDSVKGRFSISRDNAKNTVYLQMNNLKPEDTAV YDCNIDPGSRLWGKDYWGQGTQVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0492] 294 IL-2R0 QVQLQESGGGLVQAGGSLRLSCLASGRTFSTYDMAWFRQAPGKEPA 720

[0493] VHH 63 LAAAI LSGGNTY YADS VKGR FT I S RDNAKNTVFLQMNS LKPEDTAV YYCAADRSPDGRGRSQFDIWGQGIQVTVSSPKSCDKTHTCPPCPAP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0494] 295 IL-2R0 QVQLQESGGGLVQPGGSLRLSCVASGNSIEPYGMGWYRQAHGKERE 721

[0495] VHH 71 LVALITARGSTNYVDSVKGRFTMSRDNAKNAVYLQMNSLKPEDTAV YYCNGVTRDRQRYLGVWGQGTLVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA

[0496]

[0497] LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYATTORNEY DOCKET NO. 180802-049202 / PCT

[0498] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0499] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0500] PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0501] 296 IL-2R0 QVQLQESGGGLVQPGGSLRLSCWSGNSIEPYGMGWYRQAHGKERE 722

[0502] VHH 74 LVALI TARGSTNYIDS VKGRFTMS RDNAKNAVYLQMNS LKPEDTAV YYCNGVTRDRQRYLGVWGQGTLVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0503] 297 IL-2R0 QVQLQESGGGLVQPGGSLRLSCWSGSIFNINLMGWYRQAPGNQRE 723

[0504] VHH 75 LVARI TGDGI TNYADS VKGRFTI SRDNAKNTVYLQMNS LVPEDTAV YYCNARRGSFGWNYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFS CS VMHEALHNHYTQKS LS LSPGK

[0505] 298 IL-2R0 QVQLQESGGGMVQPGGSLRLSCAASESLVADNAMGWYRRAPGKERE 724

[0506] VHH 77 LVAYIGPGGSTDYADSVKGRFTVSRDNAKNTMYLQMSSLKPEDTAV YYCNILGRQLPWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0507] 299 IL-2R0 QVQLVESGGGLVQAGGSLRLSCAGSGRTFSSYAMGWFRQAPGKERE 725

[0508] VHH 105 FVAAINWSGNSTYYADSVKGRFTISRDNAKNTGYLQMNSLKPEDTA VYTCVAGPRRVGATSVEYDYWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0509] 300 IL-2R0 QVQLVESGGGLVQAGGSLRLSCLASGGRTFSRYDMAWFRQAPGKEP 726

[0510] VHH 108 ELAAAI LSGGNTYYADSVKGRFTI SRDNAKNTVFLQMNSLKPEDTA VYYCATDRSPGGRGRSQFDIWGQGIQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0511] 301 IL-2R0 QVQLVESGGGLVQAGGSLRLSCVASGRTFSRYDMAWFRQAPGKEEP 727

[0512] VHH 112 ELAAAI LSGGTSYYGDSVKGRFTISRDNAKNTVYLQMNSLKPEDTA VYYCAADRSPNGRSRSQFDIWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0513] 302 IL-2R0 QVQLVESGGGLVQPGGSLRLSCAASGFTFSRYAMSWVRQVPGKGLE 728

[0514]

[0515] VHH 118 WVSGISASSGDTEYADAVKGRFTISRDNARNTLYLQLNSLKPVDTAATTORNEY DOCKET NO. 180802-049202 / PCT

[0516] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0517] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0518] VY YCAKHTGS E I NTTS TGGRGQGTQVTVS S PKS CDKTHTCPP CP AP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0519] 303 IL-2R0 QVQLVESGGGLVQPGGSLRLSCAASGFTFSRYAMSWVRQVPGKGLE 729

[0520] VHH 119 WVSGISASSGSTEYADAVKGRFTISRDNARNTLYLQLNSLKPEDTA VY YCAKHAGS E I NTTS TGGGGQGTQVTVS S PKS CDKTHTCPP CP AP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0521] 304 IL-2R0 QVQLVESGGGLVQPGGSLRLSCAASGFTFSRYAMSWVRQVPGKGLE 730

[0522] VHH 121 WVSGISASSGTTEYADAVKGRFTISRDNARNTLYLHLNSLKPEDTA VY YCAKHAGS E I NTTS TGGGGQGTQVTVS S PKS CDKTHTCPP CP AP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0523] 305 IL-2R0 QVQLVESGGGLVQPGGSLRLSCAASGFTFSRYAMSWVRQVPGKGLE 731

[0524] VHH 122 WVSGISASSSSTEYADAVKGRFTISRDNARNTLYLQLNSLKPEDTA VY YCAKHAGS E I NTTS HGGGGQGTQVTVS S PKS CDKTHTCPP CP AP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0525] 306 IL-2R0 QVQLVESGGGLVQPGGSLRLSCAASGFTFSRYAMSWVRQVPGKGLE 732

[0526] VHH 123 WVSGISASSSSTEYADAVKGRFTISRDNARNTLYLQLSSLKPEDTA VY YCAKHEGS YVNS TS HGGGGQGTQVTVS S PKS CDKTHTCPP CP AP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0527] 307 IL-2R0 QVQLVESGGGLVQPGGSLRLSCAASGSILRINHMGWYRQAPGKERE 733

[0528] VHH 128 LVAAI TSGGSTNYADSVKGRFTI SRDNTRNTVYLQMNS LKPEDTAV YYCHADLQDTRTGPFRYDYWGQGTQVTVSSPKSCDKTHTCPPCPAP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0529] 308 IL-2R0 QVQLVESGGGLVQPGGSLRLSCAASGSISSINAMDWYRQAPGKERE 734

[0530] VHH 129 LVAGISSGGTTNYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAV YYCHVDLSDTRTGPFRFDYWGQGTQVTVSSPKSCDKTHTCPPCPAP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS

[0531]

[0532] NKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKATTORNEY DOCKET NO. 180802-049202 / PCT

[0533] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0534] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0535] GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0536] 309 IL-2R0 QVQLVESGGGLVQPGGSLRLSCTASGFTLENYGIAWFRQAPGKERE 735

[0537] VHH 130 GVSCI SRSDGSTYHLYSADS AKGRFTI SRDNAKNTVYLQMNS LKPE DTAVYYCATEGDCRGSPPGLEVWGQGTPVTVSSPKSCDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKF NWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKC KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0538] 310 IL-2R0 QVQLVESGGGLVQPGGSLRLSCVASGISIEPYGMGWYRQAHGKERE 736

[0539] VHH 132 LVALI TARGSTNS VDS VKGRFTMS RDNAKNAVYLQMNNLKPEDTAV YYCNGVTRDRQRYLGVWGQGTLVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0540] 311 IL-2R0 QVQLVESGGGLVQPGGSLRLSCVASGNSIEAYGMGWYRQAHGKERE 737

[0541] VHH 135 LVALI TARGSTS YVDS VKGRFTMS RDNAKNAVYLQMNS LS PEDTAV YYCNGVTRDYQRYLGVWGQGTLVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0542] 312 IL-2R0 QVQLVESGGGLVQPGGSLRLSCVASGNSIEIYGMGWYRQAHGKERE 738

[0543] VHH 136 LVALITARGSTSYVDSVKGRFTMSRDNAKNAVYLQMNSLKPEDTAV YYCNGVTPDRQRYLGVWGQGTLVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0544] 313 IL-2R0 QVQLVESGGGLVQPGGSLRLSCVASGNSIKDNGMGWYRQAPGKERE 739

[0545] VHH 138 LVALITARGSTSYVDSVKGRFTMSRDNAKNAVYLQMNSLKPEDTAV YYCNGVTRDYQRYLGVWGQGTLVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0546] 314 IL-2R0 QVQLVESGGGLVQPGGSLRLSCVASGNSIKINGMGWYRQAPGKERE 740

[0547] VHH 140 LVALITARGSTSYIDSVKGRFTMSRDNAKNAVYLQMNSLKPEDTAV YYCNGVTPDRQRYIGVWGQGTLVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0548] 315 IL-2R0 QVQLVESGGGLVQPGGSLRLSCVASGRSIRIYGMGWYRQAPGKERE 741

[0549]

[0550] VHH 141 LVALITARGSTSYIDSVKGRFTMSRDNAENAVYLQMNSLKPEDTAVATTORNEY DOCKET NO. 180802-049202 / PCT

[0551] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0552] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0553] YYCNGVTPDRQRYLGVWGQGTLVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0554] 316 IL-2R0 QVQLVESGGGLVQVGDSLRLSCAASGRTFSKDFMAWFRQAPGKERE 742

[0555] VHH 144 FVAAINWSEGNTRYLTSVMGRFTI SRDI SRDNAKNTGYLQMNSLKP EDTAVYYCAVSSGTIYGPYDDWGQGTQVTVSSPKSCDKTHTCPPCP APELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK VSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0556] 317 IL-2R0 QVQLVESGGGSVQAGDSLRLSCAASGFTFSRYAMSWVRQVPGKGLE 743

[0557] VHH 157 WVSGISASSSSTEYAGAVKGRFTISRDNARNTLYLQLNSLKPEDTA VY YCAKHAGS E I NTTS TGGGGQGTQVTVS S PKS CDKTHTCPP CP AP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0558] 319 IL-2Ry QVQLVESGGGLVQGGGSLRLSCAASGLTSSNNWGWYRQAPGKQRE 745

[0559] VHH 15 LVAI LATTGNTRYGEAAKGRFTI SRDNTKNTVYLQMNS LKPEDTAV YYCNLWLPNSVYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FS CS VMHEALHNHYTQKS LS LSPGK

[0560] 320 IL-2Ry QVQLQESGGGLVQAGGSLRLSCVASGSIFSSNAMAWYRQAPGKQRE 746

[0561] VHH 18 LVAI ITSGGTTDYPDSVKGRFTISRDNAKNTVYLQMNTLKPEDTAV YYCNDPTWLTKGLDNDYWGQGTQVTVSSPKSCDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0562] 321 IL-2Ry QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLE 747

[0563] VHH 29 WVSGINSGGGSTSYADSVKGRFTISRDNAKNTLYLQMNSLKPEDSA VYYCAKIGRDASSWETQGQGTQVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0564] 322 IL-2Ry QVQLVESGGGLVQAGGSLRLSCAASGSTFGFVAMAWYRQAPGKQRE 748

[0565] VHH 30 LVANI RNDGRI DYTDS VKGRFTI SRDNAKNTLYLQMI SLKPEDTAV YFCYGARVGSGATADFWGQGTQVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA

[0566]

[0567] LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYATTORNEY DOCKET NO. 180802-049202 / PCT

[0568] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0569] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0570] PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0571] 323 IL-2Ry QVQLQESGPGLVKPSQTLSLTCTVSGGSITADYYYWSWIRQPPGKG 749

[0572] VHH41 LEWMGAIGYSGITYYSPSVKSRTAISRDTSKNQLTLQLRSVTPEDT AVYYCARGLVGGWFRAEYDYRGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0573] 324 IL-2Ry EVQLVESGGGLVQAGGSLRLSCAASGRTFSGYAMGWFRQAPGKERE 750

[0574] VHH45 FVTAI S WSGGTTYYADSVKGRFTI SRDNAKNTVYLQMDSLKPEDTA VYYCAATTFESGNGEYDVWGQGTQVTVSSPKSCDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0575] 325 IL-2Ry QVQLVESGGALVQPGGSLRLSCAASGFTFGGYAMGWVRQAPGKGLE 751

[0576] VHH 51 WLSTISYGGSGTTYADSVKDRFTISRDNAKNTVYLEMNSLKPEDTA VYTCGKYGRPFYYSHYWEKADYDYWGQGTQVTVSSPKSCDKTHTCP PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKS RWQQGNVF S CS VMHEALHNH YTQKS L S L SPGK

[0577] 326 IL-2Ry QVQLVESGGGLVQPGGSLRLSCAGSRSIFSGNPMAWFRQAPGKQRE 752

[0578] VHH 57 LVALVSSGGSHTDYADSVLGRFTISRDDAKNMVYLQMNSLKPEDTA VYYCNHPVDTPLTKWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVE VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK

[0579] 327 IL-2Ry EVQLVESGGGLVQAGGSLRLSCAASGISLSINPMVWYRQAPGKQRE 753

[0580] VHH 60 WVADI SSS DMTRYADS VKGRFI TSRDNARNGVNLQMNRLEPEDTAV YYCDVPDPHNGVDYWGKGILVTVSSPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVE VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK

[0581] 328 IL-2Ry QVQLQESGGGLVQAGGSLRLSCAASESIAGINYMAWYRQAPGAKQR 754

[0582] VHH 89 ELVARIASVGSRYYYADSVKGRCTIARDNAKNTMDLQMNSLKPEDT GVYYCAADWSGAAWTYWGQGTQVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0583] 329 IL-2Ry EVQLVESGGGLVQTGGSLRLSCAASGSTFSINAMGWYRQAPGKQRE 755

[0584]

[0585] VHH 90 LVASIASGDRTYYADSVKGRFTISRANAKNTVYLQMNSLKPEDTAVATTORNEY DOCKET NO. 180802-049202 / PCT

[0586] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0587] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0588] YYCYADTPMI IWAQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0589] 330 IL-2Rγ QVQLVESGGGLVQPGGSLRLACAASGSISSINYMGWFRQAPGKQRE 756

[0590] VHH 97 LVAVISSDGRTNYGDSAKGRFTISRDNAKNTVYLQMNSLKPEDTAV YLCNGVTGSRVDRGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK

[0591] 331 IL-2Rγ QVQLQESGGGLVQAGGSLRLSCAASGRTFSVTHMGWFRRAPGKERE 757

[0592] VHH 98 FAAVIRWDSGNTAYADSVKGRFTISRDTTKNMVYLQMNSLKPEDTA VYYCAASNLTSTTYVYWGQGTQVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0593] 332 IL-2Rγ QLQLVESGGGLVQPGGSLRLSCTVSGSAFSITAMGWYRQPPGQQRE 758

[0594] VHH 99 LVAS I ANGGVTKYADSVEGRFTI SRDNAKNAVYLQMNSLKPEDTAV YLCYADSDGPRKNLLI YWGKGTQVTVSSPKSCDKTHTCPPCPAPEL LGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVD GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0595] 333 IL-2Rγ QVQLQESGGGLVHPGGSLRLSCAASASILSINAMGWYRQAPGKQRE 759

[0596] VHH 109 LVAVIKIVAGTYTANYADSVKGRFAISRDNAKNTLYLQMNSLKPED TAVYYCNAGSASSTQYRPNYWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0597] 334 IL-2Rγ QVQLQESGGGLVQAGGSLRLSCAASGSIFSRNAMGWFRQAPGKQRE 760

[0598] VHH 116 LVAVI S I DGRTY I ADS VQGR FT I S RDNAKNTVYLQMNS LKPEDTAV YYCAAGQTTMTSLPSYWGQGTQVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0599] 335 IL-2Rγ QVQLVESGGGLVQAGGSLRLSCAASGRTFSRYVAGWFRQAPGKERE 761

[0600] VHH 121 FVAAVSWSGVGAYYVDSVKGRFTISRDNAKNTVYLQMNSLKPEDTA VYYCTAGTMARAPEYWGQGTQVTVSAPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL

[0601]

[0602] PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPATTORNEY DOCKET NO. 180802-049202 / PCT

[0603] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0604] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0605] SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFS CS VMHEALHNHYTQKS LS LSPGK

[0606] 336 IL-2Rγ QVQLVESGGGLVQAGDSLRLSCAASGRIFSSYLMGWFRQAPGKDRE 762

[0607] VHH 124 FVGAVDRSGANTYHADSVKGRFTISRDNAKNMVYLQMNSLKPEDTA VYYCASGPRSAWSSGDYAVWGQGTQVTVSSPKSCDKTHTCPPCPAP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0608] 337 IL-2Rγ QVQLVESGGGLVQAGGSLRLSCVASGLAFSSYHMGWFRQAPGLERE 763

[0609] VHH 128 FVAVINPSGGGTYYTDSVKGRFTISRDNAKNTVYLQMNSLKPEDTA VYLCAGSNIGETSVRTGRFPAWGQGTQVTVSSPKSCDKTHTCPPCP APELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK VSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0610] 338 IL-2Rγ QVQLVESGGGTVQPGDSLTLSCAASGLTFARYTMGWYRQAPGKQRQ 764

[0611] VHH 131 LVAGISSDGRTNYADSVKGRFTISRDNAKNTLYLQMNSLKPEDTAV YYCDVATDLTLRTVLG FWGQGTQVTVS S PKS CDKTHTCPP CP APEL LGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVD GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0612] 339 IL-2Rγ QVQLVESGGGSVQPGGSLTLSCAASGTTDRLDIMAWHRQPPGQQRE 765

[0613] VHH 138 LVAI ITRDGRANYADSVKGRFTISRDNAKNTVYLRMSNVKPEDTAV YVCYGGEFPNLNYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FS CS VMHEALHNHYTQKS LS LSPGK

[0614] 340 IL-2Rγ EVQLVESGGGLVQPGGSLRLSCAASGSIFSGNAMAWYRQPPGKQRE 766

[0615] VHH 143 LVAAI TSGS S TH YVDS VKGR FT I S RDNAKNTVYLQMNS LKPEDTAV YYCNAQERVYELGYDEGSWGQGTQVTVSSPKSCDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0616] 341 IL-2Rγ EVQLVESGGGLVQPGGSLRLSCAASGSISSIAYMGWYRQVPGKQRD 767

[0617] VHH 173 LAAL I GSDS VTR YADS VKGR FT I S RDNAKNTVYLQMNS LQ PDDTAV YYCTGGIQSSYDMAWKEYWGQGTQVTVSSPKSCDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0618] 342 IL-2Rγ QLQLVESGGGLVQAGGSLRLSCVASGTTFSIAYMGWYRQAPGKQRE 768

[0619]

[0620] VHH 184 LVAL I GNEDS TR YAES AKGR FT I S RDNAKNTVYLQMNS LKPEDTANATTORNEY DOCKET NO. 180802-049202 / PCT

[0621] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0622] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0623] YYCTAGAADQQNEYRVYWGQGTQVTVSSPKSCDKTHTCPPCPAPEL LGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVD GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0624] 343 IL-2Rγ QVQLVESGGGLVQAGGSLRLSCAASGSLGRTTFMGWYRQAPGNERE 769

[0625] VHH 185 FVAQ FGSGGS TNYVDTVKGR FT I S SDNAKNRVYLQMNS LKPEDTAV YYCYALTYDSGDFRNYWGQGTQVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0626] 344 IL-2Rγ QVQLVESGGGLVQAGGSLRLSCVASGSRFNINDMGWYRQAPGKQRE 770

[0627] VHH 198 LVATAGRGGTTTYGDSVKGRFTISGDNAKNIVYLQMNSLKPEDTAV YYCNAADFMVTYWGKGTLVTVSSPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK

[0628] 345 IL-2Rγ QVQLQESGGGLMQPGGSLRLSCAAAGSFFGIAAMGWYRQAPGQQRE 771

[0629] VHH 207 LVASVAHDGRRYYADSVKGRFTISGDNAKRTAGLQMNSLKPEDTGV YYCYADDHSYGI IYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVE VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK

[0630] 346 IL-2Rγ QVQLVESGGGLVQAGGSLRLSCAASSSIRGINAFGWYRQPAGNQRF 772

[0631] VHH 216 LVARI IGGDSTYYADSVRGRFTISRDNAKSTVYLQMNSLNVDDTAV YYCAAGWTGLKWENWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVE VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK

[0632] 347 IL-2Rβ QVQLVESGGGLVQAGGSLRLSCAASGRTFSSSTMAWFRQPPGKERE 773

[0633] FVARISWSGSITSYADSVKGRFTVSRDNARNTVYLQMNSLKAEDTA VYYCAARISSSGHLGYKYWGQGTQVTVSSPKSCDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0634] 400 IL2R-β QVQLVESGGGLVQAGGSLRLSCLASGGRTFSRYDMAWFRQAPGKEP 774

[0635] VHH108 ELAAAI LSGGNTYYADSVKGRFTI SRDNAKNTVFLQMNSLKPEDTA hFc tag VYYCATDRSPGGRGRSQFDIWGQGIQVTVSSGGGGSASTKGPSVFP L234A, LAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV L235A, LQSSGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKS

[0636]

[0637] D265A CDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCWVAATTORNEY DOCKET NO. 180802-049202 / PCT

[0638] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0639] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0640] (LALADA VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQ

[0641] ) CH1- DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE CH2-CH3 LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

[0642] 401 IL2R-γ QVQLVESGGGLVQPGGSLRLSCAGSRSIFSGNPMAWFRQAPGKQRE 775

[0643] VHH57 LVALVSSGGSHTDYADSVLGRFTISRDDAKNMVYLQMNSLKPEDTA CL1 Kappa VY YCNH PVDTPLTKWGQGTQVTVS S GGGGSRTVAAPSVFI FPPSDE QLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK D S TY S L S S TLTL S KAD YE KHKVYACE VTHQGL S S PVTKS FNRGE C

[0644] 402 IL2R-β QVQLVESGGGLVQAGGSLRLSCLASGGRTFSRYDMAWFRQAPGKEP 776

[0645] ABTx-452 ELAAAI LSGGNTYYADSVKGRFTI SRDNAKNTVFLQMNSLKPEDTA P102A VYYCATDRSAGGRGRSQFDIWGQGIQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0646] 403 IL2R-β QVQLVESGGGLVQAGGSLRLSCLASGGRTFSRYDMAWFRQAPGKEP 777

[0647] ABTx-452 ELAAAI LSGGNTYYADSVKGRFTI SRDNAKNTVFLQMNSLKPEDTA P102G VYYCATDRSGGGRGRSQFDIWGQGIQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0648] 404 IL2R-β QVQLVESGGGLVQAGGSLRLSCLASGGRTFSRYDMAWFRQAPGKEP 778

[0649] ABTx-452 ELAAAI LSGGNTYYADSVKGRFTI SRDNAKNTVFLQMNSLKPEDTA Pl 02 A VYYCATDRSAKGRGRSQFDIWGQGIQVTVSSPKSCDKTHTCPPCPA G103K PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0650] 405 IL2R-β QVQLVESGGGLVQAGGSLRLSCLASGGRTFSRYDMAWFRQAPGKEP 779

[0651] ABTx-452 ELAAAI LSGGNTYYADSVKGRFTI SRDNAKNTVFLQMNSLKPEDTA Pl 02 A VYYCATDRSARGRGRSQFDIWGQGIQVTVSSPKSCDKTHTCPPCPA G103R PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0652] 406 IL2R-β QVQLVESGGGLVQAGGSLRLSCLASGGRTFSRYDMAWFRQAPGKEP 780

[0653] ABTx-452 ELAAAI LSGGNTYYADSVKGRFTI SRDNAKNTVFLQMNSLKPEDTA P102G VYYCATDRSGKGRGRSQFDIWGQGIQVTVSSPKSCDKTHTCPPCPA G103K PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0654] 407 IL2R-β QVQLVESGGGLVQAGGSLRLSCLASGGRTFSRYDMAWFRQAPGKEP 781

[0655] ABTx-452 ELAAAI LSGGNTYYADSVKGRFTI SRDNAKNTVFLQMNSLKPEDTA

[0656]

[0657] VYYCATDRSGRGRGRSQFDIWGQGIQVTVSSPKSCDKTHTCPPCPAATTORNEY DOCKET NO. 180802-049202 / PCT

[0658] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0659] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0660] P102G PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW G103R YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0661] 455 IL2Rβ QVQLVE SGGGLVQTGE SLRLS CAASGRTVS TY PMAWFRQAPGKERE 782

[0662] VHH1-2 FVSTISWNGGDTYYADSVKGRFTISKDNAKNTVYLQMNSLKPEDTA VYYCAAHRRRYATSWSRSPDEYDYWGQGTQVTVSSPKSCDKTHTCP PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKS RWQQGNVF S CS VMHEALHNH YTQKS L S L SPGK

[0663] 456 IL2Rβ EVQLVESGGGLVQPGGSLRLSCAASGFTLDDYAIGWFRQAPGKERE 783

[0664] VHH4-2 GVREGVSCISSSDGTTYSADSVKGRFTISRDNAKNTVYLQMNSLKP EDTAVYYCATVGSSCRNSDRPLEVWGQGTLVTVSSPKSCDKTHTCP PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKS RWQQGNVF S CS VMHEALHNH YTQKS L S L SPGK

[0665] 458 IL2Rβ QVQLVESGGGLVQAGGSMRLSCAAATRTFDNYAMGWFRQAPAKERE 785

[0666] VHH10-2 SVAVISWSGSSTDYVDSVKGRFTISRDNAKNMVYLQMNSLKPEDTA VYYCAALRRGWQPRGGPYEVDTWGQGTQVTVSSPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0667] 459 IL2Rβ QVQLQESGGGLVQAGGSLRLSCAAATRTFNNYAMAWFRQAPAKERE 786

[0668] VHH15-2 SVAVISWSGSSTDYVDSVKGRFTISRDNAKNTVYLQMNSLKPEDTA VYYCAALRRGWQPRGGPYEVDTWGQGTQVTVSSPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0669] 460 IL2Rβ QLQLVESGGGWVQAGGSLRLSCVFSGHAFSGYSMAWFRQAPAKERE 787

[0670] VHH18-2 SVAWNWSGSTTDYVHSVKGRFTISRDNAKNTVYLQMNSLKPEDTA VYYCAALQRGTVQPRGGPYEVDTWGQGTQVTVSSPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0671] 461 IL2Rβ QVQLVESGGGLVQAGGSLRLSCAASGRTFSRYFMGWFRQTPGKERE 788

[0672] VHH31-2 FVAALRWSTGSAYGANSVKGRFTISRDNDKNTVHLHMNSLKPEDTA VYYCAASSQDYVSDYTRLSVYDYWGQGTQVTVSSPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK

[0673]

[0674] CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTATTORNEY DOCKET NO. 180802-049202 / PCT

[0675] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0676] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0677] CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0678] 462 IL2Rβ QVQLVESGGGLVQAGGSLTLSCAASGRTFSRYFMGWFRQTPGKERE 789

[0679] VHH39-2 FVAALRWSTGSAYGANSVKGRFTISRDNAKNTVSLHMNSLKPEDTA VYYCAASSQDYVSDYTRLSI YDYWGQGTQVTVSSPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0680] 463 IL2Rβ QVQLVESGGGLVQAGDSLRLSCAASGRTFSSYVMGWFRQTPGKERD 790

[0681] VHH42-2 FVAVISESDGRTHYADSVKGRFTISRDNVKNMVYLQMNSLKPEDTA VYYCAGALGSKYGSTWRGDFASWGQGTQVTVSSPKSCDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKF NWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKC KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0682] 464 IL2Rβ QVQLVESGGGLVQAGGSLKLSCVASGRTFSTYGMGWFRQAPGKERE 791

[0683] VHH43-2 FVAAVAWSGGPTFYSDSVKGRFTMSRDNAKNTVYLQMNSLKAEDTG VYYCARARLPYGLGKSSSDFGPWGQGTQVTVSSPKSCDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKF NWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKC KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0684] 465 IL2Rβ QVQLQE SGGGLVQSGGSLKLS CAASGM I LS I FR I NDMGWYRQAPGK 792

[0685] VHH45-2 QRELVGSISSGGTTNYADSVKGRFTISRDNAKNTTSLQMNSLKPED TAVY YCNANI KFVRWR PPRD YWGRGTQVTVS S PKS CDKTHTCPP CP APELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK VSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0686] 466 IL2Rβ QVQLVESGGGLVQPGGSLRLSCAASGFTLDDYAIGWFRQAPGKERE 793

[0687] VHH48-2 GVSCISSSDGSTYSADSVKGRFTISRDNAKNTVYLQMNSLKPEDTA VYYCATVGSSCRNSDRPLEVWGQGTLVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0688] 467 IL2Rβ QVQLVESGGGLVQPGGSLRLSCAASGFTLDDYAIGWFRQAPGKGRE 794

[0689] VHH52-2 GVSCISSSDGSTYSADSVKGRFTISRDNAKNTVYLQMNSLKPEDTA VYYCATVGSRCRNSDRPLEVWGQGTLVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0690] 468 IL2Rβ EVQLVESGGGLVQPGGSLRLSCAASGFTLDDYAIGWFRQAPGKGRE 795

[0691]

[0692] VHH54-2 GVSCISSSDGSTYSADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAATTORNEY DOCKET NO. 180802-049202 / PCT

[0693] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0694] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0695] VYYCATVGSDCRNSDRPLEVWGQGTLVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0696] 469 IL2Rβ EVQLVESGGGLVQAGGSLRLSCAASGRTFSNYAVGWFRQAPGKERE 796

[0697] VHH57-2 FVALINWSGDDTYYAHAVKGRFTISRDNAKNTVYLQMNSVKPDDTA VYYCAANPAGGSSYDRTYPYWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0698] 470 IL2Rβ EVQLVESGGGLVQPGGSLRLSCAASGFTLDDYAIGWFRQAPGKGRE 797

[0699] VHH62-2 GVSCISSSDGSTYSADSVKGRFTISRDNAKNTVYLQMNSLKPEDTG VYYCATVGSSCRNSDRDLEVWGQGTLVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0700] 471 IL2Rβ QLQLVESGGGLVQPGGSLRLSCTASGFTFSSYAMSWVRQAPGKGLE 798

[0701] VHH67-2 WVSS INSGGDSTTYADSVKGRFTI SRDNAKNTLYLQMNSLKPEDTA VYYCAKWSDSTGVAGHATGGWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0702] 472 IL2Rβ QVQLQESGGGLVQPGGSLRLSCAASGFTLDDYAIGWFRQAPGKERE 799

[0703] VHH68-2 GVSCISSSDGSTYSADSVKGRFTISRDNAKNTVYLQMNSLKPEDTA VYYCATVGSSCRNQDRDLEVWGQGTLVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0704] 473 IL2Rβ QVQLQESGGGSVQPGGSLRLSCAASGFTLDDYAIGWFRQAPGKGRE 800

[0705] VHH71-2 GVSCISSSDGSTYSADSVKGRFTISRDNAKNTVYLQMNRLKPEDTA VYYCATVGSSCRDSDRPLEVWGQGTLVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0706] 474 IL2Rβ EVQLVESGGGLVQAGGSLRLSCAASGFTFDDYAMNWVRQAPGKGLE 801

[0707] VHH83-2 WVSAISWNGDDTNYADSVKGRFTISRDNAKNTLYLQMNSLKSEDTA VYYCAKGSLPTLDGSATGGGQGTQVTVSSPKSCDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSN

[0708]

[0709] KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGATTORNEY DOCKET NO. 180802-049202 / PCT

[0710] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0711] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0712] FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0713] 475 IL2Rβ QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLE 802

[0714] VHH84-2 WVSAIDSGGGSTDYADSVKGRFTISRDNAKSTLYLQMNSLKPEDTA VYYCAKFEGAGLYGRSHGGGQGTQVTVSSPKSCDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0715] 476 IL2Rβ QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLE 803

[0716] VHH85-2 WVSGINSGGGSTDYADSVKGRFTISRDNAKNTLYLQMNSLKPEDTA VYYCAKFEGDGLYGRSHGGGQGTQVTVSSPKSCDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0717] 477 IL2Rβ QVQLVESGGGLVQPGGSLRLSCAATGTIFSRNIMGWYRQAPGKERE 804

[0718] VHH86-2 LVADIASGGSIKYADSAKGRFTISRDNAKNTMDLQMNILNPEDTAV YYCNVRHRASFMLTYVEVWGQGTLVTVSSPKSCDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0719] 478 IL2Rβ QLQLVESGGGLVQPGGSLRLTCAASGFTFSRYPMSWARQAPGKGLE 805

[0720] VHH87-2 WVSTLSQDGGTTAYEPSVKGRFTISRDNAKNTLYLQMNNLEPEDTA VYFCAKGPPPFGPETTWGQGTQVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0721] 479 IL2Rβ QVQLVESGGGLVQAGGSLRLSCAASGI I FGINAWAWAWYRQAPGKQ 806

[0722] VHH88-2 RELVAVITSGGITNYTDFVKGRFTISRDNALKAVYLQMNSPKPEDT GVYFCNIRAYTGHNGFWGQGIQVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0723] 480 IL2Rβ QLQLVESGGGLVQPGGSLRLSCAASRSIESINGMGWYRQAPGKQRE 807

[0724] VHH92-2 LVAFISRSGSTMYADSVKARFTISRDNAKNTVYLQMNSLKPEDTAV YYCNVAGYGGSHYWEWGQGTQVTVSSPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFS CS VMHEALHNHYTQKS LS LSPGK

[0725] 481 IL2Rβ QVQLQESGGGLVQPGGSLRLSCAASRSIDSINAMGWYRQAPGKQRE 808

[0726]

[0727] VHH93-2 LI TI I TRSGS TM YGDS VKGR FT I S RDNAKNTVYLQMNS LKAEDTAVATTORNEY DOCKET NO. 180802-049202 / PCT

[0728] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0729] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0730] YYCNVAGYGGSHFWEWGQGTQVTVSSPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFS CS VMHEALHNHYTQKS LS LSPGK

[0731] 482 IL2Rβ QVQLVESGGGLVQAGGSLRLSCAASGRTSSSHSMGWFRQAPGKARE 809

[0732] VHH96-2 FVADINWKSGISNYADSLKGRFAISRDSAKNTGYLQMNSLKPEDTA VYYCAASKDGRTYDYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFS CS VMHEALHNHYTQKS LS LSPGK

[0733] 483 IL2Rβ QVQLVESGGGLVQPGGSLRLSCAASGIAFSSYIMGWYRQAPGKQRE 810

[0734] VHH99-2 LVATITASGNLKDYIDSVKGRFAISRDNAKNSVYLQMNNLKPDDTA LYQCNLGIGPRNDYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVE VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK

[0735] 484 IL2Rβ EVQLVESGGGLVQPGGSLRLSCAASGIAFSSYIMGWYRQAPGKQRE 811

[0736] VHH 100-2 LVATISASGNLKDYIDSVKGRFAISRDNAKNSVYLQMNNLKPDDTA LYQCNLGIGPRNEYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVE VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK

[0737] 485 IL2Rβ EVQLVESGGGLVQAGGSLRLSCAGSGDI FSFI PMAWYRQAPGKQRE 812

[0738] VHH108-2 WVAT I TTSGATTYTDS VKGR FAI S RGNDKKTVYLQMNS LR PEDTAV YYCNVANAAVSRNWGPGTQVTVSSPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FS CS VMHEALHNHYTQKS LS LSPGK

[0739] 486 IL2Rβ QVQLVESGGGLVQAGGSLRLSCAGSGDI FSFI PMAWYRQAPGKQRE 813

[0740] VHH 112-2 WVAT I TTSGTTTYTDS VKGR FT I S RDNVKKTWLQMNS LR PEDTAV YYCNVANAAVYRNWGPGTQVTVSSPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FS CS VMHEALHNHYTQKS LS LSPGK

[0741] 487 IL2Rβ QVQLVESGGGLVQAGGSLRLSCTGSGDI FSFI PMAWYRQAPGKQRE 814

[0742] VHH113-2 WVAT I TTS GTTT YTDS VKGR STIS RGNDKKTVYLQMNS LR PE DTAV YYCNVANAAVSRNWGPGTQVTVSSPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA

[0743]

[0744] PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDATTORNEY DOCKET NO. 180802-049202 / PCT

[0745] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0746] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0747] IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FS CS VMHEALHNHYTQKS LS LSPGK

[0748] 488 IL2Rβ QVQLQESGGGLVQPGGSLRLSCAASGISVSRYAMGWYRQPPGKQRE 815

[0749] VHH 117-2 LVAVI LS ADTTNYADS VKGR FT I S RDNAKNTVYLQMNS LKPEDTAV YFCNEIGKVHSWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0750] 489 IL2Rβ QVQLVESGGGLVQPGGSLRLSCAASGISVSRYAMGWYRQPPGKQRE 816

[0751] VHH118-2 LVAV I L S ADTTN YAD P VKGR FT I S RDNAKNTVYLQMNS LKPE DTAV YFCNEIGKVHSWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0752] 490 IL2Rβ QVQLQESGGGLVQPGGSLRLSCAVSESIFSMYMMGWYRQAPGKQRE 817

[0753] VHH 125 -2 LVAI VS RGGATNYADS VKGR FT I S RDDAKNTVYLQMNS LE PEDTAV YYCNEVGQTLHWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0754] 491 IL2Rβ QVQLVESGGGLVQPGGSLRLSCAASGISVSRYAMGWYRQPPGKQRE 818

[0755] VHH133-2 LVAVI LS ADTTNYADS VKGR FT I S RDNAKNTVYLQMNS LKPEDTAV YFCNEIGKVHPWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0756] 492 IL2Rβ QVQLVE SGGGLVQAGGSLRLS CAQSGGS R I NAMGWYRQAPGKQREL 819

[0757] VHH141-2 VAALI PGGNTRYADSVKGRFTI SRDNAKNTVYLQMNSLKPDDTAVY YCNEVGRLWDWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNA KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK

[0758] 493 IL2Rβ QVQLVESGGGLVQPGGSLRLSCAASGTFFSGTGWWYREAPGKRRE 820

[0759] VHH148-2 WIATVSVEDNTYYADSVKGRFTISKDNAKNTAFLQLNSLKPEDTAV YYCKASNYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV MHEALHNHYTQKSLSLSPGK

[0760] 536 IL2Rβ EVQLVESGGGLVQAGGSLRLSCAASGSVADIVTMAWYRQTPGKQRE 823

[0761]

[0762] VHH 149-2 LVAYITRGDITYYSDFAKGRFTISRDNARNTVALQGLNLRPEDTAVATTORNEY DOCKET NO. 180802-049202 / PCT

[0763] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0764] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0765] YYCKGAAGLAEYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK

[0766] 537 IL2Rβ QVQLVESGGGLVQPGGSLRLSCAASGFTFDSYVMSWVRQAPGKGLE 824

[0767] VHH154-2 WVSDISTDGGVATYIDSVKGRFTISRDNAKNTLYLQMNSLKAEDTA VYYCAKDLFPDGTTTWGMLVPYDYWGQGTQVTVSSPKSCDKTHTCP PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKS RWQQGNVF S CS VMHEALHNH YTQKS L S L SPGK

[0768] 538 IL2Rβ EVQLVESGGGLVQAGGSLRLSCAASGRTFSSYGVGWFRQAPGKDRE 825

[0769] VHH170-2 FVAGINWSGGETYYADSMKGRFTISRDNAKNAVYLQMNSLKPEDTA VYGCAACYACSFKDDYTYNYWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0770] 539 IL2Rβ EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLE 826

[0771] VHH175-2 WVSAIDSGGGSTEYADSVKGRFTISRDNAKNTLYLQLNSLKPEDSA VYYCAKFEGAMLAGISRSWGQGTRVTVSSPKSCDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0772] 540 IL2Rβ QLQLVESGGGLVQAGGSLRLSCTASGSTFSSYAMGWYRQAPGKQRE 827

[0773] VHH201-2 LVAYISSAGSTDYTSSVKGRFAISRDNAKNTVYLQMNSLKPEDTAV YYCNELGRIASWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0774] 541 IL2Rβ QLQLVESGGGLVQPGGSLRLSCAASGFTLDYYAIGWFRQAPGKERE 828

[0775] VHH214-2 GVSCINSSDGRTYSADSVKGRFTISRDNAKNTVYLQMNSLKPEDTA VYYCATVPGACTVAAGTSHDTGYLEVWGQGTLVTVSSPKSCDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDP EVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGK EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0776] 542 IL2Rβ QLQLVESGGGLVQPGGSLRLSCAASGFTLDYYAMGWFRQAPGKERE 829

[0777] VHH215-2 GVSCINSDGRTYSADSVKGRFTISRDNAKNTVYLQMNSLKSEDTAV YYCATVGNSCVGDKEGDLEVWGQGTLVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV

[0778]

[0779] SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVATTORNEY DOCKET NO. 180802-049202 / PCT

[0780] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0781] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0782] KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0783] 543 IL2Rβ QLQLVESGGGLVRPGGSLRLSCAASGFTLDYYAIGWFRQAPGKERE 830

[0784] VHH220-2 GVSCISSSDGSTYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTA VYYCATLSECVGGTVPDLEVWGQGTLVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0785] 544 IL2Rβ QVQLQESGGGLVQPGGSLRLSCAASGSFFSINAMGWYRQAPGNQRE 831

[0786] VHH228-2 LVATIRTGEGSTNYAHSVKGRFTISKDNAKNTVYLQMNSLKPEDTA VYYCNANSVRDWSGKRYLEVWGQGTLVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0787] 545 IL2Rβ QVQLQESGGGSVHSGESLRLSCAASGSFFSINAMGWYRQAPGNQRE 832

[0788] VHH230-2 LVATIRTGEGSTNYAHSVKGRFTISKDNAKNTVYLQMNSLKPEDTA VYYCNANSVRDWSGERYLEVWGQGTLVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0789] 546 IL2Rβ QVQLVESGGGLVEVGGSLTLSCAASGRTFSSYAMAWFRQAPGKGRE 833

[0790] VHH234-2 FVAAISWSGGTYYADSVKGRFTISRDNAKNSVYLHMNHLKPEDTAD YYCSADFSGRGWGPGVRYDYWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0791] 547 IL2Rβ QVQLVESGGGLVQAGDSLRLSCAASGRAFSTYAMGWFRQPPGKERE 834

[0792] VHH235-2 FVAG IDWSGDSTHY PADS VKGR FT I S RDNAKNTVYLQMNS LKPE DT AVYYCAAD PRGS LVMGNS WI YWGQGTQVTVS S PKS CDKTHTCPP CP APELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK VSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0793] 548 IL2Rβ QVQLVESGGGLVQAGDSLRLSCAASGRTFSMYAWAWFRQAPGKERE 835

[0794] VHH236-2 LVAS I VWSGEMSNYADSVKGRFTI SRDNAKNTVYLQMYSLKPEDTA VYYCAARTVFSETYHTWGQGTQVTVSSPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPGK

[0795] 549 IL2Rβ QVQLVESGGGLVQAGGSLRLSCAASESTFSIKSWGMGWYRRAPGKQ 836

[0796]

[0797] VHH241-2 RELVAVI TSGGS TNYADS VKGR FT I S RDNAKNTVYLQMNS LKPEDAATTORNEY DOCKET NO. 180802-049202 / PCT

[0798] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0799] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0800] AVYYCNEIGRVWDWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FS CS VMHEALHNHYTQKS LS LSPGK

[0801] 550 IL2Rβ QVQLVESGGGLVQAGGSLRLSCAASGRAFSSSAMGWFRQAPGKERE 837

[0802] VHH245-2 FVAAI S WSGDSTHYEDSVKERF I I SRDNAKNTVYLQMNSLKPEDTA VY YCAADTFRRTMVAGNS WNYWGQGTQVTVS S PKS CDKTHTCPP CP APELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK VSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0803] 551 IL2Rβ QVQLVESGGGLVQAGGSLRLSCAASGRTFISYGVGWFRQAPGKERE 838

[0804] VHH246-2 FVAGINWSGDETYYANSVKGRFTISRDNAKNAVFLQMNSLKPEDTA VYYCAACFACSFKDDYTYNYWGRGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0805] 552 IL2Rβ QVQLVESGGGLVQAGGSLRLSCAASGRTFRNDDMLGWFRQAPGKER 839

[0806] VHH247-2 EFVATITWSGIMTSYTDSVKGRFTISRDSAKNMGYLEMKRLKPEDT AVYYCATGVKVGTSRYDYVYWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0807] 553 IL2Rβ QVQLVESGGGLVQAGGSLRLSCAASGRTFRNYDMLGWFRQAPGKER 840

[0808] VHH248-2 EFVATITWSGIMISYTDSVKGRFTISRDSAKNMGYLEMKRLKPEDT AVYYCATGEKVGTSRYDYVYWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0809] 554 IL2Rβ QVQLVESGGGLVQAGGSLRLSCAASGRTFSNYAMGWFRQAPGKERE 841

[0810] VHH249-2 FLATYSWSHRSTYYADSVKGRFTISRDNVKNTVYLQMNSLSPEDTA VYYCAAGRLTTIATKGDDGYDYWGQGTQVTVSSPKSCDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKF NWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKC KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0811] 555 IL2Rβ QVQLVESGGGLVQAGGSLRLSCAASGRTFSNYAVGWFRQAPGKERE 842

[0812] VHH258-2 FVALINWSGDDTYYANAVKGRFTVSRDNAKNTVYLQMNSVKPGDMA VYYCAANPAGGSSFDRTYPYWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV

[0813]

[0814] SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVATTORNEY DOCKET NO. 180802-049202 / PCT

[0815] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0816] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0817] KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0818] 556 IL2Rβ QVQLVESGGGLVQAGGSLRLSCAASGRTFSSYAMGWFRQAPGKERE 843

[0819] VHH265-2 FVAAISSSGGTTLYEDSVKGRFTISRDNAKNTVYLQMNSLKAEDTA VYYCILDSDPTRGSLVRGNSWDYRGQGTQVTVSSPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0820] 557 IL2Rβ QVQLVESGGGLVQAGGSLRLSCASSGFAFSNYAMGWFRQAPGKERE 844

[0821] VHH272-2 FVAVI S FTGGVAYDADSVQGRFRI SRENAKNTVYLQMNSLKPEDTA VYYCAARRYYGSRLDREYDYWGQGTQVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0822] 558 IL2Rβ QVQLVESGGGLVQAGGSMRLSCAAATRTFDNYAMGWFRQAPAKERE 845

[0823] VHH275-2 SVAVISWSGSSTDYVDSVKGRFTISRDNAKNMVYLQMNSLKPEDTA VYYCAALRRGAVQPRGGPYEVDTWGQGTQVTVSSPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0824] 559 IL2Rβ QVQLVESGGGLVQPGGSLRLSCAASENILDVDIMGWFRQAPGKQRE 846

[0825] VHH277-2 SLAAISVIGGTAYEDSVKGRFTISVDNAKNTAYLQMNSLKPDDTAI YYCNLRRVRPRI IDYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFS CS VMHEALHNHYTQKS LS LSPGK

[0826] 560 IL2Rβ QVQLVESGGGLVQPGGSLRLSCAASGFRFSGNFIGWYRQAPGKQRE 847

[0827] VHH280-2 LVAY I S SGGGTTYADS VKGR FT I S RDNAKNTVYLQMNS LKPEDTAV YYCNEVGAVYNWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS CS VMHEALHNHYTQKS LS LSPGK

[0828] 561 IL2Rβ QVQLVESGGGLVQPGGSLRLSCAASGFTLDYYAIGWFRQAPGKERE 848

[0829] VHH285-2 GVSCISSSDGNTYSADSVKGRFTISRDTAKNTVYLQMNSLKPEDTA VYYCATVPGGCTVTHSTEPQERYLEVWGQGTLVTVSSPKSCDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDP EVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGK EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0830] 562 IL2Rβ QVQLVESGGGLVQPGGSLRLSCAASGRTFTTLDMGWFRQAPGKERE 849

[0831]

[0832] VHH290-2 FVGGIDWSGAMTKYADSVKGRFSISRDNAKNTVSLQMNSLKPEDSAATTORNEY DOCKET NO. 180802-049202 / PCT

[0833] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0834] Antibod Antibody Sequence3SEQ y Descriptio ID Identifie n2NO r

[0835] LYYCAAKSYLRGSFVAGDWGQGTQVTVSSPKSCDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0836] 563 IL2RP QVQLVESGGGLVQPGGSLRLSCAASGSFFSISAMGWYRQAPGNQRE 850

[0837] VHH294-2 LVATIRTGGGSTNYADSVKGRFTISKDNAKNTVYLQMNSLKPEDTA VYYCNADSVRDWSGKRYLEVWGQGTLVTVSSPKSCDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0838] 564 IL2RP QVQLVESGGGLVQPGGSLRLSCAQSGGSRINAMGWYRQAPGKQREL 851

[0839] VHH295-2 VAALI PGGNTRYADSVKGRFTI SRDNAKNTVYLQMNSLKPDDTAVY YCNEVGRLWGWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNA KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK

[0840] 565 IL2RP QVQLVESGGGLVQTGGSLRLSCAASGRTFSTYPMAWYRQAPGKERE 852

[0841] VHH304-2 FVSTISWNGGDTYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTA VYYCAVHRRRYASSWSRSPDEYDYWGQGTQVTVSSPKSCDKTHTCP PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKS RWQQGNVF S CS VMHEALHNH YTQKS L S L SPGK

[0842] 566 IL2RP QVQLVESGGGLVQVGDSLRLSCAASGRTFSSYAMGWFRQAPGKERE 853

[0843] VHH305-2 FVAAI S WSGGSTYYADSVKGRFTI SRDNAKNTVYLQMNSLKPEDTA VY YCAS DLQR YGLG YG PGTVYENWGQGTQVTVS S PKS CDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVK FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0844] 567 IL2RP QVQLVESGGGLVRPGGSLRLSCVASGSIFSMMAMGWYRQAPGKQRD 854

[0845] VHH307-2 MVAY I HS SGGTNYADS VRGR FT I S RDNAKNTM YLQMS S LKPEDTAV YYCNEVGRLWPWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS

[0846]

[0847] CS VMHEALHNHYTQKS LS LSPGK

[0848] Table B provides CDR sequences calculated according to the indicated methods for a representative VHH domain capable of binding IL2RP, namely VHH antibody 536 of Table A.

[0849] In various embodiments, any of the VHH domains capable of binding IL2RP listed in Table AATTORNEY DOCKET NO. 180802-049202 / PCT

[0850] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0851] contain one or more CDRs containing amino acids aligning to a region in the below multiple sequence alignment corresponding to a CDR of VHH antibody 536 listed in Table A (e.g., a CDR1 containing those amino acids corresponding to GSVAD- - IV (SEQ ID NO: 857), which is the portion of the multiple sequence alignment corresponding to GSVADIV (SEQ ID NO: 858) in the below alignment).

[0852] Table B. CDR amino acid sequences calculated according to the indicated numbering schemes for antibody 536 of Table A.

[0853] CDR Numbering CDR Sequence SEQ ID

[0854] Method Used NO

[0855] to Calculate

[0856] the CDR

[0857] CDR1 Chothia GSVADIV 858

[0858] CDR1 AbM GSVADIVTMA 859

[0859] CDR1 Kabat IVTMA 860

[0860] CDR1 Contact DIVTMA 861

[0861] CDR1 IMGT GSVADIVT 862

[0862] CDR2 Chothia TRGDI 863

[0863] CDR2 AbM YITRGDITY 864

[0864] CDR2 Kabat YITRGDITYYSDFA 865

[0865] KG CDR2 Contact LVAYITRGDITY 866

[0866] CDR2 IMGT I TRGDI T 867

[0867] CDR3 Chothia AAGLAEY 868

[0868] CDR3 AbM AAGLAEY 868

[0869] CDR3 Kabat AAGLAEY 868

[0870] CDR3 Contact KGAAGLAE 869

[0871]

[0872] CDR3 IMGT KG AAGLAEY 870

[0873] A multiple sequence alignment of representative VHH antibodies capable of binding IL2RP is provided below. The hFc domain of VHH antibody 536 is shown in bold in the below multiple sequence alignment, and the regions of the alignment corresponding to CDR domains of the VHH domain of antibody 536 calculated using the Chothia numbering scheme are shown in bold underlined text.

[0874] 536 EVQLVESGGGLVQAGGSLRLSCAAS -■GSVAD- -IV TMAWYRQTPGKQ - RELVAY

[0875] 478 QLQLVESGGGLVQPGGSLRLTCAAS- GFTFS- -RY- > PMSWARQAPGKG- ■ LEWVST

[0876] 474 EVQLVESGGGLVQAGGSLRLSCAAS -GFTFD- -DY - AMNWVRQAPGK - LEWSA

[0877] 537 QVQLVESGGGLVQPGGSLRLSCAAS - GFTFD - - SY VMSWVRQAPGKG - ■ LE VSD

[0878] 291 QLQLVESGGGLVQPGGSLRLSCAAS -GFTFS- -RY - AMSWVRQVPGK - LEWSG

[0879] 306 QVQLVESGGGLVQPGGSLRLSCAAS - GFTFS - - RY- > AMSWVRQVPGKG - ■ LEWVSG

[0880] 317 QVQLVESGGGSVQAGDSLRLSCAAS -GFTFS- -RY - AMSWVRQVPGKG - LEWVSG 289 QLQLVESGGGLVQPGGSLRLSCAAS -GFTFS- -RY- > AMSWVRQVPGKG- ■ LEWVSG

[0881] 302 QVQLVESGGGLVQPGGSLRLSCAAS -GFTFS- -RY - AMSWVRQVPGKG - LEWVSG

[0882] 290 QLQLVESGGGLVQPGGSLRLSCAAS -GFTFS- -RY- > AMSWVRQVPGKG- ■ LEWVSG

[0883] 304 QVQLVESGGGLVQPGGSLRLSCAAS -GFTFS- -RY - AMSWVRQVPGKG - LEWVSGATTORNEY DOCKET NO. 180802-049202 / PCT

[0884] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0885] 305 QVQLVESGGGLVQPGGSLRLSCAAS - GFTFS - - RY -AMSWVRQVPGKG- - LEWVSG 303 QVQLVESGGGLVQPGGSLRLSCAAS - GFTFS - - Y - AMSWVRQVPGKG - - LEWVSG 292 QLQLVESGGGLVQPGGSLRLSCAAS - GFTFS - - SY -AMSWVRQAPGKG- - LEWVSA 471 QLQLVESGGGLVQPGGSLRLSCTAS - GFTFS - - SY - AMSWVRQAPGKG - - LEWVSS 539 EVQLVESGGGLVQPGGSLRLSCAAS - GFTFS - - SY -AMSWVRQAPGKG- - LEWVSA 475 QVQLVESGGGLVQPGGSLRLSCAAS - GFTFS - - SY - AMSWVRQAPGKG - - LEWVSA 476 QVQLVESGGGLVQPGGSLRLSCAAS - GFTFS - - S Y -AMSWVRQAPGKG- - LEWVSG 278 EVQLVESGGGPVQAGGSLRLSCAAS-GRTFTFSRH - DMGWFRQS PGKE - - REFVAG 552 QVQLVESGGGLVQAGGSLRLSCAAS - GRTFR - -ND DMLGWFRQAPGKE - - REFVAT 553 QVQL VE SGGG LVQAGGS LRLSC AAS - GRTFR - - NY DMLGWFRQAPGKE- - REFVAT 287 EVQLVESGGGLVQAGGSLRLSCWS - GYTFN - -NY - NMAWFRQAPGKE HELERE FV S 557 QVQL VE SGGG L VQ GG S LRL S C S S - GFAFS - - NY - MGWFRQAPGKE - -REFVAV 280 QVQLVESGGGSVQAGGSLRLSCAAS- IRTFS- -SD - SMAWFRQAPGKE - -REFVGG 463 QVQLVESGGGLVQAGDSLRLSCAAS - GRTFS - - SY -VMGWFRQ PGKE- -RDFVAV 461 QVQLVESGGGLVQAGGSLRLSCAAS - GRTFS - - RY - FMGWFRQTPGKE - -REFVAA 462 QVQLVESGGGLVQAGGSLTLSCAAS - GRTFS - - RY - FMGWFRQTPGKE - -REFVAA 279 QVQL VE SGGGLVQAGG S L RL S CAAS - GRT FS - - G Y - AMAWFRQAPGKE - -REFVAG 286 EVQLVESGGGLVQAGGSLRLSCVAS - GRTFS - - RY - DMAWFRQAPGKE - EPELAAA 301 QVQLVESGGGLVQAGGSLRLSCVAS ■■ GRTFS - - RY - DMAWFRQAPGKE ■■ EPELAAA 294 QVQLQESGGGLVQAGGSLRLSCLAS ■■ GRTFS - -TY - DMAWFRQAPGKE - - PALAAA 407 QVQLVESGGGLVQAGGSLRLSCLASGGRTFS - - RY - DMAWFRQAPGKE ■■ - PELA A 406 QVQLVESGGGLVQAGGSLRLSCLASGGRTFS - -RY - DMAWFRQAPGKE - - PELAAA 405 QVQLVESGGGLVQAGGSLRLSCLASGGRTFS - - RY - DMAWFRQAPGKE ■■ - PELAAA 404 QVQLVESGGGLVQAGGSLRLSCLASGGRTFS - -RY - DMAWFRQAPGKE - - PELAAA 300 QVQLVESGGGLVQAGGSLRLSCLASGGRTFS - - RY - DMAWFRQAPGKE ■■ - PELAAA 402 QVQLVESGGGLVQAGGSLRLSCLASGGRTFS - -RY - DMAWFRQAPGKE - - PELAAA 403 QVQLVESGGGLVQAGGSLRLSCLASGGRTFS - - RY - DMAWFRQAPGKE ■■ - PELAAA 562 QVQLVESGGGLVQPGGSLRLSCAAS -GRTFT- -TL -DMGWFRQAPGKE- -REFVGG 455 QVQLVESGGGLVQTGESLRLSCAAS -GRTVS- -TY - PMAWFRQAPGKE ■■ -REFVST 565 QVQLVESGGGLVQTGGSLRLSCAAS ■■ GRTFS - -TY - MAWYRQAPGKE - -REFVST 281 QVQLVESGGGLVQAGGSLRLSCA S -GRTFS- -DI - NMAWFRQAPGKE ■■ -RDFVAG 316 QVQLVESGGGLVQVGDSLRLSCAAS - GRTFS - - KD - FMAWFRQAPGKE - -REFVAA 546 QVQLVESGGGLVEVGGSLTLSCAAS -GRTFS- -SY - AMAWFRQAPGKG - -REFVAA 347 QVQLVESGGGLVQAGGSLRLSCAAS -GRTFS - -SS - TMAWFRQPPGKE - -REFVAR 548 QVQLVESGGGLVQAGDSLRLSCAAS -GRTFS- -MY - AWAWFRQAPGKE - -RELVAS 554 QVQLVESGGGLVQAGGSLRLSCAAS - GRTFS - -NY - AMGWFRQAPGKE - -RE FLAT 566 QVQLVESGGGLVQVGDSLRLSCAAS -GRTFS- -SY - AMGWFRQAPGKE - -REFVAA 299 QVQLVESGGGLVQAGGSLRLSCAGS - GRTFS - - SY - AMGWFRQAPGKE - -REFVAA 550 QVQLVESGGGLVQAGGSLRLSCAAS - GRAFS - - S S - AMGWFRQAPGKE - -REFVAA 547 QVQLVESGGGLVQAGDSLRLSCAAS - GRAFS - - TY - AMGWFRQPPGKE - -REFVAG 469 EVQLVESGGGLVQAGGSLRLSCAAS -GRTFS- -NY - AVGWFRQAPGKE - -REFVAL 555 QVQLVESGGGLVQAGGSLRLSCAAS - GRTFS - -NY - AVGWFRQAPGKE - -REFVAL 482 QVQLVESGGGLVQAGGSLRLSCAAS -GRTSS- -SH - SMGWFRQAPGK - -REFVAD 538 EVQLVESGGGLVQAGGSLRLSCAAS - GRTFS - - SY - GVGWFRQAPGKD - -REFVAG 551 QVQLVESGGGLVQAGGSLRLSCAAS - GRTFI - - SY - GVGWFRQAPGKE - -REFVAG 559 QVQLVESGGGLVQPGGSLRLSCAAS - ENILD- -VD - IMGWFRQAPGKQ- -RESLAA 479 QVQLVESGGGLVQAGGSLRLSCAAS - GI I FGIN. AW - AWA YRQAPGKQ - -RELVAV 464 QVQLVESGGGLVQAGGSLRLSCVAS - GRTFS - - TY - GMGWFRQAPGKE - -REFV A 460 QLQLVESGGGWVQAGGSLRLSCVFS - GHAFS - -GY - SMAWFRQAPAKE - -RESVAV 457 QVQLVESGGGLVQAGGSLRLSCAAS - TQTFT- - SY - SMGWFRQAPAKE - -REYVAV 459 QVQLQE SGGGLVQ GGSLRLS C A - TR TFN - - NY - MAWFRQAPAKE - -RESVAV 458 QVQLVESGGGLVQAGGSMRLSCAAA-TRTFD- -NY - AMGWFRQAPAKE - -RESVAV 558 QVQLVE SGGGLVQ GGSMRLS C AA - TR TFD - - NY - MGWFRQAPAKE - -RESVAV 493 QVQL VE SGGGLVQ PGG S LRL S C AA S - GT F F S - - GT - GWWYREAPGKR - -REWIAT 314 QVQLVESGGGLVQPGGSLRLSCVAS - GNS I K- - IN - GMGWYRQAPGKE - -RELVAL 313 QVQLVESGGGLVQPGGSLRLSCVAS - GNS I K- - DN - GMGWYRQAPGKE - -RELVAL 315 QVQLVESGGGLVQPGGSLRLSCVAS-GRSIR- - IY - GMGWYRQAPGKE - -RELVALATTORNEY DOCKET NO. 180802-049202 / PCT

[0886] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0887] 311 QVQLVESGGGLVQPGGSLRLSCVAS-GNSIE- -AY- - GMGWYRQAHGKE RELVAL 312 QVQLVESGGGLVQPGGSLRLSCVAS-GNSIE- - IY- - GMGWYR Q AHGKE RELVAL 310 QVQLVESGGGLVQPGGSLRLSCVAS-GISIE- -PY- - GMGWYRQAHGKE RELVAL 295 QVQLQESGGGLVQPGGSLRLSCVAS-GNSIE- -PY- - GMGWYR Q AHGKE RELVAL 296 QVQLQESGGGLVQPGGSLRLSCWS -GNSIE- -PY- - GMGWYRQAHGKE RELVAL 486 QVQLVESGGGLVQAGGSLRLSCAGS-GDIFS- -FI - - PMAWYR Q APGKQ REWVAT 485 EVQLVESGGGLVQAGGSLRLSCAGS-GDIFS- -FI - - PMAWYRQAPGKQ REWAT 487 QVQLVESGGGLVQAGGSLRLSCTGS-GDIFS- -FI - - PMAWYRQAPGKQ REWVAT 477 QVQLVESGGGLVQPGGSLRLSCAAT-GTI FS- -RN- - IMGWYRQAPGKE RELVAD 285 EVQLVESGGGLVQAGGSLRLSCAAS-GRTFN- -SN- - AMGWFREAPGKE REFVAA 298 QVQLQESGGGMVQPGGSLRLSCAAS-ESLVA- -DN- - AMGWYRRAPGKE RELVAY 284 QVHLVQSGGGWVHPGGSLRLSCVAS-GTIGS- - IG- - AMGWYRQAPGKE REMVAE 282 QVQLVESGGGWVQPGGSLRLSCVAS-GSIGS- - IG- - AMGWYRQAPGKE REMVAE 283 QVQLVESGGGWVQPGGSLRLSCVAS-GSIGS- - IG- - AMGWYRQAPGKE REMVAE 309 QVQLVESGGGLVQPGGSLRLSCTAS-GFTLE- -NY- - GIAWFRQAPGKE REGVSC 541 QLQLVESGGGLVQPGGSLRLSCAAS-GFTLD- -YY- - AIGWFRQAPGKE REGVSC 542 QLQLVESGGGLVQPGGSLRLSCAAS -GFTLD- -YY- - AMGWFRQAPGKE REGVSC 543 QLQLVESGGGLVRPGGSLRLSCAAS-GFTLD- - YY- - AIGWFRQAPGKE REGVSC GFTLD - ■■ Y Y - Al GWFRQAPGKE 288 QLQLVESGGGLVQPGGS GFNLD- -YH- > AIGWFRQAPGKE GFTLD - ■■ DY - Al GWFRQAPGKG 470 GFTLD- -DY- > Al GWFRQAPGKG GFTLD - ■■ DY - Al GWFRQAPGKE 468 GFTLD- -DY > Al GWFRQAPGKG 467 GFTLD - - DY - Al GWFRQAPGKG 456 GFTLD - - DY > AIGWFRQAPGKE: 466 GFTLD - - DY - Al GWFRQAPGKE 483 QVQLVESGGGLVQPGGS -RELVAT 484 GIAFS- -SY - IMGWYRQAPGKQ - RELVAT GM ILS - - I FRINDMGWYRQAPGKQ -RELVGS 545 GSFFS- - IN - AMGWYRQAPGNQ - RELVAT 3LRLSCAAS GS FFS - - I S AMGWYRQAPGNQ -RELVAT 544 GSFFS- - IN - AMGWYRQAPGNQ -RELVAT QVQLQESGGGLVQAGGSLRLSCLAS -RELVAY QVQLQESGGGLVQPGGSLRLSCWS GS I FN- - IN - LMGWYRQAPGNQ -RELVAR QLQLVESGGGLVQPGGSLRLSCAAS - RS IE- SIN > GMGWYRQAPGKQ 481 - RS I D - S I N - AMGWYRQAPGKQ -RELITI QVQLVESGGGLVQAGGSLRLSCAAS

[0888] 490 QVQLQESGGGLVQPGGSLRLSCAVS ES I FS - - MY MMGWYRQAPGKQ -RELVAI QVQLVESGGGLVQAGGSLRLSCAAS ESTFS I KSW > GMGWYRRAPGKQ 540 QLQLVESGGGLVQAGGSLRLSCTAS GSTFS - - SY AMGWYRQAPGKQ -RELVAY QVQL VE SGGGLVQ PGG S LRL S C AAS GS I LR - - I N > HMGWYRQAPGKE GS I S S - - 1 N AMDWYRQAPGKE > RELVAG 488 QVQLQESGGGLVQPGGSLRLSCAAS - GI SVS - - RY - AMGWYRQPPGKQ - RELVAV 489 QVQLVESGGGLVQPGGSLRLSCAAS - GI SVS - - RY - AMGWYRQPPGKQ - RELVAV 491 QVQLVESGGGLVQPGGSLRLSCAAS - GI SVS - - RY - AMGWYRQPPGKQ - RELVAV 492 QVQLVESGGGLVQAGGSLRLSCAQS - GGS -R- - IN - AMGWYRQAPGKQ - RELVAA 564 QVQLVESGGGLVQPGGSLRLSCAQS - GGS -R- - IN - AMGWYRQAPGKQ - RELVAA 567 QVQLVESGGGLVRPGGSLRLSCVAS - GS I FS - -MM - AMGWYRQAPGKQ - RDMVAY

[0889]

[0890] 560 QVQLVESGGGLVQPGGSLRLSCAAS -GFRFS- -GN - FIGWYRQAPGKQ - RELVAY536ITRGDITY - Y- SDFAKGRFT - 1 SRDNARNTVALQGLNLRPEDTAVYYCKGA - 478 LSQDGGTT - AY- EPSVKGRFT - 1 SRDNAKNTLYLQMNNLEPEDTAVYFCAK - 74 ISWNGDDT - NY-ADSVKGRFT - ISRDNAKNTLYLQMNSLKSEDTAVYYCAKGS- - 537 ISTDGGV - TY- IDSVKGRFT - ISRDNAKNTLYLQMNSLKAEDTAVYYCAKDLFP 291 I S SS SS ST - E Y - AD KGRFT - 1 SRDNARNTLYLQLNSLKPEDTAVYYCAKHEG - 306 I S S SS ST - E Y - ADAVKGR FT - I SRDNARNTLYLQLS SLKPEDTAVYYC AKHEG -ATTORNEY DOCKET NO. 180802-049202 / PCT

[0891] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0892] 317 ISASSSST EY-AGAVKGRFT ISRDNARNTLYLQLNSLKPEDTAVYYCAKHAG- 289 ISASSEST EY-ADAVKGRFT I SRDNARNALYLQLNSLKPEDTAVYYC AKHAG - 302 ISASSGDT EY-ADAVKGRFT ISRDNARNTLYLQLNSLKPVDTAVYYCAKHTG- 290 ISASSGTT EY-ADAVKGRFT I SRDNARNTLYLHLNSLKPEDTAVYYC AKHAG - 304 ISASSGTT EY-ADAVKGRFT ISRDNARNTLYLHLNSLKPEDTAVYYCAKHAG- 305 ISASSSST EY-ADAVKGRFT I SRDNARNTLYLQLNSLKPEDTAVYYC AKHAG - 303 ISASSGST EY-ADAVKGRFT ISRDNARNTLYLQLNSLKPEDTAVYYCAKHAG- 292 INSAGGST MY- ADSVKGRFT ISRDNAKNTLYLQMSSLKPEDTAVYYCAKHD-- 471 INSGGDST TY-ADSVKGRFT ISRDNAKNTLYLQMNSLKPEDTAVYYCAKWSDS 539 IDSGGGST E Y-ADSVKGRFT I SRDNAKNTLYLQLNSLKPEDSAVYYCAKFE - - 475 IDSGGGST DY-ADSVKGRFT I SRDNAKSTLYLQMNSLKPEDTAVY YCAKFE - - 476 INSGGGST DY-ADSVKGRFT I SRDNAKNTLYLQMNSLKPEDTAVYYCAKFE - - 278 ITWSSSST LY-EDSVEGRFT ISRDNAKKEMVYLQMTSLNVEDTAVYYCAAGRSY 552 ITWSGIMT SY-TDSVKGRFT ISRDSAKNMGYLEMKRLKPEDTAVYYCATGVK- 553 ITWSGIMI SY-TDSVKGRFT ISRDSAKNMGYLEMKRLKPEDTAVYYCATGEK- 287 ITWSGSHT YY-ADSMKGRFT ISRDNAKNTVTLQMNSLKPEDSAVYLCAMPPYA 557 ISFTGGVA -YDADSVQGRFR ISRENAKNTVYLQMNSLKPEDTAVYYCAARRYY 280 VTWSGGNT LY-GDSVKGRFT ISRDNAKNTVYLQMNSLKFEDTAVYYCAAARYY 463 ISESDGRT HY- DSVKGRFT ISRDNVKNMVYLQMNSLKPEDTAVYYCAGALGS 461 LRWSTGSA ■■ YGANSVKGRFT ISRDNDKNTVHLHMNSLKPEDTAVYYCAASSQD 62 LRWSTGSA -YGANSVKGRFT I SRDNAKNTVS LHMNS LKPEDTAVY YCAAS S QD 279 ITSISGTT LY-GDSVKGRFT ISRDNAKNTSYLRMNSLKPEDTAVYYCAANRRG 286 ILSGGISY -Y-GDSVKGRFT ISRDNAKNTVYLQMNSLKPEDTAVYYCAADRSP 301 ILSGGTSY -Y-GDSVKGRFT ISRDNAKNTVYLQMNSLKPEDTAVYYCAADRSP 2 4 ILSGGNTY -Y- DSVKGRFT ISRDNAKNTVFLQMNSLKPEDTAVYYCAADRSP 407 ILSGGNTY -Y-ADSVKGRFT ISRDNAKNTVFLQMNSLKPEDTAVYYCATDRSG 406 ILSGGNTY -Y-ADSVKGRFT ISRDNAKNTVFLQMNSLKPEDTAVYYCATDRSG 405 ILSGGNTY -Y-ADSVKGRFT ISRDNAKNTVFLQMNSLKPEDTAVYYCATDRSA 404 ILSGGNTY -Y-ADSVKGRFT ISRDNAKNTVFLQMNSLKPEDTAVYYCATDRSA 300 ILSGGNTY -Y-ADSVKGRFT ISRDNAKNTVFLQMNSLKPEDTAVYYCATDRSP 402 ILSGGNTY -Y-ADSVKGRFT ISRDNAKNTVFLQMNSLKPEDTAVYYCATDRSA 403 ILSGGNTY -Y-ADSVKGRFT ISRDNAKNTVFLQMNSLKPEDTAVYYCATDRSG 562 IDWSGAMT KY-ADSVKGRFS- I SRDNAKNTVSLQMNSLKPEDSALYYCAAKS - - 455 ISWNGGDT YY- ADSVKGRFT- ISKDNAKNTVYLQMNSLKPEDTAVYYCAAHRRR 565 ISWNGGDT YY- ADSVKGRFT- ISRDNAKNTVYLQMNSLKPEDTAVYYCAVHRRR 281 ITWSSRST LY- ADSVGGRFT- ISRDNAKSTVYLQMNSLKPEDTAVYYCAATRNA 316 INWSEGNT RY- LTSVMGRFTI SRDISRDNAKNTGYLQMNSLKPEDTAVYYCAVS - 546 ISWSGGTY - Y-ADSVKGRFT - I SRDNAKNSVYLHMNHLKPEDTADYYCSADFSG 347 ISWSGSIT SY-ADSVKGRFT - VSRDNARNTVYLQMNSLKAEDTAVYYCAARI - - 548 IVWSGEMS NY-ADSVKGRFT - 1 SRDNAKNTVYLQMYSLKPEDTAVYYCAA - 554 YSWSHRST YY - DSVKGRFT - 1 SRDNVKNTVYLQMNSLS PEDTAVYYCAAGRLT 566 ISWSGGST YY-ADSVKGRFT - ISRDNAKNTVYLQMNSLKPEDTAVYYCASDLQR 299 INWSGNST YY - DSVKGRFT - 1 SRDNAKNTG YLQMNSLKPEDTAVYTCVAGPRR 550

[0893]

[0894] ISWSGDST HY- EDSVKERFI - I SRDNAKNTVYLQMNSLKPEDTAVYYCAADTFR 547 IDWSGDST HYPADSVKGRFT - ISRDNAKNTVYLQMNSLKPEDTAVYYCAADPRG 469 INWSGDDT YY-AH VKGRFT - ISRDNAKNTVYLQMNSVKPDDTAVYYCAANPAG 555 INWSGDDT YY-ANAVKGRFT - VSRDNAKNTVYLQMNSVKPGDMAVYYCAANPAG 482 INWKSGIS NY- ADSLKGRFA - 1 SRDSAKNTGYLQMNSLKPEDTAVYYCA - 538 INWSGGET YY-ADSMKGRFT - ISRDNAKNAVYLQMNSLKPEDTAVYGCAACYAC 551 INWSGDET YY-ANSVKGRFT - ISRDNAKNAVFLQMNSLKPEDTAVYYCAACFAC 559 ISVIGGTA - Y- EDSVKGRFT - 1 SVDNAKNTAYLQMNSLKPDDTAI YYCNL - 479 ITSGGITN - Y- TDFVKGRFT - 1 SRDNALKAVYLQMNSPKPEDTGVYFCN - 464 VAWSGGPT FY-SDSVKGRFT - MSRDNAKNTVYLQMNSLKAEDTGVYYCARARLP 460 VNWSGSTT DY-VHSVKGRFT - ISRDNAKNTVYLQMNSLKPEDTAVYYCAALQRG 457 VNWSGSTT DY- ADSVKGRFT - 1 SRDNAKNTVSLQMNSLKPEDTAVYYCAALRRG 459 ISWSGSST DY-VDSVKGRFT - ISRDNAKNTVYLQMNSLKPEDTAVYYCAALRRG 458 ISWSGSST DY-VDSVKGRFT - ISRDNAKNMVYLQMNSLKPEDTAVYYCAALRRGATTORNEY DOCKET NO. 180802-049202 / PCT

[0895] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0896] 558 I SWSGSST - DY - VDSVKGRFT- - ISRDNAKNMVYLQMNSLKPEDTAVYYCAALRRG 493 VS VEDNTY - Y - ADSVKGR FT- - I SKDNAKNTAFLQLNSLKPEDTAVYYCKAS - 314 ITARGSTS - Y- IDSVKGRFT- - MSRDNAKNAVYLQMNSLKPEDTAVYYCNGV - 313 ITARGSTS - Y- VDSVKGRFT- - MSRDNAKNAVYLQMNSLKPEDTAVYYCNGV - 315 ITARGSTS - Y- IDSVKGRFT- - MSRDNAENAVYLQMNSLKPEDTAVYYCNGV - 311 ITARGSTS - Y- VDSVKGRFT- - MSRDNAKNAVYLQMNSLS PEDTAVY YCNGV - 312 ITARGSTS - Y- DSVKGRFT- - MSRDNAKNAVYLQMNSLKPEDTAVYYCNGV--- 310 ITARGSTN - S -VDSVKGRFT- - MSRDNAKNAVYLQMNNLKPEDTAVYYCNGV - 295 ITARGSTN - Y - VDSVKGRFT- - MSRDNAKNAVYLQMNSLKPEDTAVYYCNGV--- 296 ITARGSTN - Y- IDSVKGRFT- - MSRDNAKNAVYLQMNSLKPEDTAVYYCNGV - 486 ITTSGTTT - Y - DSVKGRFT- - I SRDNVKKTVVLQMNSLR PEDTAVY YCNV - 485 I TTSGATT - Y - TDSVKGR F - - ISRGNDKKTVYLQMNSLRPEDTAVYYCNV - 487 ITTSGTTT - Y - DSVKGRST- - I SRGNDKKTVYLQMNSLR PEDTAVY YCNV - 477 I SGGS IK - Y- ADSAKGRFT- - ISRDNAKNTMDLQMNILNPEDTAVYYCNVRHR-285 I RTGGRTY - Y - DSVKGRFT- - ISRGNAKNTVYLQMNSLKPEDTAVYYCAADTSG 298 I G PGGS TD - Y - DSVKGR F - - VSRDNAKNTMYLQMSSLKPEDTAVYYC IL - 284 I S RDGI N - Y - DSVKGRFT- - ISRDNPQNTIYLQM SLKPEDTAVYSCNANVLY 282 I S RDG I TN - Y - ADSVKGR F - - ISRDNPQNTIYLQMNSLKPEDTAVYSCNADVLY 283 TRDGI - Y- DSVKGRFT- - ISRDNPQNTIYLQMNSLKPEDTAVYSCNADVLY 309 ISRSDGSTYHLYS- ADSAKGRFT- - I SRDNAKNTVYLQMNSLKPEDTAVYYCATEGD ■■ 5 1 INSSDGRT - YSADSVKGRFT- - ISRDNAKNTVYLQMNSLKPEDTAVYYCATVPGA 542 INSDGRT- > YSADSVKGRFT- - ISRDNAKNTVYLQMNSLKSEDTAVYYCATVGNS 543 ISSSDGST - YY- DSVKGRFT- - ISRDNAKNTVYLQMNSLKPEDTAVYYCATLSEC 561 ISSSDGN YSADSVKGRFT- - ISRDTAKNTVYLQMNSLKPEDTAVYYCATVPGG 288 ISSGDGST - YSADSVKGRFT- - ISRDNAKNTVYLQMNSLKPEDTAVYYCATVPYG 473 ISSSDGST YSADSVKGRFT- - ISRDNAKNTVYLQMNRLKPEDTAVYYCATVGSS 470 ISSSDGST - YSADSVKGRFT- - ISRDNAKNTVYLQMNSLKPEDTGVYYCATVGSS 472 ISSSDGST YSADSVKGRFT- - ISRDNAKNTVYLQMNSLKPEDTAVYYCATVGSS 468 ISSSDGST - YSADSVKGRFT- - ISRDNAKNTVYLQMNSLKPEDTAVYYCATVGSD 467 ISSSDGST YSADSVKGRFT- - ISRDNAKNTVYLQMNSLKPEDTAVYYCATVGSR 456 ISSSDGTT - YSADSVKGRFT- - ISRDNAKNTVYLQMNSLKPEDTAVYYCATVGSS 466 ISSSDGST - YSADSVKGRFT- - ISRDNAKNTVYLQMNSLKPEDTAVYYCATVGSS 483 ITASGNLK - DY- IDSVKGRFA- - I SRDNAKNS VYLQMNNLKPDDTALYQC - - 484 ISASGNLK - DY- IDSVKGRFA- - I SRDNAKNS VYLQMNNLKPDDTALYQC > - 465 I S SGGTT - Y - ADSVKGRFT - - I SRDNAKNTTSLQMNSLKPEDTAVYYCNANI K-545 I RTG EG S T - NY - H S VKG R F - - ISKDNAKNTVYLQMNSLKPEDTAVYYCNANSVR 563 I RTGGGST - NY - ADSVKGRFT - - ISKDNAKNTVYLQMNSLKPEDTAVYYCNADSVR 544 I RTG EG S T - NY - H S VKG R F - - ISKDNAKNTVYLQMNSLKPEDTAVYYCNANSVR 293 I TSSGRTD - Y - GDSVKGRFS - - I SRDNAKNTVYLQMNNLKPEDTAVYDCNI D - 297 ITGDGITN - Y- DSVKGRFT- - I SRDNAKNTVYLQMNSLVPEDTAVYYCNA - 480 I S R S G S TM - Y - AD S VKAR F T - - ISRDNAKNTVYLQMNSLKPEDTAVYYCN - 481 ITRSGSTM - Y-GDSVKGRFT- - I SRDNAKNTVYLQMNSLKAEDTAVYYCNV - 556 I S SSGGTT - LY - EDSVKGRFT - - I SRDNAKNTVYLQMNSLKAEDTAVYYCILD - 490 VSRGGATN - Y- DSVKGRFT- - ISRDDAKNTVYLQMNSLEPEDTAVYYCNEV - 549 ITSGGSTN - Y- ADSVKGRFT- - I SRDNAKNTVYLQMNSLKPEDAAVYYCNE I - 540 I S SA. GSTD - Y - TS SVKGRFA- - ISRDNAKNTVYLQMNSLKPEDTAVYYCNEL - 307 ITSGGSTN - Y- ADSVKGRFT- - ISRDNTRNTVYLQMNSLKPEDTAVYYCHADLQD 308 I S SGGTTN - Y - DSVKGRFT- - ISRDNAKNTVYLQMNSLKPEDTAVYYCHVDLSD 488 ILSADTTN - Y- ADSVKGRFT- - I SRDNAKNTVYLQMNSLKPEDTAVYFCNE I - 489 ILSADTTN - Y- A PVKGRFT- - I SRDNAKNTVYLQMNSLKPEDTAVYFCNE I - 491 ILSADTTN - Y- ADSVKGRFT- - I SRDNAKNTVYLQMNSLKPEDTAVYFCNE I - 492 LI PGGNTR - Y- DSVKGRFT- - ISRDNAKNTVYLQMNSLKPDDTAVYYCNEV - 564 L I PGGNTR - Y - ADSVKGR F - - ISRDNAKNTVYLQMNSLKPDDTAVYYCNEV - 567 IHSSGGTN - Y- ADSVRGRFT- - ISRDNAKNTMYLQMSSLKPEDTAVYYCNEV - 560 I S SGGGTT - Y - ADSVKGR F - - ISRDNAKNTVYLQMNSLKPEDTAVYYCNEV -536----------AGLAEYW---GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPATTORNEY DOCKET NO. 180802-049202 / PCT

[0897] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0898] 478 > GPPPFGPETT - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 474 > - LPTLDGSATGG - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 537 DGTT - TWGMLVPYDYW - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 291 > -sv i NS TS HGGG - GQGTQVTVS S PKS CDKTHTCP PC PAPELLGGPS VFLFPP 306 - SYVNSTSHGGG - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 317 -SE TTTS TGGG - GQGTQVTVS S PKS CDKTHTC PC PAPELLGGPS VFLFPP 289 - gEINTTS TGGG - GRGTQVTVS S PKS CDKTHTCP PC PAPE LLGG S VFLF P P 302 - SEINTTSTGGR - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPS FLFPP 290 - gEINTTS TGGG - GQGTQVTVS S PKS CDKTHTCP PC PAPE LLGG PS VFLF P P 304 - SEINTTSTGGG - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPS VFLFPP 305 - gEITTS HGGG - GQGTQVTVS S PKS CDKTHTCP PC PAPE LLGG PS VFLF P P 303 - SEINTTSTGGG - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPS VFLFPP 292 - TYTYESRSQGR - GQGTQVLVSSPKS CDKTHTCPPCPAPELLGG PSVFLFPP 471 - TGVAGHATGGW - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPS VFLFPP 539 - GAMLAGISRSW - GQGTRVTVSSPKS CDKTHTCPPCPAPELLGG PSVFLFPP 475 - GAGLYGRSHGG - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPS VFLFPP 476 - GDGLYGRSHGG - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGG PSVFLFPP 278 - VDRSSAWVNYW - GKGTLVTVSSPKS CDKTHTCPPCPAPELLGGPS VFLFPP 552. VGTSRYDYVYW - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 553 >. VGTSRYDYVYW - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPS VFLFPP 287 YGP- ■ AYGSGTR DY - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 557 > GSRLDREYDYW GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPS VFLFPP 280 RA--. LTSNQRNYDTW - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 463 KY- ■ GSTWRGDFASW - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPS VFLFPP 461 YVS- DYTRLSVYDYW GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 462 YVS- > DYTRLSIYDYW GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPS VFLFPP 279 V ■. VTRTATNFES - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 286 >.. DGRSRSQFDIW - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPS VFLFPP 301. NGRSRSQFDIW - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 294.. DGRGRSQFDIW - GQGIQVTVSSPKS CDKTHTCPPCPAPELLGGPS VFLFPP 407 ■. RGRGRSQFDI - GQGIQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 406 - - RGRGRSQFDIW - GQGIQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 405 - - RGRGRSQFDIW - GQGIQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 404 - - RGRGRSQFDIW - GQGIQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 300 - - GGRGRSQFDIW - GQGIQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 402 - - GGRGRSQFDIW - GQGIQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 403 - - GGRGRSQFDIW - GQGIQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 562 - - YLRGS FVAGDW - GQGTQVTVS S PKS CDKTHTCPPCPAPELLGG PS VFLFPP 455 YATS- > WSRSPDEYDYW GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 565 YAS S WSRSPDEYDYW GQGTQVTVS S PKS CDKTHTCPPCPAPELLGG PS VFLFPP 281 - LTRVNTPYDYW GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 316 - - SGTI YG PYDDW GQGTQVTVS S PKS CDKTHTCPPCPAPELLGG PS VFLFPP 546 R - - GWG PG VR YD YW GQGTQVTVS S PKS CDKTHTCP PC PAPE LLGG PS VFLF PP 347 > - gSSGHLGYKYW - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 548 - R TVFS ETYHTW - GQGTQVTVS S PKS CDKTHTCP PC PAPELLGGPS VFLFPP 554 TI - ATKGDDGYDY - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 566 YGL - G YG PG TVYENW - GQGTQVTVS S PKS CDKTHTCP PC P PELLGG PS VFLF PP 299 > - VGATSVEYDY - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 550 R - TMVAGNSWNYW - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 547 > - SLVMGNSWIYW - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 469 - GSSYDRTYPYW - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 555 - GSSFDRTYPYW - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 482 - ASKDGRTYDYW - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 538 - SFKDDYTYNY - GQGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 551 - SFKDDYTYNYW - GRGTQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPP 559 - RRVRPR 11 DYW - GQGTQVTVS S PKS CDKTHTCPPCPAPELLGGPS VFLFPP 479 - IRAYTGHNGFW - GQGIQVTVSSPKS CDKTHTCPPCPAPELLGGPSVFLFPPATTORNEY DOCKET NO. 180802-049202 / PCT

[0899] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0900] 464 YG> - LGKSSSDFGPW- -GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 460 TVQ - PRGGPYEVDT - -GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 457 WQ - RRGGPYEVDTW - -GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 459 WQ - PRGGPYEVDTW - -GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 458 WQ - PRGGPYEVDTW - -GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 558 AVQ - PRGGPYEVDTW - -GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 493 > - NYW~ - GQGTQVTVS S PKS CDKTHTC PC PAPE LLGG PS VFLFP P 314 -> TPDRQRYIGVW- -GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 313 > - TRDYQRYLGVW - - GQGTLVTVS S PKS CDKTHTCP PC PAPE LLGG PS VFLF P P 315 > - TPDRQRYLGVW- -GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 311 > - TRDYQRYLGVW - - GQGTLVTVS S PKS CDKTHTCP PC PAPE LLGG PS VFLF P P 312 > - TPDRQRYLGVW- -GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 310 > - TRDRQRYLGVW - - GQGTLVTVS S PKS CDKTHTCP PC PAPE LLGG PS VFLF P P 295 > - TRDRQRYLGVW- -GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 296 > - TRDRQRYLGVW - - GQGTLVTVS S PKS CDKTHTCP PC PAPE LLGG PS VFLF P P4«6> - ANAAVYRNW - -GPGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 485 -> ANAAVSRNW- - G PGTQVTVS S PKS CDKTHTCP PC PAPE LLGG PS VFLF P P 487 - KAAVSRNW- -GPGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP >

[0901]

[0902] -GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 285 S- - ■ YDSSRSDFTSW - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 298 > ■. GRQLPW - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 284 K- ■■ ■ RINFYYPEYFW - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 282 K ■. RSNFYYREDF - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 283!<■■ ■■ ■ RSNFYYREDFW - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 309 >. CRGSPPGLEVW - GQGTPVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 5 1 CTVAAG-TSHDTGYLEVW - GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 542 C ■. VGDKEGDLEVW - GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 543 >. VGGTVPDLEVW - GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 561 CTVTHS-TEPQERYLEVW - GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 288 CI GSSGGGADYRSLEVW - GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 473 > ■. CRDSDRPLEVW - GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 470 > - - CRNSDRDLEVW GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 472 > - - CRNQDRDLEVW GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 468 > - - CRNSDRPLEVW GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 467 > - - CRNSDRPLEVW GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 456 > - - CRNSDRPLEVW GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 466 > - - CRNSDRPLEV GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 483 > - - NLGIGPRNDYW GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 484 > - - NLGIGPRNEYW GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 465 > - - FVRWRPPRDYW GRGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 545 > - - DWSGERYLEVW GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 563 > - - DWSGKRYLEVW GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 544 > - - DWSGKRYLEVW GQGTLVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 293 - PGSRLWGKDYW GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 297 - RRGSFGWNYW GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 480 > - AGYGGSHYWEW GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 481 - AGYGGSHFWEW - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 556 - SDPTRGSL- VRGNSWDYRGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 490-> GQTLHW- GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 49 > - GRVWDW-- GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 40 - GRI SW- GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 307 - TRTGPFRYDYW- GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 308 -> TRTGPFRFDYW- GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 488 -> GKVHSW- GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 489 -> GKVHSW- GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 491 -> GKVHPW- GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 492 -> GRLWDW- GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPATTORNEY DOCKET NO. 180802-049202 / PCT

[0903] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0904] 554 - GRLWGW - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP567- GRLWPW - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 550 - GAVYNW - GQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPP 536 KPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 478 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 474 KPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 537 KPKDTL ISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 291 KPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 306 KPKDTL ISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 317 KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 289 KPKDTL ISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 302 KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 290 KPKDTL ISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 304 KPKDTLMI SRTPEVTCAATVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 305 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 303 KPKDTLMI SRTPEVTCAATVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 292 KPKDTL ISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 471 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVEX3VEVHNAKTKPREEQYNSTYRWSV 539 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 475 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVEX3VEVHNAKTKPREEQYNSTYRWSV 476 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 278 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVEX3VEVHNAKTKPREEQYNSTYRWSV 552 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 553 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVEX3VEVHNAKTKPREEQYNSTYRWSV 287 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 557 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVEX3VEVHNAKTKPREEQYNSTYRWSV 280 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 463 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVEX3VEVHNAKTKPREEQYNSTYRWSV 461 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 462 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVEX3VEVHNAKTKPREEQYNSTYRWSV 279 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFWYVDGVEVHNAKTKPREEQYNSTYRWSV 286 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 301 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFWYVDGVEVHNAKTKPREEQYNSTYRWSV 294 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 407 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFWYVDGVEVHNAKTKPREEQYNSTYRWSV 406 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 405 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFWYVDGVEVHNAKTKPREEQYNSTYRWSV 404 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 300 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFWYVDGVEVHNAKTKPREEQYNSTYRWSV 402 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 403 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFWYVDGVEVHNAKTKPREEQYNSTYRWSV 562 KPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 455 KPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 565 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 281 KPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 316 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 546 KPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 347 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 548 KPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 554 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 566 KPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 299 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 550 KPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 547 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 469 KPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 555 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVATTORNEY DOCKET NO. 180802-049202 / PCT

[0905] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0906] 482 KPKDTLMISRTPEVTCVWDVSHEDPEVKFT4WYVDGVEVHNAKTKPREEQYNSTYRWSVc8 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 551 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFT4WYVDGVEVHNAKTKPREEQYNSTYRVVSV 559 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 479 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFT4WYVDGVEVHNAKTKPREEQYNSTYRVVSV 464 KPKJ5TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 460 KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 457 KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 459 KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 458 KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 558 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY JSTYRVVSV 493 KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 314 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY JSTYRVVSV 313 KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 315 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY JSTYRVVSV 311 KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 312 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY JSTYRVVSV 310 KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 295 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVEX3VEVHNAKTKPREEQYNSTYRWSV 296 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 486 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHFFAKTKPREEQYNSTYRVVSV 485 KPKDTLMISF3TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 487 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 477 KPKDTLMISF3TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 285 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHFFAKTKPREEQYNSTYRVVSV 298 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 284 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHFFAKTKPREEQYNSTYRVVSV 282 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 283 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVEXSVEVHNAKTKPREEQYNSTYRWSV 309 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 541 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVEX3VEVHNAKTKPREEQYNSTYRWSV 542 KPKDTLMISRTPEVTCWVDVSHEDPEVKF YVDGVEVHNAKTKPREEQYNSTYRWSV 543 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 561 KPKDTLMISRTPEVTCWVDVSHEDPEVKF YVDGVEVHNAKTKPREEQYNSTYRWSV 288 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 473 KPKDTLMISRTPEVTCWVDVSHEDPEVKFWYVDGVEVHNAKTKPREEQYNSTYRWSV 470 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 472 KPKDTLMISRTPEVTCWVDVSHEDPEVKFWYVDGVEVHNAKTKPREEQYNSTYRWSV 468 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 467 KPKDTLMISRTPEVTCWVDVSHEDPEVKFWYVDGVEVHNAKTKPREEQYNSTYRWSV 456 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 466 KPKDTLMISRTPEVTCWVDVSHEDPEVKFWYVDGVEVHNAKTKPREEQYNSTYRWSV 483 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 484 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFT4WYVDGVEVHNAKTKPREEQYNSTYRVVSV 465 KPKJ5TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 545 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFT4WYVDGVEVHNAKTKPREEQYNSTYRVVSV 563 KPKJ5TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 544 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFT4WYVDGVEVHNAKTKPREEQYNSTYRVVSV 293 KPKJ5TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 297 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFT4WYVDGVEVHNAKTKPREEQYNSTYRVVSV 480 KPKJ5TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 481 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFT4WYVDGVEVHNAKTKPREEQYNSTYRVVSV

[0907]

[0908] KPKJ5TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 490 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFT4WYVDGVEVHNAKTKPREEQYNSTYRVVSV 54 * KPKJ5TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 540 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFT4WYVDGVEVHNAKTKPREEQYNSTYRVVSV 307 KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVATTORNEY DOCKET NO. 180802-049202 / PCT

[0909] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0910] 308 KPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 488 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 489 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFT4WYVDGVEVHNAKTKPREEQYNSTYRVVSV 491 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 492 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSV 564 KPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 567 KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY JSTYRVVSV 560 KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV 536 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 478 LTVLHQDWLI4GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 474 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 537 LTVLHQDWLI4GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 291 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 306 LTVLHQDWLI4GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 317 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 289 LTVLHQDWLI4GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 302 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 290 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 304 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 305 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 303 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 2 2 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 471 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 539 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 475 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 76 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 278 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 552 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 553 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 287 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 557 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 280 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 463 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 461 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 462 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 279 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 286 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 301 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 2 4 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 407 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 406 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 405 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 404 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 300 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 402 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 403 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 562 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 455 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 565 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 281 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 316 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 546 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 347 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 548 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 554 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 566 LTVLHQDWLNGKEYKCKVSNKALPAP I EKT I SKAKGQ PRE PQV TL PPS RDELTKNQVSLATTORNEY DOCKET NO. 180802-049202 / PCT

[0911] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0912] 299 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 550 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 547 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 469 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 555 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 482 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 538 LTVLHQDWLI4GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 551 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 559 LTVLHQDWLI4GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 479 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 464 LTVLHQDWLI4GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 460 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 457 LTVLHQDWLI4GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 459 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 458 LTVLHQDWLI4GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 558 LTVLHQDWLNGKEYKCKVSNKALPAP I EKT I SKAKGQ PRE PQVYTL PPS RDELTKNQVSL 493 LTVLHQDWLI4GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 314 LTVLHQDWLNGKEYKCKVSNKALPAP I EKT I S KGQ PRE PQVYTL PPS RDELTKNQVSL 313 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 315 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 311 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 312 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 310 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 295 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 2 6 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 86 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 485 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 87 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 477 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 285 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 298 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 284 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 282 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 283 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 309 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 541 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 542 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 543 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 561 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 288 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 473 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 470 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 472 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 468 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 467 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 456 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 466 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 483 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 484 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 465 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 545 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 563 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 544 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 293 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 297 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 480 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 481 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLATTORNEY DOCKET NO. 180802-049202 / PCT

[0913] ELECTRONIC DEPOSIT DATE: January 14, 2026 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL

[0914] 490 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 549 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 540 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 307 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 308 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 488 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 489 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 491 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 492 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 564 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL

[0915] 560 LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL 536 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 478 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 474 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 537 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 291 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 306 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 317 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 289 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 302 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 290 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 304 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 305 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 303 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 292 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 471 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 539 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 475 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 476 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 278 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 552 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 553 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 287 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 557 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 280 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 463 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 461 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 462 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 279 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 286 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 301 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 294 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 407 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 406 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 405 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 404 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 300 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 402 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 403 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 562 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 455 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 565 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 281 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 316 TCLVKGEYPSDIAVEWESNGQPENNYKTTPPVLDSDGSEFLYSKLTVDKSRWQQGNVFSCATTORNEY DOCKET NO. 180802-049202 / PCT

[0916] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0917] 546 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 3 7 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 548 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 554 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 566 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 299 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 550 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 547 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 469 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 555 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 482 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 538 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 551 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 559 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 479 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 464 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 460 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 457 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 459 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 58 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 558 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 93 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 314 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 313 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 315 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 311 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 312 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 310 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 295 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 296 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 486 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 485 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 487 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 477 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 285 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 298 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 284 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 282 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 283 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 309 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 541 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 542 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 543 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 561 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 288 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 473 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 470 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 472 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 468 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 467 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 456 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 466 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 483 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 484 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 465 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 545 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 563 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCATTORNEY DOCKET NO. 180802-049202 / PCT

[0918] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0919] 544 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 293 TCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 297 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 480 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 481 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 556 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 490 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 549 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 540 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 307 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 308 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 88 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 489 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 491 TC VKGFYPSDI VEWESNGQPEN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 492 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 564 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 567 TCLVKGFYPSDI VEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC 560 TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 536 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 823)

[0920] 478 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 805)

[0921] 474 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 801)

[0922] 537 SVMHEALHNHYTQKSLSLS PGK (SEQ ID NO: 824)

[0923] 291 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 717)

[0924] 306 SVMHEALHNHYTQKSLSLS PGK (SEQ ID NO: 732)

[0925] 317 SVMHEALHNHYTQKSLSLS GK (SEQ ID NO: 743)

[0926] 289 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 715)

[0927] 302 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 728)

[0928] 290 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 716)

[0929] 304 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 730)

[0930] 305 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 731)

[0931] 303 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 729)

[0932] 292 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 718)

[0933] 471 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 798)

[0934] 539 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 826)

[0935] 475 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 802)

[0936] 476 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 803)

[0937] 278 SVMHEALHNHYTQKSLSLS PGK (SEQ ID NO: 704)

[0938] 552 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 839)

[0939] 553 SVMHEALHNHYTQKSLSLS PGK (SEQ ID NO: 840)

[0940] 287 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 713)

[0941] 557 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 844)

[0942] 280 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 706)

[0943] 463 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 790)

[0944] 461 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 788)

[0945] 462 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 789)

[0946] 279 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 705)

[0947] 286 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 712)

[0948] 301 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 727)

[0949] 294 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 720)

[0950] 407 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 781)

[0951] 406 SVMHEALHNHYTQKSLSLS PGK (SEQ ID NO: 780)

[0952] 405 SVMHEALHNHYTQKSLSLS PGK (SEQ ID NO: 779)ATTORNEY DOCKET NO. 180802-049202 / PCT ELECTRONIC DEPOSIT DATE: January 14, 2026 404 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 778) 300 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 726) 402 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 776) 403 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 777) 562 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 849) 455 SVMHEALHNHYTQKSLSLS GK (SEQ ID NO 782)

[0953] SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 852) 281 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 707) 316 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 742) 546 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 833) 347 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 773) 548 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 835) 554 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 841)

[0954] SVMHEALHNHYTQKSLSLS GK (SEQ ID NO 853) 299 SVMHEALHNHYTQKSLSLS GK (SEQ ID NO 725) 550 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 837) 547 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 834) 469 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 796) 555 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 842) 482 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 809) 538 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 825) 551 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 838) 559 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 846) 479 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 806) 464 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 791) 460 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 787) 457 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 784) 459 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 786) 458 SVMHEALHNHYTQKSLSLS GK (SEQ ID NO 785) 558 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 845) 493 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 820) 314 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 740) 313 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 739) 315 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 741) 311 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 737) 312 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 738) 310 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 736) 295 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 721) 296 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 722) 486 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 13) 485 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 812) 487 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 814) 477 SVMHEALHNHYTQKSLSLS GK (SEQ ID NO 804) 285 SVMHEALHNHYTQKSLSLS GK (SEQ ID NO 711) 298 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 724) 284 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 710) 282 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 708) 283 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 709) 309 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 735) 541 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 828) 542 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 829) 543 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 830)ATTORNEY DOCKET NO. 180802-049202 / PCT

[0955] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0956] 561 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 848)

[0957] 288 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 714)

[0958] 473 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 800)

[0959] 470 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 797)

[0960] 472 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 799)

[0961] 468 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 795)

[0962] 467 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 794)

[0963] 456 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 783)

[0964] 466 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 793)

[0965] 483 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 810)

[0966] 484 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 811)

[0967] 465 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 792)

[0968] 545 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 832)

[0969] 563 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 850)

[0970] 544 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 831)

[0971] 293 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 719)

[0972] 297 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 723)

[0973] 480 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 807)

[0974] 481 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 808)

[0975] 556 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 843)

[0976] 490 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 817)

[0977] 549 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 836)

[0978] 540 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 827)

[0979] 307 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 733)

[0980] 308 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 734)

[0981] 488 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 815)

[0982] 489 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 816)

[0983] 491 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 818)

[0984] 492 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 819)

[0985] 564 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 851)

[0986] 567 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 854)

[0987] 560 SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO 847)

[0988] Table C provides CDR sequences calculated according to the indicated methods for a representative VHH domain capable of binding IL2Ry, namely VHH antibody 323 of Table A.

[0989] In various embodiments, any of the VHH domains capable of binding IL2Ry listed in Table A contain one or more CDRs containing amino acids aligning to a region in the below multiple sequence alignment corresponding to a CDR of VHH antibody 323 listed in Table A (e.g., a CDR3 containing those amino acids corresponding to GL - VGGWFR - AEYDY (SEQ ID NO: 872), which is the portion of the multiple sequence alignment corresponding to GLVGGWFRAEYDY (SEQ ID NO: 873) in the below alignment).

[0990] Table C. CDR amino acid sequences calculated according to the indicated numbering schemes for antibody 323 of Table A.

[0991] CDR Numbering CDR Sequence SEQ ID

[0992]

[0993] Method Used NOATTORNEY DOCKET NO. 180802-049202 / PCT

[0994] ELECTRONIC DEPOSIT DATE: January 14, 2026

[0995] to Calculate

[0996] the CDR

[0997] CDR Chothia GGSITADYY 874

[0998] CDR1 AbM GGSITADYYYWS 875

[0999] CDR1 Kabat ADYYYWS 876

[1000] CDR1 Contact TADYYYWS 877

[1001] CDR1 IMGT GGSITADYYY 878

[1002] CDR1 Chothia GYSGI 879

[1003] CDR2 AbM AIGYSGITY 880

[1004] CDR2 Kabat AIGYSGITYYSPSV 881

[1005] KS CDR2 Contact WMGAIGYSGITY 882

[1006] CDR2 IMGT IGYSGIT 883

[1007] CDR2 Chothia GLVGGWFRAEYDY 873

[1008] CDR3 AbM GLVGGWFRAEYDY 873

[1009] CDR3 Kabat GLVGGWFRAEYDY 873

[1010] CDR3 Contact ARGLVGGWFRAEYD 884

[1011] CDR3 IMGT ARGLVGGWFRAEYD 885

[1012]

[1013] Y

[1014] A multiple sequence alignment of representative VHH antibodies capable of binding IL2Ry is provided below. The hFc domain of VHH antibody 323 is shown in bold in the below multiple sequence alignment, and the regions of the alignment corresponding to CDR domains of the VHH domain of antibody 323 calculated using the Chothia numbering scheme are shown in bold underlined text.

[1015] 323 QVQLQESGPGLVKPSQTLSLTCTVSGGSITADYYYWSWIRQPPG - KGLEWMGAI GYS 110 QVQLQESGGGSVQAGGSLRLSCAASG - - YTYRDYYMGWFRQAPG - REREGVAS I YTRGSR 321 QVQLVESGGGLVQPGGSLRLSCAASG - - FTFSSYPMSWVRQAPG - KGLEWVSG I NSG

[1016] 325 QVQLVESGGALVQPGGSLRLSCAASG- - FTFGGYAMGWVRQAPG-KGLEWLSTI - SYG

[1017] 339 QVQLVESGGGSVQPGGSLTLSCAASG- -TTDRLDIMAWHRQPPG-QQRELVAII T-R

[1018] 327 EVQLVESGGGLVQAGGSLRLSCAASG - - I SLS INPMVWYRQAPG - KQREWVADI - S - S 343 QVQLVESGGGLVQAGGSLRLSCAASG- -SLGRTTFMGWYRQAPG-NEREFVAQF G-S

[1019] 332 QLQLVESGGGLVQPGGSLRLSCTVSG - - SAFS ITAMGWYRQPPG - QQRELVAS I - A-N

[1020] 331 QVQLQESGGGLVQAGGSLRLSCAASG - - RTFSVTHMGWFRRAPG - KEREFAAVI RWD

[1021] 337 QVQLVESGGGLVQAGGSLRLSCVASG - - LAFSSYHMGWFRQAPG-LEREFVAVI - NPS 3 5 QVQLQESGGGLMQPGGSLRLSCAAAG--SFFGIAAMGWYRQAPG-QQRELVASV - A-H

[1022] 346 QVQLVESGGGLVQAGGSLRLSCAASS - - SIRGINAFGWYRQPAG-NQRFLVARI - 1 -G

[1023] 333 QVQLQESGGGLVHPGGSLRLSCAASA- -SI LS INAMGWYRQAPG - KQRELVAVI - KI V

[1024] 322 QVQLVESGGGLVQAGGSLRLSCA SG - - STFGFVAMAWYRQAPG - KQRELVANI - R-N

[1025] 336 QVQLVESGGGLVQAGDSLRLSCAASG - - RI FSSYLMGWFRQAPG - KDREFVGAV - DRS 319 QVQLVESGGGLVQGGGSLRLSCAASG- -LTSSNNWGWYRQAPG-KQRELVAIL - A-T

[1026] 342 QLQLVESGGGLVQAGGSLRLSCVASG - - TTFS I AYMGWYRQAPG - KQRELVALI - G-N

[1027] 326 QVQLVESGGGLVQPGGSLRLSCAGSR - - S I FSGNPMAWFRQAPG - KQRELVALV - SSG

[1028] 3 1 EVQLVESGGGLVQPGGSLRLSCAASG - - S I SS I AYMGWYRQVPG - KQRDLAALI - G-S

[1029] 328 QVQLQESGGGLVQAGGSLRLSCAASE - - S I AGINYMAWYRQAPGAKQRELVARI - ASV

[1030] 338 QVQLVESGGGTVQPGDSLTLSCAASG - - LTFARYTMGWYRQAPG - KQRQLVAGI - S - S

[1031] 318 QVQLVESGGGLVQAGGSLRLSCAASR - - RTSS YYVMGWFRQAPG - KEREFVAGI - TWG

[1032] 320 QVQLQESGGGLVQAGGSLRLSCVASG - - S I FS SNAMAWYRQAPG - KQRELVAI I - T - S

[1033] 324 EVQLVESGGGLVQAGGSLRLSCAASG - - RTFSGYAMGW FRQAPG - KEREFVTAI - SWS 335 QVQLVESGGGLVQAGGSLRLSCAASG- -RTFSRYVAGWFRQAPG-KEREFVAAV - SWSATTORNEY DOCKET NO. 180802-049202 / PCT

[1034] ELECTRONIC DEPOSIT DATE: January 14, 2026

[1035] 33 QVQLQESGGGLVQAGGSLRLSCAASG - - SI FSRNAMGWFRQAPG - KQRELVAVI - S - 1 330 QVQLVESGGGLVQPGGSLRLACAASG - - S I SS INYMGWFRQAPG - KQRELVAVI S - S 344 QVQLVESGGGLVQAGGSLRLSCVASG - - SRFNINDMGWYRQAPG - KQRELVATA G - R 329 EVQLVESGGGLVQTGGSLRLSCAASG - - STFS INAMGWYRQAPG - KQRELVAS I A- S 340 EVQLVESGGGLVQPGGSLRLSCAASG - - S I FSGNAMAWYRQPPG - KQRELVAAI - T- S G - ITYYSPSVKSRTAISRDTSKNQLTLQLRSVTPEDTAVYYCARGL - VGGWFR- EG--STRYSSSVEGRFTITLDTAKNTLYLQMNSLKPEDTAMYYCAADDRTWLPRVQLGGP GG - - STS YADSVKGRFTI SRDNAKNTLYLQMNSLKPEDSAVYYCAKIGRD ASSWET- GS--GTTYADSVKDRFTISRDNAKNTVYLEMNSLKPEDTAVYTCGKYGRPFYYSHYWEK- DG - - RANYADSVKGRFTI SRDNAKNTVYLRMS KPEDTAVYVCYGGE FP NLN - SD--MTRYADSVKGRFIISRDNARNGVNLQMNRLEPEDTAVYYCDVP -> DPHNGV- GG - - STNYVDTVKGRFTI SSDNAKNR VYLQMNSLKPEDTAVYYCYALTYD SGDFRN- GG--VTKYADSVEGRFTISRDNAKNAVYLQMNSLKPEDTAVYLCYAD - SDGPRK- SG--NTAYADSVKGRFTISRDTTKNMVYLQMNSLKPEDTAVYYCAAS > - NLTSTT- GG - - GTYYTDSVKGRFTI SRDNAKNTVYLQMNSLKPEDTAVYLCAGSN IG ETSVRT- DG--RRYYADSVKGRFTISGDNAKRTAGLQMNSLKPEDTGVYYCYAD - DHSYGI-

[1036]

[1037] GD--STYYADSVRGRFTISRDNAKSTVYLQMNSLNVDDTAVYYCAAG > - WTG- AGTYTANYADSVKGRFAISRDNAKNTLYLQMNSLKPEDTAVYYCNAGSAS > - STQYRP- DG ■■ - RI DYTDSVKGRFTI SRDNAKNTLYLQMI SLKPEDTAVYFCYGA > - RVGSGA- GA ■■ ■■ NTYHADS VKGRFTI SRDNAKNMVYLQMNSLKPEDTAVYYCASG - RSAWS S - TG- -NTRYGEAAKGRF'riSRDNTKNTVYLQMNSLKPEDTAVYYCNLV - VLPNSV- ED ■■ ■■ STRYAESAKGRFTI SRDNAKNTVYLQMNSLKPEDTANYYCTAG- > -AADQQN- GS ■■ - HTDYADSVLGRFTI SRDDAKNMVYLQMNSLKPEDTAVY YCNHP - DTPLTK- DS ■■ ■■ VTR YADSVKGRFTI SRDNAKNTVYLQMNSLQPDDTAVYYCTGGI QS SY - DMAWKE - GS ■■ - RYYYADSVKGRCTI ARDNAKNTMDLQMNSLKPEDTGVY YCAAD. • WSG- DG ■■ ■■ RTNYADSVKGRFTI SRDNAKNTLYLQMNSLKPEDTAVYYCDVAT - DLTLRT- VG- -DTYYKDGVKGRFTISRDNAKNTVYLQMSSLKPEDTAVYYCAT - - ADVWPS GG--TTDYPDSVKGRFTISRDNAKNTVYLQMNTLKPEDTAVYYCNDPT -WLTKG- GG ■■ - TTYYADSVKGRFTI SRDNAKNTVYLQMDSLKPEDTAVY YCAA - TFESGN- GV ■■ ■■ GAYYVDS VKGRFTI SRDNAKNTVYLQMNSLKPEDTAVYYCTAG - > - TMARAP - DG - - RTYI DSVQGRFTI SRDNAKNTVYLQMNSLKPEDTAVYYCAAGQTT MTSLPS - DG - - RTNYGDSAKGRFTI SRDNAKNTVYLQMNSLKPEDTAVYLCNG - VTGSRV- GG - - TTTYGDSVKGRFTI SGDNAKNI VYLQMNSLKPEDTAVYYCNAADF - MVT > - GD - - RTYYADS VKGRFTI SRANAKNTVYLQMNSLKPEDTAVYYCYAD > - - -

[1038]

[1039] GS - - STHYVDSVKGRFTI SRDNAKNTVYLQMNSLKPEDTAVYYCNAQER > - VYELGY-323" -AEYDYRGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 110 RENEYNYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 321 - - QGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 325 --ADYDYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 339 - - YWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 327 - -D - YWGKGILVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 343 - YWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 332 --NLLIYWGKGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 331 - YVYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 337 - -GRFPAWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 345 --I - YWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 346 --LKWENWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 333 --N - YWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 322 - - T- ADFWGQGTQVTVSS PKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPE 336 - -GDYAVWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 319 - YWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 342 --EYRVYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 326 - WGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 341 > - YWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 328 - - AAWTYWGQGTQVTVSS PKSCDKTHTC PPCPAPELLGGPSVFL FP PKPKDTLM I S RTPEATTORNEY DOCKET NO. 180802-049202 / PCT

[1040] ELECTRONIC DEPOSIT DATE: January 14, 2026

[1041] 338 --V-LGFWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 318 LSYDYTYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 320 --LDNDYWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 324 --GEYDWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 335 - - E - YWGQGTQVTVSAPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 334 - YWGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 330 - DRGQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 344 - YWGKGTLVTVSS PKSCDKTHTC PPCPAPELLGGPSVFL FP PKPKDTLM I S RTPE 329 - -TPMI I WAQGTQVTVSSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 340 - - D- EGSWGQGTQVTVSS PKSCDKTHTC PPCPAPELLGGPSVFL FP PKPKDTLM I S RTPE 323 VTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE 110 VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE 321 VTCWVDVSHEDPEVKFIWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKE 325 VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE 339 VTCWVDVSHEDPEVKFIWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKE 327 VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE 343 VTCWVDVSHEDPEVKFIWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKE 332 VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDv LNGKE 331 VTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKE 337 VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDv LNGKE 345 VTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKE 346 VTCVVVD...

Claims

1. ATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 2026CLAIMSWhat is claimed:

1. A method for the selective activation and / or expansion of an immune effector cell, the method comprising contacting an immune effector cell engineered to express an IL2RP polypeptide variant comprising an amino acid alteration selected from the group consisting of R107G, W48R, Q50R, Q60R, H62R, W64R, D66G, R67G, D102G, I103V, W116R, N129S, and F217S or comprising an epitope tag with a bispecific antibody containing an antigen binding domain capable of selectively binding to the IL2RP polypeptide variant and an antigen binding domain capable of specifically binding to an fL2Ry polypeptide expressed by the cell, thereby selectively activating and / or expanding the immune effector cell.

2. The method of claim 1, wherein the immune effector cell is an NK cell or a T cell.

3. The method of claim 2, wherein the immune effector cell is a tumor infiltrating lymphocyte.

4. The method of claim 1, wherein the immune effector cell expresses the IL2RP polypeptide variant comprising the epitope tag.

5. The method of claim 1, wherein the immune effector cell expresses the IL2RP polypeptide variant comprising the amino acid alteration selected from the group consisting of R107G, W48R, Q50R, Q60R, H62R, W64R, D66G, R67G, D102G, I103V, W116R, N129S, and F217S.

6. The method of claim 4 or claim 5, wherein the method further comprises preparing the engineered immune effector cell by contacting an immune effector cell with a polynucleotide expressing the IL2RP polypeptide variant.

7. The method of claim 6, wherein the polynucleotide is present in a lentiviral vector.

8. The method of claim 6, wherein preparing the engineered immune effector cell comprises incorporating the polynucleotide into the genome of the immune effector cell.ATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 20269. The method of claim 4, wherein the epitope tag comprises the amino acid sequence PDRKAAVSHWQQ (SEQ ID NO: 690).

10. The method of claim 1, wherein the cell is a mammalian cell,11. The method of claim 8, wherein the method further comprises preparing the engineered immune effector cells by contacting an immune effector cell with a base editor system comprising a base editor comprising an adenosine deaminase domain and a nucleic acid programmable DNA binding (napDNAbp) domain, and a guide RNA, or one or more polynucleotides encoding the base editor system or a component thereof, wherein the guide RNA directs the base editor to effect a nucleotide alteration in an IL2RP polynucleotide to yield an IL2RP polynucleotide encoding the IL2RP polypeptide variant.

12. The method of claim 11, wherein the adenosine deaminase domain is a TadA*8e, TadA*8.20, TadA*9.1, or TadA*9.52.

13. The method of claim 11, wherein the guide RNA comprises a spacer comprising at least 10 contiguous nucleotides of a spacer sequence listed in Table 1.

14. The method of claim 13, wherein the spacer comprises the nucleic acid sequence CCUGAGGGUGCUGUGCCGUG (SEQ ID NO: 1046; sgRNA123).

15. The method of claim 11, wherein the napDNAbp domain is an SpCas9 nickase.

16. The method of claim 15, wherein the SpCas9 nickase comprises the alteration D10A referenced to SEQ ID NO: 197.

17. The method of claim 11, wherein the base editor is a fusion protein comprising a peptide linker connecting the adenosine deaminase domain to the napDNAbp domain.

18. The method of claim 17, wherein the peptide linker comprises a sequence selected from the group consisting of: EGGSEEEEESGS (SEQ ID NO: 675), SKSQQFVTYE (SEQ ID NO: 677), and SGGSSGGSSGSETPGTSESATPESSGGSSGGS (SEQ ID NO: 357).ATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 202619. The method of claim 11, wherein the base editor comprises a nuclear localization signal.

20. The method of claim 11, wherein the base editor comprises an amino acid sequence with at least 85% identity to a sequence selected from the amino acid sequences listed in Table 2.

21. The method of claim 11, wherein contacting the immune effector cell with the base editor system comprises contacting the immune effector cell with a lipid nanoparticle comprising mRNA encoding the base editor and the guide RNA.

22. The method of claim 21, wherein the lipid nanoparticle comprises the ionizable lipid IZ4.

23. The method of claim 1, wherein the antigen binding domains are VHH domains.

24. The method of claim 23, wherein the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant comprises cluster of differentiation (CDR) 1, CDR2, and CDR3 amino acid sequences of an IL-2RP VHH domain amino acid sequence listed in Table A corresponding to CDR1, CDR2, or CDR3 sequences listed in Table B and calculated using a numbering method selected from Chothia, AbM, Kabat, Contact, and IMGT.

25. The method of claim 24, wherein the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant comprises a CDR1 comprising the amino acid sequence TQTFTSY (SEQ ID NO: 1063), a CDR2 comprising the amino acid sequence NWSGS (SEQ ID NO: 1064), and a CDR3 comprising the amino acid sequence LRRGVVQRRGGPYEVDT (SEQ ID NO: 1065).

26. The method of claim 24 or claim 25, wherein the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant comprises an amino acid sequence with at least 85% identity to an IL-2RP VHH domain amino acid sequence listed in Table A.

27. The method of claim 26, wherein the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant comprises an amino acid sequence with at least about 90% identity to the following amino acid sequence:QVQLVESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSVATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 2026KGRFT I SRDNAKNTVS LQMNS LKPEDTAVYYCAALRRGVVQRRGGP YE VDTWGQGTQVTVS S(SEQ IDNO: 1069).

28. The method of claim 23, wherein the antigen binding domain capable of selectively binding to the IL2Ry polypeptide comprises cluster of differentiation (CDR) 1, CDR2, and CDR3 amino acid sequences of an IL-2Ry VHH domain amino acid sequence listed in Table A corresponding to CDR1, CDR2, or CDR3 sequences listed in Table C and calculated using a numbering method selected from Chothia, AbM, Kabat, Contact, and IMGT.

29. The method of claim 28, wherein the antigen binding domain capable of selectively binding to the fL2Ry polypeptide comprises a CDR1 comprising the amino acid sequence RRTSSYY (SEQ ID NO: 1066), a CDR2 comprising the amino acid sequence TWGVGD (SEQ ID NO: 1067), and a CDR3 comprising the amino acid sequence ADVWPSALSYDYTY (SEQ ID NO: 1068).

30. The method of claim 28 or claim 29, wherein the antigen binding domain capable of selectively binding to the IL2RY polypeptide comprises an amino acid sequence with at least 85% identity to an IL-2Ry VHH domain amino acid sequence listed in Table A.

31. The method of claim 30, wherein the antigen binding domain capable of selectively binding to the IL2RY polypeptide variant comprises an amino acid sequence with at least about 90% identity to the following amino acid sequence:Q VQL VE S GGGL VQAGGS LRLS CAAS RRTS S Y YVMGWFRQAPGKERE F VAG I TWGVGDT Y YKDGV KGRFTISRDNAKNTVYLQMSSLKPEDTAVYYCATADVWPSALSYDYTYWGQGTQVTVSS (SEQ ID NO: 1070).

32. The method of claim 23, wherein the bispecific antibody comprises from N-terminus to C-terminus:A) [A]-[B]-[Fc]; orB) [B]-[A]-[Fc];wherein:i) A comprises the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant;ATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 2026ii) B comprises the antigen binding domain capable of specifically binding to the IL2Ry polypeptide; andiii) Fc comprises a human Fc domain or an hIgG4 Fc domain.

33. The method of claim 1, wherein the bispecific antibody comprises an amino acid sequence with at least 85% identity to a sequence listed in Table E.

34. The method of claim 33, wherein the bispecific antibody comprises an amino acid sequence with at least 85% identity to an amino acid sequence selected from the group consisting of:QVQLVESGGGLVQAGGSLRLSCAASRRTSSYYVMGWFRQAPGKEREFVAGITWGVGDTYYKDGVKGRFTISRDNAKNTVYLQMSSLKPEDTAVYYCATADVWPSALSYDYTYWGQGTQVTVSSGGGGS QVQLVESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSVKGRFTISRDNAKNTVSLQMNSLKPEDTAVYYCAALRRGVVQRRGGPYEVDTWGQGTQVTVSSPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 1062; ABTx698);QVQLVESGGGLVQAGGSLRLSCAASGSLGRTTFMGWYRQAPGNEREFVAQFGSGGSTNYVDTVK GRFTISSDNAKNRVYLQMNSLKPEDTAVYYCYALTYDSGDFRNYWGQGTQVTVSSGGGGSQVQL VESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSVKGRF T I SRDNAKNTVS LQMNS LKPEDTAVYYCAALRRGVVQRRGGP YE VDTWGQGTQVTVS S PKS CDK THTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT LPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO: 988; ABTx619);QVQLVESGGGLVQAGGSLRLSCAASGSLGRTTFMGWYRQAPGNEREFVAQFGSGGSTNYVDTVK GRFTISSDNAKNRVYLQMNSLKPEDTAVYYCYALTYDSGDFRNYWGQGTQVTVSSGGGGSQLQL VESGGGLVQPGGSLRLTCAASGFTFSRYPMSWARQAPGKGLEWVSTLSQDGGTTAYEPSVKGRF TISRDNAKNTLYLQMNNLEPEDTAVYFCAKGPPPFGPETTWGQGTQVTVSSPKSCDKTHTCPPC PAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO: 999; ABTx630); andATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 2026 QVQLVESGGGLVQAGGSLRLSCAASGSLGRTTFMGWYRQAPGNEREFVAQFGSGGSTNYVDTVK GRFTISSDNAKNRVYLQMNSLKPEDTAVYYCYALTYDSGDFRNYWGQGTQVTVSSGGGGSQVQL VESGGGLVQAGGSLRLSCAASGIIFGINAWAWAWYRQAPGKQRELVAVITSGGITNYTDFVKGR FTISRDNALKAVYLQMNSPKPEDTGVYFCNIRAYTGHNGFWGQGIQVTVSSPKSCDKTHTCPPC PAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 1000; ABTx631).

35. The method of claim 1, wherein the immune effector cell is in vivo or in vitro.

36. The method of claim 1, further comprising engineering the immune effector cell to express a chimeric antigen receptor containing an antigen binding domain capable of binding an antigen associated with a disease or disorder.

37. The method of claim 36, wherein the disease or disorder is a neoplasia.

38. The method of claim 1, wherein the IL2RP polypeptide variant comprises the R107G amino acid alteration.

39. A method for treating a neoplasia in a subject in need thereof, the method comprising selectively activating and / or expanding an immune effector cell in the subject according to the method of any one of claims 1-34.

40. The method of claim 39, wherein the method comprises intratumorally administering to the subject the lipid nanoparticle defined in claim 21 or claim 22.

41. The method of claim 39 further comprising engineering the immune effector cell ex vivo to express the IL2RP polypeptide variant and subsequently administering the immune effector cells to the subject.

42. The method of claim 41, wherein the immune effector cell is a tumor infiltrating lymphocyte isolated from a tumor of the subject.ATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 202643. A base editor system, the base editor system comprising a base editor comprising an adenosine deaminase domain and a nucleic acid programmable DNA binding (napDNAbp) domain, and a guide RNA, or one or more polynucleotides encoding the base editor system or a component thereof, wherein the guide RNA directs the base editor to effect a nucleotide alteration in an IL2RP polynucleotide to yield an IL2RP polynucleotide encoding an IL2RP polypeptide variant comprising an amino acid alteration selected from the group consisting of W48R, Q50R, Q60R, H62R, W64R, D66G, R67G, D102G, I103V, R107G, W116R, N129S, and F217S.

44. The base editor system of claim 43, wherein the adenosine deaminase domain is a TadA*8e, TadA*8.20, TadA*9.1, or TadA*9.52.

45. The base editor system of claim 43, wherein the guide RNA comprises a spacer comprising at least 10 contiguous nucleotides of a spacer sequence listed in Table 1.

46. The base editor system of claim 45, wherein the spacer comprises the nucleic acid sequence CCUGAGGGUGCUGUGCCGUG (SEQ ID NO: 1046; sgRNA123).

47. The base editor system of claim 43, wherein the napDNAbp domain is an SpCas9 nickase.

48. The base editor system of claim 47, wherein the SpCas9 nickase comprises the alteration D10A referenced to SEQ ID NO: 197.

49. The base editor system of claim 43, wherein the base editor is a fusion protein comprising a peptide linker connecting the adenosine deaminase domain to the napDNAbp domain.

50. The base editor system of claim 49, wherein the peptide linker comprises a sequence selected from the group consisting of: EGGSEEEEESGS (SEQ ID NO: 675), SKSQQFVTYE (SEQ ID NO: 677), and SGGSSGGSSGSETPGTSESATPESSGGSSGGS (SEQ ID NO: 357).

51. The base editor system of claim 43, wherein the base editor comprises a nuclear localization signal.ATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 202652. The base editor system of claim 43, wherein the base editor comprises an amino acid sequence with at least 85% identity to a sequence selected from the amino acid sequences listed in Table 2.

53. The base editor system of claim 43, wherein the IL2RP polypeptide variant comprises an R107G amino acid alteration.

54. A method for preparing an immune effector cell expressing an IL2RP polynucleotide encoding an IL2RP polypeptide variant comprising an amino acid alteration selected from the group consisting of W48R, Q50R, Q60R, H62R, W64R, D66G, R67G, D102G, I103V, R107G, W116R, N129S, and F217S, the method comprising contacting the cell with the base editor system of any one of claims 39-49.

55. The method of claim 54, wherein contacting the immune effector cell with the base editor system comprises contacting the cell with a lipid nanoparticle comprising mRNA encoding the base editor and the guide RNA.

56. The method of claim 55, wherein the lipid nanoparticle further comprises ionizable lipid IZ4.

57. An immune effector cell prepared according to the method of any one of claims 54-56.

58. A polynucleotide or set of polynucleotides encoding the base editor system of any one of claims 43-53.

59. A vector or set of vectors comprising the polynucleotide or set of polynucleotides of claim 58.

60. A lipid nanoparticle comprising the base editor system of any one of claims 43-53.

61. The lipid nanoparticle of claim 60 further comprising the ionizable lipid IZ4.ATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 202662. The lipid nanoparticle of claim 60 comprising mRNA encoding the base editor, and the guide RNA.

63. A method for treating a neoplasia in a subject in need thereof, the method comprising intratumorally administering to the subject the lipid nanoparticle of any one of claims 60-62 or a lentiviral vector encoding an IL2RP polypeptide variant comprising an epitope tag and subsequently administering to the subject the bispecific antibody defined in any one of claims 23-34.

64. A method for treating a neoplasia in a subject in need thereof, the method comprising administering to the subject an immune effector cell engineered to express an IL2RP polypeptide variant comprising an epitope tag or the amino acid alteration R107G and subsequently administering to the subject the bispecific antibody defined in any one of claims 23-34.

65. The method of claim 64, further comprising engineering the immune effector cell to express a chimeric antigen receptor containing an antigen binding domain capable of binding an antigen associated with the neoplasia.

66. A bispecific antibody containing an antigen binding domain capable of selectively binding to an IL2RP polypeptide variant comprising an R107G amino acid alteration or to an epitope tag comprising the amino acid sequence PDRKAAVSHWQQ (SEQ ID NO: 690) and an antigen binding domain capable of specifically binding to a wild-type IL2Rγ polypeptide, wherein the antigen binding domains are VHH domains.

67. The bispecific antibody of claim 66, wherein the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant comprises cluster of differentiation (CDR) 1, CDR2, and CDR3 amino acid sequences of an IL-2RP VHH domain amino acid sequence listed in Table A corresponding to CDR1, CDR2, or CDR3 sequences listed in Table B and calculated using a numbering method selected from Chothia, AbM, Kabat, Contact, and IMGT.

68. The bispecific antibody of claim 67, wherein the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant comprises a CDR1 comprising the amino acid sequence TQTFTSY (SEQ ID NO: 1063), a CDR2 comprising the amino acid sequenceATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 2026NWSGS (SEQ ID NO: 1064), and a CDR3 comprising the amino acid sequence LRRGVVQRRGGPYEVDT (SEQ ID NO: 1065).

69. The bispecific antibody of claim 67 or claim 68, wherein the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant comprises an amino acid sequence with at least 85% identity to an IL-2RP VHH domain amino acid sequence listed in Table A70. The bispecific antibody of claim 69, wherein the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant comprises an amino acid sequence with at least about 90% identity to the following amino acid sequence:QVQLVESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSV KGRFT I SRDNAKNTVS LQMNS LKPEDTAVYYCAALRRGVVQRRGGP YE VDTWGQGTQVTVS S(SEQ ID NO: 1069).

71. The bispecific antibody of claim 66, wherein the antigen binding domain capable of selectively binding to the IL2Ry polypeptide comprises cluster of differentiation (CDR) 1, CDR2, and CDR3 amino acid sequences of an IL-2Ry VHH domain amino acid sequence listed in Table A corresponding to CDR1, CDR2, or CDR3 sequences listed in Table C and calculated using a numbering method selected from Chothia, AbM, Kabat, Contact, and IMGT.

72. The bispecific antibody of claim 71, wherein the antigen binding domain capable of selectively binding to the IL2RY polypeptide comprises a CDR1 comprising the amino acid sequence RRTSSYY (SEQ ID NO: 1066), a CDR2 comprising the amino acid sequence TWGVGD (SEQ ID NO: 1067), and a CDR3 comprising the amino acid sequence ADVWPSALSYDYTY (SEQ ID NO: 1068).

73. The bispecific antibody of claim 71 or claim 72, wherein the antigen binding domain capable of selectively binding to the IL2Ry polypeptide comprises an amino acid sequence with at least 85% identity to an IL-2Ry VHH domain amino acid sequence listed in Table A.

74. The bispecific antibody of claim 73, wherein the antigen binding domain capable of selectively binding to the IL2RY polypeptide variant comprises an amino acid sequence with at least about 90% identity to the following amino acid sequence:ATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 2026Q VQL VE S GGGL VQAGGS LRLS CAAS RRTS S Y YVMGWFRQAPGKERE F VAG I TWGVGDT Y YKDGV KGRFTISRDNAKNTVYLQMSSLKPEDTAVYYCATADVWPSALSYDYTYWGQGTQVTVSS (SEQ ID NO: 1070).

75. The bispecific antibody of claim 66, wherein the bispecific antibody comprises from N-terminus to C -terminus:A) [A]-[B]-[Fc]; orB) [B]-[A]-[Fc];wherein:i) A comprises the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant;ii) B comprises the antigen binding domain capable of specifically binding to the IL2Ry polypeptide; andiii) Fc comprises a human Fc domain or an hIgG4 Fc domain.

76. The bispecific antibody of claim 66, wherein the bispecific antibody comprises an amino acid sequence with at least 85% identity to a sequence listed in Table E.

77. The bispecific antibody of claim 76, wherein the bispecific antibody comprises an amino acid sequence with at least 85% identity to an amino acid sequence selected from the group consisting of:QVQLVESGGGLVQAGGSLRLSCAASRRTSSYYVMGWFRQAPGKEREFVAGITWGVGDTYYKDGVKGRFTISRDNAKNTVYLQMSSLKPEDTAVYYCATADVWPSALSYDYTYWGQGTQVTVSSGGGGS QVQLVESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSVKGRFTISRDNAKNTVSLQMNSLKPEDTAVYYCAALRRGVVQRRGGPYEVDTWGQGTQVTVSSPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 1062; ABTx698);QVQLVESGGGLVQAGGSLRLSCAASGSLGRTTFMGWYRQAPGNEREFVAQFGSGGSTNYVDTVK GRFTISSDNAKNRVYLQMNSLKPEDTAVYYCYALTYDSGDFRNYWGQGTQVTVSSGGGGSQVQL VESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSVKGRF T I SRDNAKNTVS LQMNS LKPEDTAVYYCAALRRGVVQRRGGP YE VDTWGQGTQVTVS S PKS CDK THTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 2026 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT LPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 988; ABTx619);QVQLVESGGGLVQAGGSLRLSCAASGSLGRTTFMGWYRQAPGNEREFVAQFGSGGSTNYVDTVK GRFTISSDNAKNRVYLQMNSLKPEDTAVYYCYALTYDSGDFRNYWGQGTQVTVSSGGGGSQLQL VESGGGLVQPGGSLRLTCAASGFTFSRYPMSWARQAPGKGLEWVSTLSQDGGTTAYEPSVKGRF TISRDNAKNTLYLQMNNLEPEDTAVYFCAKGPPPFGPETTWGQGTQVTVSSPKSCDKTHTCPPC PAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 999; ABTx630); and QVQLVESGGGLVQAGGSLRLSCAASGSLGRTTFMGWYRQAPGNEREFVAQFGSGGSTNYVDTVK GRFTISSDNAKNRVYLQMNSLKPEDTAVYYCYALTYDSGDFRNYWGQGTQVTVSSGGGGSQVQL VESGGGLVQAGGSLRLSCAASGIIFGINAWAWAWYRQAPGKQRELVAVITSGGITNYTDFVKGR FTISRDNALKAVYLQMNSPKPEDTGVYFCNIRAYTGHNGFWGQGIQVTVSSPKSCDKTHTCPPC PAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 1000; ABTx631).

78. A VHH domain, or an antigen-binding fragment thereof, capable of selectively binding to an IL2RP polypeptide variant comprising an R107G amino acid alteration, wherein the VHH domain comprises cluster of differentiation (CDR) 1, CDR2, and CDR3 amino acid sequences of an IL-2RP VHH domain amino acid sequence listed in Table A corresponding to CDR1, CDR2, or CDR3 sequences listed in Table B and calculated using a numbering method selected from Chothia, AbM, Kabat, Contact, and IMGT.

79. The VHH domain of claim 78, wherein the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant comprises a CDR1 comprising the amino acid sequence TQTFTSY (SEQ ID NO: 1063), a CDR2 comprising the amino acid sequence NWSGS (SEQ ID NO: 1064), and a CDR3 comprising the amino acid sequence LRRGVVQRRGGPYEVDT (SEQ ID NO: 1065).ATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 202680. The VHH domain of claim 78, wherein the VHH domain comprises a VHH domain listed in Table A.

81. The VHH domain of claim 80, wherein the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant comprises the following amino acid sequence:QVQLVESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSV KGRFT I SRDNAKNTVS LQMNS LKPEDTAVYYCAALRRGVVQRRGGP YE VDTWGQGTQVTVS S(SEQ IDNO: 1069).

82. A VHH domain, or an antigen-binding fragment thereof, capable of selectively binding to a wild-type IL2Ry polypeptide, wherein the VHH domain comprises cluster of differentiation (CDR) 1, CDR2, and CDR3 amino acid sequences of an IL-2Ry VHH domain amino acid sequence listed in Table A corresponding to CDR1, CDR2, or CDR3 sequences listed in Table C and calculated using a numbering method selected from Chothia, AbM, Kabat, Contact, and IMGT.

83. The VHH domain of claim 82, wherein the antigen binding domain capable of selectively binding to the IL2Ry polypeptide comprises a CDR1 comprising the amino acid sequence RRTSSYY (SEQ ID NO: 1066), a CDR2 comprising the amino acid sequence TWGVGD (SEQ ID NO: 1067), and a CDR3 comprising the amino acid sequence ADVWPSALSYDYTY (SEQ ID NO: 1068).

84. The VHH domain of claim 82, wherein the VHH domain comprises a VHH domain listed in Table A.

85. The VHH domain of claim 84, wherein the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant comprises the following amino acid sequence:QVQLVESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSV KGRFT I SRDNAKNTVS LQMNS LKPEDTAVYYCAALRRGVVQRRGGP YE VDTWGQGTQVTVS S(SEQ IDNO: 1069).

86. A polynucleotide encoding the VHH domain of any one of claims 78-85.

87. A VHH antibody comprising an amino acid sequence listed in Table A.ATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 202688. A polynucleotide encoding the VHH antibody of claim 87.

89. A bispecific antibody comprising an amino acid sequence listed in Table E.

90. A polynucleotide encoding the bispecific antibody of claim 89.

91. A kit comprising the base editor system of any one of claims 43-53, the immune effector cell of claim 57, the polynucleotide or set of polynucleotides of claim 58, the vector or set of vectors of claim 59, the lipid nanoparticle of any one of claims 60-62, the bispecific antibody of any one of claims 66—77 or 89, the VHH domain of any one of claims 78-85, or the VHH antibody of claim 87, and a container.

92. A composition comprising a polynucleotide encoding a base editor, wherein the base editor comprises an adenosine deaminase domain selected from the group consisting of TadA*8e, TadA*8.20, TadA*9.1, or TadA*9.52 and an SpCas9 nickase domain comprising a D10A amino acid alteration, and a guide RNA comprising a spacer comprising a spacer sequence listed in Table 1.

93. The composition of claim 92, wherein the polynucleotide encoding the base editor is an mRNA.

94. The composition of claim 92 formulated in a lipid nanoparticle (LNP).

95. The composition of claim 94, wherein the LNP comprises the ionizable lipid IZ4.

96. The composition of claim 92, wherein the spacer sequence is CCUGAGGGUGCUGUGCCGUG (SEQ ID NO: 1046; sgRNA123).

97. A lipid nanoparticle comprising mRNA encoding a base editor, wherein the base editor comprises an adenosine deaminase domain selected from the group consisting of TadA*8e, TadA*8.20, TadA*9.1, or TadA*9.52 and an SpCas9 nickase domain comprising a D10A amino acid alteration, and a guide RNA comprising a spacer comprising a spacer sequence listed in Table 1ATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 202698. The lipid nanoparticle of claim 97, wherein the lipid nanoparticle comprises the ionizable lipid IZ4.

99. The lipid nanoparticle of claim 97, wherein the spacer sequence is CCUGAGGGUGCUGUGCCGUG (SEQ ID NO: 1046; sgRNA123).

100. A method for treating a neoplasia in a subject in need thereof, the method comprising intratumorally administering to the subject a lipid nanoparticle comprising mRNA encoding a base editor, wherein the base editor comprises an adenosine deaminase domain selected from the group consisting of TadA*8e, TadA*8.20, TadA*9.1, or TadA*9.52 and an SpCas9 nickase domain comprising a D10A amino acid alteration, and a guide RNA comprising a spacer comprising a spacer sequence listed in Table 1.

101. The method of claim 100 further comprising administering to the subject a bispecific antibody after administration of the lipid nanoparticle, wherein the bispecific antibody comprises an amino acid sequence with at least 95% identity to a sequence listed in Table E.

102. The method of claim 100, wherein the method results in a reduction in size of a tumor in the subject that is distinct from the tumor into which the lipid nanoparticle was intratumorally administered.

103. A method for the selective activation and / or expansion of an immune effector cell, the method comprising contacting an immune effector cell engineered to express an IL2RP polypeptide variant comprising an R107G amino acid alteration with a bispecific antibody containing an antigen binding domain capable of selectively binding to the IL2RP polypeptide variant and an antigen binding domain capable of specifically binding to an IL2Ry polypeptide expressed by the cell, wherein the bispecific antibody comprises an amino acid sequence with at least 90% identity to the following sequence:Q VQL VE S GGGL VQAGGS LRLS CAAS RRTS S Y YVMGWFRQAPGKERE F VAG I TWGVGDT Y YKDGV KGRFTISRDNAKNTVYLQMSSLKPEDTAVYYCATADVWPSALSYDYTYWGQGTQVTVSSGGGGS QVQLVESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSV KGRFT I SRDNAKNTVS LQMNS LKPEDTAVYYCAALRRGVVQRRGGP YE VDTWGQGTQVTVS S PK SCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGVATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 2026 EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP QVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 1062), wherein the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant comprises a cluster of differentiation 1 (CDR) 1 comprising the amino acid sequence TQTFTSY (SEQ ID NO: 1063), a CDR2 comprising the amino acid sequence NWSGS (SEQ ID NO: 1064), and a CDR3 comprising the amino acid sequence LRRGVVQRRGGPYEVDT (SEQ ID NO: 1065), and wherein the antigen binding domain capable of selectively binding to the IL2RY polypeptide comprises a CDR1 comprising the amino acid sequence RRTSSYY (SEQ ID NO: 1066), a CDR2 comprising the amino acid sequence TWGVGD (SEQ ID NO: 1067), and a CDR3 comprising the amino acid sequence ADVWPSALSYDYTY (SEQ ID NO: 1068),thereby selectively activating and / or expanding the immune effector cell.

104. A method for treating a neoplasia in a subject in need thereof, the method comprising administering to a subject comprising an immune effector cell engineered to express an IL2RP polypeptide variant comprising the amino acid alteration R107G a bispecific antibody containing an antigen binding domain capable of selectively binding to the IL2RP polypeptide variant and an antigen binding domain capable of specifically binding to an IL2Ry polypeptide expressed by the cell, wherein the bispecific antibody comprises an amino acid sequence with at least 90% identity to the following sequence:Q VQL VE S GGGL VQAGGS LRLS CAAS RRTS S Y YVMGWFRQAPGKERE F VAG I TWGVGDT Y YKDGV KGRFTISRDNAKNTVYLQMSSLKPEDTAVYYCATADVWPSALSYDYTYWGQGTQVTVSSGGGGS QVQLVESGGGLVQAGGSLRLSCAASTQTFTSYSMGWFRQAPAKEREYVAVVNWSGSTTDYLDSV KGRFT I SRDNAKNTVS LQMNS LKPEDTAVYYCAALRRGVVQRRGGP YE VDTWGQGTQVTVS S PK SCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP QVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 1062), wherein the antigen binding domain capable of selectively binding to the IL2RP polypeptide variant comprises a cluster of differentiation 1 (CDR) 1 comprising the amino acid sequence TQTFTSY (SEQ ID NO: 1063), a CDR2 comprising the amino acid sequence NWSGS (SEQ ID NO: 1064), and a CDR3 comprising the amino acid sequence LRRGVVQRRGGPYEVDT (SEQ ID NO: 1065), and wherein the antigen binding domain capable of selectively binding to the IL2RY polypeptide comprises a CDR1 comprising the amino acid sequence RRTSSYY (SEQ ID NO: 1066), a CDR2ATTORNEY DOCKET NO. 180802-049202 / PCTELECTRONIC DEPOSIT DATE: January 14, 2026comprising the amino acid sequence TWGVGD (SEQ ID NO: 1067), and a CDR3 comprising the amino acid sequence ADVWPSALSYDYTY (SEQ ID NO: 1068).

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