Mono and bispecif antigen-binding molecules that bind to AAV particles and uses thereof

Abstract

Provided herein are anti-adeno-associated virus (AAV) antibodies and antigen fragments thereof, as well as multispecific antibodies (e.g., bispecific antibodies) that bind to both a capsid of an AAV particle and a molecule on a cell surface i.e. ASGR1, CACNG1 or TfR, related molecular complexes, affinity matrices, and pharmaceutical compositions, and methods of use thereof.

Description

Attorney Docket No.250298.000954 ANTIGEN-BINDING MOLECULES THAT BIND TO AAV PARTICLES AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 657,211, filed June 7, 2024, U.S. Provisional Patent Application No. 63 / 702,752, filed October 3, 2024, and U.S. Provisional Patent Application No. 63 / 804,176, filed May 12, 2025, the contents of each of which is hereby incorporated by reference in its entirety for all purposes. SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML file format and is hereby incorporated by reference in its entirety. Said XML copy, created on May 30, 2025, is named 250298_000954_SL.xml and is 1,536,977 bytes in size. FIELD OF THE DISCLOSURE

[0003] The present disclosure relates to antigen-binding molecules, including antibodies or antigen-binding fragments thereof, that bind to a capsid of an adeno-associated virus (AAV) particle. In particular, the disclosure provides multispecific antigen-binding molecules such as multispecific antibodies, e.g., bispecific antibodies, or antigen-binding fragments thereof, that bind to a capsid of an AAV and / or a molecule on a cell surface, as well as related molecular complexes and pharmaceutical compositions. Methods for using the antibodies (e.g., multispecific antibodies) disclosed herein, molecular complexes and / or pharmaceutical composition are also provided. BACKGROUND

[0004] Viral particles have emerged as vectors for gene therapy and the treatment of disease. Viral vectors, such as those based on the genome of adeno-associated virus (AAV), offer promising platforms for gene delivery. Despite advances providing the ability to direct AAV infection, retargeted AAV as a gene delivery vehicle remains less than ideal, at least in part, due to limited success from the efforts to redirect vector tropism. The efficiency of AAV vector-mediated gene delivery to different cell types also varies greatly. One possible mechanism for inefficient AAV transduction of certain cells may be a lack of cellular receptor(s) to mediate virus binding and entry. There remains a need for selective and restrictive targeting ^ ^Attorney Docket No.250298.000954 of AAVs with enhanced cellular binding and transduction capabilities. SUMMARY OF THE DISCLOSURE

[0005] In general, the present disclosure provides antibodies that bind to a capsid of an adeno-associated virus (AAV) particle, and multispecific antibodies such as, for example, bispecific antibodies, which can bind both to the capsid of an AAV particle and a molecule (i.e., a target molecule) on a cell surface, and methods of use thereof. By binding to both a capsid of an AAV and a target cell surface molecule, the antibodies described herein can bridge the virus to target cell surfaces that are not naturally targeted by the virus, thereby redirecting virus delivery and transduction.

[0006] In one aspect, provided herein is a multispecific antibody, or a multispecific antigen- binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a second heavy chain region of a second Fab (“Fab2”) operably linked to a second Fc domain (“Fc2”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); and d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”); wherein e) ABD1 or ABD2 binds to a capsid of an adeno-associated virus (AAV) particle, and the other of ABD1 or ABD2 binds to a molecule on a cell surface; f) Fc1 and / or Fc2 are derived from an IgG4 heavy chain constant region; and g) the first light chain and the second light chain comprise the same amino acid sequence.

[0007] In some embodiments, ABD1 binds to the capsid of the AAV particle and ABD2 binds to the molecule on the cell surface.

[0008] In some embodiments, ABD2 binds to the capsid of the AAV particle and ABD1 binds to the molecule on the cell surface.

[0009] In some embodiments, Fc1 and Fc2 form an Fc heterodimer.

[0010] In some embodiments, the Fc1 and / or Fc2 in the Fc heterodimer comprise a knob-in- hole mutation as compared to a wild type Fc domain.

[0011] In some embodiments, one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions S354C and T366W (according to EU numbering) as compared to a wild type Fc domain, and the other of Fc1 and Fc2 in the Fc heterodimer comprises amino acid ^ ^Attorney Docket No.250298.000954 substitutions Y349C, T366S, L368A, and Y407V (according to EU numbering) as compared to a wild type Fc domain.

[0012] In some embodiments, at least one of Fc1 and Fc2 in the Fc heterodimer comprises a star mutation as compared to a wild type Fc domain.

[0013] In some embodiments, one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid mutations H435R and / or Y436F (according to EU numbering) as compared to a wild type Fc domain.

[0014] In some embodiments, Fc1 and / or Fc2 comprises the amino acid sequence of SEQ ID NO: 1345 or 1365, or a variant thereof.

[0015] In some embodiments, the first light chain and the second light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof.

[0016] In some embodiments, ABD1 or ABD2 bind to the capsid of the AAV particle, and ABD1 or ABD2 comprises: h) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10; or i) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 71, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10.

[0017] In some embodiments, ABD1 or ABD2 binds to the capsid of the AAV particle, and ABD1 or ABD2 comprises: j) an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or k) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 71, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof.

[0018] In some embodiments, ABD1 or ABD2 binds to the capsid of the AAV particle, and ABD1 or ABD2 comprises: l) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or m) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 73, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 75, and an HCDR3 comprising the ^ ^Attorney Docket No.250298.000954 amino acid sequence of SEQ ID NO: 77; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0019] In some embodiments, the molecule on the cell surface is asialoglycoprotein receptor 1 (ASGR1), transferrin receptor (TfR), or calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1).

[0020] In some embodiments, the molecule on the cell surface is TfR.

[0021] In some embodiments, ABD1 or ABD2 binds to TfR, and ABD1 or ABD2 comprises: n) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; o) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 511, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; p) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 531, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or q) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 552, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0022] In some embodiments, ABD1 or ABD2 binds to TfR, and ABD1 or ABD2 comprises: r) an HCVR that comprises the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; s) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; t) an HCVR that comprises the amino acid sequence of SEQ ID NO: 531, or a variant thereof and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or u) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 552, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID ^ ^Attorney Docket No.250298.000954 NO: 10, or a variant thereof.

[0023] In some embodiments, ABD1 or ABD2 binds to TfR, and ABD1 or ABD2 comprises: v) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; w) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 512, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 513, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 514; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; x) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 532, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 533, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 534; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or y) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 553, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 554, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 555; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0024] In another aspect, provided herein is a multispecific antibody or multispecific antigen- binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a second heavy chain region of a second Fab (“Fab2”) operably linked to a second Fc domain (“Fc2”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); and d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”), wherein e) ABD1 binds to a capsid of an AAV particle; f) ABD2 binds to TfR; g) Fc1 comprises the amino acid sequence of SEQ ID NO: 1365, or a variant thereof; ^ ^Attorney Docket No.250298.000954 h) Fc2 comprises the amino acid sequence of SEQ ID NO: 1345, or a variant thereof; and, i) the first light chain and second light chain comprise the same amino acid sequence.

[0025] In some embodiments, the first light chain and the second light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof.

[0026] In some embodiments, ABD1 binds to the capsid of the AAV particle, and ABD1 comprises: j) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or k) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 71, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0027] In some embodiments, ABD1 binds to the capsid of the AAV particle, and ABD1 comprises: l) an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or m) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 71, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof.

[0028] In some embodiments, ABD1 binds to the capsid of the AAV particle, and ABD1 comprises: n) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or o) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 73, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 75, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 77; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0029] In some embodiments, ABD2 binds to TfR, and ABD2 comprises: p) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the ^ ^Attorney Docket No.250298.000954 amino acid sequence of SEQ ID NO: 501, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; q) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 511, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; r) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 531, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or s) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 552, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0030] In some embodiments, ABD2 binds to TfR, and ABD2 comprises: t) an HCVR that comprises the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; u) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; v) an HCVR that comprises the amino acid sequence of SEQ ID NO: 531, or a variant thereof and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or w) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 552, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof.

[0031] In some embodiments, ABD1 or ABD2 binds to TfR, and ABD1 or ABD2 comprises: x) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; y) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 512, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 513, and an HCDR3 comprising the ^ ^Attorney Docket No.250298.000954 amino acid sequence of SEQ ID NO: 514; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; z) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 532, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 533, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 534; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or aa) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 553, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 554, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 555; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0032] In another aspect, provided herein is a multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”), said Fc1 operably linked to a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a third heavy chain region of a third Fab (“Fab3”) operably linked to a second Fc domain (“Fc2”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”); and e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); wherein f) at least one of ABD1, ABD2, and ABD3 binds to a capsid of an AAV particle, and the other(s) of ABD1, ABD2, and ABD3 bind to a molecule on a cell surface; g)^Fc1 and / or Fc2 are derived from an IgG4 heavy chain constant region; and h) the first light chain, the second light chain, and the third light chain comprise the same amino acid sequence; or the first light chain and the second light chain comprise the same amino acid sequence and the third light chain comprises a different amino acid sequence.

[0033] In some embodiments, two of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and one of ABD1, ABD2, and ABD3 binds to the molecule on the cell surface. ^ ^Attorney Docket No.250298.000954

[0034] In some embodiments, ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD3 binds to the molecule on the cell surface.

[0035] In some embodiments, ABD3 binds to the capsid of the AAV particle, and ABD1 and ABD2 bind to the molecule on the cell surface.

[0036] In some embodiments, Fc1 and Fc2 form an Fc heterodimer.

[0037] In some embodiments, the Fc1 and / or Fc2 in the Fc heterodimer comprise a knob-in- hole mutation as compared to a wild type Fc domain.

[0038] In some embodiments, one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions S354C and T366W (according to EU numbering) as compared to a wild type Fc domain, and the other of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions Y349C, T366S, L368A, and Y407V (according to EU numbering) as compared to a wild type Fc domain.

[0039] In some embodiments, at least one of Fc1 and Fc2 in the Fc heterodimer comprises a star mutation as compared to a wild type Fc domain.

[0040] In some embodiments, one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid mutations H435R and / or Y436F (according to EU numbering) as compared to a wild type Fc domain.

[0041] In some embodiments, Fc1 and / or Fc2 comprises the amino acid sequence of SEQ ID NO: 1345 or 1365, or a variant thereof.

[0042] In some embodiments, the first light chain, the second light chain, and the third light chain comprise the amino acid sequence of SEQ ID NO: 20 or 813, or a variant thereof.

[0043] In some embodiments, the first light chain and the second light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof, and the third light chain comprises the amino sequence of SEQ ID NO: 813, or a variant thereof.

[0044] In some embodiments, the second heavy chain region is linked to the Fc domain via a linker.

[0045] In some embodiments, the linker is or comprises a multimer of GnS (SEQ ID NO: 239) or SGn (SEQ ID NO: 240), wherein n is an integer from 1 to 10.

[0046] In some embodiments, the linker is or comprises a multimer of G4S (SEQ ID NO: 242).

[0047] In some embodiments, the linker is G4Sx3 (SEQ ID NO: 1115).

[0048] In some embodiments, at least one of ABD1, ABD2, and ABD3 binds to the capsid of the AAV particle, and ABD1, ABD2, and / or ABD3 comprises: i) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid ^ ^Attorney Docket No.250298.000954 sequence of SEQ ID NO: 10 or 803, or a variant thereof; or j) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 71, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 803, or a variant thereof.

[0049] In some embodiments, at least one of ABD1, ABD2, and ABD3 binds to the capsid of the AAV particle, and ABD1, ABD2, ABD3 comprises: k) an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10 or 803, or a variant thereof; or l) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 71, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10 or 803, or a variant thereof.

[0050] In some embodiments, at least one of ABD1, ABD2, and ABD3 binds to the capsid of the AAV particle, and ABD1, ABD2, and / or ABD3 comprises: m) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12 or 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14 or 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16 or 809; or n) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 73, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 75, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 77; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12 or 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14 or 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16 or 809.

[0051] In some embodiments, the molecule on the cell surface is ASGR1, TfR, or CACNG1.

[0052] In some embodiments, the molecule on the cell surface is TfR.

[0053] In some embodiments, the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and ABD1, ABD2, and / or ABD3 comprises: o) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; p) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the ^ ^Attorney Docket No.250298.000954 amino acid sequence of SEQ ID NO: 511, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; q) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 531, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or r) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 552, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0054] In some embodiments, the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and ABD1, ABD2, and / or ABD3 comprises: s) an HCVR that comprises the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; t) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; u) an HCVR that comprises the amino acid sequence of SEQ ID NO: 531, or a variant thereof and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or v) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 552, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof.

[0055] In some embodiments, the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and ABD1, ABD2, and / or ABD3 comprises: w) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; x) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 512, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 513, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 514; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID ^ ^Attorney Docket No.250298.000954 NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; y) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 532, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 533, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 534; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or z) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 553, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 554, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 555; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0056] In some embodiments, the molecule on the cell surface is CACNG1.

[0057] In some embodiments, the other(s) of ABD1, ABD2, and ABD3 binds to CACNG1, and ABD1 or ABD2 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0058] In some embodiments, the other(s) of ABD1, ABD2, and ABD3 binds to CACNG1, and ABD1 or ABD2 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0059] In some embodiments, the other(s) of ABD1, ABD2, and ABD3 binds to CACNG1, and ABD1 or ABD2 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 801; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 809.

[0060] In another aspect, provided herein is a multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”), said Fc1 operably linked to a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a third heavy ^ ^Attorney Docket No.250298.000954 chain region of a third Fab (“Fab3”) operably linked to a second Fc domain (“Fc2”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”); and e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); wherein f) ABD1 and ABD2 bind to a capsid of an AAV particle; g) ABD3 binds to TfR; h) Fc1 comprises the amino acid sequence of SEQ ID NO: 1365, or a variant thereof; i) Fc2 comprises the amino acid sequence of SEQ ID NO: 1345, or a variant thereof; and, j) the first light chain, the second light chain, and the third light chain comprise the same amino acid sequence.

[0061] In some embodiments, the first light chain, the second light chain, and the third light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof.

[0062] In some embodiments, the second heavy chain region is linked to the Fc domain via a linker.

[0063] In some embodiments, the linker is G4Sx3 (SEQ ID NO: 1115).

[0064] In some embodiments, ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD1 and ABD2 comprises: k) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 803, or a variant thereof; or l) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 71, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 803, or a variant thereof.

[0065] In some embodiments, ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD1 and ABD2 comprises: m) an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or n) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 71, or a ^ ^Attorney Docket No.250298.000954 variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof.

[0066] In some embodiments, ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD1 and ABD2 comprises: o) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or p) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 73, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 75, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 77; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0067] In some embodiments, ABD3 binds to TfR, and ABD3 comprises: q) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; r) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 511, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; s) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 531, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or t) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 552, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0068] In some embodiments, ABD3 binds to TfR, and ABD3 comprises: u) an HCVR that comprises the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; v) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a ^ ^Attorney Docket No.250298.000954 variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; w) an HCVR that comprises the amino acid sequence of SEQ ID NO: 531, or a variant thereof and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or x) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 552, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof.

[0069] In some embodiments, ABD3 binds to TfR, and ABD3 comprises: y) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; z) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 512, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 513, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 514; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; aa) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 532, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 533, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 534; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or bb) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 553, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 554, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 555; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0070] In another aspect, provided herein is a multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”), said Fc1 operably linked to a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a third heavy chain region of a third Fab (“Fab3”) operably linked to a second Fc domain (“Fc2”); ^ ^Attorney Docket No.250298.000954 c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”); and e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); wherein f) ABD1 and ABD2 bind to a capsid of an AAV particle; g) ABD3 binds to CACNG1; h) Fc1 comprises the amino acid sequence of SEQ ID NO: 1365, or a variant thereof; i) Fc2 comprises the amino acid sequence of SEQ ID NO: 1345, or a variant thereof; and j) the first light chain and the second light chain comprise the same amino acid sequence and the third light chain comprises an different amino acid sequence.

[0071] In some embodiments, the first light chain and the second light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof.

[0072] In some embodiments, the third light chain comprises the amino acid sequence of SEQ ID NO: 813, or a variant thereof.

[0073] In some embodiments, the second heavy chain region is linked to the Fc domain via a linker.

[0074] In some embodiments, the linker is G4Sx3 (SEQ ID NO: 1115).

[0075] In some embodiments, ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD1 and ABD2 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10.

[0076] In some embodiments, ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD1 and ABD2 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0077] In some embodiments, ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD1 and ABD2 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ^ ^Attorney Docket No.250298.000954 ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0078] In some embodiments, ABD3 binds to CACNG1, and ABD3 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0079] In some embodiments, ABD3 binds to CACNG1, and ABD3 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0080] In some embodiments, ABD3 binds CACNG1, and ABD3 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 801; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 809.

[0081] In another aspect, provided herein is a multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”), said Fc1 operably linked to a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a third heavy chain region of a third Fab (“Fab3”) operably linked to a second Fc domain (“Fc2”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”); and e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); wherein f) ABD1 and ABD2 bind to a capsid of an AAV particle; g) ABD3 binds to CACNG1; h) Fc1 comprises the amino acid sequence of SEQ ID NO: 1365, or a variant thereof; i) Fc2 comprises the amino acid sequence of SEQ ID NO: 1345, or a variant thereof; and ^ ^Attorney Docket No.250298.000954 j) the first light chain, the second light chain, and the third light chain comprise the same amino acid sequence.

[0082] In some embodiments, the first light chain, the second light chain, and the third light chain comprise the amino acid sequence of SEQ ID NO: 813, or a variant thereof.

[0083] In some embodiments, the second heavy chain region is linked to the Fc domain via a linker.

[0084] In some embodiments, the linker is G4Sx3 (SEQ ID NO: 1115).

[0085] In some embodiments, ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD1 and ABD2 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0086] In some embodiments, ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD1 and ABD2 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0087] In some embodiments, ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD1 and ABD2 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 809.

[0088] In some embodiments, ABD3 binds to CACNG1, and ABD3 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0089] In some embodiments, ABD3 binds to CACNG1, and ABD3 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0090] In some embodiments, ABD3 binds CACNG1, and ABD3 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, an HCDR2 comprising ^ ^Attorney Docket No.250298.000954 the amino acid sequence of SEQ ID NO: 799, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 801; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 809.

[0091] In another aspect, provided herein is a multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to an Fc domain, said Fc domain operably linked to a first scFv comprising a first antigen-binding domain (“ABD1”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a second heavy chain region of a second Fab (“Fab2”) operably linked to an Fc domain, said Fc domain operably linked to a second scFv comprising a second antigen-binding domain (“ABD2”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a third antigen-binding domain (“ABD3”); and d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a fourth antigen-binding domain (“ABD4”); wherein e) at least one of ABD1, ABD2, ABD3, and ABD4 binds to a capsid of an AAV particle, and the other(s) of ABD1, ABD2, ABD3, and ABD4 bind to CACNG1; f) the Fc domain is derived from an IgG4 heavy chain constant region; and g) the first light chain and the second light chain comprise the same amino acid sequence.

[0092] In some embodiments, two of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and two of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1.

[0093] In some embodiments, ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD3 and ABD4 binds to CACNG1.

[0094] In some embodiments, ABD3 and ABD4 bind to the capsid of the AAV particle, and ABD1 and ABD2 binds to CACNG1.

[0095] In some embodiments, the Fc domain comprises the amino acid sequence of SEQ ID NO: 1397, or a variant thereof.

[0096] In some embodiments, the first light chain and the second light chain comprise the amino acid sequence of SEQ ID NO: 813, or a variant thereof.

[0097] In some embodiments, the first scFv and / or the second scFv are linked to the Fc domain via a linker.

[0098] In some embodiments, the linker is or comprises a multimer of GnS (SEQ ID NO: 239) or SGn (SEQ ID NO: 240), wherein n is an integer from 1 to 10. ^ ^Attorney Docket No.250298.000954

[0099] In some embodiments, the linker is or comprises a multimer of G4S (SEQ ID NO: 242).

[0100] In some embodiments, the linker is G4Sx3 (SEQ ID NO: 1115).

[0101] In some embodiments, at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 1159, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 1157, or a variant thereof.

[0102] In some embodiments, at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 1159, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 1157, or a variant thereof.

[0103] In some embodiments, at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0104] In some embodiments, the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0105] In some embodiments, the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0106] In some embodiments, the other(s) of ABD1, ABD2, ABD3, and ABD4 binds CACNG1, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and an HCDR3 comprising the amino acid ^ ^Attorney Docket No.250298.000954 sequence of SEQ ID NO: 801; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 809.

[0107] In another aspect, provided herein is a multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first scFv comprising a first antigen-binding domain (“ABD1”) operably linked to an Fc domain, said Fc domain operably linked to a first heavy chain region of a first Fab (“Fab1”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a second scFv comprising a second antigen-binding domain (“ABD2”) operably linked to an Fc domain, said Fc domain operably linked to a second heavy chain region of a second Fab (“Fab2”) ; c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a third antigen-binding domain (“ABD3”); and d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a fourth antigen-binding domain (“ABD4”); wherein e) at least one of ABD1, ABD2, ABD3, and ABD4 binds to a capsid of an AAV particle, and the other(s) of ABD1, ABD2, ABD3, and ABD4 bind to CACNG1; f) the Fc domain is derived from an IgG4 heavy chain constant region; and g) the first light chain and the second light chain comprise the same amino acid sequence.

[0108] In some embodiments, two of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and two of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1.

[0109] In some embodiments, ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD3 and ABD4 binds to CACNG1.

[0110] In some embodiments, ABD3 and ABD4 bind to the capsid of the AAV particle, and ABD1 and ABD2 binds to CACNG1.

[0111] In some embodiments, the Fc domain comprises the amino acid sequence of SEQ ID NO: 1397, or a variant thereof.

[0112] In some embodiments, the first light chain and the second light chain comprise the sequence of SEQ ID NO: 20 or 813, or a variant thereof.

[0113] In some embodiments, the first Fab and / or the second Fab is linked to the Fc domain via a linker.

[0114] In some embodiments, the linker is or comprises a multimer of GnS (SEQ ID NO: 239) or SGn (SEQ ID NO: 240), wherein n is an integer from 1 to 10.

[0115] In some embodiments, the linker is or comprises a multimer of G4S (SEQ ID NO: ^ ^Attorney Docket No.250298.000954 242).

[0116] In some embodiments, the linker is G4Sx3 (SEQ ID NO: 1115).

[0117] In some embodiments, at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1157, or a variant thereof.

[0118] In some embodiments, at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10 or 1157, or a variant thereof.

[0119] In some embodiments, at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0120] In some embodiments, the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0121] In some embodiments, the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803 or 1352, or a variant thereof.

[0122] In some embodiments, the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 801; and / or an LCDR1 comprising the amino acid sequence of ^ ^Attorney Docket No.250298.000954 SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 809.

[0123] In another aspect, provided herein is a multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to an Fc domain, said Fc domain operably linked to a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a third heavy chain region of a third Fab (“Fab3”) operable liked to an Fc domain, said Fc domain operably linked to a fourth heavy chain region of a fourth Fab (“Fab4”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ADB2”); e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); and f) a sixth polypeptide chain comprising a fourth light chain that pairs with the fourth heavy chain region to form Fab4, wherein Fab4 comprises a fourth antigen-binding domain (“ABD4”); wherein g) at least one of ABD1, ABD2, ABD3, and ABD4 binds to a capsid of an AAV particle, and the other(s) of ABD1, ABD2, ABD3, and ABD4 bind to CACNG1; h) the Fc domain is derived from an IgG4 heavy chain constant region; and i) the first light chain, the second light chain, the third light chain, and the fourth light chain comprise the same amino acid sequence.

[0124] In some embodiments, two of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and two of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1.

[0125] In some embodiments, ABD1 and ABD3 bind to the capsid of the AAV particle, and ABD2 and ABD4 binds to CACNG1.

[0126] In some embodiments, ABD2 and ABD4 bind to the capsid of the AAV particle, and ABD1 and ABD3 binds to CACNG1.

[0127] In some embodiments, the first light chain, the second light chain, the third light chain, and the fourth light chain comprise the amino acid sequence of SEQ ID NO: 813, or a variant thereof.

[0128] In some embodiments, the Fc domain is linked to the second heavy chain region ^ ^Attorney Docket No.250298.000954 and the fourth heavy chain region via a linker.

[0129] In some embodiments, the linker is or comprises a multimer of GnS (SEQ ID NO: 239) or SGn (SEQ ID NO: 240), wherein n is an integer from 1 to 10.

[0130] In some embodiments, the linker is or comprises a multimer of G4S (SEQ ID NO: 242).

[0131] In some embodiments, the linker is G4Sx3 (SEQ ID NO: 1115).

[0132] In some embodiments, at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0133] In some embodiments, at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0134] In some embodiments, at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 809.

[0135] In some embodiments, the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0136] In some embodiments, the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

[0137] In some embodiments, the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to ^ ^Attorney Docket No.250298.000954 CACNG1, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 801; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 809.

[0138] In another aspect, provided herein is a multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to an Fc domain, said Fc domain operably linked to a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a third heavy chain region of a third Fab (“Fab3”) operable liked to an Fc domain, said Fc domain operably linked to a fourth heavy chain region of a fourth Fab (“Fab4”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ADB2”); e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); and f) a sixth polypeptide chain comprising a fourth light chain that pairs with the fourth heavy chain region to form Fab4, wherein Fab4 comprises a fourth antigen-binding domain (“ABD4”); wherein g) at least one of ABD1, ABD2, ABD3, and ABD4 binds to a capsid of an AAV particle, and the other(s) of ABD1, ABD2, ABD3, and ABD4 bind to TfR; h) the Fc domain is derived from an IgG4 heavy chain constant region; and i) the first light chain, the second light chain, the third light chain, and the fourth light chain comprise the same amino acid sequence.

[0139] In some embodiments, two of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and two of ABD1, ABD2, ABD3, and ABD4 binds to TfR.

[0140] In some embodiments, ABD1 and ABD3 bind to TfR, and ABD2 and ABD4 binds to the capsid of the AAV particle.

[0141] In some embodiments, ABD2 and ABD4 bind to TfR, and ABD1 and ABD3 binds to the capsid of the AAV particle. ^ ^Attorney Docket No.250298.000954

[0142] In some embodiments, the first light chain, the second light chain, the third light chain, and the fourth light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof.

[0143] In some embodiments, the Fc domain is linked to the second heavy chain region and the fourth heavy chain region via a linker.

[0144] In some embodiments, the linker is or comprises a multimer of GnS (SEQ ID NO: 239) or SGn (SEQ ID NO: 240), wherein n is an integer from 1 to 10.

[0145] In some embodiments, the linker is or comprises a multimer of G4S (SEQ ID NO: 242).

[0146] In some embodiments, the linker is G4Sx3 (SEQ ID NO: 1115).

[0147] In some embodiments, at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0148] In some embodiments, at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0149] In some embodiments, at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0150] In some embodiments, the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to TfR, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0151] In some embodiments, the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to TfR, and ABD1, ABD2, ABD3, and / or ABD4 comprises: ^ ^Attorney Docket No.250298.000954 an HCVR that comprises the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0152] In some embodiments, the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to TfR, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0153] In another aspect, provided herein is a multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”), said Fc1 operably linked to a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a second Fc domain (“Fc2”), said Fc2 operably linked to a third heavy chain region of a third Fab (“Fab3”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ADB2”); and e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); wherein f) at least one of ABD1, ABD2, and ABD3 binds to a capsid of an AAV particle, and the other(s) of ABD1, ABD2, and ABD3 bind to TfR; g) Fc1 and / or Fc2 are derived from an IgG4 heavy chain constant region; and h) the first light chain, the second light chain, and the third light chain comprise the same amino acid sequence.

[0154] In some embodiments, two of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and one of ABD1, ABD2, and ABD3 binds to TfR.

[0155] In some embodiments, two of ABD1, ABD2, and ABD3 bind to TfR, and one of ABD1, ABD2, and ABD3 binds to the capsid of the AAV particle.

[0156] In some embodiments, ABD1 binds to TfR, and ABD2 and ABD3 binds to the ^ ^Attorney Docket No.250298.000954 capsid of the AAV particle.

[0157] In some embodiments, ABD1 binds to the capsid of the AAV particle, and ABD2 and ABD3 binds to TfR.

[0158] In some embodiments, Fc1 and Fc2 form an Fc heterodimer.

[0159] In some embodiments, the Fc1 and / or Fc2 in the Fc heterodimer comprise a knob- in-hole mutation as compared to a wild type Fc domain.

[0160] In some embodiments, one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions S354C and T366W (according to EU numbering) as compared to a wild type Fc domain, and the other of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions Y349C, T366S, L368A, and Y407V (according to EU numbering) as compared to a wild type Fc domain.

[0161] In some embodiments, at least one of Fc1 and Fc2 in the Fc heterodimer comprises a star mutation as compared to a wild type Fc domain.

[0162] In some embodiments, one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid mutations H435R and / or Y436F (according to EU numbering) as compared to a wild type Fc domain.

[0163] In some embodiments, Fc1 and / or Fc2 comprises the amino acid sequence of SEQ ID NO: 1397 or 1511, or a variant thereof.

[0164] In some embodiments, the first light chain, the second light chain, and the third light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof.

[0165] In some embodiments, Fc1 and / or Fc2 is linked to the second heavy chain region and the third heavy chain region via a linker.

[0166] In some embodiments, the linker is or comprises a multimer of GnS (SEQ ID NO: 239) or SGn (SEQ ID NO: 240), wherein n is an integer from 1 to 10.

[0167] In some embodiments, the linker is or comprises a multimer of G4S (SEQ ID NO: 242).

[0168] In some embodiments, the linker is G4Sx3 (SEQ ID NO: 1115).

[0169] In some embodiments, at least one of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and ABD1, ABD2, and / or ABD3 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0170] In some embodiments, at least one of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and ABD1, ABD2, and / or ABD3 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, ^ ^Attorney Docket No.250298.000954 and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0171] In some embodiments, at least one of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and ABD1, ABD2, and / or ABD3 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0172] In some embodiments, the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and ABD1, ABD2, and / or ABD3 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0173] In some embodiments, the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0174] In some embodiments, the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and ABD1, ABD2, and / or ABD3 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 14.

[0175] In some embodiments, i) ABD1 binds to TfR; j) ABD2 and ABD3 bind to the capsid of the AAV particle; k) Fc1 comprises the amino acid sequence of SEQ ID NO: 1397, or a variant thereof; and l) Fc2 comprises the amino acid sequence of SEQ ID NO: 1511, or a variant thereof.

[0176] In another aspect, provided herein is a multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a second heavy ^ ^Attorney Docket No.250298.000954 chain region of a second Fab (“Fab2”) operably linked to a second Fc domain (“Fc2”), said Fc2 operably linked to a third heavy chain region of a third Fab (“Fab3”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”); and e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); wherein f) at least one of ABD1, ABD2, and ABD3 binds to a capsid of an AAV particle, and the other(s) of ABD1, ABD2, and ABD3 bind to TfR; g) Fc1 and / or Fc2 are derived from an IgG4 heavy chain constant region; and h) the first light chain, the second light chain, and the third light chain comprise the same amino acid sequence.

[0177] In some embodiments, two of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and one of ABD1, ABD2, and ABD3 binds to TfR.

[0178] In some embodiments, two of ABD1, ABD2, and ABD3 bind to TfR, and one of ABD1, ABD2, and ABD3 binds to the capsid of the AAV particle.

[0179] In some embodiments, ABD2 and ABD3 bind to the capsid of the AAV particle, and ABD1 binds to TfR.

[0180] In some embodiments, ABD2 and ABD3 bind to TfR, and ABD1 binds to the capsid of the AAV particle.

[0181] In some embodiments, Fc1 and Fc2 form an Fc heterodimer.

[0182] In some embodiments, the Fc1 and / or Fc2 in the Fc heterodimer comprise a knob- in-hole mutation as compared to a wild type Fc domain.

[0183] In some embodiments, one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions S354C and T366W (according to EU numbering) as compared to a wild type Fc domain, and the other of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions Y349C, T366S, L368A, and Y407V (according to EU numbering) as compared to a wild type Fc domain.

[0184] In some embodiments, at least one of Fc1 and Fc2 in the Fc heterodimer comprises a star mutation as compared to a wild type Fc domain.

[0185] In some embodiments, one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid mutations H435R and / or Y436F (according to EU numbering) as compared to a wild type Fc domain. ^ ^Attorney Docket No.250298.000954

[0186] In some embodiments, Fc1 and / or Fc2 comprises the amino acid sequence of SEQ ID NO: 1397 or 1511, or a variant thereof.

[0187] In some embodiments, the first light chain, the second light chain, and the third light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof.

[0188] In some embodiments, Fc2 is linked to the third heavy chain region via a linker.

[0189] In some embodiments, the linker is or comprises a multimer of GnS (SEQ ID NO: 239) or SGn (SEQ ID NO: 240), wherein n is an integer from 1 to 10.

[0190] In some embodiments, the linker is or comprises a multimer of G4S (SEQ ID NO: 242).

[0191] In some embodiments, the linker is G4Sx3 (SEQ ID NO: 1115).

[0192] In some embodiments, at least one of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and ABD1, ABD2, and / or ABD3 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0193] In some embodiments, at least one of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and ABD1, ABD2, and / or ABD3 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0194] In some embodiments, at least one of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and ABD1, ABD2, and / or ABD3 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0195] In some embodiments, the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and ABD1, ABD2, and / or ABD3 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0196] In some embodiments, the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and ABD1, ABD2, and / or ABD3 comprises: ^ ^Attorney Docket No.250298.000954 an HCVR that comprises the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

[0197] In some embodiments, the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and ABD1, ABD2, and / or ABD3 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 14.

[0198] In some embodiments, i) ABD1 binds to TfR; j) ABD2 and ABD3 bind to the capsid of the AAV particle; k) Fc1 comprises the amino acid sequence of SEQ ID NO: 1397, or a variant thereof; and l) Fc2 comprises the amino acid sequence of SEQ ID NO: 1511, or a variant thereof.

[0199] In some embodiments, the AAV is wild type.

[0200] In some embodiments, the AAV particle comprises one or more mutations in one or more AAV capsid proteins inhibiting the natural tropism of said AAV particle.

[0201] In some embodiments, the multispecific antibody or multispecific antigen-binding fragment is a bispecific antibody or bispecific antigen-binding fragment thereof.

[0202] In another aspect, provided herein is a pharmaceutical composition comprising the multispecific antibodies or multispecific antigen-binding fragments as described herein, and a pharmaceutically acceptable carrier or excipient.

[0203] In another aspect, provided herein is a molecular complex comprising an AAV particle bound to one or more multispecific antibodies and / or multispecific antigen-binding fragments as described herein.

[0204] In some embodiments, the AAV particle comprises one or more mutations in one or more AAV capsid proteins inhibiting the natural tropism of said AAV particle.

[0205] In another aspect, provided herein is a pharmaceutical composition comprising the molecular complex as described herein and a pharmaceutically acceptable carrier or excipient.

[0206] In another aspect, provided herein is a method of preparing the molecular complex as described herein, comprising incubating the AAV particle in the presence of the one or more multispecific antibodies and / or multispecific antigen-binding fragments under conditions allowing specific binding of said one or more multispecific antibodies and / or multispecific antigen-binding fragments to said AAV particle capsid.

[0207] In another aspect, provided herein is a method for targeting an AAV particle to a ^ ^Attorney Docket No.250298.000954 cell expressing a molecule on the cell surface, comprising contacting the cell with the molecular complex as described herein, or the pharmaceutical composition as described herein, wherein said molecular complex comprises one or more multispecific antibodies and / or multispecific antigen-binding fragments which bind to said molecule on the cell surface.

[0208] In another aspect, provided herein is a method for delivering a polynucleotide to a cell expressing a molecule on the cell surface, comprising contacting the cell with the molecular complex as described herein or the pharmaceutical composition as described herein, wherein said molecular complex comprises the AAV particle comprising said polynucleotide and bound to one or more multispecific antibodies and / or multispecific antigen-binding fragments which bind to said molecule on the cell surface.

[0209] In some embodiments, the cell is in a subject and the molecular complex is administered to the subject.

[0210] In some embodiments, the AAV particle does not target the cell in the absence of the one or more multispecific antibodies and / or multispecific antigen-binding fragments.

[0211] In various embodiments, any of the features or components of embodiments discussed above or herein may be combined, and such combinations are encompassed within the scope of the present disclosure. Any specific value discussed above or herein may be combined with another related value discussed above or herein to recite a range with the values representing the upper and lower ends of the range, and such ranges are encompassed within the scope of the present disclosure.

[0212] Other embodiments will become apparent from a review of the ensuing detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0213] Figures 1A-1L depict graphs of binding activities of the anti-adeno-associated virus (AAV) antibodies described herein to various adeno-associated virus (AAV) serotypes. RLU, relative light units.

[0214] Figures 2A-2J depict graphs showing immunoglobulin gamma Fc receptor I (FcGR- 1) AAV retargeting by anti-AAV antibodies derived using next-generation sequencing (NGS) / mass spectrometry (MS) methods (Figures 2A-2F) and by anti-AAV antibodies derived from hybridoma (Figures 2G-2J) described herein for various AAV serotypes.

[0215] Figure 3 shows a schematic representation of alternative format antibody designs for bispecific antibodies of the present disclosure. Exemplary bispecific antibodies target AAV and Asialoglycoprotein Receptor 1 (ASGR1). Star mutations are depicted with an asterisk (*) and knob-in-hole (KiH) mutations are depicted with a triangle (e.g., ^). ^ ^Attorney Docket No.250298.000954

[0216] Figure 4 displays a description of alternative format bispecific antibody molecules described herein.

[0217] Figure 5 illustrates an example rationale for anti-AAV antibody selection.

[0218] Figures 6A-6J depict graphs of binding affinities of alternative format antibodies described herein (e.g., anti-AAV x anti-ASGR1 [also called AAV x ASGR1, and the like, herein] bispecific antibodies) to an AAV2 heparin binding mutant (HBM) serotype. The AAV2-HBM serotype contains R585A, R588A mutations. RLU, relative light units.

[0219] Figures 7A-7B illustrate that bispecific antibodies can effectively retarget adeno- associated virus (AAV) to the central nervous system (CNS). A schematic representation of anti-transferrin receptor (TfR) x anti-AAV bispecific antibody retargeting of AAV to the CNS is depicted in Figure 7A. A comparison of wild-type (WT) AAV9, covalent-platform control and bispecific platform retargeting of AAV to cerebellum, cortex, and hippocampus is shown in Figure 7B. BBB, blood-brain barrier.

[0220] Figures 8A-8B demonstrate that liver detargeting can be controlled by modulating antibody concentration [Ab] and / or use of a detargeting capsid. A comparison of transduction efficiency between the covalent platform and the bispecific platform evaluated using cDNA quantitation is shown in Figure 8A. A comparison between detargeted AAV9 and WT AA9 using the bispecific platform in cerebellum and liver is shown in Figure 8B. IHC, immunohistochemistry.

[0221] Figure 9 shows a schematic representation of anti-AAV x anti-CACNG1 (also called AAV x CACNG1, and the like, herein) alternative format (AF) antibodies AF70 and AF71.^AF70 comprises anti-AAV#70 scFv fused to the N-terminus of anti-CACNG1 REGN10717 hIgG1 N297G antibody. AF71 comprises anti-AAV#70 scFv fused to the C-terminus of anti-CACNG1 REGN10717 hIgG1 N297G antibody. Disulfide bonds are indicated by S-S.

[0222] Figure 10 shows flow cytometry data illustrating co-incubation of AAV9 W503A with AF70 (top two rows) and AF71 (bottom two rows) resulted in improved transduction efficiency over control AAV without antibody on HEK 293 cells overexpressing mouse CACNG1 (mCACNG1). Transduction efficiency was optimal between molar ratios of 1 AAV to 1 antibody (AAV:Ab ratio 1:1) and 1 AAV to 9 antibodies (AAV:Ab ratio 1:9) as assessed by percent (%) GFP positive cells.

[0223] Figure 11 depicts line graphs showing co-incubation of AAV9 W503A with AF70 (top) and AF71 (bottom) resulted in improved transduction efficiency over control AAV without antibody on HEK 293 cells overexpressing mouse CACNG1 (mCACNG1). Transduction efficiency was optimal between molar ratios of 1 AAV to 1 antibody (AAV:Ab ratio 1:1) and 1 AAV to 9 antibodies (AAV:Ab ratio 1:9) as assessed by mean fluorescence intensity (MFI).

[0224] Figure 12 shows flow cytometry data illustrating co-incubation of AAV9 W503A with ^ ^Attorney Docket No.250298.000954 AF70 (top two rows) and AF71 (bottom two rows) resulted in improved AAV transduction efficiency over control AAV without antibody on HEK 293 cells overexpressing human CACNG1 (hCACNG1). Transduction efficiency was optimal between molar ratios of 1 AAV to 1 antibody (AAV:Ab ratio 1:1) and 1 AAV to 9 antibodies (AAV:Ab ratio 1:9) as assessed by percent (%) GFP positive cells.

[0225] Figure 13 depicts line graphs showing co-incubation of AAV9 W503A with AF70 (top) and AF71 (bottom) resulted in improved AAV transduction efficiency over control AAV without antibody on HEK 293 cells overexpressing human CACNG1 (hCACNG1). Transduction efficiency was optimal between molar ratios of 1 AAV to 1 antibody (AAV:Ab ratio 1:1) and 1 AAV to 9 antibodies (AAV:Ab ratio 1:9) as assessed by mean fluorescence intensity (MFI).

[0226] Figure 14 shows immunohistochemical staining of differentiated C2C12 myotubes for Myosin Heavy Chain (MyHC) and demonstration that incubation of AAV with AF70 and AF71 enhanced transduction into the myotubes as determined by GFP fluorescence.

[0227] Figure 15 shows immunohistochemical staining of differentiated human myotubes for Myosin Heavy Chain (MyHC) and demonstration that incubation of AAV with AF70 and AF71 enhanced transduction into the myotubes as determined by GFP fluorescence. Human myotubes were most efficiently transduced with AAV complexed with AF71 at molar ratio 1:3 and 1:9.

[0228] Figures 16A-16D demonstrate incubation of AAV with AF70 and AF71 enhanced transduction into differentiated C2C12 myotubes as determined by quantification of GFP positive cells.

[0229] Figures 17A-17D demonstrate incubation of AAV with AF70 and AF71 enhanced transduction into differentiated human myotubes as determined by quantification of GFP positive cells.

[0230] Figures 18A-18B show non-limiting examples of anti-AAV x anti-mTfR (also called AAV x mTfR, and the like, herein) alternative format (AF) antibodies described herein. Star mutations are depicted with an asterisk (*) and knob-in-hole (KiH) mutations are depicted with a triangle (e.g., ^).

[0231] Figure 19 shows an example experimental setup used to test alternative format antibodies binding to AAV9W503A virus by ELISA.

[0232] Figure 20 depicts ELISA data for anti-AAV x anti-mTfR alternative format antibodies binding to AAV9W503A.

[0233] Figure 21 shows a schematic diagram of a FLuc assay protocol used to test retargeting of AAV9W503A using mTfR alternative format antibodies on 293T cells expressing mTfR receptor. ^ ^Attorney Docket No.250298.000954

[0234] Figure 22 shows a line graph of data generated in experiments testing AAV9W503A retargeting using anti-AAV x anti-mTfR alternative format antibodies on mTfR293T cells.

[0235] Figures 23A-23C illustrate a retargeting assay using AAV9 scCBH.eGFP.

[0236] Figures 24A-24B show in vitro test infection results for in vivo injection samples.

[0237] Figures 25A-25F depict anti-AAV x anti-mTfR liver and brain (hippocampus, cortex, and cerebellum) green fluorescent protein (GFP) staining for control groups (Figure 25A) and alternative format designs, anti-AAV x anti-mTfR AF1 (Figure 25B), anti-AAV x anti-mTfR AF3 (Figure 25C), anti-AAV x anti-mTfR AF5 (Figure 25D), anti-AAV x anti-mTfR AF7 (Figure 25E), and anti-AAV x anti-mTfR AF9 (Figure 25F).

[0238] Figure 26 shows relative RNA expression of GFP in liver samples as determined by RT-qPCR.

[0239] Figure 27 shows RNA expression of GFP in brain samples as determined by RT- qPCR.

[0240] Figures 28A-28D depict GFP staining in brain, heart, and liver tissues from mice receiving AAV9 (Figures 28A-28B) or AAV9W503A (Figures 28C and 28D) complexed with anti-AAV x anti-mTfR alternative format AF7 at AAV vector genome (VG) to antibody (Ab) ratios (VG:Ab ratios) of 1:9 and 1:3.

[0241] Figures 29A-29I depict anti-AAV x anti-mTfR alternative format designs AF3 and AF7. Figure 29A provides a description of anti-AAV x anti-mTfR alternative format designs AF3 and AF7. Star mutations are depicted with an asterisk (*) and knob-in-hole (KiH) mutations are depicted with a triangle (e.g., ^). Figures 29B-29E show examples of anti-AAV x anti-mTfR AF3 amino acid sequences (Figure 29B) and corresponding nucleotide sequences (Figures 29C-29E). Figures 29F-29I show examples of anti-AAV x anti-mTfR AF7 amino acid sequences (Figure 29F) and corresponding nucleotide sequences (Figures 29G- 29I). Figure discloses “3xG4S” as SEQ ID NO: 1115.

[0242] Figures 30A-30G depict anti-AAV x anti-CACNG1 alternative format designs AF70 and AF71. Figure 30A provides a description of anti-AAV x anti-CACNG1 alternative format designs AF70 and AF71. Figures 30B-30G show examples of anti-AAV x anti-CACNG1 AF70 amino acid sequences (Figure 30B) and corresponding nucleotide sequences (Figures 30C- 30D). Figures 30E-30G show examples of anti-AAV x anti-CACNG1 AF71 amino acid sequences (Figure 30E) and corresponding nucleotide sequences (Figures 30F-30G). Figure discloses “3xG4S” as SEQ ID NO: 1115 and “4xG4S” as SEQ ID NO: 1161.

[0243] Figure 31 illustrates anti-AAV x anti-CACNG1 bispecific antibody enhancement of transduction into CACNG1 overexpressing 293 cells. GFP expression was assessed by flow cytometry and is shown as % GFP positive cells (top panels) or MFI of GFP expressing cells (bottom panels). ^ ^Attorney Docket No.250298.000954

[0244] Figure 32 depicts an example of a study design for testing Hu37 complexed with anti-AAV x anti-CACNG12x2 antibodies in D2.MDX mice.

[0245] Figure 33 shows in vitro transduction in HEK293-hCACNG1 of complexes prepared for in vivo study.^

[0246] Figures 34A-34C illustrate improved Hu37 transduction in muscle tissues when complexed with an 2x2 anti-AAV x anti-CACNG1 alternative format antibody.

[0247] Figures 35A-35B illustrate bispecific antibody enhancement of Hu37 transduction into skeletal muscle.

[0248] Figures 36A-36B depict anti-AAV x anti-ASGR alternative format designs AF21 (REGN16199), AF22 (REGN16200), AF29, AF30 (REGN16204), AF32 (REGN16202), AF37, AF41, AF60A, AF61A, AF62, and AF63. Figure 36A provides a description of anti-AAV x anti- ASGR alternative format designs AF21 (REGN16199), AF22 (REGN16200), AF29, AF30 (REGN16204), and AF32 (REGN16202). Figure 36B provides a description of anti-AAV x anti-ASGR alternative format designs AF37, AF41, AF60A, AF61A, AF62, and AF63. Figure discloses “3xG4S” as SEQ ID NO: 1115 and “4xG4S” as SEQ ID NO: 1161.

[0249] Figures 37A-37B depict IVIS (In Vivo Imaging Instrument, Perkin Elmer) data illustrating retargeting of AAV to liver with AF30 and AF32.

[0250] Figure 38 depicts IVIS data that demonstrate retargeting of multiple serotypes to liver with AF30.

[0251] Figures 39A-39D depict IVIS & PK qPCR data that demonstrate retargeting to liver with antibodies comprised of either one or two anti-AAV binding arms.

[0252] Figures 40A-40C depict IVIS, PK qPCR, & ELISA data that demonstrate antibody can effectively retarget AAV when dosed prior to AAV administration.

[0253] Figures 41A-41B depict IVIS & PK qPCR data that demonstrate retargeting of REGN16199 with and without Fc.

[0254] Figures 42A-42F depict IVIS, PK qPCR, & RNA Taqman data that demonstrate successful targeting with linear Fab formats.

[0255] Figure 43 depicts PK qPCR data of serum samples 24 hours after administration of various antibody formats complexed with AAV.

[0256] Figure 44 depicts IVIS data that demonstrate retargeting of AAV with a variety of different antibody formats.

[0257] Figure 45 depicts IVIS data that demonstrate retargeting of AAV with antibody comprised of one anti-AAV arm and one anti-ASGR1 arm.

[0258] Figures 46A-46I depict anti-AAV x anti-ASGR alternative format designs AF1, AF5, and AF9. Figures 46A-46C show examples of anti-AAV x anti-ASGR AF1 amino acid sequences (Figure 46A) and corresponding nucleotide sequences (Figures 46B-46C). ^ ^Attorney Docket No.250298.000954 Figures 46D-46F show examples of anti-AAV x anti-ASGR AF5 amino acid sequences (Figure 46D) and corresponding nucleotide sequences (Figures 46E-46F). Figures 46G-46I show examples of anti-AAV x anti-ASGR AF9 amino acid sequences (Figure 46G) and corresponding nucleotide sequences (Figures 46H-46I). Figure discloses “3xG4S” as SEQ ID NO: 1115 and “4xG4S” as SEQ ID NO: 1161.

[0259] Figures 47A-47I depict anti-AAV x anti-mTfR alternative format designs AF1, AF5, and AF9. Figures 47A-47C show examples of anti-AAV x anti-mTfR AF1 amino acid sequences (Figure 47A) and corresponding nucleotide sequences (Figures 47B-47C). Figures 47D-47F show examples of anti-AAV x anti-mTfR AF5 amino acid sequences (Figure 47D) and corresponding nucleotide sequences (Figures 47E-47F). Figures 47G-47I show examples of anti-AAV x anti-mTfR AF9 amino acid sequences (Figure 47G) and corresponding nucleotide sequences (Figures 47H-47I). Figure discloses “3xG4S” as SEQ ID NO: 1115 and “4xG4S” as SEQ ID NO: 1161.

[0260] Figure 48^shows a schematic representation of anti-AAV x anti-CACNG1 alternative format (AF) antibodies AF70, AF71, AF71x, AF72a, AF72b, AF73, AF74A, AF74B, and AF76. Star mutations are depicted with an asterisk (*) and knob-in-hole (KiH) mutations are depicted with a triangle (^).Figure discloses “3xG4S” as SEQ ID NO: 1115, “G4S” as SEQ ID NO: 242, and “4xG4S” as SEQ ID NO: 1161.

[0261] Figures 49A-49B show flow cytometry data illustrating that co-incubation of AAV Hu37 with AF71, AF71x, AF72a, AF73, AF74A, and AF74B resulted in improved transduction efficiency over control AAV without antibody on HEK 293 cells overexpressing human CACNG1 (hCACNG1). Transduction efficiency was optimal between molar ratios of 1 AAV to 1 antibody (AAV:Ab ratio 1:1) and 1 AAV to 9 antibodies (AAV:Ab ratio 1:9) as assessed by percent (%) GFP positive cells (Figure 49A) and Median Fluorescence Intensity (MFI) (Figure 49B).

[0262] Figures 50A-50E^ illustrate bispecific antibody enhancement of Hu37 transductioninto skeletal muscle. Transduction levels are shown for the following skeletal muscles: tongue (Figure 50A), gastrocnemius (gastroc) / soleus (Figure 50B), and tibialis anterior (TA) (Figure 50C). Transduction levels for the heart (Figure 50D) and liver (Figure 50E) are also depicted.

[0263] Figures 51A-51C depict examples of amino acid sequences (Figure 51A) and corresponding nucleotide sequences (Figures 51B-51C) for anti-AAV x anti-CACNG1 alternative format design AF71x.

[0264] Figures 52A-52C depict examples of amino acid sequences (Figure 52A) and corresponding nucleotide sequences (Figures 52B-52C) for anti-AAV x anti-CACNG1 alternative format design AF72a.

[0265] Figures 53A-53C depict examples of amino acid sequences (Figure 53A) and ^ ^Attorney Docket No.250298.000954 corresponding nucleotide sequences (Figures 53B-53C) for anti-AAV x anti-CACNG1 alternative format design AF72b.

[0266] Figures 54A-54C depict examples of amino acid sequences (Figure 54A) and corresponding nucleotide sequences (Figures 54B-54C) for anti-AAV x anti-CACNG1 alternative format design AF73.

[0267] Figures 55A-55E depict examples of amino acid sequences (Figures 55A-55B) and corresponding nucleotide sequences (Figures 55C-55E) for anti-AAV x anti-CACNG1 alternative format design AF74A.

[0268] Figures 56A-56D depict examples of amino acid sequences (Figure 56A) and corresponding nucleotide sequences (Figures 56B-56D) for anti-AAV x anti-CACNG1 alternative format design AF74B.

[0269] Figures 57A-57C depict examples of amino acid sequences (Figure 57A) and corresponding nucleotide sequences (Figures 57B-57C) for anti-AAV x anti-CACNG1 alternative format design AF76.

[0270] Figures 58A-58B^ show schematic representations of anti-AAV x anti-humantransferrin receptor (hTfR) (also called AAV x hTfR herein) antibodies DB7035B, DB7043B, DB7045B, DB7047B, DB8035B, DB8043B, DB8045B, and DB8047B (Davis body orientation), as well as alternative format (AF) (i.e., Altibody) antibodies AF7035B, AF7043B, AF7045B, AF7047B, AF8035B, AF8043B, AF8045B, and AF8047B. Star mutations are depicted with an asterisk (*) and knob-in-hole (KiH) mutations are depicted with a triangle ^). Figure 58B discloses “3xG4S” as SEQ ID NO: 1115.

[0271] Figures 59A-59B show flow cytometry data illustrating co-incubation of AAV9 with DB7035B, DB7043B, DB7045B, DB7047B, DB8035B, DB8043B, DB8045B, and DB8047B, resulted in improved transduction efficiency over control AAV9 without antibody on 3T3 cells overexpressing human TfR (hTfR). Transduction efficiency was assessed by percent (%) GFP positive cells (Figure 59A) and Median Fluorescence Intensity (MFI) (Figure 59B).

[0272] Figures 60A-60B show flow cytometry data illustrating co-incubation of AAV9 with AF7035B, AF7043B, AF7045B, AF7047B, AF8035B, AF8043B, AF8045B, and AF8047B, resulted in improved transduction efficiency over control AAV9 without antibody on 3T3 cells overexpressing human TfR (hTfR). Transduction efficiency was assessed by percent (%) GFP positive cells (Figure 60A) and Median Fluorescence Intensity (MFI) (Figure 60B).

[0273] Figures 61A-61D illustrate bispecific antibody enhancement of AAV9 transduction into different brain areas. Bispecific antibody enhancement of AAV9 transduction into the hippocampus, cerebellum, and cortex are shown in Figures 61A-61C, respectively.^In addition to hippocampus (CA2 region), cerebellum, and cortex, Figure 61D illustrates bispecific antibody AF7045B enhancement of AAV9 transduction into medulla, olfactory bulb, thalamus, ^ ^Attorney Docket No.250298.000954 striatum, hypothalamus, and midbrain.

[0274] Figure 62 illustrates quantification of green fluorescent protein (GFP) in the cortex of hTfR mice (7229KO) by measuring the percent (%) GFP area.

[0275] Figures 63A-63C illustrate quantification of mRNA levels in the brain (Figure 63A), liver (Figure 63B), and heart (Figure 63C) of hTfR mice (7229KO).

[0276] Figures 64A-64D depict examples of amino acid sequences (Figure 64A) and corresponding nucleotide sequences (Figures 64B-64D) for anti-AAV x anti-hTFR Davis body design DB7035B.

[0277] Figures 65A-65D depict examples of amino acid sequences (Figure 65A) and corresponding nucleotide sequences (Figures 65B-65D) for anti-AAV x anti-hTFR Davis body design DB7043B.

[0278] Figures 66A-66D depict examples of amino acid sequences (Figure 66A) and corresponding nucleotide sequences (Figures 66B-66D) for anti-AAV x anti-hTFR Davis body design DB7045B.

[0279] Figures 67A-67D depict examples of amino acid sequences (Figure 67A) and corresponding nucleotide sequences (Figures 67B-67D) for anti-AAV x anti-hTFR Davis body design DB7047B.

[0280] Figures 68A-68D depict examples of amino acid sequences (Figure 68A) and corresponding nucleotide sequences (Figures 68B-68D) for anti-AAV x anti-hTFR Davis body design DB8035B.

[0281] Figures 69A-69D depict examples of amino acid sequences (Figure 69A) and corresponding nucleotide sequences (Figures 69B-69D) for anti-AAV x anti-hTFR Davis body design DB8043B.

[0282] Figures 70A-70D depict examples of amino acid sequences (Figure 70A) and corresponding nucleotide sequences (Figures 70B-70D) for anti-AAV x anti-hTFR Davis body design DB8045B.

[0283] Figures 71A-71D depict examples of amino acid sequences (Figure 71A) and corresponding nucleotide sequences (Figures 71B-71D) for anti-AAV x anti-hTFR Davis body design DB8047B.

[0284] Figures 72A-72D depict examples of amino acid sequences (Figure 72A) and corresponding nucleotide sequences (Figures 72B-72D) for anti-AAV x anti-hTFR alternative format design AF7035B.

[0285] Figures 73A-73D depict examples of amino acid sequences (Figure 73A) and corresponding nucleotide sequences (Figures 73B-73D) for anti-AAV x anti-hTFR alternative format design AF7043B.

[0286] Figures 74A-74D depict examples of amino acid sequences (Figure 74A) and ^ ^Attorney Docket No.250298.000954 corresponding nucleotide sequences (Figures 74B-74D) for anti-AAV x anti-hTFR alternative format design AF7045B.

[0287] Figures 75A-75D depict examples of amino acid sequences (Figure 75A) and corresponding nucleotide sequences (Figures 75B-75D) for anti-AAV x anti-hTFR alternative format design AF7047B.

[0288] Figures 76A-76D depict examples of amino acid sequences (Figure 76A) and corresponding nucleotide sequences (Figures 76B-76D) for anti-AAV x anti-hTFR alternative format design AF8035B.

[0289] Figures 77A-77D depict examples of amino acid sequences (Figure 77A) and corresponding nucleotide sequences (Figures 77B-77D) for anti-AAV x anti-hTFR alternative format design AF8043B.

[0290] Figures 78A-78D depict examples of amino acid sequences (Figure 78A) and corresponding nucleotide sequences (Figures 78B-78D) for anti-AAV x anti-hTFR alternative format design AF8045B.

[0291] Figures 79A-79D depict examples of amino acid sequences (Figure 79A) and corresponding nucleotide sequences (Figures 79B-79D) for anti-AAV x anti-hTFR alternative format design AF8047B.

[0292] Figures 80A-80B^show examples of structures of multispecific binding molecules (MBMs) of the disclosure. Figure 80A shows the structure of a MBM comprising: i) a first polypeptide chain comprising (in an N- to C-terminal orientation) a^single domain antibody (sdAb) (e.g., VHH), an optional linker, a CH2 domain, a CH3 domain, an optional linker, a variable heavy (VH) domain, and a CH1 domain; ii) a second polypeptide chain comprising (in an N- to C-terminal orientation) a variable light (VL) domain and a constant domain of a light chain (CL) associated with the VH and CH1 domains; iii) a third polypeptide chain comprising (in an N- to C-terminal orientation) a^single-chain Fv (scFv), an optional linker, a CH2 domain, a CH3 domain, an optional linker, a VH domain, and a CH1 domain; and iv) a fourth polypeptide chain comprising (in an N- to C-terminal orientation) a VL domain and a CL domain associated with the VH and CH1 domains. Figure 80B shows the structure of a MBM comprising:^i) a first polypeptide chain comprising (in an N- to C-terminal orientation) a sdAb (e.g., VHH), an optional linker, a CH2 domain, a CH3 domain, an optional linker, a VH domain, and a CH1 domain; ii) a second polypeptide chain comprising (in an N- to C-terminal orientation) a VL domain and a CL domain associated with the VH and CH1 domains; iii) a third polypeptide chain comprising (in an N- to C-terminal orientation) a sdAb (e.g., VHH), an optional linker, a CH2 domain, a CH3 domain, an optional linker, a VH domain, and a CH1 domain; and iv) a fourth polypeptide chain comprising (in an N- to C-terminal orientation) a VL domain and a CL domain associated with the VH and CH1 domains. ^ ^Attorney Docket No.250298.000954

[0293] Figures 81A-81B^show examples of structures of^anti-AAV x anti-TfR alternative format designs REGN23091 (also referred to as AF7 herein) (Figure 81A) and REGN22198 (Figure 81B).

[0294] Figures 82A-82B^ show examples of structures of^ anti-AAV x anti-CACNG1alternative format designs REGN20586 (also referred to as AF71 herein) (Figure 82A) and REGN22008 (also referred to as AF71x herein) (Figure 82B).

[0295] Figure 83 illustrates bispecific antibody enhancement of AAV9 transduction into the brain using different AAV and antibody complexing conditions along with sequential dosing of antibody and AAV. F / T, freeze and thaw.

[0296] Figure 84 illustrates anti-AAV x anti-CACNG1 bispecific antibody enhancement of AAV9 W503A transduction into skeletal muscle. Transduction levels are shown for the following skeletal muscles: gastrocnemius and quadriceps. Transduction level for the heart and liver are also depicted.

[0297] Figure 85 shows improved transduction efficiency of AAV9 with AFT5 and AFT8 alternative format antibodies over control AAV9 without antibody on 3T3 cells overexpressing human TfR (hTfR). The left panel depicts transduction as percent GFP expression. The right panel depicts transduction in terms of median fluorescence intensity (MFI).

[0298] Figures 86A-86B show schematics of AFT5 (Figure 86A) and AFT8 (Figure 86B).

[0299] Figures 87A-87D depict examples of amino acid sequences (Figure 87A) and corresponding nucleotide sequences (Figures 87B-87D) for anti-AAV x anti-hTFR alternative format design AFT8.

[0300] Figures 88A-88C depict examples of amino acid sequences (Figure 88A) and corresponding nucleotide sequences (Figures 88B-88C) for anti-AAV x anti-hTFR alternative format design AFT5.

[0301] Figures 89A-89D depict examples of amino acid sequences (Figure 89A) and corresponding nucleotide sequences (Figures 89B-89D) for anti-AAV x anti-hTFR REGN22198. DETAILED DESCRIPTION

[0302] Before the present disclosure is described, it is to be understood that this disclosure is not limited to particular methods and experimental conditions described, as such methods and conditions may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims. ^ ^Attorney Docket No.250298.000954

[0303] Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, the preferred methods and materials are now described. All patents, applications, and non-patent publications mentioned in this specification are incorporated herein by reference in their entireties. Definitions

[0304] 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 this disclosure belongs. As used herein, the term “about”, when used in reference to a particular recited numerical value, means that the value may vary from the recited value by no more than 1%. For example, as used herein, the expression “about 100” includes 99 and 101 and all values in between (e.g., 99.1, 99.2, 99.3, 99.4, etc.).^

[0305] The term “antigen” encompasses any agent (e.g., protein, peptide, polysaccharide, glycoprotein, glycolipid, nucleotide, portions thereof, or combinations thereof) that, when introduced into an immunocompetent host is recognized by the immune system of the host and is capable of eliciting an immune response by the host.

[0306] The term “epitope” can refer to an antigenic determinant that interacts with a specific antigen-binding site in the variable region of an antibody molecule known as a paratope. A single antigen may have more than one epitope. Thus, different antibodies may bind to different areas on an antigen and may have different biological effects. Epitopes may be either conformational or linear. A conformational epitope is produced by spatially juxtaposed amino acids from different segments of the linear polypeptide chain. A linear epitope is one produced by adjacent amino acid residues in a polypeptide chain. In certain circumstance, an epitope may include moieties of saccharides, phosphoryl groups, or sulfonyl groups on the antigen. Epitopes may also be defined as structural or functional. Functional epitopes are generally a subset of structural epitopes and are defined as those residues that directly contribute to the affinity of the interaction between a major histocompatibility complex (MHC) molecule and the antigen.

[0307] The term “antigen-binding molecule” refers in its broadest sense to a molecule that specifically binds to an antigen. In certain embodiments, an antigen-binding molecule is an antibody or an antigen-binding fragment of an antibody, including, e.g., multispecific antibodies such as bispecific antibodies or fragments thereof.

[0308] The term “multispecific antigen-binding molecule” or “multispecific binding molecule” or “MBM” includes molecules (e.g., antibodies and antigen-binding fragments of antibodies) that bind two or more (e.g., three or four) different epitopes or antigens. In some cases, the multispecific antigen-binding molecules are bispecific (e.g., bispecific antibodies). ^ ^Attorney Docket No.250298.000954 In some cases, the multispecific antigen-binding molecules are trispecific. In some cases, the multispecific antigen-binding molecules are tetraspecific. According to certain exemplary embodiments, the present disclosure includes multispecific (e.g., bispecific) antigen-binding molecules (e.g., antibodies) that specifically bind a capsid of an AAV particle and a molecule of a cell surface. Such antigen-binding molecules may be referred to herein as, e.g., “anti- AAV x anti-cell surface molecule” or other similar terminology (e.g., anti-AAV / anti-cell surface molecule).

[0309] The term “antigen-binding domain” or “ABD” as used herein can refer to the portion of an antigen-binding molecule that is capable of specific binding to an antigen. In certain embodiments, without limitation, a multispecific antigen-binding molecule of the disclosure may comprise a first ABD (“ABD1”), a second ABD (“ABD2”), a third ABD (“ABD3”), and / or a fourth ABD (“ABD4”), each of which may be part of, e.g., an scFv or a Fab.

[0310] The term “antibody”, as used herein, means any antigen-binding molecule or molecular complex comprising at least one complementarity determining region (CDR) that specifically binds to or interacts with a particular antigen. The term “antibody” includes immunoglobulin molecules comprising four polypeptide chains, two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds, as well as multimers thereof (e.g., IgM). The term “antibody” also includes immunoglobulin molecules consisting of four polypeptide chains, two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds. Each heavy chain comprises a heavy chain variable region (abbreviated herein as HCVR or VH) and a heavy chain constant region. The heavy chain constant region comprises three domains, CH1, CH2, and CH3. Each light chain comprises a light chain variable region (abbreviated herein as LCVR or VL) and a light chain constant region. The light chain constant region comprises one domain (CL1). The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDRs), interspersed with regions that are more conserved, termed framework regions (FR). Each VH and VL is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. In different embodiments of the disclosure, the FRs of the anti-AAV antibody or anti-cell surface molecule antibody (or antigen-binding portion thereof) may be identical to the human germline sequences or may be naturally or artificially modified. An amino acid consensus sequence may be defined based on a side-by-side analysis of two or more CDRs.

[0311] The term “antibody”, as used herein, also includes antigen-binding fragments of full antibody molecules. The terms “antigen-binding fragment” of an antibody, “antigen-binding portion” of an antibody, and the like, as used herein, include any naturally occurring, ^ ^Attorney Docket No.250298.000954 enzymatically obtainable, synthetic, or genetically engineered polypeptide or glycoprotein that specifically binds to an antigen to form a complex. Antigen-binding fragments of an antibody may be derived, e.g., from full antibody molecules using any suitable standard techniques such as proteolytic digestion or recombinant genetic engineering techniques involving the manipulation and expression of DNA encoding antibody variable and optionally constant domains. Such DNA is known and / or is readily available from, e.g., commercial sources, DNA libraries (including, e.g., phage-antibody libraries), or can be synthesized. The DNA may be sequenced and manipulated chemically or by using molecular biology techniques, for example, to arrange one or more variable and / or constant domains into a suitable configuration, or to introduce codons, create cysteine residues, modify, add, or delete amino acids, etc.

[0312] Non-limiting examples of antigen-binding fragments include: (i) Fab fragments; (ii) F(ab')2 fragments; (iii) Fd fragments; (iv) Fv fragments; (v) single-chain Fv (scFv) molecules; (vi) dAb fragments; and (vii) minimal recognition units consisting of the amino acid residues that mimic the hypervariable region of an antibody (e.g., an isolated complementarity determining region (CDR) such as a CDR3 peptide), or a constrained FR3- CDR3-FR4 peptide. Other engineered molecules, such as domain-specific antibodies, single domain antibodies, domain-deleted antibodies, chimeric antibodies, CDR-grafted antibodies, diabodies, triabodies, tetrabodies, minibodies, nanobodies (e.g., monovalent nanobodies, bivalent nanobodies, etc.), small modular immunopharmaceuticals (SMIPs), and shark variable IgNAR domains, are also encompassed within the expression “antigen- binding fragment,” as used herein.

[0313] An antigen-binding fragment of an antibody will typically comprise at least one variable domain. The variable domain may be of any size or amino acid composition and will generally comprise at least one CDR which is adjacent to or in frame with one or more framework sequences. In antigen-binding fragments having a VHdomain associated with a VL domain, the VH and VL domains may be situated relative to one another in any suitable arrangement. For example, the variable region may be dimeric and contain VH-VH, VH-VL, or VL-VLdimers. Alternatively, the antigen-binding fragment of an antibody may contain a monomeric VH or VL domain.

[0314] In certain embodiments, an antigen-binding fragment of an antibody may contain at least one variable domain covalently linked to at least one constant domain. Non-limiting, exemplary configurations of variable and constant domains that may be found within an antigen-binding fragment of an antibody of the present disclosure include: (i) VH-CH1; (ii) VH- CH2; (iii) VH-CH3; (iv) VH-CH1-CH2; (v) VH-CH1-CH2-CH3; (vi) VH-CH2-CH3; (vii) VH-CL; (viii) VL- CH1; (ix) VL-CH2; (x) VL-CH3; (xi) VL-CH1-CH2; (xii) VL-CH1-CH2-CH3; (xiii) VL-CH2-CH3; and ^ ^Attorney Docket No.250298.000954 (xiv) VL-CL. In any configuration of variable and constant domains, including any of the exemplary configurations listed above, the variable and constant domains may be either directly linked to one another or may be linked by a full or partial hinge or linker region. A hinge region may consist of at least 2 (e.g., 5, 10, 15, 20, 40, 60, or more) amino acids which result in a flexible or semi-flexible linkage between adjacent variable and / or constant domains in a single polypeptide molecule. Moreover, an antigen-binding fragment of an antibody of the present disclosure may comprise a homo-dimer or hetero-dimer (or other multimer) of any of the variable and constant domain configurations listed above in non- covalent association with one another and / or with one or more monomeric VHor VLdomain (e.g., by disulfide bond(s)).

[0315] As with full antibody molecules, antigen-binding fragments may be monospecific or multispecific (e.g., bispecific). A bispecific antigen-binding fragment of an antibody will typically comprise at least two different variable domains, wherein each variable domain is capable of specifically binding to a separate antigen or to a different epitope on the same antigen. Any multispecific antibody format, including the non-limiting example formats disclosed herein, may be adapted for use in the context of an antigen-binding fragment of an antibody of the present disclosure using routine techniques available in the art.

[0316] The terms “complementarity determining region” or “CDR,” as used herein, can refer to the sequences of amino acids within antibody variable regions which confer antigen specificity and binding affinity. In general, there are three CDRs in each heavy chain variable region (HCDR1, HCDR2, HCDR3) and three CDRs in each light chain variable region (LCDR1, LCDR2, LCDR3).

[0317] Exemplary conventions that can be used to identify the boundaries of CDRs include, e.g., the Kabat definition, the Chothia definition, the ABS definition, and the IMGT definition. See, e.g., Kabat, 1991, “Sequences of Proteins of Immunological Interest,” National Institutes of Health, Bethesda, Md. (Kabat numbering scheme); Al-Lazikani et al., 1997, J. Mol. Biol.273:927-948 (Chothia numbering scheme); Martin et al., 1989, Proc. Natl. Acad. Sci. USA 86:9268-9272 (ABS numbering scheme); and Lefranc et ai, 2003, Dev. Comp. Immunol.27:55-77 (IMGT numbering scheme). Public databases are also available for identifying CDR sequences within an antibody.

[0318] The term “single domain antibody” or “sdAb” as used herein can refer to an antibody or antigen binding fragment thereof comprising a single binding domain (e.g., heavy chain variable region) capable of binding a target molecule without pairing with a corresponding CDR-containing polypeptide (e.g., a light chain). An sdAb or sdAb fragment can be derived from a VHH or from a non-antibody scaffold protein, for example a designed ankyrin repeat protein (darpin), an avimer, an anticalin / lipocalin, a centyrin, or a fynomer. A ^^^ ^Attorney Docket No.250298.000954 sdAb typically lacks a CH1 domain and thus cannot associate with a light chain.

[0319] The term “VHH” refers to a variable region of an antibody consisting of only a heavy chain, e.g., an antibody of camelid or cartilaginous fish origin. A VHH variable region can bind to a target molecule in the absence of a light chain. A basic VHH has the following structure from the N-terminus to the C-terminus: FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, in which FR1 to FR4 refer to framework regions 1 to 4, respectively, and in which CDR1 to CDR3 refer to the complementarity determining regions 1 to 3.

[0320] The term “single chain Fv” or “scFv” as used herein can refer to a polypeptide chain comprising the VHand VLdomains of an antibody, where these domains are present in a single polypeptide chain.

[0321] The term “Fab” can refer to a pair of polypeptide chains, the first polypeptide chain comprising a variable heavy (VH) domain of an antibody N- terminal to a first constant domain (referred to herein as C1), and the second polypeptide chain comprising a variable light (VL) domain of an antibody N-terminal to a second constant domain (referred to herein as C2) capable of pairing with the first constant domain. In a native antibody, the VHis N- terminal to the first constant domain (CH1) of the heavy chain and the VL is N- terminal to the constant domain of the light chain (CL). The Fabs of the disclosure can be arranged according to the native orientation or include domain substitutions or swaps on that facilitate correct VH and VL pairings, particularly where the antigen-binding molecules of the disclosure comprise non-identical Fabs. For example, it is possible to replace the CH1 and CL domain pair in a Fab with a CH3-domain pair to facilitate correct modified Fab-chain pairing in heterodimeric antigen-binding molecules. It is also possible to reverse CH1 and CL, so that the CH1 is attached to VLand CL is attached to the VH, a configuration generally known as Crossmab. Alternatively, or in addition to, the use of substituted or swapped constant domains, correct chain pairing can be achieved by the use of universal light chains that can pair with both variable regions of a heterodimeric antigen-binding molecules of the disclosure.

[0322] The term “universal light chain” as used herein in the context of an antigen-binding molecule described herein can refer to a light chain polypeptide capable of pairing with the heavy chain region of a first Fab to form the first Fab and capable of pairing with the heavy chain region of a second Fab to form the second Fab. Universal light chains are also known as “common light chains.”

[0323] The term “Fc domain” can refer to a portion of the heavy chain that pairs with the corresponding portion of another heavy chain. The term “Fc region” can refer to the region of antibody-based binding molecules formed by association of two heavy chain Fc domains. The two Fc domains within the Fc region may be the same or different from one another. In ^ ^Attorney Docket No.250298.000954 a native antibody the Fc domains are typically identical, but for the purpose of producing the antigen-binding molecules of the disclosure, one or both Fc domains might advantageously be modified to allow for heterodimerization, e.g., via a knob-in-hole interaction and / or for purification, e.g., via star mutations.

[0324] As used herein, the term “derived from” indicates a relationship between a first and a second molecule. It generally can refer to structural similarity between the first molecule and a second molecule and does not connote or include a process or source limitation on a first molecule that is derived from a second molecule.

[0325] The term “specifically binds” as used herein means that an antigen-binding molecule forms a complex with a target antigen that is relatively stable under physiologic conditions. Specific binding can be characterized by a KD of about 5x10-2M or less (e.g., less than 5x10-2M, less than 10-2M, less than 5x10-2M, less than 10-3M, less than 5x10-4M, less than 10-4M, less than 5x10-5M, less than 10-5M, less than 5x10-6M, less than 10-6M, less than 5x10-7M, less than 10-7M, less than 5x10-8M, less than 10-8M, less than 5x10-9M, less than 10-9M, or less than 10-10M). Methods for determining the binding affinity of an antibody or an antibody fragment, e.g., an antigen-binding molecule or antigen-binding domain, to a target antigen are well known in the art and include, for example, equilibrium dialysis, surface plasmon resonance (e.g., Biacore assays), fluorescent-activated cell sorting (FACS) binding assays, and the like. An antigen-binding molecule that specifically binds to a target antigen from one species can, however, have cross-reactivity to the target antigen from one or more other species.

[0326] The term “operably linked” as used herein can refer to a functional relationship between two or more regions of a polypeptide chain in which the two or more regions are linked so as to produce a functional polypeptide.

[0327] The term “substantial identity” or “substantially identical,” when referring to a nucleic acid or fragment thereof, indicates that, when optimally aligned with appropriate nucleotide insertions or deletions with another nucleic acid (or its complementary strand), there is nucleotide sequence identity in at least about 90%, and more preferably at least about 95%, 96%, 97%, 98%, or 99% of the nucleotide bases, as measured by any well- known algorithm of sequence identity, such as FASTA, BLAST, or Gap, as discussed below. A nucleic acid molecule having substantial identity to a reference nucleic acid molecule may, in certain instances, encode a polypeptide having the same or substantially similar amino acid sequence as the polypeptide encoded by the reference nucleic acid molecule.

[0328] As applied to polypeptides, the term “substantial similarity” or “substantially similar” means that two peptide sequences, when optimally aligned, such as by the programs GAP or BESTFIT using default gap weights, share at least 95% sequence identity, even more ^ ^Attorney Docket No.250298.000954 preferably at least 98% or 99% sequence identity. Preferably, residue positions which are not identical differ by conservative amino acid substitutions. A “conservative amino acid substitution” is one in which an amino acid residue is substituted by another amino acid residue having a side chain (R group) with similar chemical properties (e.g., charge or hydrophobicity). In general, a conservative amino acid substitution will not substantially change the functional properties of a protein. In cases where two or more amino acid sequences differ from each other by conservative substitutions, the percent sequence identity or degree of similarity may be adjusted upwards to correct for the conservative nature of the substitution. Means for making this adjustment are well-known to those of skill in the art. See, e.g., Pearson (1994) Methods Mol. Biol.24: 307-331, herein incorporated by reference. Examples of groups of amino acids that have side chains with similar chemical properties include (1) aliphatic side chains: glycine, alanine, valine, leucine, and isoleucine; (2) aliphatic-hydroxyl side chains: serine and threonine; (3) amide-containing side chains: asparagine and glutamine; (4) aromatic side chains: phenylalanine, tyrosine, and tryptophan; (5) basic side chains: lysine, arginine, and histidine; (6) acidic side chains: aspartate and glutamate, and (7) sulfur-containing side chains are cysteine and methionine. Preferred conservative amino acids substitution groups are: valine-leucine-isoleucine, phenylalanine- tyrosine, lysine-arginine, alanine-valine, glutamate-aspartate, and asparagine-glutamine. Alternatively, a conservative replacement is any change having a positive value in the PAM250 log-likelihood matrix disclosed in Gonnet et al. (1992) Science 256: 1443-1445, herein incorporated by reference. A “moderately conservative” replacement is any change having a nonnegative value in the PAM250 log-likelihood matrix.

[0329] Sequence similarity for polypeptides, which is also referred to as sequence identity, is typically measured using sequence analysis software. Protein analysis software matches similar sequences using measures of similarity assigned to various substitutions, deletions, and other modifications, including conservative amino acid substitutions. For instance, GCG software contains programs such as Gap and Bestfit which can be used with default parameters to determine sequence homology or sequence identity between closely related polypeptides, such as homologous polypeptides from different species of organisms or between a wild type protein and a mutein thereof. See, e.g., GCG Version 6.1. Polypeptide sequences also can be compared using FASTA using default or recommended parameters, a program in GCG Version 6.1. FASTA (e.g., FASTA2 and FASTA3) provides alignments and percent sequence identity of the regions of the best overlap between the query and search sequences (Pearson (2000) supra). Another preferred algorithm when comparing a sequence of the disclosure to a database containing a large number of sequences from different organisms is the computer program BLAST, especially BLASTP or TBLASTN, using ^ ^Attorney Docket No.250298.000954 default parameters. See, e.g., Altschul et al. (1990) J. Mol. Biol.215:403-410 and Altschul et al. (1997) Nucleic Acids Res.25:3389-402, each herein incorporated by reference.

[0330] The term “subject” or “patient” as used herein includes all members of the animal kingdom including non-human primates and humans. Anti-AAV Antibodies and Antigen-Binding Fragments Thereof

[0331] In a one aspect, provided herein are antibodies and antigen-binding fragments thereof that bind a capsid of an AAV particle (also known as “anti-AAV antibodies” herein). In some embodiments, the capsid comprises any of various wild-type and / or non-wild-type AAV capsid protein(s) described herein. In some embodiments, the antibodies and / or antigen- binding fragments thereof bind an epitope on a capsid described herein. The anti-AAV antibodies provided herein, or antigen-binding portions thereof, may be included as part of a multispecific antigen-binding molecule, e.g., a multispecific antibody or multispecific antigen- binding fragment thereof, described herein.

[0332] “AAV” is an abbreviation for adeno-associated virus and may be used to refer to the virus itself or derivatives thereof. AAVs are members of the Parvovirus family of small, non- enveloped, single-stranded DNA viruses. Generally, a wildtype AAV genome is 4.7 kb and is characterized by two inverted terminal repeats (ITR) and two open reading frames (ORFs), rep and cap. The wildtype rep reading frame encodes four proteins of molecular weight 78 kD (“Rep78”), 68 kD (“Rep68”), 52 kD (“Rep52”) and 40 kD (“Rep 40”). Rep78 and Rep68 are transcribed from the p5 promoter, and Rep52 and Rep40 are transcribed from the p19 promoter. These proteins function mainly in regulating the transcription and replication of the AAV genome. The wildtype cap reading frame encodes three structural (capsid) viral proteins (VPs) having molecular weights of 83-85 kD (VP1), 72-73 kD (VP2) and 61-62 kD (VP3). More than 80% of total proteins in an AAV virion (capsid) comprise VP3; in mature virions VP1, VP2, and VP3 are found at relative abundance of approximately 1:1:10, although ratios of 1:1:8 have been reported. Padron et al. (2005) J. Virology 79:5047-58.

[0333] The genomic sequences of various serotypes of AAV, as well as the sequences of the native inverted terminal repeats (ITRs), Rep proteins, and capsid subunits are known in the art. Such sequences may be found in the literature or in public databases such as GenBank. See, e.g., GenBank Accession Numbers NC_002077 (AAV1), AF063497 (AAV1), NC001401 (AAV-2), AF043303 (AAV2), NC_001729 (AAV3), NC_001829 (AAV4), U89790 (AAV4), NC_006152 (AAV5), AF513851 (AAV7), AF513852 (AAV8), and NC_006261 (AAV8); the disclosures of which are incorporated by reference herein for teaching AAV nucleic acid and amino acid sequences. See also, e.g., Srivistava et al. (1983) J. Virology 45:555; Chiorini et al. (1998) J. Virology 71:6823; Chiorini et al. (1999) J. Virology 73: 1309; ^ ^Attorney Docket No.250298.000954 Bantel-Schaal et al. (1999) J. Virology 73:939; Xiao et al. (1999) J. Virology 73:3994; Muramatsu et al. (1996) Virology 221:208; Shade et al.,(1986) J. Virol.58:921; Gao et al. (2002) Proc. Nat. Acad. Sci. USA 99: 11854; Moris et al. (2004) Virology 33:375-383; US Patent Publication 20170130245; international patent publications WO 00 / 28061, WO 99 / 61601, WO 98 / 11244; and U.S. Pat. No.6,156,303, each of which is incorporated by reference in its entirety by reference.

[0334] “AAV” encompasses all subtypes and both naturally occurring and modified forms (e.g., recombinant forms), except where stated otherwise. AAV includes primate AAV (e.g., AAV type 1 (AAV1), primate AAV type 2 (AAV2), primate AAV type 3 (AAV3), primate AAV3B, primate AAV type 4 (AAV4), primate AAV type 5 (AAV5), primate AAV type 6 (AAV6), primate AAV6.2, primate AAV type 7 (AAV7), primate AAV type 8 (AAV8), primate AAV type 9 (AAV9), AAV10, AAV type hu11 (AAV hu11), AAV11, AAV12, AAV13, AAVDJ, Anc80L65, AAV2G9, AAVLK03, AAV type rh32.33 (AAVrh.32.33), AAV retro (AAV retro), AAV PHP.B, AAV PHP.eB, AAV PHP.S, AAVrh.64R1, AAVhu.37, AAVrh.8, AAV2 / 8, etc.; non-primate animal AAV (e.g., avian AAV (AAAV)) and other non-primate animal AAV such as mammalian AAV (e.g., bat AAV, sea lion AAV, bovine AAV, canine AAV, equine AAV, caprine AAV, and ovine AAV etc.), squamate AAV (e.g., snake AAV, bearded dragon AAV), etc., “Primate AAV” can refer to AAV generally isolated from primates. Similarly, “non- primate animal AAV” can refer to AAV isolated from non-primate animals.

[0335] The term “capsid protein,” “Cap protein”, and the like, includes a protein that is part of the capsid of the virus. For adeno-associated viruses, the capsid proteins are generally referred to as VP1, VP2, and / or VP3, and may be encoded by the single cap gene. The three AAV capsid proteins can be produced in nature an overlapping fashion from the cap ORF alternative translational start codon usage, although all three proteins use a common stop codon. The ORF of a wildtype cap gene encodes from 5’ to 3’ three alternative start codons: “the VP1 start codon,” “the VP2 start codon,” and “the VP3 start codon”; and one “common stop codon”. The largest viral protein, VP1, is generally encoded from the VP1 start codon to the “common stop codon.” VP2 is generally encoded from the VP2 start codon to the common stop codon. VP3 is generally encoded from the VP3 start codon to the common stop codon. Accordingly, VP1 comprises at its N-terminus sequence that it does not share with the VP2 or VP3, referred to as the VP1-unique region (VP1-u). The VP1-u region is generally encoded by the sequence of a wildtype cap gene starting from the VP1 start codon to the “VP2 start codon.” VP1-u comprises a phospholipase A2 domain (PLA2), which may be important for infection, as well as nuclear localization signals which may aid the virus in targeting to the nucleus for uncoating and genome release. The VP1, VP2, and VP3 capsid proteins share the same C-terminal sequence that makes up the ^ ^Attorney Docket No.250298.000954 entirety of VP3, which may also be referred to herein as the VP3 region. The VP3 region is encoded from the VP3 start codon to the common stop codon. VP2 has an additional ~ 60 amino acids that it shares with the VP1. This region is called the VP1 / VP2 common region.

[0336] In some embodiments, an antibody, or an antigen-binding fragment thereof that binds to a capsid of an AAV particle described may bind to an epitope on the capsid. In some embodiments, the antibody may comprise any of the antibodies, e.g., multispecific antibodies, such as bispecific antibodies, which bind to the capsid of an AAV particle disclosed herein. In some embodiments, a multispecific antibody disclosed herein may comprise, for example, comprise a first binding domain that binds to a capsid of an AAV particle. In some embodiments, the first binding domain binds to an epitope on the capsid of the AAV particle. The AAV particle capsid may comprise wild-type and / or non-wildtype AAV capsid proteins. In some embodiments, the epitope may comprise any of various serotype- specific or serotype-non-specific (i.e., “universal”) epitopes understood by one of ordinary skill in the art. In some embodiments, the epitope may comprise, e.g., any amino acid residues set forth in Tables 19-26, or variants of variants, derivatives, or epitopes combinations thereof.

[0337] In some embodiments, an antibody, or an antigen-binding fragment thereof that binds to a capsid of an AAV particle described herein may bind to an epitope on the capsid which is comprised of any amino acid residues of a capsid protein VP1, VP2, or VP3, or a combination thereof. The AAV particle can be derived from any AAV serotype described herein. In some embodiments, an antibody, or an antigen-binding fragment thereof can bind to any amino acid residue, or any combination thereof, of any variable region of a capsid, or any combination thereof, e.g., a variable region comprised of a capsid protein VP1, VP2, or VP3, or a combination thereof (e.g., variable region I, II, III, IV, V, VI, VII, VIII, IX, or a combination thereof, as described in Emmanuel, et al., Journal of Virology, 2022, 96, 3).

[0338] As a non-limiting example, an antibody, or an antigen-binding fragment thereof that binds to a capsid of an AAV particle described herein may bind to an epitope of an AAV1 capsid comprised of any amino acid residue or combination thereof of a variable region I, II, III, IV, V, VI, VII, VIII, IX, or combination thereof. The antibody, or an antigen-binding fragment thereof may bind to AAV1 at any of residues 456–459, 492–499, 582, 583, 588– 591, 593–595, 597, or any combination thereof, as described in Tseng, et al.,^Front Immunol. 2014, 5: 9.

[0339] As a non-limiting example, an antibody, or an antigen-binding fragment thereof that binds to a capsid of an AAV particle described herein may bind to an epitope of an AAV2 capsid comprised of any amino acid residue or combination thereof of a variable region I, II, III, IV, V, VI, VII, VIII, IX, or combination thereof. The antibody, or an antigen-binding ^ ^Attorney Docket No.250298.000954 fragment thereof may bind to AAV2 at any of residues 253, 254, 258, 261-264, 272–281, 369–378, 381, 384, 385, 474–483, 492–502, 534, 548, 556, 560–573, 585–589, 601–610, 658–660, 708, 717, or any combination thereof, as described in Tseng, et al.,^Front Immunol. 2014, 5: 9.

[0340] As a non-limiting example, an antibody, or an antigen-binding fragment thereof that binds to a capsid of an AAV particle described herein may bind to an epitope of an AAV5 capsid comprised of any amino acid residue or combination thereof of a variable region I, II, III, IV, V, VI, VII, VIII, IX, or combination thereof. The antibody, or an antigen-binding fragment thereof may bind to AAV5 at any of residues 246, 254–261, 374, 375, 483, 485– 492, 494, 496, 499-501, 530, 532–538, 653, 654, 656, 657, 704–708, or any combination thereof as described in Tseng, et al.,^Front Immunol.2014, 5: 9.

[0341] As a non-limiting example, an antibody, or an antigen-binding fragment thereof that binds to a capsid of an AAV particle described herein may bind to an epitope of an AAV8 capsid comprised of any amino acid residue or combination thereof of a variable region I, II, III, IV, V, VI, VII, VIII, IX, or combination thereof. The antibody, or an antigen-binding fragment thereof may bind to AAV8 at any of residues 586–591 or any combination thereof as described in Tseng, et al.,^Front Immunol.2014, 5: 9.

[0342] As a non-limiting example, an antibody, or an antigen-binding fragment thereof that binds to a capsid of an AAV particle described herein may bind to an epitope of an AAV9 capsid comprised of any amino acid residue or combination thereof of a variable region I, II, III, IV, V, VI, VII, VIII, IX, or combination thereof. The antibody, or an antigen-binding fragment thereof may bind to AAV9 at any of residues 221, 228, 246-248, 250-256, 258– 260, any of residues 262–273 of variable region I, any of residues 274, 275, 278, 291, 293, 324, 325, any of residues 327-333 of variable region II, any of residues 334, 335, 338, 341, 363-365, 369-373, 375, 376, any of residues 382-387, 389, 391 of variable region III, any of residues 438–441, 443, any of residues 446, 448, 449, 451-460, 462, 464-473 of variable region IV, any of residues 488, 491-501, 503-506, 510–515 of variable region V, any of residues 528-534, 545 of variable region VI, any of residues 547-560 of variable region VII, residue 572, any of residues 579, 584, 587–590 of variable region VIII, any of residues 651- 653, 655-676, 678, any of residues 701–720, 722, 724-728 of variable region IX, or any of residues 730, 731, or any combination thereof, as described in Emmanuel, et al., Journal of Virology, 2022, 96, 3.

[0343] In some embodiments, a Cap protein, e.g., a VP1 capsid protein as described herein, a VP2 capsid protein as described herein, and / or a VP3 capsid protein as described herein, can be modified to comprise any number of various capsid modifications, e.g., one or more of a point mutation (e.g., amino acid substitutions, deletions, and / or insertions), a ^ ^Attorney Docket No.250298.000954 detectable label, a member of a protein:protein binding pair, etc.

[0344] In some embodiments, the one or more point mutation(s) in a capsid protein (e.g., a VP1, VP2, and / or VP3 capsid protein) described herein can result in detargeting a viral particle comprising the mutant capsid protein from its natural target cell. Detargeting of a viral particle from its natural target cell can be important especially if systemic versus local or loco-regional administration of the viral particles is intended, as uptake of the viral particles by the natural target cell can limit the effective dose of the viral particles. Accordingly, point mutations can be those that reduce the transducing activity of a viral particle which is mediated by the natural receptor of the viral particle by at least 50%, preferably at least 80%, especially at least 95%. In some embodiments, detargeting mutations disclosed herein can involve deletion or replacement of one or more an amino acids which can be involved in binding of the respective viral particle to its natural receptor. Such point mutations can enable an efficient detargeting of the viral particle from cells expressing the natural receptor or, for targeting purposes, can increase specificity of the respective mutant viral particle for a new target cell.

[0345] In some embodiments, a capsid protein (e.g., a VP1, VP2, and / or VP3 capsid protein) of the present disclosure can be modified to comprise an inserted heterologous amino acid sequence (e.g., a peptide insertion described herein or an additional peptide insertion, such as a peptide comprising, consisting essentially of, or consisting of any of various targeting molecules described herein) capable of retargeting or redirecting a viral particle described herein. “Retargeting” or “redirecting” may include a scenario in which a wild-type viral particle targets several cells within a tissue and / or several organs within an organism, and general targeting of the cells, tissues, and / or organs is reduced or abolished by insertion of a heterologous amino acid sequence, and retargeting the viral particle to more a specific cell in the tissue or a specific organ in the organism is achieved with the inserted heterologous amino acid sequence which can, e.g., bind a marker expressed by a specific cell. Such retargeting or redirecting may also include a scenario in which the wild- type viral particle targets a tissue, and targeting of the tissue is reduced or abolished by insertion of the heterologous amino acid sequence, and retargeting to a completely different tissue is achieved with the inserted heterologous amino acid sequence.

[0346] One or more of detargeting and / or retargeting mutation(s) and / or insertion(s) can be introduced into capsid proteins of any of various AAV serotypes disclosed herein. Such detargeting and / or retargeting mutation(s) and / or insertion(s) can result in detargeting and / or retargeting of an AAV particle comprising a mutant capsid protein from or to specific cells within a tissue and / or organs within an organism. For example, cells, tissues, and / or organs which may be detargeted and / or detargeted by AAV particles comprising mutant capsids ^ ^Attorney Docket No.250298.000954 may include or be derived from, without limitation, liver, skeletal muscle, vascular and / or smooth muscle, cardiac muscle, nervous system (e.g., brain, spinal cord, neurons, glia, ependymal cells), eye (e.g., retina and retinal cells including photoreceptors such as rods and cones, RPE, etc.), lung, heart, pancreas, kidney, and epithelium.

[0347] In various embodiments, an AAV2 serotype is preferred for use in the compositions and / or methods of the present disclosure. In some embodiments the capsid of the AAV2 particle can comprise one or more amino acid mutations within a heparan sulfate proteoglycan (HSPG) binding domain of the AAV2 capsid. In some embodiments, the capsid of the AAV2 particle can comprise one or more amino acid mutations within a laminin receptor (LamR) binding domain, e.g., a 37 / 67-kDa LamR binding domain, of the AAV2 capsid. In some embodiments, the capsid of the AAV2 particle can comprise one or more mutations at an amino acid position(s) selected from amino acid position(s) R484, R487, R585, R588, and K532 (VP1 numbering), and a combination thereof, relative to a wild-type AAV2 capsid. In certain embodiments, the capsid of the AAV2 particle comprises a mutation at amino acid position R585 and / or R588. In some embodiments, the capsid of the AAV2 particle comprises one or more amino acid substitutions at an amino acid position(s) selected from R484A, R487A, R487G, K532A, K532D, R585A, R585S, R585Q, R588A, and R588T, and any combination thereof, relative to a wild-type AAV2 capsid. In some embodiments, the capsid of the AAV2 particle comprises an amino acid substitution R585A and / or R588A. AAV2 R585 corresponds to AAV9 S586 and AAV8 Q588 and AAV2 R588 corresponds to AAV9 A589 and AAV8 T591. Thus, when AAV9 is used, the capsid of the AAV9 particle can comprise a mutation at amino acid position S586 and / or A589. Similarly, when AAV8 is used, the capsid of the AAV8 particle can comprise a mutation at amino acid position Q588 and / or T591. In some embodiments, the capsid of the AAV2 particle comprises one or more insertion(s) at amino acid position G453 or N587, or a combination thereof.

[0348] In some embodiments, an AAV9 serotype is used in the compositions and / or methods of the present disclosure. In some embodiments, the capsid of the AAV9 particle can comprise one or more amino acid mutations within a galactose binding domain of the AAV9 capsid. In some embodiments, the capsid of the AAV9 particle can comprise one or more mutations at an amino acid position(s) selected from amino acid position(s) D271, N272, Y446, S469, N470, A742, V473, W503, E500, P504, and Q590 (VP1 numbering), and a combination thereof, relative to a wild-type AAV9 capsid. In certain embodiments, the capsid of the AAV9 particle comprises a mutation at amino acid position N272 and / or W503. In some embodiments, the capsid of the AAV9 particle comprises one or more amino acid substitutions selected from K532A, K532D, R484A, R487A, R585A, R585S, R585Q, R487G, ^ ^Attorney Docket No.250298.000954 R588A, and R588T, and any combination thereof, relative to a wild-type AAV2 capsid. In some embodiments, the capsid of the AAV9 particle comprises an amino acid substitution N272A and / or W503A, relative to a wild-type AAV9 capsid. In some embodiments, the capsid of the AAV9 particle comprises one or more insertion(s) at amino acid position G453, A587, or A589, or a combination thereof.

[0349] In some embodiments, an AAV1 serotype is used in the compositions and / or methods of the present disclosure. In some embodiments, the capsid of the AAV1 particle can comprise one or more amino acid mutations within a sialic acid binding domain, e.g., an N-linked sialic acid binding domain, of the AAV1 capsid. In some embodiments, the capsid of the AAV1 particle can comprise one or more amino acid mutations within a binding domain of the AAV1 capsid essential for binding adeno-associated virus receptor (AAVR). In some embodiments, the capsid of the AAV1 particle can comprise one or more mutations at an amino acid position(s) selected from amino acid position(s) N500 (which corresponds to AAV2 E499 and AAV9 E500), K531, and K531 (VP1 numbering), and a combination thereof, relative to a wild-type AAV1 capsid. In some embodiments, the capsid of the AAV1 particle comprises one or more amino acid substitutions selected from N500E, K531A, and K531E, and any combination thereof, relative to a wild-type AAV1 capsid.

[0350] In some embodiments, an AAV6 serotype is used is used in the compositions and / or methods of the present disclosure. In some embodiments, the capsid of the AAV6 particle can comprise one or more amino acid mutations within a sialic acid binding domain, e.g., an N-linked sialic acid binding domain, of the AAV6 capsid. In some embodiments, the capsid of the AAV6 particle can comprise one or more amino acid mutations within a heparan sulfate proteoglycan (HSPG) binding domain of the AAV6 capsid. In some embodiments, the capsid of the AAV6 particle can comprise one or more amino acid mutations within an epidermal growth factor receptor (EGFR) binding domain of the AAV6 capsid. In some embodiments, the capsid of the AAV6 particle can comprise an amino acid mutation at amino acid position N500 (which corresponds to AAV2 E499 and AAV9 E500) (VP1 numbering), relative to a wild-type AAV6 capsid. In some embodiments, the capsid of the AAV6 particle comprises amino acid substitution N500E relative to a wild-type AAV6 capsid. In some embodiments, the capsid of the AAV6 particle comprises an insertion at amino acid position Q585.

[0351] In some embodiments, an AAV8 serotype is used is used in the compositions and / or methods of the present disclosure. In some embodiments, the capsid of the AAV8 particle can comprise one or more amino acid mutations within a laminin receptor (LamR) binding domain, e.g., a 37 / 67-kDa LamR binding domain, of the AAV8 capsid. In some embodiments, the capsid of the AAV8 particle comprises an insertion at amino acid position ^ ^Attorney Docket No.250298.000954 N590 (VP1 numbering).

[0352] In some embodiments, an AAV5 serotype is used in the compositions and / or methods of the present disclosure. In some embodiments, the capsid of the AAV5 particle can comprise one or more amino acid mutations within a sialic acid binding domain, e.g., an N-linked sialic acid binding domain, of the AAV5 capsid. In some embodiments, the capsid of the AAV5 particle can comprise one or more amino acid mutations within a platelet-derived growth factor receptor (PDGFR) of the AAV5 capsid. In some embodiments, the capsid of the AAV5 particle can comprise a mutation at amino acid position T571 (VP1 numbering) relative to a wild-type AAV5 capsid. In some embodiments, the capsid of the AAV5 particle comprises an amino acid substitution T571S relative to a wild-type AAV5 capsid.

[0353] In some embodiments, an avian AAV is used in the compositions and / or methods of the present disclosure. In some embodiments, the capsid of the avian AAV particle comprises an insertion at amino acid position(s) G444 or K580 (VP1 numbering), or a combination thereof.

[0354] In some embodiments, an bearded dragon AAV is used in the compositions and / or methods of the present disclosure. In some embodiments, the capsid of the bearded dragon AAV particle comprises an insertion at amino acid position(s) G436 or T573 (VP1 numbering), or a combination thereof.

[0355] The phrase “inverted terminal repeat” or “ITR” includes symmetrical nucleic acid sequences in the genome of adeno-associated viruses required for efficient replication. ITR sequences are located at each end of the AAV DNA genome. The ITRs serve as the origins of replication for viral DNA synthesis and are essential cis components for generating AAV particles, e.g., packaging into AAV particles.

[0356] AAV ITR comprise recognition sites for replication proteins Rep78 or Rep68. A “D” region of the ITR comprises the DNA nick site where DNA replication initiates and provides directionality to the nucleic acid replication step. An AAV replicating in a mammalian cell typically comprises two ITR sequences.

[0357] A single ITR may be engineered with Rep binding sites on both strands of the “A” regions and two symmetrical D regions on each side of the ITR palindrome. Such an engineered construct on a double-stranded circular DNA template allows Rep78 or Rep68 initiated nucleic acid replication that proceeds in both directions. A single ITR is sufficient for AAV replication of a circular particle. In methods of producing an AAV viral particle of the disclosure, the rep encoding sequence encodes a Rep protein or Rep protein equivalent that is capable of binding an ITR comprised on the transfer plasmid.

[0358] The Cap proteins of the disclosure, when expressed with appropriate Rep proteins by a packaging cell, may encapsidate a transfer plasmid comprising a nucleotide of interest ^ ^Attorney Docket No.250298.000954 and an even number of two or more ITR sequences. In some embodiments, a transfer plasmid comprises one ITR sequence. In some embodiments, a transfer plasmid comprises two ITR sequences.

[0359] Either Rep78 and / or Rep68 bind to unique and known sites on the sequence of the ITR hairpin, and act to break and unwind the hairpin structures on the end of an AAV genome, thereby providing access to replication machinery of the viral replication cell. As is well-known, Rep proteins may be expressed from more than one ORF comprising nucleotide sequence encoding any combination of Rep78, Rep68, Rep 52, and / or Rep40 by use of separate nucleotide sequences operably linked to at least one expression control sequence for expression in a viral replication cell, each producing one or more of Rep78, Rep68, Rep 52, and / or Rep40 Rep proteins. Alternatively, Rep proteins may be expressed individually from an ORF comprising a nucleotide sequence encoding any one of Rep78, Rep68, Rep 52, or Rep40 by use of separate nucleotide sequences operably linked to one expression control sequence for expression in a packaging cell, each producing only one Rep78, Rep68, Rep 52, or Rep40 Rep protein. In another embodiment, Rep proteins may be expressed from one ORF comprising nucleotide sequences encoding Rep78 and Rep52 Rep proteins operably linked to at least one expression control sequence for expression in a viral replication cell each producing Rep78 and Rep52 Rep protein.

[0360] A “chimeric AAV capsid protein” includes an AAV capsid protein that comprises amino acid sequences, e.g., portions, from two or more different AAV and that is capable of forming and / or forms an AAV viral capsid / viral particle. A chimeric AAV capsid protein is encoded by a chimeric AAV capsid gene, e.g., a chimeric nucleotide comprising a plurality, e.g., at least two, nucleic acid sequences, each of which plurality is identical to a portion of a capsid gene encoding a capsid protein of distinct AAV, and which plurality together encodes a functional chimeric AAV capsid protein. Association of a chimeric capsid protein to a specific AAV indicates that the capsid protein comprises one or more portions from a capsid protein of that AAV and one or more portions from a capsid protein of a different AAV. For example, a chimeric AAV2 capsid protein includes a capsid protein comprising one or more portions of a VP1, VP2, and / or VP3 capsid protein of AAV2 and one or more portions of a VP1, VP2, and / or VP3 capsid protein of a different AAV.

[0361] Sequence identifiers corresponding to exemplary anti-AAV antibodies provided herein are listed in Table 1 and Table 2. Table 1 sets forth the amino acid sequence identifiers of the heavy chain variable regions (HCVRs) and light chain variable regions (LCVRs), heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), as well as heavy chain (HC) and light chain (LC) of the exemplary anti-AAV antibodies and antigen- ^ ^Attorney Docket No.250298.000954 binding fragments. Table 2 sets forth the sequence identifiers of the nucleic acid molecules encoding the HCVRs, LCVRs, HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 LCDR3, HC, and LC of the exemplary anti-AAV antibodies and antigen-binding fragments described herein. Corresponding Fab and “standard mAb” (i.e., mAb comprising a constant region derived from IgG4 subclass) pairs are listed consecutively within Table 1 and Table 2. Non-limiting examples of amino acid sequences and nucleotide sequences of the anti-AAV antibodies are also listed below. Table 1. Amino Acid Sequence Identifiers for Anti-AAV Antibodies^^^ ^Attorney Docket No.250298.000954^ Table 2. Nucleic Acid Sequence Identifiers for Anti-AAV Antibodies^^^ ^Attorney Docket No.250298.000954REGN13876 HCVR DNA Sequence CAGGTGCACCTGCAAGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCC CTCTCCTGCACTGTCTCTGGTGATTCCATCAGAAGTGGTGGTTACTACTGGAGTTGGAT CCGCCAGCAGCCAGGAAGGGGCCTGGAATGGATTGGTTTCATCCATCAGAGTGACAG GTCCTACTATAACCCGTCCCTCATGAATCGACTCACCATGTCAGTAGACACGTCTAAGA ATCAATTCTCCCTGAAACTGACCTCTGTGACTGCCGCGGACACGGCCGTGTATTACTGT GCGAGAGATCGGGACACCATGGTTCGGGGAAGCATTACAACTTCCGGCCACTTCATTG ACTACTGGGGCCAGGGAACCCTGATCACCGTCTCCTCA (SEQ ID NO: 1) HCVR Amino Acid Sequence QVHLQESGPGLVKPSQTLSLSCTVSGDSIRSGGYYWSWIRQQPGRGLEWIGFIHQSDRSY YNPSLMNRLTMSVDTSKNQFSLKLTSVTAADTAVYYCARDRDTMVRGSITTSGHFIDYWGQ GTLITVSS (SEQ ID NO: 2) HCDR1 DNA Sequence GGTGATTCCATCAGAAGTGGTGGTTACTAC (SEQ ID NO: 3) HCDR1 Amino Acid Sequence GDSIRSGGYY (SEQ ID NO: 4) HCDR2 DNA Sequence ATCCATCAGAGTGACAGGTCC ^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 5) HCDR2 Amino Acid Sequence IHQSDRS (SEQ ID NO: 6) HCDR3 DNA Sequence GCGAGAGATCGGGACACCATGGTTCGGGGAAGCATTACAACTTCCGGCCACTTCATTG ACTAC (SEQ ID NO: 7) HCDR3 Amino Acid Sequence ARDRDTMVRGSITTSGHFIDY (SEQ ID NO: 8) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 9) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 10) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 11) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 12) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 13) ^ ^Attorney Docket No.250298.000954 LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 14) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 15) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 16) HC DNA Sequence CAGGTGCACCTGCAAGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCC CTCTCCTGCACTGTCTCTGGTGATTCCATCAGAAGTGGTGGTTACTACTGGAGTTGGAT CCGCCAGCAGCCAGGAAGGGGCCTGGAATGGATTGGTTTCATCCATCAGAGTGACAG GTCCTACTATAACCCGTCCCTCATGAATCGACTCACCATGTCAGTAGACACGTCTAAGA ATCAATTCTCCCTGAAACTGACCTCTGTGACTGCCGCGGACACGGCCGTGTATTACTGT GCGAGAGATCGGGACACCATGGTTCGGGGAAGCATTACAACTTCCGGCCACTTCATTG ACTACTGGGGCCAGGGAACCCTGATCACCGTCTCCTCAGCCTCCACCAAGGGCCCATC GGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGG CTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGC CCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGC AACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATG GTCCCCCATGA (SEQ ID NO: 17) HC Amino Acid Sequence QVHLQESGPGLVKPSQTLSLSCTVSGDSIRSGGYYWSWIRQQPGRGLEWIGFIHQSDRSY YNPSLMNRLTMSVDTSKNQFSLKLTSVTAADTAVYYCARDRDTMVRGSITTSGHFIDYWGQ GTLITVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP AVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP* (SEQ ID NO: 18) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA ^^^ ^Attorney Docket No.250298.000954 CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 19) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 20) REGN13877 (NAC67604) HCVR DNA Sequence CAGGTGCAGCTGCAGGAGTCGGGCCCAGTACTGGTGAAGCCTTCGGAGACCCTGTCC CTCACCTGCACTGTCTCTGGTGACTCCATCAGTAATTACTACTGGAGCTGGATCCGGCA GTCCCCAGGGAAGGGACTGGAGTGGATTGGGTATATCTATTACAGTGGCGGCACCAAC TACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAATAGACACGTCCAAGCGCCACTT CTCCCTGAAGCTGAACTCTGTGATCGCAGCGGACACGGCCGTATATTACTGTGCGAGA GCCCCTGTCACCATGGTTCGGGGAGTCATTACTTACAACTACCACTACGCTATGGACGT CTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 21) HCVR Amino Acid Sequence QVQLQESGPVLVKPSETLSLTCTVSGDSISNYYWSWIRQSPGKGLEWIGYIYYSGGTNYNP SLKSRVTISIDTSKRHFSLKLNSVIAADTAVYYCARAPVTMVRGVITYNYHYAMDVWGQGTT VTVSS (SEQ ID NO: 22) HCDR1 DNA Sequence GGTGACTCCATCAGTAATTACTAC (SEQ ID NO: 23) HCDR1 Amino Acid Sequence GDSISNYY (SEQ ID NO: 24) ^ ^Attorney Docket No.250298.000954 HCDR2 DNA Sequence ATCTATTACAGTGGCGGCACC (SEQ ID NO: 25) HCDR2 Amino Acid Sequence IYYSGGT (SEQ ID NO: 26) HCDR3 DNA Sequence GCGAGAGCCCCTGTCACCATGGTTCGGGGAGTCATTACTTACAACTACCACTACGCTAT GGACGTC (SEQ ID NO: 27) HCDR3 Amino Acid Sequence ARAPVTMVRGVITYNYHYAMDV (SEQ ID NO: 28) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 9) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 10) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 11) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 12) ^ ^Attorney Docket No.250298.000954 LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 13) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 14) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 15) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 16) HC DNA Sequence CAGGTGCAGCTGCAGGAGTCGGGCCCAGTACTGGTGAAGCCTTCGGAGACCCTGTCC CTCACCTGCACTGTCTCTGGTGACTCCATCAGTAATTACTACTGGAGCTGGATCCGGCA GTCCCCAGGGAAGGGACTGGAGTGGATTGGGTATATCTATTACAGTGGCGGCACCAAC TACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAATAGACACGTCCAAGCGCCACTT CTCCCTGAAGCTGAACTCTGTGATCGCAGCGGACACGGCCGTATATTACTGTGCGAGA GCCCCTGTCACCATGGTTCGGGGAGTCATTACTTACAACTACCACTACGCTATGGACGT CTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGT CTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTG CCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCT GACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTC AGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAAC GTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTC CCCCATGA (SEQ ID NO: 29) HC Amino Acid Sequence QVQLQESGPVLVKPSETLSLTCTVSGDSISNYYWSWIRQSPGKGLEWIGYIYYSGGTNYNP SLKSRVTISIDTSKRHFSLKLNSVIAADTAVYYCARAPVTMVRGVITYNYHYAMDVWGQGTT VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP* (SEQ ID NO: 30) LC DNA Sequence ^ ^Attorney Docket No.250298.000954 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 19) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 20) REGN13878 HCVR DNA Sequence CAATTGCAACTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA CTCTCATGTGCCGCCTCTGGATTCAGTTTCAGTAGTTATGGCATGCACTGGGTCCGCCA GACTCCAGGCAAGGGACTGGAGTGGGTGACATTTATATCATATGACGGAAGTTATGATT ACTATTTAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACATTTCCAAGAACACA TTGTATTTGCAAATGAACAGCCTGAGAATTGAGGACACGGCTGTCTATTACTGTGCGAG CGGCCTCACTGGCCCTACGAGGTGGTATTTCGATCTCTGGGGCCGTGGCACCCTGGT CACTGTCTCCTCC (SEQ ID NO: 31) HCVR Amino Acid Sequence QLQLVESGGGVVQPGRSLRLSCAASGFSFSSYGMHWVRQTPGKGLEWVTFISYDGSYDY YLDSVKGRFTISRDISKNTLYLQMNSLRIEDTAVYYCASGLTGPTRWYFDLWGRGTLVTVSS (SEQ ID NO: 32) HCDR1 DNA Sequence GGATTCAGTTTCAGTAGTTATGGC (SEQ ID NO: 33) ^ ^Attorney Docket No.250298.000954 HCDR1 Amino Acid Sequence GFSFSSYG (SEQ ID NO: 34) HCDR2 DNA Sequence ATATCATATGACGGAAGTTATGAT (SEQ ID NO: 35) HCDR2 Amino Acid Sequence ISYDGSYD (SEQ ID NO: 36) HCDR3 DNA Sequence GCGAGCGGCCTCACTGGCCCTACGAGGTGGTATTTCGATCTC (SEQ ID NO: 37) HCDR3 Amino Acid Sequence ASGLTGPTRWYFDL (SEQ ID NO: 38) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 9) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 10) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 11) LCDR1 Amino Acid Sequence ^ ^Attorney Docket No.250298.000954 QSISSY (SEQ ID NO: 12) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 13) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 14) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 15) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 16) HC DNA Sequence CAATTGCAACTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA CTCTCATGTGCCGCCTCTGGATTCAGTTTCAGTAGTTATGGCATGCACTGGGTCCGCCA GACTCCAGGCAAGGGACTGGAGTGGGTGACATTTATATCATATGACGGAAGTTATGATT ACTATTTAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACATTTCCAAGAACACA TTGTATTTGCAAATGAACAGCCTGAGAATTGAGGACACGGCTGTCTATTACTGTGCGAG CGGCCTCACTGGCCCTACGAGGTGGTATTTCGATCTCTGGGGCCGTGGCACCCTGGT CACTGTCTCCTCCGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCC AGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTC CCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCT CCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACAC CAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGA (SEQ ID NO: 39) HC Amino Acid Sequence QLQLVESGGGVVQPGRSLRLSCAASGFSFSSYGMHWVRQTPGKGLEWVTFISYDGSYDY YLDSVKGRFTISRDISKNTLYLQMNSLRIEDTAVYYCASGLTGPTRWYFDLWGRGTLVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP* (SEQ ID NO: 40) ^ ^Attorney Docket No.250298.000954 LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 19) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 20) REGN13879 HCVR DNA Sequence GAGGTGCAGTTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGA CTCTCCTGTGCAGTCTCTGGATTCACCTTTAGCAACTATGCCATGAGTTGGGTCCGCCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGGTTTTAGTGGAAGTGGTGGTAGCAC ATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATACCAAGAAC ACGCTGTATCTGCAAATGAACATCCTGAGAGGCGAGGACACGGCCGTATATTATTGTG CGAAAAATCGGGTACGTGGATATAGTGGCCACCATCTTGACTACTGGGGCCAGGGAAC CCCGGTCACCGTCTCCTCA (SEQ ID NO: 41) HCVR Amino Acid Sequence EVQLLESGGGLVQPGGSLRLSCAVSGFTFSNYAMSWVRQAPGKGLEWVSGFSGSGGSTY YADSVKGRFTISRDNTKNTLYLQMNILRGEDTAVYYCAKNRVRGYSGHHLDYWGQGTPVT VSS (SEQ ID NO: 42) HCDR1 DNA Sequence GGATTCACCTTTAGCAACTATGCC ^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 43) HCDR1 Amino Acid Sequence GFTFSNYA (SEQ ID NO: 44) HCDR2 DNA Sequence TTTAGTGGAAGTGGTGGTAGCACA (SEQ ID NO: 45) HCDR2 Amino Acid Sequence FSGSGGST (SEQ ID NO: 46) HCDR3 DNA Sequence GCGAAAAATCGGGTACGTGGATATAGTGGCCACCATCTTGACTAC (SEQ ID NO: 47) HCDR3 Amino Acid Sequence AKNRVRGYSGHHLDY (SEQ ID NO: 48) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 9) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 10) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT ^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 11) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 12) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 13) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 14) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 15) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 16) HC DNA Sequence GAGGTGCAGTTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGA CTCTCCTGTGCAGTCTCTGGATTCACCTTTAGCAACTATGCCATGAGTTGGGTCCGCCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGGTTTTAGTGGAAGTGGTGGTAGCAC ATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATACCAAGAAC ACGCTGTATCTGCAAATGAACATCCTGAGAGGCGAGGACACGGCCGTATATTATTGTG CGAAAAATCGGGTACGTGGATATAGTGGCCACCATCTTGACTACTGGGGCCAGGGAAC CCCGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCC CTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTA CTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCA CACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCA GCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGA (SEQ ID NO: 49) HC Amino Acid Sequence EVQLLESGGGLVQPGGSLRLSCAVSGFTFSNYAMSWVRQAPGKGLEWVSGFSGSGGSTY YADSVKGRFTISRDNTKNTLYLQMNILRGEDTAVYYCAKNRVRGYSGHHLDYWGQGTPVT VSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP* ^^^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 50) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 19) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 20) REGN13880 (NAC67600) HCVR DNA Sequence CAGGTACACCTGCAGGAGTCGGGCCCAGGACTGGTGATGCCTTCACAGATCCTGTCCC TCTCCTGCGTTATTTCTGGTGACTCCATCAGAAATGGCGGCTATTATTGGACCTGGACC CGCCAGCAACCAGGGAAGGGCCTGGAGTGGATCGGTCACATCCACTATAGTGAAAGG ACCTCCCACAATCCGTCCCTCCAGAGTCGCGTTATTATGTCAATAGACACGTCTGAGAA TAAGTTCTCCCTGAAACTGACCTCAGTGACTGTCGCGGACACGGCCATATATTATTGTG CGCGAGGTCGGGACACCATGGTTCGGGGATCCATTACAACTTCCGGCCACTTCATTGA CTCCTGGGGTCAGGGAGCCCTGGTCACCGTCTCCTCA (SEQ ID NO: 51), or CAGGTACACCTCCAGGAGTCGGGCCCAGGACTGGTGATGCCTTCACAGATCCTGTCCC TCTCCTGCGTTATTTCTGGTGACTCCATCAGAAATGGCGGCTATTATTGGACCTGGACC CGCCAGCAACCAGGGAAGGGCCTGGAGTGGATCGGTCACATCCACTATAGTGAAAGG ACCTCCCACAATCCGTCCCTCCAGAGTCGCGTTATTATGTCAATAGACACGTCTGAGAA TAAGTTCTCCCTGAAACTGACCTCAGTGACTGTCGCGGACACGGCCATATATTATTGTG CGCGAGGTCGGGACACCATGGTTCGGGGATCCATTACAACTTCCGGCCACTTCATTGA CTCCTGGGGTCAGGGAGCCCTGGTCACCGTCTCCTCA ^^^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 1109) (silent mutation underlined in sequence above), or CAGGTACACCTGCAGGAGTCGGGCCCAGGACTGGTGATGCCTTCACAGATCCTGTCCC TCTCCTGCGTTATTTCTGGTGACTCCATCAGAAATGGCGGCTATTATTGGACCTGGACC CGCCAGCAACCAGGGAAGTGTCTGGAGTGGATCGGTCACATCCACTATAGTGAAAGGA CCTCCCACAATCCGTCCCTCCAGAGTCGCGTTATTATGTCAATAGACACGTCTGAGAAT AAGTTCTCCCTGAAACTGACCTCAGTGACTGTCGCGGACACGGCCATATATTATTGTGC GCGAGGTCGGGACACCATGGTTCGGGGATCCATTACAACTTCCGGCCACTTCATTGAC TCCTGGGGTCAGGGAGCCCTGGTCACCGTCTCCTCA (SEQ ID NO: 1158) (Cys mutation underlined in sequence above), or CAGGTACACCTCCAGGAGTCGGGCCCAGGACTGGTGATGCCTTCACAGATCCTGTCCC TCTCCTGCGTTATTTCTGGTGACTCCATCAGAAATGGCGGCTATTATTGGACCTGGACC CGCCAGCAACCAGGGAAGTGCCTGGAGTGGATCGGTCACATCCACTATAGTGAAAGGA CCTCCCACAATCCGTCCCTCCAGAGTCGCGTTATTATGTCAATAGACACGTCTGAGAAT AAGTTCTCCCTGAAACTGACCTCAGTGACTGTCGCGGACACGGCCATATATTATTGTGC GCGAGGTCGGGACACCATGGTTCGGGGATCCATTACAACTTCCGGCCACTTCATTGAC TCCTGGGGTCAGGGAGCCCTGGTCACCGTCTCCTCA (SEQ ID NO: 1275) (2 silent mutations underlined in sequence above) HCVR Amino Acid Sequence QVHLQESGPGLVMPSQILSLSCVISGDSIRNGGYYWTWTRQQPGKGLEWIGHIHYSERTSH NPSLQSRVIMSIDTSENKFSLKLTSVTVADTAIYYCARGRDTMVRGSITTSGHFIDSWGQGA LVTVSS (SEQ ID NO: 52), or QVHLQESGPGLVMPSQILSLSCVISGDSIRNGGYYWTWTRQQPGKCLEWIGHIHYSERTSH NPSLQSRVIMSIDTSENKFSLKLTSVTVADTAIYYCARGRDTMVRGSITTSGHFIDSWGQGA LVTVSS (SEQ ID NO: 1159) (Cys mutation underlined in sequence above) HCDR1 DNA Sequence GGTGACTCCATCAGAAATGGCGGCTATTAT (SEQ ID NO: 53) HCDR1 Amino Acid Sequence GDSIRNGGYY (SEQ ID NO: 54) HCDR2 DNA Sequence ^ ^Attorney Docket No.250298.000954 ATCCACTATAGTGAAAGGACC (SEQ ID NO: 55) HCDR2 Amino Acid Sequence IHYSERT (SEQ ID NO: 56) HCDR3 DNA Sequence GCGCGAGGTCGGGACACCATGGTTCGGGGATCCATTACAACTTCCGGCCACTTCATTG ACTCC (SEQ ID NO: 57) HCDR3 Amino Acid Sequence ARGRDTMVRGSITTSGHFIDS (SEQ ID NO: 58) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 9), or GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCTGTGGGACACGACTGGAGATTAAA (SEQ ID NO: 1156) (Cys mutation underlined in sequence above) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 10), or DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGCGTRLEIK ^^^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 1157) (Cys mutation underlined in sequence above) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 11) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 12) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 13) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 14) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 15) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 16) HC DNA Sequence CAGGTACACCTGCAGGAGTCGGGCCCAGGACTGGTGATGCCTTCACAGATCCTGTCCC TCTCCTGCGTTATTTCTGGTGACTCCATCAGAAATGGCGGCTATTATTGGACCTGGACC CGCCAGCAACCAGGGAAGGGCCTGGAGTGGATCGGTCACATCCACTATAGTGAAAGG ACCTCCCACAATCCGTCCCTCCAGAGTCGCGTTATTATGTCAATAGACACGTCTGAGAA TAAGTTCTCCCTGAAACTGACCTCAGTGACTGTCGCGGACACGGCCATATATTATTGTG CGCGAGGTCGGGACACCATGGTTCGGGGATCCATTACAACTTCCGGCCACTTCATTGA CTCCTGGGGTCAGGGAGCCCTGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATC GGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGG CTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGC CCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGC AACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATG GTCCCCCATGA ^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 59), or CAGGTACACCTCCAGGAGTCGGGCCCAGGACTGGTGATGCCTTCACAGATCCTGTCCC TCTCCTGCGTTATTTCTGGTGACTCCATCAGAAATGGCGGCTATTATTGGACCTGGACC CGCCAGCAACCAGGGAAGGGCCTGGAGTGGATCGGTCACATCCACTATAGTGAAAGG ACCTCCCACAATCCGTCCCTCCAGAGTCGCGTTATTATGTCAATAGACACGTCTGAGAA TAAGTTCTCCCTGAAACTGACCTCAGTGACTGTCGCGGACACGGCCATATATTATTGTG CGCGAGGTCGGGACACCATGGTTCGGGGATCCATTACAACTTCCGGCCACTTCATTGA CTCCTGGGGTCAGGGAGCCCTGGTCACCGTCTCCTCAGCCTCAACCAAGGGACCGTC CGTGTTTCCCCTCGCTCCTTCATCAAAATCAACTTCCGGCGGAACCGCAGCGCTGGGC TGCCTCGTGAAGGATTACTTCCCCGAGCCTGTGACCGTGTCCTGGAACTCGGGCGCCC TGACCTCCGGTGTCCACACGTTCCCCGCGGTCCTTCAGTCCTCCGGCTTGTATTCCCT GTCGTCCGTCGTGACCGTCCCGAGCAGCAGCCTGGGAACTCAGACCTACATCTGCAAC GTGAACCACAAGCCGTCGAACACCAAGGTCGATAAGAAAGTGGAGCCGAAGTCGTGC GACAAAACTCATACA (SEQ ID NO: 1107) (silent mutation underlined in sequence above) HC Amino Acid Sequence QVHLQESGPGLVMPSQILSLSCVISGDSIRNGGYYWTWTRQQPGKGLEWIGHIHYSERTSH NPSLQSRVIMSIDTSENKFSLKLTSVTVADTAIYYCARGRDTMVRGSITTSGHFIDSWGQGA LVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP* (SEQ ID NO: 60), or QVHLQESGPGLVMPSQILSLSCVISGDSIRNGGYYWTWTRQQPGKGLEWIGHIHYSERTSH NPSLQSRVIMSIDTSENKFSLKLTSVTVADTAIYYCARGRDTMVRGSITTSGHFIDSWGQGA LVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT (SEQ ID NO: 1108) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG ^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 19), or GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGT (SEQ ID NO: 1145), or GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 1500) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 20) REGN13881 HCVR DNA Sequence CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCC CTCTCCTGCACTGTCTCTCGTGGCTCCATCAGCAGTGGTGGTTACTATTGGAGCTGGAT CCGCCAGCACCCAGGGAAGGGCCTGGAGTGGATTGGATACATCCATTATAGTGAGAG ^^^ ^Attorney Docket No.250298.000954 GACCTACTACAACCCGTCCCTCAAGAGTCGAGTTACCATGTCAGTTGACACGTCTAAGA ACCAGTTCTCCCTGAAGCTGACCTCTGTGACTGCCGCGGACACGGCCGTGTATTATTG TGCGAGAGATCGGGACACCATGGTTCGGGGAGTCATTACAACTTCCGGCCACTTCATT GACGACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA (SEQ ID NO: 61) HCVR Amino Acid Sequence QVQLQESGPGLVKPSQTLSLSCTVSRGSISSGGYYWSWIRQHPGKGLEWIGYIHYSERTYY NPSLKSRVTMSVDTSKNQFSLKLTSVTAADTAVYYCARDRDTMVRGVITTSGHFIDDWGQ GTLVTVSS (SEQ ID NO: 62) HCDR1 DNA Sequence CGTGGCTCCATCAGCAGTGGTGGTTACTAT (SEQ ID NO: 63) HCDR1 Amino Acid Sequence RGSISSGGYY (SEQ ID NO: 64) HCDR2 DNA Sequence ATCCATTATAGTGAGAGGACC (SEQ ID NO: 65) HCDR2 Amino Acid Sequence IHYSERT (SEQ ID NO: 56) HCDR3 DNA Sequence GCGAGAGATCGGGACACCATGGTTCGGGGAGTCATTACAACTTCCGGCCACTTCATTG ACGAC (SEQ ID NO: 66) HCDR3 Amino Acid Sequence ARDRDTMVRGVITTSGHFIDD (SEQ ID NO: 67) LCVR DNA Sequence ^ ^Attorney Docket No.250298.000954 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 9) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 10) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 11) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 12) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 13) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 14) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 15) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 16) HC DNA Sequence ^ ^Attorney Docket No.250298.000954 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCC CTCTCCTGCACTGTCTCTCGTGGCTCCATCAGCAGTGGTGGTTACTATTGGAGCTGGAT CCGCCAGCACCCAGGGAAGGGCCTGGAGTGGATTGGATACATCCATTATAGTGAGAG GACCTACTACAACCCGTCCCTCAAGAGTCGAGTTACCATGTCAGTTGACACGTCTAAGA ACCAGTTCTCCCTGAAGCTGACCTCTGTGACTGCCGCGGACACGGCCGTGTATTATTG TGCGAGAGATCGGGACACCATGGTTCGGGGAGTCATTACAACTTCCGGCCACTTCATT GACGACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCA TCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTG GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGC GCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACT CCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCT GCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATA TGGTCCCCCATGA (SEQ ID NO: 68) HC Amino Acid Sequence QVQLQESGPGLVKPSQTLSLSCTVSRGSISSGGYYWSWIRQHPGKGLEWIGYIHYSERTYY NPSLKSRVTMSVDTSKNQFSLKLTSVTAADTAVYYCARDRDTMVRGVITTSGHFIDDWGQ GTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP* (SEQ ID NO: 69) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 19) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 20) ^ ^Attorney Docket No.250298.000954 REGN13882 (NAC67606) HCVR DNA Sequence GAGGTGCACTTATTGGACTCTGGCGGAGGCTTGGTTCAGTCGGGGGAGTCCCTGAGA CTCTCCTGTACAGTCTCTGGAGTCACTTTTGAAAACCTTGTCATGAACTGGGTCCGGCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCGCAAGTGTTGGAGGTCGTTATACTGGCGC GGTCTTCGCAGACTCAGTGAGGGGCCGGTTCACGATCTCCAGAGACCATTCCGAGAAT ACGCTCTTTCTGCACATGAGCAGCCTGAGAGCCGAGGACACGGCCGTTTATTTTTGTAC GAAAGATTCCTCTGTCCTGATTCGGGGAGTCATTAGTACAAACTACTTCTATAGTATGGA CGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 70) HCVR Amino Acid Sequence EVHLLDSGGGLVQSGESLRLSCTVSGVTFENLVMNWVRQAPGKGLEWVASVGGRYTGAV FADSVRGRFTISRDHSENTLFLHMSSLRAEDTAVYFCTKDSSVLIRGVISTNYFYSMDVWG QGTTVTVSS (SEQ ID NO: 71) HCDR1 DNA Sequence GGAGTCACTTTTGAAAACCTTGTC (SEQ ID NO: 72) HCDR1 Amino Acid Sequence GVTFENLV (SEQ ID NO: 73) HCDR2 DNA Sequence GTTGGAGGTCGTTATACTGGCGCG (SEQ ID NO: 74) HCDR2 Amino Acid Sequence VGGRYTGA (SEQ ID NO: 75) HCDR3 DNA Sequence ACGAAAGATTCCTCTGTCCTGATTCGGGGAGTCATTAGTACAAACTACTTCTATAGTATG GACGTC (SEQ ID NO: 76) ^ ^Attorney Docket No.250298.000954 HCDR3 Amino Acid Sequence TKDSSVLIRGVISTNYFYSMDV (SEQ ID NO: 77) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 9) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 10) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 11) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 12) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 13) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 14) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 15) LCDR3 Amino Acid Sequence ^ ^Attorney Docket No.250298.000954 QQSYSTPPIT (SEQ ID NO: 16) HC DNA Sequence GAGGTGCACTTATTGGACTCTGGCGGAGGCTTGGTTCAGTCGGGGGAGTCCCTGAGA CTCTCCTGTACAGTCTCTGGAGTCACTTTTGAAAACCTTGTCATGAACTGGGTCCGGCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCGCAAGTGTTGGAGGTCGTTATACTGGCGC GGTCTTCGCAGACTCAGTGAGGGGCCGGTTCACGATCTCCAGAGACCATTCCGAGAAT ACGCTCTTTCTGCACATGAGCAGCCTGAGAGCCGAGGACACGGCCGTTTATTTTTGTAC GAAAGATTCCTCTGTCCTGATTCGGGGAGTCATTAGTACAAACTACTTCTATAGTATGGA CGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATC GGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGG CTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGC CCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGC AACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATG GTCCCCCATGA (SEQ ID NO: 78) HC Amino Acid Sequence EVHLLDSGGGLVQSGESLRLSCTVSGVTFENLVMNWVRQAPGKGLEWVASVGGRYTGAV FADSVRGRFTISRDHSENTLFLHMSSLRAEDTAVYFCTKDSSVLIRGVISTNYFYSMDVWG QGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHT FPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP* (SEQ ID NO: 79) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 19) LC Amino Acid Sequence ^ ^Attorney Docket No.250298.000954 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 20) REGN13883 HCVR DNA Sequence CAGGAGCAACTACAACAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCC CTCACCTGCGCTGTCCATGGTGGGTCATTCAGTGGTTACTACTGGAGTTGGATCCGCC AGCCCCCCGGGAAGGGGCTGGAGTGGATTGGGGAAATCTATCCTAGTGGAGGCACCA ACCAAAATCCGTCCCTCAAGAGTCGAGTCACCATATCACTAGACATGTCCCAGAACCAG TTCTCCCTGAGGCTGAACTCTGTGACCGCCGCGGACACGGCTGTATATTACTGTGCGA GACGGAATTGGGACGGATACTTTGACTTCTGGGGCCAGGGAATTAAGGTCACTGTCTC CTCA (SEQ ID NO: 80) HCVR Amino Acid Sequence QEQLQQWGAGLLKPSETLSLTCAVHGGSFSGYYWSWIRQPPGKGLEWIGEIYPSGGTNQ NPSLKSRVTISLDMSQNQFSLRLNSVTAADTAVYYCARRNWDGYFDFWGQGIKVTVSS (SEQ ID NO: 81) HCDR1 DNA Sequence GGTGGGTCATTCAGTGGTTACTAC (SEQ ID NO: 82) HCDR1 Amino Acid Sequence GGSFSGYY (SEQ ID NO: 83) HCDR2 DNA Sequence ATCTATCCTAGTGGAGGCACC (SEQ ID NO: 84) HCDR2 Amino Acid Sequence IYPSGGT (SEQ ID NO: 85) HCDR3 DNA Sequence ^ ^Attorney Docket No.250298.000954 GCGAGACGGAATTGGGACGGATACTTTGACTTC (SEQ ID NO: 86) HCDR3 Amino Acid Sequence ARRNWDGYFDF (SEQ ID NO: 87) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 9) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 10) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 11) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 12) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 13) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 14) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC ^^^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 15) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 16) HC DNA Sequence CAGGAGCAACTACAACAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCC CTCACCTGCGCTGTCCATGGTGGGTCATTCAGTGGTTACTACTGGAGTTGGATCCGCC AGCCCCCCGGGAAGGGGCTGGAGTGGATTGGGGAAATCTATCCTAGTGGAGGCACCA ACCAAAATCCGTCCCTCAAGAGTCGAGTCACCATATCACTAGACATGTCCCAGAACCAG TTCTCCCTGAGGCTGAACTCTGTGACCGCCGCGGACACGGCTGTATATTACTGTGCGA GACGGAATTGGGACGGATACTTTGACTTCTGGGGCCAGGGAATTAAGGTCACTGTCTC CTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCAC CTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGT GACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGT CCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGC TTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG ACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGA (SEQ ID NO: 88) HC Amino Acid Sequence QEQLQQWGAGLLKPSETLSLTCAVHGGSFSGYYWSWIRQPPGKGLEWIGEIYPSGGTNQ NPSLKSRVTISLDMSQNQFSLRLNSVTAADTAVYYCARRNWDGYFDFWGQGIKVTVSSAS TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP* (SEQ ID NO: 89) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 19) ^ ^Attorney Docket No.250298.000954 LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 20) REGN13884 HCVR DNA Sequence CAGGTGCAACTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA CTCTCCTGTGCAGCGTCTGGATTCACCTTCAGTAGCTATGGCATACACTGGGTCCGCC AGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCACTTATATGGTATGATGGAAGTAATAA ATACTATACAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACA CGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAAGACACGGCTGTGTATTACTGTGC GAGAGATAGAGTGCGATCGTATAGCTGGAACTACTTTGACTACTGGGGCCAGGGAACC CTGGTCACCGTCTCCTCA (SEQ ID NO: 90) HCVR Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGIHWVRQAPGKGLEWVALIWYDGSNKY YTDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRVRSYSWNYFDYWGQGTLVT VSS (SEQ ID NO: 91) HCDR1 DNA Sequence GGATTCACCTTCAGTAGCTATGGC (SEQ ID NO: 92) HCDR1 Amino Acid Sequence GFTFSSYG (SEQ ID NO: 93) HCDR2 DNA Sequence ATATGGTATGATGGAAGTAATAAA (SEQ ID NO: 94) HCDR2 Amino Acid Sequence IWYDGSNK ^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 95) HCDR3 DNA Sequence GCGAGAGATAGAGTGCGATCGTATAGCTGGAACTACTTTGACTAC (SEQ ID NO: 96) HCDR3 Amino Acid Sequence ARDRVRSYSWNYFDY (SEQ ID NO: 97) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 9) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 10) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 11) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 12) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 13) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 14) ^ ^Attorney Docket No.250298.000954 LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 15) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 16) HC DNA Sequence CAGGTGCAACTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA CTCTCCTGTGCAGCGTCTGGATTCACCTTCAGTAGCTATGGCATACACTGGGTCCGCC AGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCACTTATATGGTATGATGGAAGTAATAA ATACTATACAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACA CGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAAGACACGGCTGTGTATTACTGTGC GAGAGATAGAGTGCGATCGTATAGCTGGAACTACTTTGACTACTGGGGCCAGGGAACC CTGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCT GCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACT TCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACA CCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGT GCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGC AACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGA (SEQ ID NO: 98) HC Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGIHWVRQAPGKGLEWVALIWYDGSNKY YTDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRVRSYSWNYFDYWGQGTLVT VSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP* (SEQ ID NO: 99) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC ^ ^Attorney Docket No.250298.000954 TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 19) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 20) REGN13885 HCVR DNA Sequence GAGGTGCAACTGGTGGAATCTGGAGGAGGCTTGGTCCAGCCTGGGGGTTCCCTGAGA CTCTCCTGTGCAGCCTCTGGGTTCATCGTCAGTAACAACTATATGAGATGGGTCCGCCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCTCGGTCATTTATAGTGGTGGTGGCACATA CTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGACACAATTCCAAGAACACG ATATATCTTCAAATGAACAGCCTGCGAATTGAGGACACGGCCGTGTATTATTGTGCGAG AGAAGATAGCCACTCGTCGGAAAGTTATGACTACTTCTACGGCATGGACGTCTGGGGC CAAGGGACCACGGTCACCGTCTCCCCA (SEQ ID NO: 100) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFIVSNNYMRWVRQAPGKGLEWVSVIYSGGGTYY ADSVKGRFTISRHNSKNTIYLQMNSLRIEDTAVYYCAREDSHSSESYDYFYGMDVWGQGTT VTVSP (SEQ ID NO: 101) HCDR1 DNA Sequence GGGTTCATCGTCAGTAACAACTAT (SEQ ID NO: 102) HCDR1 Amino Acid Sequence GFIVSNNY (SEQ ID NO: 103) HCDR2 DNA Sequence ATTTATAGTGGTGGTGGCACA (SEQ ID NO: 104) ^ ^Attorney Docket No.250298.000954 HCDR2 Amino Acid Sequence IYSGGGT (SEQ ID NO: 105) HCDR3 DNA Sequence GCGAGAGAAGATAGCCACTCGTCGGAAAGTTATGACTACTTCTACGGCATGGACGTC (SEQ ID NO: 106) HCDR3 Amino Acid Sequence AREDSHSSESYDYFYGMDV (SEQ ID NO: 107) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 9) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 10) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 11) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 12) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 13 LCDR2 Amino^ ^Attorney Docket No.250298.000954 AAS (SEQ ID NO: 14) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 15) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 16) HC DNA Sequence GAGGTGCAACTGGTGGAATCTGGAGGAGGCTTGGTCCAGCCTGGGGGTTCCCTGAGA CTCTCCTGTGCAGCCTCTGGGTTCATCGTCAGTAACAACTATATGAGATGGGTCCGCCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCTCGGTCATTTATAGTGGTGGTGGCACATA CTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGACACAATTCCAAGAACACG ATATATCTTCAAATGAACAGCCTGCGAATTGAGGACACGGCCGTGTATTATTGTGCGAG AGAAGATAGCCACTCGTCGGAAAGTTATGACTACTTCTACGGCATGGACGTCTGGGGC CAAGGGACCACGGTCACCGTCTCCCCAGCCTCCACCAAGGGCCCATCGGTCTTCCCC CTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTC AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCG TGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCA CAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGA (SEQ ID NO: 108) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFIVSNNYMRWVRQAPGKGLEWVSVIYSGGGTYY ADSVKGRFTISRHNSKNTIYLQMNSLRIEDTAVYYCAREDSHSSESYDYFYGMDVWGQGTT VTVSPASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPP* (SEQ ID NO: 109) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ^^^ ^Attorney Docket No.250298.000954 ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 19) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 20) REGN13070 HCVR DNA Sequence CAATTGCAACTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA CTCTCATGTGCCGCCTCTGGATTCAGTTTCAGTAGTTATGGCATGCACTGGGTCCGCCA GACTCCAGGCAAGGGACTGGAGTGGGTGACATTTATATCATATGACGGAAGTTATGATT ACTATTTAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACATTTCCAAGAACACA TTGTATTTGCAAATGAACAGCCTGAGAATTGAGGACACGGCTGTCTATTACTGTGCGAG CGGCCTCACTGGCCCTACGAGGTGGTATTTCGATCTCTGGGGCCGTGGCACCCTGGT CACTGTCTCCTCC (SEQ ID NO: 110) HCVR Amino Acid Sequence QLQLVESGGGVVQPGRSLRLSCAASGFSFSSYGMHWVRQTPGKGLEWVTFISYDGSYDY YLDSVKGRFTISRDISKNTLYLQMNSLRIEDTAVYYCASGLTGPTRWYFDLWGRGTLVTVSS (SEQ ID NO: 111) HCDR1 DNA Sequence GGATTCAGTTTCAGTAGTTATGGC (SEQ ID NO: 112) HCDR1 Amino Acid Sequence GFSFSSYG (SEQ ID NO: 113) HCDR2 DNA Sequence ATATCATATGACGGAAGTTATGAT ^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 114) HCDR2 Amino Acid Sequence ISYDGSYD (SEQ ID NO: 115) HCDR3 DNA Sequence GCGAGCGGCCTCACTGGCCCTACGAGGTGGTATTTCGATCTC (SEQ ID NO: 116) HCDR3 Amino Acid Sequence ASGLTGPTRWYFDL (SEQ ID NO: 117) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 118) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 119) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 120) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 121) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 122) ^ ^Attorney Docket No.250298.000954 LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 123) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 124) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 125) HC DNA Sequence CAATTGCAACTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA CTCTCATGTGCCGCCTCTGGATTCAGTTTCAGTAGTTATGGCATGCACTGGGTCCGCCA GACTCCAGGCAAGGGACTGGAGTGGGTGACATTTATATCATATGACGGAAGTTATGATT ACTATTTAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACATTTCCAAGAACACA TTGTATTTGCAAATGAACAGCCTGAGAATTGAGGACACGGCTGTCTATTACTGTGCGAG CGGCCTCACTGGCCCTACGAGGTGGTATTTCGATCTCTGGGGCCGTGGCACCCTGGT CACTGTCTCCTCCGCCTCTACAAAGGGACCTTCTGTGTTTCCTCTGGCTCCTTGTTCTA GATCTACATCTGAATCTACAGCTGCTCTGGGATGTCTGGTGAAGGATTATTTTCCTGAA CCTGTGACAGTGTCTTGGAATTCTGGAGCTCTGACATCTGGAGTGCATACATTTCCTGC TGTGCTGCAGTCTTCTGGACTGTATTCTCTGTCTTCTGTGGTGACAGTGCCTTCTTCTTC TCTGGGAACAAAGACATATACATGTAATGTGGATCATAAGCCTTCTAATACAAAGGTGG ATAAGAGAGTGGAATCTAAGTATGGACCTCCTTGTCCTCCTTGTCCTGCTCCTGGCGGT GGCGGACCTTCTGTGTTTCTGTTTCCTCCTAAGCCTAAGGATACACTGATGATCTCTAG AACACCTGAAGTGACATGTGTGGTGGTGGATGTGTCTCAGGAAGATCCTGAAGTGCAG TTTAATTGGTATGTGGATGGAGTGGAAGTGCATAATGCTAAGACAAAGCCTAGAGAAGA ACAGTTTAATTCTACATATAGAGTGGTGTCTGTGCTGACAGTGCTGCATCAGGATTGGC TGAATGGAAAGGAATATAAGTGTAAGGTGTCTAATAAGGGACTGCCTTCTTCTATCGAA AAGACAATCTCTAAGGCTAAGGGACAGCCTAGAGAACCTCAGGTGTATACACTGCCTC CTTCTCAGGAAGAAATGACAAAGAATCAGGTGTCTCTGACATGTCTGGTGAAGGGATTT TATCCTTCTGATATCGCTGTGGAATGGGAATCTAATGGACAGCCTGAAAATAATTATAAG ACAACACCTCCTGTGCTGGATTCTGATGGATCTTTTTTTCTGTATTCTAGACTGACAGTG GATAAGTCTAGATGGCAGGAAGGAAATGTGTTTTCTTGTTCTGTGATGCATGAAGCTCT GCATAATAGATTTACACAGAAGTCTCTGTCTCTGTCTCCTGGAAAGTAG (SEQ ID NO: 126) HC Amino Acid Sequence QLQLVESGGGVVQPGRSLRLSCAASGFSFSSYGMHWVRQTPGKGLEWVTFISYDGSYDY YLDSVKGRFTISRDISKNTLYLQMNSLRIEDTAVYYCASGLTGPTRWYFDLWGRGTLVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG ^^^ ^Attorney Docket No.250298.000954 LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPGGGGPSVFLF PPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS CSVMHEALHNRFTQKSLSLSPGK* (SEQ ID NO: 127) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 128) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 129) REGN13071 HCVR DNA Sequence CAGGAGCAACTACAACAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCC CTCACCTGCGCTGTCCATGGTGGGTCATTCAGTGGTTACTACTGGAGTTGGATCCGCC AGCCCCCCGGGAAGGGGCTGGAGTGGATTGGGGAAATCTATCCTAGTGGAGGCACCA ACCAAAATCCGTCCCTCAAGAGTCGAGTCACCATATCACTAGACATGTCCCAGAACCAG TTCTCCCTGAGGCTGAACTCTGTGACCGCCGCGGACACGGCTGTATATTACTGTGCGA GACGGAATTGGGACGGATACTTTGACTTCTGGGGCCAGGGAATTAAGGTCACTGTCTC CTCA (SEQ ID NO: 130) HCVR Amino Acid Sequence ^ ^Attorney Docket No.250298.000954 QEQLQQWGAGLLKPSETLSLTCAVHGGSFSGYYWSWIRQPPGKGLEWIGEIYPSGGTNQ NPSLKSRVTISLDMSQNQFSLRLNSVTAADTAVYYCARRNWDGYFDFWGQGIKVTVSS (SEQ ID NO: 131) HCDR1 DNA Sequence GGTGGGTCATTCAGTGGTTACTAC (SEQ ID NO: 132) HCDR1 Amino Acid Sequence GGSFSGYY (SEQ ID NO: 133) HCDR2 DNA Sequence ATCTATCCTAGTGGAGGCACC (SEQ ID NO: 134) HCDR2 Amino Acid Sequence IYPSGGT (SEQ ID NO: 135) HCDR3 DNA Sequence GCGAGACGGAATTGGGACGGATACTTTGACTTC (SEQ ID NO: 136) HCDR3 Amino Acid Sequence ARRNWDGYFDF (SEQ ID NO: 137) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 118) LCVR Amino Acid Sequence ^ ^Attorney Docket No.250298.000954 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 119) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 120) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 121) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 122) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 123) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 124) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 125) HC DNA Sequence CAGGAGCAACTACAACAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCC CTCACCTGCGCTGTCCATGGTGGGTCATTCAGTGGTTACTACTGGAGTTGGATCCGCC AGCCCCCCGGGAAGGGGCTGGAGTGGATTGGGGAAATCTATCCTAGTGGAGGCACCA ACCAAAATCCGTCCCTCAAGAGTCGAGTCACCATATCACTAGACATGTCCCAGAACCAG TTCTCCCTGAGGCTGAACTCTGTGACCGCCGCGGACACGGCTGTATATTACTGTGCGA GACGGAATTGGGACGGATACTTTGACTTCTGGGGCCAGGGAATTAAGGTCACTGTCTC CTCAGCCTCTACAAAGGGACCTTCTGTGTTTCCTCTGGCTCCTTGTTCTAGATCTACATC TGAATCTACAGCTGCTCTGGGATGTCTGGTGAAGGATTATTTTCCTGAACCTGTGACAG TGTCTTGGAATTCTGGAGCTCTGACATCTGGAGTGCATACATTTCCTGCTGTGCTGCAG TCTTCTGGACTGTATTCTCTGTCTTCTGTGGTGACAGTGCCTTCTTCTTCTCTGGGAACA AAGACATATACATGTAATGTGGATCATAAGCCTTCTAATACAAAGGTGGATAAGAGAGT ^^^ ^Attorney Docket No.250298.000954 GGAATCTAAGTATGGACCTCCTTGTCCTCCTTGTCCTGCTCCTGGCGGTGGCGGACCT TCTGTGTTTCTGTTTCCTCCTAAGCCTAAGGATACACTGATGATCTCTAGAACACCTGAA GTGACATGTGTGGTGGTGGATGTGTCTCAGGAAGATCCTGAAGTGCAGTTTAATTGGTA TGTGGATGGAGTGGAAGTGCATAATGCTAAGACAAAGCCTAGAGAAGAACAGTTTAATT CTACATATAGAGTGGTGTCTGTGCTGACAGTGCTGCATCAGGATTGGCTGAATGGAAA GGAATATAAGTGTAAGGTGTCTAATAAGGGACTGCCTTCTTCTATCGAAAAGACAATCT CTAAGGCTAAGGGACAGCCTAGAGAACCTCAGGTGTATACACTGCCTCCTTCTCAGGA AGAAATGACAAAGAATCAGGTGTCTCTGACATGTCTGGTGAAGGGATTTTATCCTTCTG ATATCGCTGTGGAATGGGAATCTAATGGACAGCCTGAAAATAATTATAAGACAACACCT CCTGTGCTGGATTCTGATGGATCTTTTTTTCTGTATTCTAGACTGACAGTGGATAAGTCT AGATGGCAGGAAGGAAATGTGTTTTCTTGTTCTGTGATGCATGAAGCTCTGCATAATAG ATTTACACAGAAGTCTCTGTCTCTGTCTCCTGGAAAGTAG (SEQ ID NO: 138) HC Amino Acid Sequence QEQLQQWGAGLLKPSETLSLTCAVHGGSFSGYYWSWIRQPPGKGLEWIGEIYPSGGTNQ NPSLKSRVTISLDMSQNQFSLRLNSVTAADTAVYYCARRNWDGYFDFWGQGIKVTVSSAS TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPGGGGPSVFLFP PKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSC SVMHEALHNRFTQKSLSLSPGK* (SEQ ID NO: 139) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 128) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ ^ ^Attorney Docket No.250298.000954 LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 129) REGN13072 HCVR DNA Sequence CAGGTACACCTGCAGGAGTCGGGCCCAGGACTGGTGATGCCTTCACAGATCCTGTCCC TCTCCTGCGTTATTTCTGGTGACTCCATCAGAAATGGCGGCTATTATTGGACCTGGACC CGCCAGCAACCAGGGAAGGGCCTGGAGTGGATCGGTCACATCCACTATAGTGAAAGG ACCTCCCACAATCCGTCCCTCCAGAGTCGCGTTATTATGTCAATAGACACGTCTGAGAA TAAGTTCTCCCTGAAACTGACCTCAGTGACTGTCGCGGACACGGCCATATATTATTGTG CGCGAGGTCGGGACACCATGGTTCGGGGATCCATTACAACTTCCGGCCACTTCATTGA CTCCTGGGGTCAGGGAGCCCTGGTCACCGTCTCCTCA (SEQ ID NO: 140) HCVR Amino Acid Sequence QVHLQESGPGLVMPSQILSLSCVISGDSIRNGGYYWTWTRQQPGKGLEWIGHIHYSERTSH NPSLQSRVIMSIDTSENKFSLKLTSVTVADTAIYYCARGRDTMVRGSITTSGHFIDSWGQGA LVTVSS (SEQ ID NO: 141) HCDR1 DNA Sequence GGTGACTCCATCAGAAATGGCGGCTATTAT (SEQ ID NO: 142) HCDR1 Amino Acid Sequence GDSIRNGGYY (SEQ ID NO: 143) HCDR2 DNA Sequence ATCCACTATAGTGAAAGGACC (SEQ ID NO: 144) HCDR2 Amino Acid Sequence IHYSERT (SEQ ID NO: 145) HCDR3 DNA Sequence ^ ^Attorney Docket No.250298.000954 GCGCGAGGTCGGGACACCATGGTTCGGGGATCCATTACAACTTCCGGCCACTTCATTG ACTCC (SEQ ID NO: 146) HCDR3 Amino Acid Sequence ARGRDTMVRGSITTSGHFIDS (SEQ ID NO: 147) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 118) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 119) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 120) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 121) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 122) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 123) LCDR3 DNA Sequence ^ ^Attorney Docket No.250298.000954 CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 124) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 125) HC DNA Sequence CAGGTACACCTGCAGGAGTCGGGCCCAGGACTGGTGATGCCTTCACAGATCCTGTCCC TCTCCTGCGTTATTTCTGGTGACTCCATCAGAAATGGCGGCTATTATTGGACCTGGACC CGCCAGCAACCAGGGAAGGGCCTGGAGTGGATCGGTCACATCCACTATAGTGAAAGG ACCTCCCACAATCCGTCCCTCCAGAGTCGCGTTATTATGTCAATAGACACGTCTGAGAA TAAGTTCTCCCTGAAACTGACCTCAGTGACTGTCGCGGACACGGCCATATATTATTGTG CGCGAGGTCGGGACACCATGGTTCGGGGATCCATTACAACTTCCGGCCACTTCATTGA CTCCTGGGGTCAGGGAGCCCTGGTCACCGTCTCCTCAGCCTCTACAAAGGGACCTTCT GTGTTTCCTCTGGCTCCTTGTTCTAGATCTACATCTGAATCTACAGCTGCTCTGGGATGT CTGGTGAAGGATTATTTTCCTGAACCTGTGACAGTGTCTTGGAATTCTGGAGCTCTGAC ATCTGGAGTGCATACATTTCCTGCTGTGCTGCAGTCTTCTGGACTGTATTCTCTGTCTTC TGTGGTGACAGTGCCTTCTTCTTCTCTGGGAACAAAGACATATACATGTAATGTGGATC ATAAGCCTTCTAATACAAAGGTGGATAAGAGAGTGGAATCTAAGTATGGACCTCCTTGT CCTCCTTGTCCTGCTCCTGGCGGTGGCGGACCTTCTGTGTTTCTGTTTCCTCCTAAGCC TAAGGATACACTGATGATCTCTAGAACACCTGAAGTGACATGTGTGGTGGTGGATGTGT CTCAGGAAGATCCTGAAGTGCAGTTTAATTGGTATGTGGATGGAGTGGAAGTGCATAAT GCTAAGACAAAGCCTAGAGAAGAACAGTTTAATTCTACATATAGAGTGGTGTCTGTGCT GACAGTGCTGCATCAGGATTGGCTGAATGGAAAGGAATATAAGTGTAAGGTGTCTAATA AGGGACTGCCTTCTTCTATCGAAAAGACAATCTCTAAGGCTAAGGGACAGCCTAGAGAA CCTCAGGTGTATACACTGCCTCCTTCTCAGGAAGAAATGACAAAGAATCAGGTGTCTCT GACATGTCTGGTGAAGGGATTTTATCCTTCTGATATCGCTGTGGAATGGGAATCTAATG GACAGCCTGAAAATAATTATAAGACAACACCTCCTGTGCTGGATTCTGATGGATCTTTTT TTCTGTATTCTAGACTGACAGTGGATAAGTCTAGATGGCAGGAAGGAAATGTGTTTTCTT GTTCTGTGATGCATGAAGCTCTGCATAATAGATTTACACAGAAGTCTCTGTCTCTGTCTC CTGGAAAGTAG (SEQ ID NO: 148) HC Amino Acid Sequence QVHLQESGPGLVMPSQILSLSCVISGDSIRNGGYYWTWTRQQPGKGLEWIGHIHYSERTSH NPSLQSRVIMSIDTSENKFSLKLTSVTVADTAIYYCARGRDTMVRGSITTSGHFIDSWGQGA LVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPGGG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNRFTQKSLSLSPGK* ^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 149) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 128) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 129) REGN13073 HCVR DNA Sequence CAGGTGCAACTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA CTCTCCTGTGCAGCGTCTGGATTCACCTTCAGTAGCTATGGCATACACTGGGTCCGCC AGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCACTTATATGGTATGATGGAAGTAATAA ATACTATACAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACA CGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAAGACACGGCTGTGTATTACTGTGC GAGAGATAGAGTGCGATCGTATAGCTGGAACTACTTTGACTACTGGGGCCAGGGAACC CTGGTCACCGTCTCCTCA (SEQ ID NO: 150) HCVR Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGIHWVRQAPGKGLEWVALIWYDGSNKY YTDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRVRSYSWNYFDYWGQGTLVT VSS (SEQ ID NO: 151) HCDR1 DNA Sequence GGATTCACCTTCAGTAGCTATGGC ^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 152) HCDR1 Amino Acid Sequence GFTFSSYG (SEQ ID NO: 153) HCDR2 DNA Sequence ATATGGTATGATGGAAGTAATAAA (SEQ ID NO: 154) HCDR2 Amino Acid Sequence IWYDGSNK (SEQ ID NO: 155) HCDR3 DNA Sequence GCGAGAGATAGAGTGCGATCGTATAGCTGGAACTACTTTGACTAC (SEQ ID NO: 156) HCDR3 Amino Acid Sequence ARDRVRSYSWNYFDY (SEQ ID NO: 157) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 118) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 119) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT ^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 120) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 121) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 122) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 123) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 124) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 125) HC DNA Sequence CAGGTGCAACTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGA CTCTCCTGTGCAGCGTCTGGATTCACCTTCAGTAGCTATGGCATACACTGGGTCCGCC AGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCACTTATATGGTATGATGGAAGTAATAA ATACTATACAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACA CGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAAGACACGGCTGTGTATTACTGTGC GAGAGATAGAGTGCGATCGTATAGCTGGAACTACTTTGACTACTGGGGCCAGGGAACC CTGGTCACCGTCTCCTCAGCCTCTACAAAGGGACCTTCTGTGTTTCCTCTGGCTCCTTG TTCTAGATCTACATCTGAATCTACAGCTGCTCTGGGATGTCTGGTGAAGGATTATTTTCC TGAACCTGTGACAGTGTCTTGGAATTCTGGAGCTCTGACATCTGGAGTGCATACATTTC CTGCTGTGCTGCAGTCTTCTGGACTGTATTCTCTGTCTTCTGTGGTGACAGTGCCTTCT TCTTCTCTGGGAACAAAGACATATACATGTAATGTGGATCATAAGCCTTCTAATACAAAG GTGGATAAGAGAGTGGAATCTAAGTATGGACCTCCTTGTCCTCCTTGTCCTGCTCCTGG CGGTGGCGGACCTTCTGTGTTTCTGTTTCCTCCTAAGCCTAAGGATACACTGATGATCT CTAGAACACCTGAAGTGACATGTGTGGTGGTGGATGTGTCTCAGGAAGATCCTGAAGT GCAGTTTAATTGGTATGTGGATGGAGTGGAAGTGCATAATGCTAAGACAAAGCCTAGAG AAGAACAGTTTAATTCTACATATAGAGTGGTGTCTGTGCTGACAGTGCTGCATCAGGAT TGGCTGAATGGAAAGGAATATAAGTGTAAGGTGTCTAATAAGGGACTGCCTTCTTCTAT CGAAAAGACAATCTCTAAGGCTAAGGGACAGCCTAGAGAACCTCAGGTGTATACACTG CCTCCTTCTCAGGAAGAAATGACAAAGAATCAGGTGTCTCTGACATGTCTGGTGAAGGG ^^^^ ^Attorney Docket No.250298.000954 ATTTTATCCTTCTGATATCGCTGTGGAATGGGAATCTAATGGACAGCCTGAAAATAATTA TAAGACAACACCTCCTGTGCTGGATTCTGATGGATCTTTTTTTCTGTATTCTAGACTGAC AGTGGATAAGTCTAGATGGCAGGAAGGAAATGTGTTTTCTTGTTCTGTGATGCATGAAG CTCTGCATAATAGATTTACACAGAAGTCTCTGTCTCTGTCTCCTGGAAAGTAG (SEQ ID NO: 158) HC Amino Acid Sequence QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGIHWVRQAPGKGLEWVALIWYDGSNKY YTDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRVRSYSWNYFDYWGQGTLVT VSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPGGGGPS VFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST YRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNRFTQKSLSLSPGK* (SEQ ID NO: 159) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 128) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 129) REGN13074 HCVR DNA Sequence ^ ^Attorney Docket No.250298.000954 GAGGTGCAGTTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGA CTCTCCTGTGCAGTCTCTGGATTCACCTTTAGCAACTATGCCATGAGTTGGGTCCGCCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGGTTTTAGTGGAAGTGGTGGTAGCAC ATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATACCAAGAAC ACGCTGTATCTGCAAATGAACATCCTGAGAGGCGAGGACACGGCCGTATATTATTGTG CGAAAAATCGGGTACGTGGATATAGTGGCCACCATCTTGACTACTGGGGCCAGGGAAC CCCGGTCACCGTCTCCTCA (SEQ ID NO: 160) HCVR Amino Acid Sequence EVQLLESGGGLVQPGGSLRLSCAVSGFTFSNYAMSWVRQAPGKGLEWVSGFSGSGGSTY YADSVKGRFTISRDNTKNTLYLQMNILRGEDTAVYYCAKNRVRGYSGHHLDYWGQGTPVT VSS (SEQ ID NO: 161) HCDR1 DNA Sequence GGATTCACCTTTAGCAACTATGCC (SEQ ID NO: 162) HCDR1 Amino Acid Sequence GFTFSNYA (SEQ ID NO: 163) HCDR2 DNA Sequence TTTAGTGGAAGTGGTGGTAGCACA (SEQ ID NO: 164) HCDR2 Amino Acid Sequence FSGSGGST (SEQ ID NO: 165) HCDR3 DNA Sequence GCGAAAAATCGGGTACGTGGATATAGTGGCCACCATCTTGACTAC (SEQ ID NO: 166) HCDR3 Amino Acid Sequence AKNRVRGYSGHHLDY (SEQ ID NO: 167) LCVR DNA Sequence ^ ^Attorney Docket No.250298.000954 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 118) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 119) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 120) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 121) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 122) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 123) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 124) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 125) HC DNA Sequence ^ ^Attorney Docket No.250298.000954 GAGGTGCAGTTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGA CTCTCCTGTGCAGTCTCTGGATTCACCTTTAGCAACTATGCCATGAGTTGGGTCCGCCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGGTTTTAGTGGAAGTGGTGGTAGCAC ATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATACCAAGAAC ACGCTGTATCTGCAAATGAACATCCTGAGAGGCGAGGACACGGCCGTATATTATTGTG CGAAAAATCGGGTACGTGGATATAGTGGCCACCATCTTGACTACTGGGGCCAGGGAAC CCCGGTCACCGTCTCCTCAGCCTCTACAAAGGGACCTTCTGTGTTTCCTCTGGCTCCTT GTTCTAGATCTACATCTGAATCTACAGCTGCTCTGGGATGTCTGGTGAAGGATTATTTTC CTGAACCTGTGACAGTGTCTTGGAATTCTGGAGCTCTGACATCTGGAGTGCATACATTT CCTGCTGTGCTGCAGTCTTCTGGACTGTATTCTCTGTCTTCTGTGGTGACAGTGCCTTC TTCTTCTCTGGGAACAAAGACATATACATGTAATGTGGATCATAAGCCTTCTAATACAAA GGTGGATAAGAGAGTGGAATCTAAGTATGGACCTCCTTGTCCTCCTTGTCCTGCTCCTG GCGGTGGCGGACCTTCTGTGTTTCTGTTTCCTCCTAAGCCTAAGGATACACTGATGATC TCTAGAACACCTGAAGTGACATGTGTGGTGGTGGATGTGTCTCAGGAAGATCCTGAAG TGCAGTTTAATTGGTATGTGGATGGAGTGGAAGTGCATAATGCTAAGACAAAGCCTAGA GAAGAACAGTTTAATTCTACATATAGAGTGGTGTCTGTGCTGACAGTGCTGCATCAGGA TTGGCTGAATGGAAAGGAATATAAGTGTAAGGTGTCTAATAAGGGACTGCCTTCTTCTA TCGAAAAGACAATCTCTAAGGCTAAGGGACAGCCTAGAGAACCTCAGGTGTATACACTG CCTCCTTCTCAGGAAGAAATGACAAAGAATCAGGTGTCTCTGACATGTCTGGTGAAGGG ATTTTATCCTTCTGATATCGCTGTGGAATGGGAATCTAATGGACAGCCTGAAAATAATTA TAAGACAACACCTCCTGTGCTGGATTCTGATGGATCTTTTTTTCTGTATTCTAGACTGAC AGTGGATAAGTCTAGATGGCAGGAAGGAAATGTGTTTTCTTGTTCTGTGATGCATGAAG CTCTGCATAATAGATTTACACAGAAGTCTCTGTCTCTGTCTCCTGGAAAGTAG (SEQ ID NO: 168) HC Amino Acid Sequence EVQLLESGGGLVQPGGSLRLSCAVSGFTFSNYAMSWVRQAPGKGLEWVSGFSGSGGSTY YADSVKGRFTISRDNTKNTLYLQMNILRGEDTAVYYCAKNRVRGYSGHHLDYWGQGTPVT VSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPGGGGPS VFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST YRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNRFTQKSLSLSPGK* (SEQ ID NO: 169) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ^^^^ ^Attorney Docket No.250298.000954 ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 128) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 129) REGN13075 HCVR DNA Sequence CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCC CTCTCCTGCACTGTCTCTCGTGGCTCCATCAGCAGTGGTGGTTACTATTGGAGCTGGAT CCGCCAGCACCCAGGGAAGGGCCTGGAGTGGATTGGATACATCCATTATAGTGAGAG GACCTACTACAACCCGTCCCTCAAGAGTCGAGTTACCATGTCAGTTGACACGTCTAAGA ACCAGTTCTCCCTGAAGCTGACCTCTGTGACTGCCGCGGACACGGCCGTGTATTATTG TGCGAGAGATCGGGACACCATGGTTCGGGGAGTCATTACAACTTCCGGCCACTTCATT GACGACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA (SEQ ID NO: 170) HCVR Amino Acid Sequence QVQLQESGPGLVKPSQTLSLSCTVSRGSISSGGYYWSWIRQHPGKGLEWIGYIHYSERTYY NPSLKSRVTMSVDTSKNQFSLKLTSVTAADTAVYYCARDRDTMVRGVITTSGHFIDDWGQ GTLVTVSS (SEQ ID NO: 171) HCDR1 DNA Sequence CGTGGCTCCATCAGCAGTGGTGGTTACTAT (SEQ ID NO: 172) HCDR1 Amino Acid Sequence RGSISSGGYY (SEQ ID NO: 173) HCDR2 DNA Sequence ATCCATTATAGTGAGAGGACC ^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 174) HCDR2 Amino Acid Sequence IHYSERT (SEQ ID NO: 145) HCDR3 DNA Sequence GCGAGAGATCGGGACACCATGGTTCGGGGAGTCATTACAACTTCCGGCCACTTCATTG ACGAC (SEQ ID NO: 175) HCDR3 Amino Acid Sequence ARDRDTMVRGVITTSGHFIDD (SEQ ID NO: 176) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 118) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 119) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 120) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 121) LCDR2 DNA Sequence GCTGCATCC ^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 122) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 123) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 124) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 125) HC DNA Sequence CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCC CTCTCCTGCACTGTCTCTCGTGGCTCCATCAGCAGTGGTGGTTACTATTGGAGCTGGAT CCGCCAGCACCCAGGGAAGGGCCTGGAGTGGATTGGATACATCCATTATAGTGAGAG GACCTACTACAACCCGTCCCTCAAGAGTCGAGTTACCATGTCAGTTGACACGTCTAAGA ACCAGTTCTCCCTGAAGCTGACCTCTGTGACTGCCGCGGACACGGCCGTGTATTATTG TGCGAGAGATCGGGACACCATGGTTCGGGGAGTCATTACAACTTCCGGCCACTTCATT GACGACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGCCTCTACAAAGGGACCTT CTGTGTTTCCTCTGGCTCCTTGTTCTAGATCTACATCTGAATCTACAGCTGCTCTGGGAT GTCTGGTGAAGGATTATTTTCCTGAACCTGTGACAGTGTCTTGGAATTCTGGAGCTCTG ACATCTGGAGTGCATACATTTCCTGCTGTGCTGCAGTCTTCTGGACTGTATTCTCTGTCT TCTGTGGTGACAGTGCCTTCTTCTTCTCTGGGAACAAAGACATATACATGTAATGTGGA TCATAAGCCTTCTAATACAAAGGTGGATAAGAGAGTGGAATCTAAGTATGGACCTCCTT GTCCTCCTTGTCCTGCTCCTGGCGGTGGCGGACCTTCTGTGTTTCTGTTTCCTCCTAAG CCTAAGGATACACTGATGATCTCTAGAACACCTGAAGTGACATGTGTGGTGGTGGATGT GTCTCAGGAAGATCCTGAAGTGCAGTTTAATTGGTATGTGGATGGAGTGGAAGTGCATA ATGCTAAGACAAAGCCTAGAGAAGAACAGTTTAATTCTACATATAGAGTGGTGTCTGTG CTGACAGTGCTGCATCAGGATTGGCTGAATGGAAAGGAATATAAGTGTAAGGTGTCTAA TAAGGGACTGCCTTCTTCTATCGAAAAGACAATCTCTAAGGCTAAGGGACAGCCTAGAG AACCTCAGGTGTATACACTGCCTCCTTCTCAGGAAGAAATGACAAAGAATCAGGTGTCT CTGACATGTCTGGTGAAGGGATTTTATCCTTCTGATATCGCTGTGGAATGGGAATCTAA TGGACAGCCTGAAAATAATTATAAGACAACACCTCCTGTGCTGGATTCTGATGGATCTTT TTTTCTGTATTCTAGACTGACAGTGGATAAGTCTAGATGGCAGGAAGGAAATGTGTTTTC TTGTTCTGTGATGCATGAAGCTCTGCATAATAGATTTACACAGAAGTCTCTGTCTCTGTC TCCTGGAAAGTAG (SEQ ID NO: 177) HC Amino Acid Sequence ^ ^Attorney Docket No.250298.000954 QVQLQESGPGLVKPSQTLSLSCTVSRGSISSGGYYWSWIRQHPGKGLEWIGYIHYSERTYY NPSLKSRVTMSVDTSKNQFSLKLTSVTAADTAVYYCARDRDTMVRGVITTSGHFIDDWGQ GTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPG GGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREE QFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSR WQEGNVFSCSVMHEALHNRFTQKSLSLSPGK* (SEQ ID NO: 178) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 128) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 129) REGN13076 HCVR DNA Sequence GAGGTGCACTTATTGGACTCTGGCGGAGGCTTGGTTCAGTCGGGGGAGTCCCTGAGA CTCTCCTGTACAGTCTCTGGAGTCACTTTTGAAAACCTTGTCATGAACTGGGTCCGGCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCGCAAGTGTTGGAGGTCGTTATACTGGCGC GGTCTTCGCAGACTCAGTGAGGGGCCGGTTCACGATCTCCAGAGACCATTCCGAGAAT ACGCTCTTTCTGCACATGAGCAGCCTGAGAGCCGAGGACACGGCCGTTTATTTTTGTAC GAAAGATTCCTCTGTCCTGATTCGGGGAGTCATTAGTACAAACTACTTCTATAGTATGGA CGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 179) ^ ^Attorney Docket No.250298.000954 HCVR Amino Acid Sequence EVHLLDSGGGLVQSGESLRLSCTVSGVTFENLVMNWVRQAPGKGLEWVASVGGRYTGAV FADSVRGRFTISRDHSENTLFLHMSSLRAEDTAVYFCTKDSSVLIRGVISTNYFYSMDVWG QGTTVTVSS (SEQ ID NO: 180) HCDR1 DNA Sequence GGAGTCACTTTTGAAAACCTTGTC (SEQ ID NO: 181) HCDR1 Amino Acid Sequence GVTFENLV (SEQ ID NO: 182) HCDR2 DNA Sequence GTTGGAGGTCGTTATACTGGCGCG (SEQ ID NO: 183) HCDR2 Amino Acid Sequence VGGRYTGA (SEQ ID NO: 184) HCDR3 DNA Sequence ACGAAAGATTCCTCTGTCCTGATTCGGGGAGTCATTAGTACAAACTACTTCTATAGTATG GACGTC (SEQ ID NO: 185) HCDR3 Amino Acid Sequence TKDSSVLIRGVISTNYFYSMDV (SEQ ID NO: 186) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA ^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 118) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 119) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 120) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 121) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 122) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 123) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 124) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 125) HC DNA Sequence GAGGTGCACTTATTGGACTCTGGCGGAGGCTTGGTTCAGTCGGGGGAGTCCCTGAGA CTCTCCTGTACAGTCTCTGGAGTCACTTTTGAAAACCTTGTCATGAACTGGGTCCGGCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCGCAAGTGTTGGAGGTCGTTATACTGGCGC GGTCTTCGCAGACTCAGTGAGGGGCCGGTTCACGATCTCCAGAGACCATTCCGAGAAT ACGCTCTTTCTGCACATGAGCAGCCTGAGAGCCGAGGACACGGCCGTTTATTTTTGTAC GAAAGATTCCTCTGTCCTGATTCGGGGAGTCATTAGTACAAACTACTTCTATAGTATGGA CGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCTACAAAGGGACCTTCT GTGTTTCCTCTGGCTCCTTGTTCTAGATCTACATCTGAATCTACAGCTGCTCTGGGATGT ^^^^ ^Attorney Docket No.250298.000954 CTGGTGAAGGATTATTTTCCTGAACCTGTGACAGTGTCTTGGAATTCTGGAGCTCTGAC ATCTGGAGTGCATACATTTCCTGCTGTGCTGCAGTCTTCTGGACTGTATTCTCTGTCTTC TGTGGTGACAGTGCCTTCTTCTTCTCTGGGAACAAAGACATATACATGTAATGTGGATC ATAAGCCTTCTAATACAAAGGTGGATAAGAGAGTGGAATCTAAGTATGGACCTCCTTGT CCTCCTTGTCCTGCTCCTGGCGGTGGCGGACCTTCTGTGTTTCTGTTTCCTCCTAAGCC TAAGGATACACTGATGATCTCTAGAACACCTGAAGTGACATGTGTGGTGGTGGATGTGT CTCAGGAAGATCCTGAAGTGCAGTTTAATTGGTATGTGGATGGAGTGGAAGTGCATAAT GCTAAGACAAAGCCTAGAGAAGAACAGTTTAATTCTACATATAGAGTGGTGTCTGTGCT GACAGTGCTGCATCAGGATTGGCTGAATGGAAAGGAATATAAGTGTAAGGTGTCTAATA AGGGACTGCCTTCTTCTATCGAAAAGACAATCTCTAAGGCTAAGGGACAGCCTAGAGAA CCTCAGGTGTATACACTGCCTCCTTCTCAGGAAGAAATGACAAAGAATCAGGTGTCTCT GACATGTCTGGTGAAGGGATTTTATCCTTCTGATATCGCTGTGGAATGGGAATCTAATG GACAGCCTGAAAATAATTATAAGACAACACCTCCTGTGCTGGATTCTGATGGATCTTTTT TTCTGTATTCTAGACTGACAGTGGATAAGTCTAGATGGCAGGAAGGAAATGTGTTTTCTT GTTCTGTGATGCATGAAGCTCTGCATAATAGATTTACACAGAAGTCTCTGTCTCTGTCTC CTGGAAAGTAG (SEQ ID NO: 187) HC Amino Acid Sequence EVHLLDSGGGLVQSGESLRLSCTVSGVTFENLVMNWVRQAPGKGLEWVASVGGRYTGAV FADSVRGRFTISRDHSENTLFLHMSSLRAEDTAVYFCTKDSSVLIRGVISTNYFYSMDVWG QGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHT FPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPG GGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREE QFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSR WQEGNVFSCSVMHEALHNRFTQKSLSLSPGK* (SEQ ID NO: 188) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 128) ^ ^Attorney Docket No.250298.000954 LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 129) REGN13220 HCVR DNA Sequence CAGGTGCACCTGCAAGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCC CTCTCCTGCACTGTCTCTGGTGATTCCATCAGAAGTGGTGGTTACTACTGGAGTTGGAT CCGCCAGCAGCCAGGAAGGGGCCTGGAATGGATTGGTTTCATCCATCAGAGTGACAG GTCCTACTATAACCCGTCCCTCATGAATCGACTCACCATGTCAGTAGACACGTCTAAGA ATCAATTCTCCCTGAAACTGACCTCTGTGACTGCCGCGGACACGGCCGTGTATTACTGT GCGAGAGATCGGGACACCATGGTTCGGGGAAGCATTACAACTTCCGGCCACTTCATTG ACTACTGGGGCCAGGGAACCCTGATCACCGTCTCCTCA (SEQ ID NO: 189) HCVR Amino Acid Sequence QVHLQESGPGLVKPSQTLSLSCTVSGDSIRSGGYYWSWIRQQPGRGLEWIGFIHQSDRSY YNPSLMNRLTMSVDTSKNQFSLKLTSVTAADTAVYYCARDRDTMVRGSITTSGHFIDYWGQ GTLITVSS (SEQ ID NO: 190) HCDR1 DNA Sequence GGTGATTCCATCAGAAGTGGTGGTTACTAC (SEQ ID NO: 191) HCDR1 Amino Acid Sequence GDSIRSGGYY (SEQ ID NO: 192) HCDR2 DNA Sequence ATCCATCAGAGTGACAGGTCC (SEQ ID NO: 193) HCDR2 Amino Acid Sequence IHQSDRS (SEQ ID NO: 194) ^ ^Attorney Docket No.250298.000954 HCDR3 DNA Sequence GCGAGAGATCGGGACACCATGGTTCGGGGAAGCATTACAACTTCCGGCCACTTCATTG ACTAC (SEQ ID NO: 195) HCDR3 Amino Acid Sequence ARDRDTMVRGSITTSGHFIDY (SEQ ID NO: 196) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 118) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 119) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 120) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 121) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 122) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 123) ^ ^Attorney Docket No.250298.000954 LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 124) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 125) HC DNA Sequence CAGGTGCACCTGCAAGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCC CTCTCCTGCACTGTCTCTGGTGATTCCATCAGAAGTGGTGGTTACTACTGGAGTTGGAT CCGCCAGCAGCCAGGAAGGGGCCTGGAATGGATTGGTTTCATCCATCAGAGTGACAG GTCCTACTATAACCCGTCCCTCATGAATCGACTCACCATGTCAGTAGACACGTCTAAGA ATCAATTCTCCCTGAAACTGACCTCTGTGACTGCCGCGGACACGGCCGTGTATTACTGT GCGAGAGATCGGGACACCATGGTTCGGGGAAGCATTACAACTTCCGGCCACTTCATTG ACTACTGGGGCCAGGGAACCCTGATCACCGTCTCCTCAGCCTCTACAAAGGGACCTTC TGTGTTTCCTCTGGCTCCTTGTTCTAGATCTACATCTGAATCTACAGCTGCTCTGGGATG TCTGGTGAAGGATTATTTTCCTGAACCTGTGACAGTGTCTTGGAATTCTGGAGCTCTGA CATCTGGAGTGCATACATTTCCTGCTGTGCTGCAGTCTTCTGGACTGTATTCTCTGTCTT CTGTGGTGACAGTGCCTTCTTCTTCTCTGGGAACAAAGACATATACATGTAATGTGGAT CATAAGCCTTCTAATACAAAGGTGGATAAGAGAGTGGAATCTAAGTATGGACCTCCTTG TCCTCCTTGTCCTGCTCCTGGCGGTGGCGGACCTTCTGTGTTTCTGTTTCCTCCTAAGC CTAAGGATACACTGATGATCTCTAGAACACCTGAAGTGACATGTGTGGTGGTGGATGTG TCTCAGGAAGATCCTGAAGTGCAGTTTAATTGGTATGTGGATGGAGTGGAAGTGCATAA TGCTAAGACAAAGCCTAGAGAAGAACAGTTTAATTCTACATATAGAGTGGTGTCTGTGC TGACAGTGCTGCATCAGGATTGGCTGAATGGAAAGGAATATAAGTGTAAGGTGTCTAAT AAGGGACTGCCTTCTTCTATCGAAAAGACAATCTCTAAGGCTAAGGGACAGCCTAGAGA ACCTCAGGTGTATACACTGCCTCCTTCTCAGGAAGAAATGACAAAGAATCAGGTGTCTC TGACATGTCTGGTGAAGGGATTTTATCCTTCTGATATCGCTGTGGAATGGGAATCTAAT GGACAGCCTGAAAATAATTATAAGACAACACCTCCTGTGCTGGATTCTGATGGATCTTTT TTTCTGTATTCTAGACTGACAGTGGATAAGTCTAGATGGCAGGAAGGAAATGTGTTTTCT TGTTCTGTGATGCATGAAGCTCTGCATAATAGATTTACACAGAAGTCTCTGTCTCTGTCT CCTGGAAAGTAG (SEQ ID NO: 197) HC Amino Acid Sequence QVHLQESGPGLVKPSQTLSLSCTVSGDSIRSGGYYWSWIRQQPGRGLEWIGFIHQSDRSY YNPSLMNRLTMSVDTSKNQFSLKLTSVTAADTAVYYCARDRDTMVRGSITTSGHFIDYWGQ GTLITVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP AVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPGG GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQE ^ ^Attorney Docket No.250298.000954 EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSR WQEGNVFSCSVMHEALHNRFTQKSLSLSPGK* (SEQ ID NO: 198) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 128) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 129) REGN13221 HCVR DNA Sequence CAGGTGCAGCTGCAGGAGTCGGGCCCAGTACTGGTGAAGCCTTCGGAGACCCTGTCC CTCACCTGCACTGTCTCTGGTGACTCCATCAGTAATTACTACTGGAGCTGGATCCGGCA GTCCCCAGGGAAGGGACTGGAGTGGATTGGGTATATCTATTACAGTGGCGGCACCAAC TACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAATAGACACGTCCAAGCGCCACTT CTCCCTGAAGCTGAACTCTGTGATCGCAGCGGACACGGCCGTATATTACTGTGCGAGA GCCCCTGTCACCATGGTTCGGGGAGTCATTACTTACAACTACCACTACGCTATGGACGT CTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA (SEQ ID NO: 199) HCVR Amino Acid Sequence QVQLQESGPVLVKPSETLSLTCTVSGDSISNYYWSWIRQSPGKGLEWIGYIYYSGGTNYNP SLKSRVTISIDTSKRHFSLKLNSVIAADTAVYYCARAPVTMVRGVITYNYHYAMDVWGQGTT VTVSS (SEQ ID NO: 200) ^ ^Attorney Docket No.250298.000954 HCDR1 DNA Sequence GGTGACTCCATCAGTAATTACTAC (SEQ ID NO: 201) HCDR1 Amino Acid Sequence GDSISNYY (SEQ ID NO: 202) HCDR2 DNA Sequence ATCTATTACAGTGGCGGCACC (SEQ ID NO: 203) HCDR2 Amino Acid Sequence IYYSGGT (SEQ ID NO: 204) HCDR3 DNA Sequence GCGAGAGCCCCTGTCACCATGGTTCGGGGAGTCATTACTTACAACTACCACTACGCTAT GGACGTC (SEQ ID NO: 205) HCDR3 Amino Acid Sequence ARAPVTMVRGVITYNYHYAMDV (SEQ ID NO: 206) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 118) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 119) ^ ^Attorney Docket No.250298.000954 LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 120) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 121) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 122) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 123) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 124) LCDR3 Amino Acid Sequence QQSYSTPPIT (SEQ ID NO: 125) HC DNA Sequence CAGGTGCAGCTGCAGGAGTCGGGCCCAGTACTGGTGAAGCCTTCGGAGACCCTGTCC CTCACCTGCACTGTCTCTGGTGACTCCATCAGTAATTACTACTGGAGCTGGATCCGGCA GTCCCCAGGGAAGGGACTGGAGTGGATTGGGTATATCTATTACAGTGGCGGCACCAAC TACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAATAGACACGTCCAAGCGCCACTT CTCCCTGAAGCTGAACTCTGTGATCGCAGCGGACACGGCCGTATATTACTGTGCGAGA GCCCCTGTCACCATGGTTCGGGGAGTCATTACTTACAACTACCACTACGCTATGGACGT CTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCCTCTACAAAGGGACCTTCTGTG TTTCCTCTGGCTCCTTGTTCTAGATCTACATCTGAATCTACAGCTGCTCTGGGATGTCTG GTGAAGGATTATTTTCCTGAACCTGTGACAGTGTCTTGGAATTCTGGAGCTCTGACATC TGGAGTGCATACATTTCCTGCTGTGCTGCAGTCTTCTGGACTGTATTCTCTGTCTTCTGT GGTGACAGTGCCTTCTTCTTCTCTGGGAACAAAGACATATACATGTAATGTGGATCATA AGCCTTCTAATACAAAGGTGGATAAGAGAGTGGAATCTAAGTATGGACCTCCTTGTCCT CCTTGTCCTGCTCCTGGCGGTGGCGGACCTTCTGTGTTTCTGTTTCCTCCTAAGCCTAA GGATACACTGATGATCTCTAGAACACCTGAAGTGACATGTGTGGTGGTGGATGTGTCTC AGGAAGATCCTGAAGTGCAGTTTAATTGGTATGTGGATGGAGTGGAAGTGCATAATGCT ^^^^ ^Attorney Docket No.250298.000954 AAGACAAAGCCTAGAGAAGAACAGTTTAATTCTACATATAGAGTGGTGTCTGTGCTGAC AGTGCTGCATCAGGATTGGCTGAATGGAAAGGAATATAAGTGTAAGGTGTCTAATAAGG GACTGCCTTCTTCTATCGAAAAGACAATCTCTAAGGCTAAGGGACAGCCTAGAGAACCT CAGGTGTATACACTGCCTCCTTCTCAGGAAGAAATGACAAAGAATCAGGTGTCTCTGAC ATGTCTGGTGAAGGGATTTTATCCTTCTGATATCGCTGTGGAATGGGAATCTAATGGAC AGCCTGAAAATAATTATAAGACAACACCTCCTGTGCTGGATTCTGATGGATCTTTTTTTC TGTATTCTAGACTGACAGTGGATAAGTCTAGATGGCAGGAAGGAAATGTGTTTTCTTGT TCTGTGATGCATGAAGCTCTGCATAATAGATTTACACAGAAGTCTCTGTCTCTGTCTCCT GGAAAGTAG (SEQ ID NO: 207) HC Amino Acid Sequence QVQLQESGPVLVKPSETLSLTCTVSGDSISNYYWSWIRQSPGKGLEWIGYIYYSGGTNYNP SLKSRVTISIDTSKRHFSLKLNSVIAADTAVYYCARAPVTMVRGVITYNYHYAMDVWGQGTT VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPGGGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEM TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ EGNVFSCSVMHEALHNRFTQKSLSLSPGK* (SEQ ID NO: 208) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 128) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 129) ^ ^Attorney Docket No.250298.000954 REGN13284 HCVR DNA Sequence GAGGTGCAACTGGTGGAATCTGGAGGAGGCTTGGTCCAGCCTGGGGGTTCCCTGAGA CTCTCCTGTGCAGCCTCTGGGTTCATCGTCAGTAACAACTATATGAGATGGGTCCGCCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCTCGGTCATTTATAGTGGTGGTGGCACATA CTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGACACAATTCCAAGAACACG ATATATCTTCAAATGAACAGCCTGCGAATTGAGGACACGGCCGTGTATTATTGTGCGAG AGAAGATAGCCACTCGTCGGAAAGTTATGACTACTTCTACGGCATGGACGTCTGGGGC CAAGGGACCACGGTCACCGTCTCCCCA (SEQ ID NO: 209) HCVR Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFIVSNNYMRWVRQAPGKGLEWVSVIYSGGGTYY ADSVKGRFTISRHNSKNTIYLQMNSLRIEDTAVYYCAREDSHSSESYDYFYGMDVWGQGTT VTVSP (SEQ ID NO: 210) HCDR1 DNA Sequence GGGTTCATCGTCAGTAACAACTAT (SEQ ID NO: 211) HCDR1 Amino Acid Sequence GFIVSNNY (SEQ ID NO: 212) HCDR2 DNA Sequence ATTTATAGTGGTGGTGGCACA (SEQ ID NO: 213) HCDR2 Amino Acid Sequence IYSGGGT (SEQ ID NO: 214) HCDR3 DNA Sequence GCGAGAGAAGATAGCCACTCGTCGGAAAGTTATGACTACTTCTACGGCATGGACGTC (SEQ ID NO: 215) HCDR3 Amino Acid Sequence ^ ^Attorney Docket No.250298.000954 AREDSHSSESYDYFYGMDV (SEQ ID NO: 216) LCVR DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAA (SEQ ID NO: 118) LCVR Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIK (SEQ ID NO: 119) LCDR1 DNA Sequence CAGAGCATTAGCAGCTAT (SEQ ID NO: 120) LCDR1 Amino Acid Sequence QSISSY (SEQ ID NO: 121) LCDR2 DNA Sequence GCTGCATCC (SEQ ID NO: 122) LCDR2 Amino Acid Sequence AAS (SEQ ID NO: 123) LCDR3 DNA Sequence CAACAGAGTTACAGTACCCCTCCGATCACC (SEQ ID NO: 124) LCDR3 Amino Acid Sequence QQSYSTPPIT ^ ^Attorney Docket No.250298.000954 (SEQ ID NO: 125) HC DNA Sequence GAGGTGCAACTGGTGGAATCTGGAGGAGGCTTGGTCCAGCCTGGGGGTTCCCTGAGA CTCTCCTGTGCAGCCTCTGGGTTCATCGTCAGTAACAACTATATGAGATGGGTCCGCCA GGCTCCAGGGAAGGGGCTGGAGTGGGTCTCGGTCATTTATAGTGGTGGTGGCACATA CTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGACACAATTCCAAGAACACG ATATATCTTCAAATGAACAGCCTGCGAATTGAGGACACGGCCGTGTATTATTGTGCGAG AGAAGATAGCCACTCGTCGGAAAGTTATGACTACTTCTACGGCATGGACGTCTGGGGC CAAGGGACCACGGTCACCGTCTCCCCAGCCTCTACAAAGGGACCTTCTGTGTTTCCTC TGGCTCCTTGTTCTAGATCTACATCTGAATCTACAGCTGCTCTGGGATGTCTGGTGAAG GATTATTTTCCTGAACCTGTGACAGTGTCTTGGAATTCTGGAGCTCTGACATCTGGAGT GCATACATTTCCTGCTGTGCTGCAGTCTTCTGGACTGTATTCTCTGTCTTCTGTGGTGA CAGTGCCTTCTTCTTCTCTGGGAACAAAGACATATACATGTAATGTGGATCATAAGCCTT CTAATACAAAGGTGGATAAGAGAGTGGAATCTAAGTATGGACCTCCTTGTCCTCCTTGT CCTGCTCCTGGCGGTGGCGGACCTTCTGTGTTTCTGTTTCCTCCTAAGCCTAAGGATAC ACTGATGATCTCTAGAACACCTGAAGTGACATGTGTGGTGGTGGATGTGTCTCAGGAA GATCCTGAAGTGCAGTTTAATTGGTATGTGGATGGAGTGGAAGTGCATAATGCTAAGAC AAAGCCTAGAGAAGAACAGTTTAATTCTACATATAGAGTGGTGTCTGTGCTGACAGTGC TGCATCAGGATTGGCTGAATGGAAAGGAATATAAGTGTAAGGTGTCTAATAAGGGACTG CCTTCTTCTATCGAAAAGACAATCTCTAAGGCTAAGGGACAGCCTAGAGAACCTCAGGT GTATACACTGCCTCCTTCTCAGGAAGAAATGACAAAGAATCAGGTGTCTCTGACATGTC TGGTGAAGGGATTTTATCCTTCTGATATCGCTGTGGAATGGGAATCTAATGGACAGCCT GAAAATAATTATAAGACAACACCTCCTGTGCTGGATTCTGATGGATCTTTTTTTCTGTATT CTAGACTGACAGTGGATAAGTCTAGATGGCAGGAAGGAAATGTGTTTTCTTGTTCTGTG ATGCATGAAGCTCTGCATAATAGATTTACACAGAAGTCTCTGTCTCTGTCTCCTGGAAA GTAG (SEQ ID NO: 217) HC Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFIVSNNYMRWVRQAPGKGLEWVSVIYSGGGTYY ADSVKGRFTISRHNSKNTIYLQMNSLRIEDTAVYYCAREDSHSSESYDYFYGMDVWGQGTT VTVSPASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPGGGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEM TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ EGNVFSCSVMHEALHNRFTQKSLSLSPGK* (SEQ ID NO: 218) LC DNA Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCA CCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAA CCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCC ^^^^ ^Attorney Docket No.250298.000954 CGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCT GCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCCTCCGATCA CCTTCGGCCAAGGGACACGACTGGAGATTAAACGAACTGTGGCTGCACCATCTGTCTT CATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGC TGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCA ATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGA GAGTGTTAG (SEQ ID NO: 128) LC Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGQGTRLEIKRTVAAPSVFIFPPSDEQ LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYEKHKVYACEVTHQGLSSPVTKSFNRGEC* (SEQ ID NO: 129)

[0362] Provided herein are anti-AAV antibodies, or antigen-binding fragments thereof, comprising an HCVR comprising an amino acid sequence selected from any of the HCVR amino acid sequences listed in Table 1, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity thereto.

[0363] Also provided herein are anti-AAV antibodies, or antigen-binding fragments thereof, comprising an LCVR comprising an amino acid sequence selected from any of the LCVR amino acid sequences listed in Table 1, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity thereto.

[0364] Provided herein are anti-AAV antibodies, or antigen-binding fragments thereof, comprising an HCVR and an LCVR amino acid sequence pair (HCVR / LCVR) comprising any of the HCVR amino acid sequences listed in Table 1 paired with any of the LCVR amino acid sequences listed in Table 1. According to certain embodiments, the present disclosure provides antibodies, or antigen-binding fragments thereof, comprising an HCVR / LCVR amino acid sequence pair contained within any of the exemplary anti-AAV antibodies listed in Table 1. In certain embodiments, the HCVR / LCVR amino acid sequence pair is selected from SEQ ID NOs: 2 / 10 (e.g., REGN13876); 22 / 10 (e.g., REGN13877); 32 / 10 (e.g., REGN13878); 42 / 10 (e.g., REGN13879); 52 or 1159 / 10 or 1157 (e.g., REGN13880); 62 / 10 (e.g., REGN13881); 71 / 10 (e.g., REGN13882); 81 / 10 (e.g., REGN13883); 91 / 10 (e.g., REGN13884); 101 / 10 (e.g., REGN13885); 111 / 119 (e.g., REGN13070); 131 / 119 (e.g., REGN13071); 141 / 119 (e.g., REGN13072); 151 / 119 (e.g., REGN13073); 161 / 119 (e.g., ^ ^Attorney Docket No.250298.000954 REGN13074); 171 / 119 (e.g., REGN13075); 180 / 119 (e.g., REGN13076); 190 / 119 (e.g., REGN13220); 200 / 119 (e.g., REGN13221); and, 210 / 119 (e.g., REGN13284).

[0365] Provided herein are anti-AAV antibodies, or antigen-binding fragments thereof, comprising a heavy chain CDR1 (HCDR1) comprising an amino acid sequence selected from any of the HCDR1 amino acid sequences listed in Table 1 or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity.

[0366] Provided herein are anti-AAV antibodies, or antigen-binding fragments thereof, comprising a heavy chain CDR2 (HCDR2) comprising an amino acid sequence selected from any of the HCDR2 amino acid sequences listed in Table 1 or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity.

[0367] Provided herein are anti-AAV antibodies, or antigen-binding fragments thereof, comprising a heavy chain CDR3 (HCDR3) comprising an amino acid sequence selected from any of the HCDR3 amino acid sequences listed in Table 1 or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity.

[0368] Provided herein are anti-AAV antibodies, or antigen-binding fragments thereof, comprising a light chain CDR1 (LCDR1) comprising an amino acid sequence selected from any of the LCDR1 amino acid sequences listed in Table 1 or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity.

[0369] Provided herein are anti- AAV antibodies, or antigen-binding fragments thereof, comprising a light chain CDR2 (LCDR2) comprising an amino acid sequence selected from any of the LCDR2 amino acid sequences listed in Table 1 or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity.

[0370] Provided herein are anti-AAV antibodies, or antigen-binding fragments thereof, comprising a light chain CDR3 (LCDR3) comprising an amino acid sequence selected from any of the LCDR3 amino acid sequences listed in Table 1 or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity.

[0371] In some embodiments, the anti-AAV antibodies, or antigen-binding fragments thereof, described herein comprise the amino acid sequence set forth in SEQ ID NOs: 18, 198, 30, 208, 40, 127, 50, 169, 60, 1108, 1363, 1366, 149, 1362, 1379, 69, 178, 79, 1391, 1396, 188, 1390, 89, 139, 99, 159, 109, or 218, or a variant thereof having at least 40%, ^ ^Attorney Docket No.250298.000954 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NOs: 18, 198, 30, 208, 40, 127, 50, 169, 60, 1108, 1363, 1366, 149, 1362, 1379, 69, 178, 79, 1391, 1396, 188, 1390, 89, 139, 99, 159, 109, or 218. In certain embodiments, the nucleotide sequence that encodes the anti- AAV antibodies, or antigen-binding fragments thereof, comprises the nucleotide sequence that encodes the amino acid sequence of SEQ ID NOs: 18, 198, 30, 208, 40, 127, 50, 169, 60, 1108, 1363, 1366, 149, 1362, 1379, 69, 178, 79, 1391, 1396, 188, 1390, 89, 139, 99, 159, 109, or 218, or a variant thereof having at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NOs: 18, 198, 30, 208, 40, 127, 50, 169, 60, 1108, 1363, 1366, 149, 1362, 1379, 69, 178, 79, 1391, 1396, 188, 1390, 89, 139, 99, 159, 109, or 218. In certain embodiments, the nucleotide sequence that encodes the anti-AAV antibodies, or antigen-binding fragments thereof, comprises the nucleotide sequence set forth in SEQ ID NOs: 17, 197, 29, 207, 39, 126, 49, 168, 59, 1107, 148, 1378, 68, 177, 78, 187, 1389, 88, 138, 98, 158, 108, or 217, or a nucleotide sequence having at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% sequence identity with the nucleotide sequence of SEQ ID NOs: 17, 197, 29, 207, 39, 126, 49, 168, 59, 1107, 148, 1378, 68, 177, 78, 187, 1389, 88, 138, 98, 158, 108, or 217. In certain embodiments, the anti-AAV antibodies, or antigen- binding fragments thereof, comprise the amino acid sequence set forth in SEQ ID NOs: 18, 198, 30, 208, 40, 127, 50, 169, 60, 1108, 1363, 1366, 149, 1362, 1379, 69, 178, 79, 1391, 1396, 188, 1390, 89, 139, 99, 159, 109, or 218. In certain embodiments, the nucleotide sequence that encodes the anti-AAV antibodies, or antigen-binding fragments thereof, comprises the nucleotide sequence set forth in SEQ ID NOs: 17, 197, 29, 207, 39, 126, 49, 168, 59, 1107, 148, 1378, 68, 177, 78, 187, 1389, 88, 138, 98, 158, 108, or 217.

[0372] In some embodiments, the anti-AAV antibodies, or antigen-binding fragments thereof, described herein comprise the amino acid sequence set forth in SEQ ID NOs: 20, 129, or 813, or a variant thereof having at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NOs: 20, 129, or 813. In certain embodiments, the nucleotide sequence that encodes the anti-AAV antibodies, or antigen-binding fragments thereof, comprises the nucleotide sequence that encodes the amino acid sequence of SEQ ID NOs: 20, 129, or 813, or a variant thereof having at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% sequence identity with the amino acid sequence of SEQ ID NOs: 20, 129, or 813. In certain embodiments, the nucleotide sequence that encodes the anti-AAV antibodies, or antigen-binding fragments thereof, comprises the nucleotide sequence set forth in SEQ ID NOs: 19, 128, 1145, or 1500, or a nucleotide sequence having ^ ^Attorney Docket No.250298.000954 at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% sequence identity with the nucleotide sequence of SEQ ID NOs: 19, 128, 1145, or 1500. In certain embodiments, the anti-AAV antibodies, or antigen-binding fragments thereof, comprise the amino acid sequence set forth in SEQ ID NOs: 20, 129, or 813. In certain embodiments, the nucleotide sequence that encodes the anti-AAV antibodies, or antigen-binding fragments thereof, comprises the nucleotide sequence set forth in SEQ ID NOs: 19, 128, 1145, or 1500.

[0373] Provided herein are antibodies, or antigen-binding fragments thereof, comprising a set of six CDRs (i.e., HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3) contained within any of the exemplary anti-AAV antibodies listed in Table 1. In certain embodiments, the HCDR1- HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 amino acid sequences set is selected from SEQ ID NOs: 4-6-8-12-14-16 (e.g., REGN13876); 24-26-28-12-14-16 (e.g.-REGN13877); 34-36-38- 12-14-16 (e.g., REGN13878); 44-46-48-12-14-16 (e.g., REGN13879; 54-56-58-12-14-16 (e.g., REGN13880); 64-56-67-12-14-16 (e.g., REGN13881); 73-75-77-12-14-16 (e.g., REGN13882); 83-85-87-12-14-16 (e.g., REGN13883); 93-95-97-12-14-16 (e.g.- REGN13884); 103-105-107-12-14-16 (e.g., REGN13885); 113-115-117-121-123-125 (e.g.- REGN13070); 133-135-137-121-123-125 (e.g., REGN13071); 143-145-147-121-123-125 (e.g.-REGN13072); 153-155-157-121-123-125 (e.g., REGN13073); 163-165-167-121-123- 125 (e.g.-REGN13074); 173-145-176-121-123-125 (e.g., REGN13075); 182-184-186-121- 123-125 (e.g.-REGN13076); 192-194-196-121-123-125 (e.g., REGN13220); 202-204-206- 121-123-125 (e.g.-REGN13221); and-212-214-216-121-123-125 (e.g.-REGN13284).

[0374] In a related embodiment, provided herein are antibodies, or antigen-binding fragments thereof, comprising a set of six CDRs (i.e., HCDR1-HCDR2-HCDR3-LCDR1- LCDR2-LCDR3) contained within an HCVR / LCVR amino acid sequence pair as defined by any of the exemplary anti-AAV antibodies listed in Table 1. For example, provided herein are antibodies, or antigen-binding fragments thereof, comprising the HCDR1-HCDR2-HCDR3- LCDR1-LCDR2-LCDR3 amino acid sequences set contained within an HCVR / LCVR amino acid sequence pair selected from SEQ ID NOs: 2 / 10 (e.g., REGN13876); 22 / 10 (e.g., REGN13877); 32 / 10 (e.g., REGN13878); 42 / 10 (e.g., REGN13879); 52 or 1159 / 10 or 1157 (e.g., REGN13880); 62 / 10 (e.g., REGN13881); 71 / 10 (e.g., REGN13882); 81 / 10 (e.g., REGN13883); 91 / 10 (e.g., REGN13884); 101 / 10 (e.g., REGN13885); 111 / 119 (e.g., REGN13070); 131 / 119 (e.g., REGN13071); 141 / 119 (e.g., REGN13072); 151 / 119 (e.g., REGN13073); 161 / 119 (e.g., REGN13074); 171 / 119 (e.g., REGN13075); 180 / 119 (e.g., REGN13076); 190 / 119 (e.g., REGN13220); 200 / 119 (e.g., REGN13221); and, 210 / 119 (e.g., REGN13284).

[0375] In an embodiment provided herein, the anti-AAV antibody or antigen-binding ^ ^Attorney Docket No.250298.000954 fragment thereof can include: a) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 2, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; b) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 22, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; c) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 32, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; d) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 42, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; e) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 52 or 1159, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1157; f) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 62, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; g) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 71, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; h) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 81, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; i) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 91, ^ ^Attorney Docket No.250298.000954 and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; j) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 101, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 10; k) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 111, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 119; l) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 131, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 119; m) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 141, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 119; n) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 151, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 119; o) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 161, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 119; p) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 171, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 119; q) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 180, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 119; r) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 190, ^ ^Attorney Docket No.250298.000954 and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 119; s) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 200, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 119; and / or t) a heavy chain variable region (HCVR) that comprises a HCDR1, HCDR2, and HCDR3 contained within an HCVR comprising the amino acid sequence of SEQ ID NO: 210, and / or a light chain variable region (LCVR) that comprises a LCDR1, LCDR2, and LCDR3 contained within a LCVR comprising the amino acid sequence of SEQ ID NO: 119.

[0376] In an embodiment provided herein, the anti-AAV antibody or antigen-binding fragment thereof can include: a) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 4, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 6, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 8; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; b) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 24, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 26, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 28; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; c) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 34, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 36, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 38; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; d) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 44, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 46, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 48; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; e) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a ^ ^Attorney Docket No.250298.000954 LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; f) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 64, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 67; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; g) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 73, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 75, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 77; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; h) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 83, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 85, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 87; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; i) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 93, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 95, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 97; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; j) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 103, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 105, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 107; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; k) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 113, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 115, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 117; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 121, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 123, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 125; l) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 133, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 135, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 137; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 121, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 123, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 125; ^ ^Attorney Docket No.250298.000954 m) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 143, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 145, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 147; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 121, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 123, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 125; n) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 153, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 155, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 157; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 121, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 123, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 125; o) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 163, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 165, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 167; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 121, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 123, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 125; p) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 173, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 145, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 176; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 121, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 123, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 125; q) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 182, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 184, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 186; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 121, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 123, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 125; r) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 192, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 194, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 196; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 121, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 123, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 125; s) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 202, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 204, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 206; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 121, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 123, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 125; and / or t) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 212, a HCDR2 ^ ^Attorney Docket No.250298.000954 comprising the amino acid sequence of SEQ ID NO: 214, and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 216; and / or a LCDR1 comprising the amino acid sequence of SEQ ID NO: 121, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 123, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 125.

[0377] In an embodiment provided herein, the anti-AAV antibody or antigen-binding fragment thereof can include: a) a HCVR comprising the amino acid sequence of SEQ ID NO: 2, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; b) a HCVR comprising the amino acid sequence of SEQ ID NO: 22, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; c) a HCVR comprising the amino acid sequence of SEQ ID NO: 32, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; d) a HCVR comprising the amino acid sequence of SEQ ID NO: 42, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; e) a HCVR comprising the amino acid sequence of SEQ ID NO: 52 or 1159, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1157; f) a HCVR comprising the amino acid sequence of SEQ ID NO: 62, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; g) a HCVR comprising the amino acid sequence of SEQ ID NO: 71, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; h) a HCVR comprising the amino acid sequence of SEQ ID NO: 81, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; i) a HCVR comprising the amino acid sequence of SEQ ID NO: 91, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; j) a HCVR comprising the amino acid sequence of SEQ ID NO: 101, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 10; k) a HCVR comprising the amino acid sequence of SEQ ID NO: 111, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 119; l) a HCVR comprising the amino acid sequence of SEQ ID NO: 131, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 119; m) a HCVR comprising the amino acid sequence of SEQ ID NO: 141, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 119; n) a HCVR comprising the amino acid sequence of SEQ ID NO: 151, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 119; o) a HCVR comprising the amino acid sequence of SEQ ID NO: 161, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 119; ^ ^Attorney Docket No.250298.000954 p) a HCVR comprising the amino acid sequence of SEQ ID NO: 171, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 119; q) a HCVR comprising the amino acid sequence of SEQ ID NO: 180, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 119; r) a HCVR comprising the amino acid sequence of SEQ ID NO: 190, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 119; s) a HCVR comprising the amino acid sequence of SEQ ID NO: 200, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 119; and / or t) a HCVR comprising the amino acid sequence of SEQ ID NO: 210, and / or a LCVR comprising the amino acid sequence of SEQ ID NO: 119.

[0378] In an embodiment provided herein, the anti-AAV antigen-binding fragment is an Fab. In some embodiments, an anti-AAV Fab of the present disclosure includes: a) an HC that comprises the amino acid sequence of SEQ ID NO: 18, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 20, or a variant thereof; b) an HC that comprises the amino acid sequence of SEQ ID NO: 30, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 20, or a variant thereof; c) an HC that comprises the amino acid sequence of SEQ ID NO: 40, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 20, or a variant thereof; d) an HC that comprises the amino acid sequence of SEQ ID NO: 50, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 20, or a variant thereof; e) an HC that comprises the amino acid sequence of SEQ ID NO: 60 or 1108, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 20, or a variant thereof; f) an HC that comprises the amino acid sequence of SEQ ID NO: 69, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 20, or a variant thereof; g) an HC that comprises the amino acid sequence of SEQ ID NO: 79, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 20, or a variant thereof; h) an HC that comprises the amino acid sequence of SEQ ID NO: 89, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 20, or a variant thereof; ^ ^Attorney Docket No.250298.000954 i) an HC that comprises the amino acid sequence of SEQ ID NO: 99, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 20, or a variant thereof; or j) an HC that comprises the amino acid sequence of SEQ ID NO: 109, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 20, or a variant thereof.

[0379] In an embodiment provided herein, the anti-AAV antibody comprises a constant region derived from IgG4 subclass. In some embodiments, an anti-AAV Fab of the present disclosure includes: k) an HC that comprises the amino acid sequence of SEQ ID NO: 127, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 129, or a variant thereof; l) an HC that comprises the amino acid sequence of SEQ ID NO: 139, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 129, or a variant thereof; m) an HC that comprises the amino acid sequence of SEQ ID NO: 149, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 129, or a variant thereof; n) an HC that comprises the amino acid sequence of SEQ ID NO: 159, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 129, or a variant thereof; o) an HC that comprises the amino acid sequence of SEQ ID NO: 169, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 129, or a variant thereof; p) an HC that comprises the amino acid sequence of SEQ ID NO: 178, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 129, or a variant thereof; q) an HC that comprises the amino acid sequence of SEQ ID NO: 188, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 129, or a variant thereof; r) an HC that comprises the amino acid sequence of SEQ ID NO: 198, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 129, or a variant thereof; s) an HC that comprises the amino acid sequence of SEQ ID NO: 208, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 129, or a variant thereof; and / or ^ ^Attorney Docket No.250298.000954 t) an HC that comprises the amino acid sequence of SEQ ID NO: 218, or a variant thereof; and / or an LC that comprises the amino acid sequence of SEQ ID NO: 129, or a variant thereof.

[0380] The anti-AAV antibodies or antigen-binding fragments thereof described herein may bind to a capsid of an AAV particle with a KD value of about 5x10-6M or less, such as about 10-7M or less, about 10-8M or less, such as about 10-9M or less when determined by, for instance, surface plasmon resonance (SPR) technology in a BIAcore instrument using the antigen as the ligand and the antibody, Ig, antibody-binding fragment, or Fc-containing protein as the analyte (or antiligand). Cell-based binding strategies, such as fluorescent- activated cell sorting (FACS) binding assays, are also routinely used, and FACS data correlates well with other methods such as radioligand competition binding and SPR (Benedict, CA, J Immunol Methods.1997, 201(2):223-31; Geuijen, CA, et al. J Immunol Methods.2005, 302(1-2):68-77). In some embodiments, an anti-AAV antibody or antigen- binding fragment thereof described herein may bind to a capsid of an AAV particle with a KD value of about 5x10-6M to 1x10-6M (e.g., 1x10-6M, 1.5x10-6M, 2x10-6M, 3x10-6M, 4x10-6M, 5x10-6M), about 1x10-6M to 1x10-7M (e.g., 1x10-7M, 2x10-7M, 3x10-7M, 4x10-7M, 5x10-7M, 6x10-7M, 7x10-7M, 8x10-7M, 9x10-7M), about 1x10-7M to 1x10-8M (e.g., 1x10-8M, 2x10-8M, 3x10-8M, 4x10-8M, 5x10-8M, 6x10-8M, 7x10-8M, 8x10-8M, 9x10-8M), about 1x10-8M to 1x10-9M (e.g., 1x10-9M, 2x10-9M, 3x10-9M, 4x10-9M, 5x10-9M, 6x10-9M, 7x10-9M, 8x10-9M, 9x10-9M), or about 1x10-9M to 1x10-10M (e.g., 1x10-10M, 2x10-10M, 3x10-10M, 4x10-10M, 5x10-10M, 6x10-10M, 7x10-10M, 8x10-10M, 9x10-10M).

[0381] The antibody or antigen-binding protein of the disclosure may bind to the predetermined antigen or cell surface molecule (receptor) having an affinity corresponding to value that is at least ten-fold lower than its affinity for binding to a non-specific antigen (e.g., BSA). According to the present disclosure, the affinity of an antibody corresponding to a KDvalue that is equal to or less than ten-fold lower than a non-specific antigen may be considered non-detectable binding, however such an antibody may be paired with a second antigen-binding domain for the production of a multispecific antibody of the disclosure.

[0382] The term “KD” (M) can refer to the dissociation equilibrium constant of a particular antibody-antigen interaction, or the dissociation equilibrium constant of an antibody or antibody-binding fragment binding to an antigen. There is an inverse relationship between KDand binding affinity, therefore the smaller the KDvalue, the higher, i.e. stronger, the affinity. Thus, the terms “higher affinity” or “stronger affinity” relate to a higher ability to form an interaction and therefore a smaller KDvalue, and conversely the terms “lower affinity” or “weaker affinity” relate to a lower ability to form an interaction and therefore a larger KD value. In some circumstances, a higher binding affinity (or KD) of a particular molecule (e.g. ^ ^Attorney Docket No.250298.000954 antibody) to its interactive partner molecule (e.g. antigen X) compared to the binding affinity of the molecule (e.g. antibody) to another interactive partner molecule (e.g. antigen Y) may be expressed as a binding ratio determined by dividing the larger KD value (lower, or weaker, affinity) by the smaller KD(higher, or stronger, affinity), for example expressed as 5-fold or 10-fold greater binding affinity, as the case may be.

[0383] The term “kd” (sec -1 or 1 / s) refers to the dissociation rate constant of a particular antibody-antigen interaction, or the dissociation rate constant of an antibody or antibody- binding fragment. Said value is also referred to as the koff value.

[0384] The term “ka” (M-1 x sec-1 or 1 / M / s) can refer to the association rate constant of a particular antibody-antigen interaction, or the association rate constant of an antibody or antibody-binding fragment.

[0385] The term “KA” (M-1 or 1 / M) can refer to the association equilibrium constant of a particular antibody-antigen interaction, or the association equilibrium constant of an antibody or antibody-binding fragment. The association equilibrium constant is obtained by dividing the kaby the kd.

[0386] The term “EC50” or “EC50” can refer to the half maximal effective concentration, which includes the concentration of an antibody which induces a response halfway between the baseline and maximum after a specified exposure time. The EC50essentially represents the concentration of an antibody where 50% of its maximal effect is observed. In certain embodiments, the EC50 value equals the concentration of an antibody of the disclosure that gives half-maximal binding to a capsid protein of an AAV particle (e.g., a wild-type or a non- wild-type AAV capsid protein(s) or to cells expressing a molecule on a cell surface described herein, as determined by e.g., a FACS binding assay. Thus, reduced or weaker binding is observed with an increased EC50, or half maximal effective concentration value.

[0387] Also provided herein are nucleic acid molecules encoding anti-AAV antibodies or antigen-binding fragments thereof.

[0388] Provided herein are nucleic acid molecules encoding any of the HCVR amino acid sequences listed in Table 1; in certain embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCVR nucleic acid sequences listed in Table 2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity thereto.

[0389] Provided herein are nucleic acid molecules encoding any of the HCDR1 amino acid sequences listed in Table 1; in certain embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCDR1 nucleic acid sequences listed in Table 2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity thereto. ^ ^Attorney Docket No.250298.000954

[0390] Provided herein are nucleic acid molecules encoding any of the HCDR2 amino acid sequences listed in Table 1; in certain embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCDR2 nucleic acid sequences listed in Table 2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity thereto.

[0391] Provided herein are nucleic acid molecules encoding any of the HCDR3 amino acid sequences listed in Table 1; in certain embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCDR3 nucleic acid sequences listed in Table 2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity thereto.

[0392] Provided herein are nucleic acid molecules encoding any of the LCVR amino acid sequences listed in Table 1; in certain embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCVR nucleic acid sequences listed in Table 2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity thereto.

[0393] Provided herein are nucleic acid molecules encoding any of the LCDR1 amino acid sequences listed in Table 1; in certain embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCDR1 nucleic acid sequences listed in Table 2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity thereto.

[0394] Provided herein are nucleic acid molecules encoding any of the LCDR2 amino acid sequences listed in Table 1; in certain embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCDR2 nucleic acid sequences listed in Table 2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity thereto.

[0395] Provided herein are nucleic acid molecules encoding any of the LCDR3 amino acid sequences listed in Table 1; in certain embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LCDR3 nucleic acid sequences listed in Table 2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity thereto.

[0396] Provided herein are nucleic acid molecules encoding an HCVR, wherein the HCVR comprises a set of three CDRs (i.e., HCDR1-HCDR2-HCDR3), wherein the HCDR1-HCDR2- HCDR3 amino acid sequence set is as defined by any of the exemplary anti-AAV antibodies listed in Table 1.

[0397] Provided herein are nucleic acid molecules encoding an LCVR, wherein the LCVR comprises a set of three CDRs (i.e., LCDR1-LCDR2-LCDR3), wherein the LCDR1-LCDR2- ^^^^ ^Attorney Docket No.250298.000954 LCDR3 amino acid sequence set is as defined by any of the exemplary anti-AAV antibodies listed in Table 1.

[0398] Provided herein are nucleic acid molecules encoding both an HCVR and an LCVR, wherein the HCVR comprises an amino acid sequence of any of the HCVR amino acid sequences listed in Table 1, and wherein the LCVR comprises an amino acid sequence of any of the LCVR amino acid sequences listed in Table 1. In certain embodiments, the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HCVR nucleic acid sequences listed in Table 2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity thereto, and a polynucleotide sequence selected from any of the LCVR nucleic acid sequences listed in Table 2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity thereto. In certain embodiments according to this aspect of the disclosure, the nucleic acid molecule encodes an HCVR and LCVR, wherein the HCVR and LCVR are both derived from the same anti-AAV antibody listed in Table 1.

[0399] Also provided herein are nucleic acid molecules encoding any of the HC amino acid sequences listed in Table 1; in certain embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the HC nucleic acid sequences listed in Table 2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity thereto. As another example, the present disclosure provides nucleic acid molecules encoding any of the LC amino acid sequences listed in Table 1; in certain embodiments the nucleic acid molecule comprises a polynucleotide sequence selected from any of the LC nucleic acid sequences listed in Table 2, or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity thereto.

[0400] Provided herein are recombinant expression vectors capable of expressing one or more polypeptides of an anti-AAV antibody or antigen-binding fragment thereof. For example, provided herein are recombinant expression vectors comprising any of the nucleic acid molecules mentioned above, i.e., nucleic acid molecules encoding any of the HCVR, LCVR, and / or CDR sequences as set forth in Table 1. Also included within the scope of the present disclosure are host cells into which such vectors have been introduced, as well as methods of producing the antibodies or portions thereof by culturing the host cells under conditions permitting production of the antibodies or antibody fragments and recovering the antibodies and antibody fragments so produced. The term “host cell” as used herein can refer to cells into which a nucleic acid of the disclosure has been introduced. The terms “host cell” and “recombinant host cell” are used interchangeably herein. It is understood that such ^ ^Attorney Docket No.250298.000954 terms can refer to the particular subject cell and to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein. Typical host cells are eukaryotic host cells, such as mammalian host cells. Exemplary eukaryotic host cells include yeast and mammalian cells, for example vertebrate cells such as a mouse, rat, monkey, or human cell line, for example HKB11 cells, PER.C6 cells, HEK cells, or CHO cells. Multispecific Antigen-binding Molecules

[0401] The antigen-binding molecules (e.g., antibodies) of the present disclosure may be monospecific or multispecific (e.g., bispecific). Multispecific antigen-binding molecules (also referred to as “multispecific binding molecules” or “MBMs” herein) may be specific for different epitopes of one target polypeptide or may contain antigen-binding domains specific for more than one target polypeptide. See, e.g., Tutt et al., 1991, J. Immunol.147:60-69; Kufer et al., 2004, Trends Biotechnol.22:238-244. The multispecific antigen-binding molecules of the disclosure may comprise at least one antigen-binding domain that binds to a capsid of an AAV particle, and at least one antigen-binding domain that binds to a different target molecule.

[0402] The MBMs of the disclosure specifically bind to at least two different epitopes (and in some instances three or more different epitopes). The at least two different epitopes can be on the same target molecule or different target molecules. Generally, the MBMs of the disclosure specifically bind to two or more different target molecules. In some embodiments, the MBMs described herein may bind to one or more epitopes of a capsid of an AAV particle. In some, the MBMs described herein may bind to one or more epitopes of a molecule on a cell surface.

[0403] The anti-AAV monospecific antibodies or anti-AAV x anti-cell surface molecule multispecific antibodies of the present disclosure can be linked to or co-expressed with another functional molecule, e.g., another peptide or protein. For example, an antibody or fragment thereof can be functionally linked (e.g., by chemical coupling, genetic fusion, noncovalent association, or otherwise) to one or more other molecular entities, such as another antibody or antibody fragment to produce a multispecific antibody with a second or additional binding specificity.

[0404] Use of the expression “anti-AAV antibody” or “anti-cell surface molecule antibody” herein is intended to include both monospecific anti-AAV antibodies or anti-cell surface antibodies as well as multispecific antibodies (e.g., bispecific antibodies) which may ^ ^Attorney Docket No.250298.000954 comprise a first-binding domain that binds to a capsid of an AAV and a second binding domain that binds to a molecule on a cell surface. Thus, the present disclosure includes bispecific antibodies wherein one domain of an immunoglobulin binds to a capsid of an AAV particle (e.g., a capsid comprising a wild-type and / or non-wild-type AAV capsid protein(s)), and the other domain of the immunoglobulin binds to a molecule of a cell surface. The AAV- binding domain can comprise any of the CDR, HCVR / LCVR, or HC / LC amino acid sequences as set forth in Table 1 herein. The cell surface molecule-binding domain can comprise any of various CDR, HCVR / LCVR, or HC / LC amino acid sequences that bind any of various cell-surface molecules disclosed herein, or otherwise within the knowledge of one skilled in the art. As a non-limiting example, the cell surface molecule-binding domain can comprise any of CDR, HCVR / LCVR, or HC / LC amino acid sequences which bind to Asialoglycoprotein Receptor 1 (ASGR1) as set forth in Table 5 herein. Nucleic acid molecules encoding any of the CDR, HCVR / LCVR, or HC / LC amino acid sequences of the anti-AAV / anti-cell surface molecule multispecific antigen-binding molecules disclosed herein may include, for example, nucleic acid molecules comprising the polynucleotide sequences as set forth in Table 2 herein, as well as, e.g., nucleic acid molecules comprising the polynucleotide sequences as set forth in Table 6 herein.

[0405] In some embodiments, MBMs of the present disclosure may comprise two or more (e.g., three, four) antigen-binding domains. In some embodiments, the two or more (e.g., three, four) antigen-binding domains may independently be in a Fab or an scFv format.

[0406] Single chain Fv or “scFv” antibody fragments comprise the VH and VL domains of an antibody in a single polypeptide chain, are capable of being expressed as a single chain polypeptide and retain the specificity of the intact antibodies from which they are derived. Generally, an scFv polypeptide may further comprise a polypeptide linker between the VH and VL domain that enables the scFv to form the desired structure for target binding. Examples of linkers suitable for connecting the VHand VLchains of an scFV are the linkers are described herein.

[0407] Unless specified, as used herein an scFv may have the VLand VHvariable regions in either order, e.g., with respect to the N-terminal and C-terminal ends of the polypeptide, the scFv may comprise VL-linker-VH or may comprise VH-linker-VL.

[0408] As a non-limiting example, an scFv comprising VL-linker-VHwhich may be used in accordance with the disclosure may comprise the amino acid sequence of DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRF SGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPITFGCGTRLEIKGGGGSGGGGSGGGG SGGGGSQVHLQESGPGLVMPSQILSLSCVISGDSIRNGGYYWTWTRQQPGKGLEWIGHIH YSERTSHNPSLQSRVIMSIDTSENKFSLKLTSVTVADTAIYYCARGRDTMVRGSITTSGHFID ^ ^Attorney Docket No.250298.000954 SWGQGALVTVSS (SEQ ID NO: 1358), or a substantially similar sequence thereof having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity.

[0409] As another non-limiting example, an scFv comprising VL-linker-VH which may be used in accordance with the disclosure may comprise the amino acid sequence of DIQMTQSPSTLSASVGDRVTLTCRASQSISNKLAWYQQKPGKAPNLLIYKASNLESGVPSR FSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSWTFGCGTKVEIKGGGGSGGGGSGGG GSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSTYGMHWVRQAPGKCLEWVAVI WHDGSDKYYVDSVKGRFSIARDNSKNTLYLQMNSLRVEDTGIYYCARRGIRGTVFDHWG...

Claims

Attorney Docket No.250298.000954 What is claimed is:

1. A multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a second heavy chain region of a second Fab (“Fab2”) operably linked to a second Fc domain (“Fc2”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); and d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”); wherein e) ABD1 or ABD2 binds to a capsid of an adeno-associated virus (AAV) particle, and the other of ABD1 or ABD2 binds to a molecule on a cell surface; f) Fc1 and / or Fc2 are derived from an IgG4 heavy chain constant region; and g) the first light chain and the second light chain comprise the same amino acid sequence.

2. The multispecific antibody or multispecific antigen-binding fragment of claim 1, wherein ABD1 binds to the capsid of the AAV particle and ABD2 binds to the molecule on the cell surface.

3. The multispecific antibody or multispecific antigen-binding fragment of claim 1, wherein ABD2 binds to the capsid of the AAV particle and ABD1 binds to the molecule on the cell surface.

4. The multispecific antibody or multispecific antigen-binding fragment of claim 1, wherein Fc1 and Fc2 form an Fc heterodimer.

5. The multispecific antibody or multispecific antigen-binding fragment of claim 4, wherein the Fc1 and / or Fc2 in the Fc heterodimer comprise a knob-in-hole mutation as compared to a wild type Fc domain.

6. The multispecific antibody or multispecific antigen-binding fragment of claim 4 or 5, ^^^^ ^Attorney Docket No.250298.000954 wherein one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions S354C and T366W (according to EU numbering) as compared to a wild type Fc domain, and the other of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions Y349C, T366S, L368A, and Y407V (according to EU numbering) as compared to a wild type Fc domain.

7. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 4-6, wherein at least one of Fc1 and Fc2 in the Fc heterodimer comprises a star mutation as compared to a wild type Fc domain.

8. The multispecific antibody or multispecific antigen-binding fragment of claim 7, wherein one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid mutations H435R and / or Y436F (according to EU numbering) as compared to a wild type Fc domain.

9. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 1-8, wherein Fc1 and / or Fc2 comprises the amino acid sequence of SEQ ID NO: 1345 or 1365, or a variant thereof.

10. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 1-9, wherein the first light chain and the second light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof.

11. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 1 and 4-10, wherein ABD1 or ABD2 bind to the capsid of the AAV particle, and wherein ABD1 or ABD2 comprises: h) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10; or i) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 71, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO:

10.

12. The multispecific antibody or multispecific antigen-binding fragment of claim 11, wherein ABD1 or ABD2 binds to the capsid of the AAV particle, and wherein ABD1 or ABD2 comprises: j) an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, ^ ^Attorney Docket No.250298.000954 and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; k) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 71, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof.

13. The multispecific antibody or multispecific antigen-binding fragment of claim 11 or 12, wherein ABD1 or ABD2 binds to the capsid of the AAV particle, and wherein ABD1 or ABD2 comprises: l) a HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or m) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 73, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 75, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 77; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

14. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 1-13, wherein said molecule on the cell surface is asialoglycoprotein receptor 1 (ASGR1), transferrin receptor (TfR), or calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1).

15. The multispecific antibody or multispecific antigen-binding fragment of claim 14, wherein said molecule on the cell surface is TfR.

16. The multispecific antibody or multispecific antigen-binding fragment of claim 15, wherein ABD1 or ABD2 binds to TfR, and wherein ABD1 or ABD2 comprises: n) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; o) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 511, or a variant thereof, and / or an LCVR that comprises ^ ^Attorney Docket No.250298.000954 an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; p) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 531, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or q) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 552, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

17. The multispecific antibody or multispecific antigen-binding fragment of claim 16, wherein ABD1 or ABD2 binds to TfR, and wherein ABD1 or ABD2 comprises: r) an HCVR that comprises the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; s) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; t) an HCVR that comprises the amino acid sequence of SEQ ID NO: 531, or a variant thereof and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or u) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 552, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof.

18. The multispecific antibody or multispecific antigen-binding fragment of claim 16 or 17 wherein ABD1 or ABD2 binds to TfR, and wherein ABD1 or ABD2 comprises: v) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; w) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 512, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 513, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 514; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 ^ ^Attorney Docket No.250298.000954 comprising the amino acid sequence of SEQ ID NO: 16; x) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 532, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 533, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 534; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or y) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 553, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 554, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 555; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

19. A multispecific antibody or multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a second heavy chain region of a second Fab (“Fab2”) operably linked to a second Fc domain (“Fc2”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); and d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”), wherein e) ABD1 binds to a capsid of an AAV particle; f) ABD2 binds to TfR; g) Fc1 comprises the amino acid sequence of SEQ ID NO: 1365, or a variant thereof; h) Fc2 comprises the amino acid sequence of SEQ ID NO: 1345, or a variant thereof; and, i) the first light chain and second light chain comprise the same amino acid sequence.

20. The multispecific antibody or multispecific antigen-binding fragment of claim 19, wherein the first light chain and the second light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof.

21. The multispecific antibody or multispecific antigen-binding fragment of claim 19 or 20 wherein ABD1 binds to the capsid of the AAV particle, and wherein ABD1 comprises: j) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises ^ ^Attorney Docket No.250298.000954 an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or k) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 71, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

22. The multispecific antibody or multispecific antigen-binding fragment of claim 21, wherein ABD1 binds to the capsid of the AAV particle, and wherein ABD1 comprises: l) an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or m) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 71, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof.

23. The multispecific antibody or multispecific antigen-binding fragment of claim 21 or 22, wherein ABD1 binds to the capsid of the AAV particle, and wherein ABD1 comprises: n) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or o) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 73, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 75, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 77; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

24. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 19-23, wherein ABD2 binds to TfR, and wherein ABD2 comprises: p) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; q) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the ^ ^Attorney Docket No.250298.000954 amino acid sequence of SEQ ID NO: 511, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; r) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 531, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or s) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 552, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

25. The multispecific antibody or multispecific antigen-binding fragment of claim 24, wherein ABD2 binds to TfR, and wherein ABD2 comprises: t) an HCVR that comprises the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; u) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; v) an HCVR that comprises the amino acid sequence of SEQ ID NO: 531, or a variant thereof and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or w) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 552, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof.

26. The multispecific antibody or multispecific antigen-binding fragment of claim 24 or 25, wherein ABD1 or ABD2 binds to TfR, and wherein ABD1 or ABD2 comprises: x) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; y) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 512, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 513, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 514; and / or an LCDR1 comprising the amino acid sequence of SEQ ^ ^Attorney Docket No.250298.000954 ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; z) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 532, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 533, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 534; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or aa) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 553, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 554, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 555; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

27. A multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”), said Fc1 operably linked to a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a third heavy chain region of a third Fab (“Fab3”) operably linked to a second Fc domain (“Fc2”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”); and e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); wherein f) at least one of ABD1, ABD2, and ABD3 binds to a capsid of an AAV particle, and the other(s) of ABD1, ABD2, and ABD3 bind to a molecule on a cell surface; g)^Fc1 and / or Fc2 are derived from an IgG4 heavy chain constant region; and h) the first light chain, the second light chain, and the third light chain comprise the same amino acid sequence; or the first light chain and the second light chain comprise the same amino acid sequence and the third light chain comprises a different amino acid sequence.

28. The multispecific antibody or multispecific antigen-binding fragment of claim 27, ^ ^Attorney Docket No.250298.000954 wherein two of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and one of ABD1, ABD2, and ABD3 binds to the molecule on the cell surface.

29. The multispecific antibody or multispecific antigen-binding fragment of claim 28, wherein ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD3 binds to the molecule on the cell surface.

30. The multispecific antibody or multispecific antigen-binding fragment of claim 28, wherein ABD3 binds to the capsid of the AAV particle, and ABD1 and ABD2 bind to the molecule on the cell surface.

31. The multispecific antibody or multispecific antigen-binding fragment of claim 27, wherein Fc1 and Fc2 form an Fc heterodimer.

32. The multispecific antibody or multispecific antigen-binding fragment of claim 31, wherein the Fc1 and / or Fc2 in the Fc heterodimer comprise a knob-in-hole mutation as compared to a wild type Fc domain.

33. The multispecific antibody or multispecific antigen-binding fragment of claim 31 or 32, wherein one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions S354C and T366W (according to EU numbering) as compared to a wild type Fc domain, and the other of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions Y349C, T366S, L368A, and Y407V (according to EU numbering) as compared to a wild type Fc domain.

34. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 31-33, wherein at least one of Fc1 and Fc2 in the Fc heterodimer comprises a star mutation as compared to a wild type Fc domain.

35. The multispecific antibody or multispecific antigen-binding fragment of claim 34, wherein one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid mutations H435R and / or Y436F (according to EU numbering) as compared to a wild type Fc domain.

36. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 31-35, wherein Fc1 and / or Fc2 comprises the amino acid sequence of SEQ ID ^ ^Attorney Docket No.250298.000954 NO: 1345 or 1365, or a variant thereof.

37. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 27-36, wherein the first light chain, the second light chain, and the third light chain comprise the amino acid sequence of SEQ ID NO: 20 or 813, or a variant thereof.

38. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 27-36, wherein the first light chain and the second light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof, and the third light chain comprises the amino sequence of SEQ ID NO: 813, or a variant thereof.

39. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 27-38, wherein the second heavy chain region is linked to the Fc domain via a linker.

40. The multispecific antibody or multispecific antigen-binding fragment of claim 39, wherein the linker is or comprises a multimer of GnS (SEQ ID NO: 239) or SGn (SEQ ID NO: 240), wherein n is an integer from 1 to 10.

41. The multispecific antibody or multispecific antigen-binding fragment of claim 39, wherein the linker is or comprises a multimer of G4S (SEQ ID NO: 242).

42. The multispecific antibody or multispecific antigen-binding fragment of claim 41, wherein the linker is G4Sx3 (SEQ ID NO: 1115).

43. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 27-28 and 31-42, wherein at least one of ABD1, ABD2, and ABD3 binds to the capsid of the AAV particle, and wherein ABD1, ABD2, and / or ABD3 comprises: i) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 803, or a variant thereof; or j) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 71, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 803, or a variant thereof. ^ ^Attorney Docket No.250298.000954 44. The multispecific antibody or multispecific antigen-binding fragment of claim 43, wherein at least one of ABD1, ABD2, and ABD3 binds to the capsid of the AAV particle, and wherein ABD1, ABD2, ABD3 comprises: k) an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10 or 803, or a variant thereof; or l) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 71, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10 or 803, or a variant thereof.

45. The multispecific antibody or multispecific antigen-binding fragment of claim 43 or 44, wherein at least one of ABD1, ABD2, and ABD3 binds to the capsid of the AAV particle, and wherein ABD1, ABD2, and / or ABD3 comprises: m) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12 or 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14 or 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16 or 809; or n) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 73, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 75, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 77; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12 or 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14 or 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16 or 809.

46. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 27-45, wherein said molecule on the cell surface is ASGR1, TfR, or CACNG1.

47. The multispecific antibody or multispecific antigen-binding fragment of claim 46, wherein said molecule on the cell surface is TfR.

48. The multispecific antibody or multispecific antigen-binding fragment of claim 47, wherein the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and wherein ABD1, ABD2, and / or ABD3 comprises: o) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and / or an LCVR that comprises ^ ^Attorney Docket No.250298.000954 an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; p) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 511, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; q) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 531, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or r) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 552, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

49. The multispecific antibody or multispecific antigen-binding fragment of claim 48, wherein the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and wherein ABD1, ABD2, and / or ABD3 comprises: s) an HCVR that comprises the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; t) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; u) an HCVR that comprises the amino acid sequence of SEQ ID NO: 531, or a variant thereof and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; v) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 552, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof.

50. The multispecific antibody or multispecific antigen-binding fragment of claim 48 or 49, wherein the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and wherein ABD1, ABD2, and / or ABD3 comprises: w) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and / or an LCDR1 comprising the amino acid sequence of SEQ ^ ^Attorney Docket No.250298.000954 ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; x) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 512, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 513, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 514; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; y) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 532, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 533, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 534; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or z) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 553, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 554, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 555; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

51. The multispecific antibody or multispecific antigen-binding fragment of claim 46, wherein said molecule on the cell surface is CACNG1.

52. The multispecific antibody or multispecific antigen-binding fragment of claim 51, wherein the other(s) of ABD1, ABD2, and ABD3 binds to CACNG1, and wherein ABD1 or ABD2 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

53. The multispecific antibody or multispecific antigen-binding fragment of claim 52, wherein the other(s) of ABD1, ABD2, and ABD3 binds to CACNG1, and wherein ABD1 or ABD2 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

54. The multispecific antibody or multispecific antigen-binding fragment of claim 52 or 53, ^ ^Attorney Docket No.250298.000954 wherein the other(s) of ABD1, ABD2, and ABD3 binds to CACNG1, and wherein ABD1 or ABD2 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 801; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

809.

55. A multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”), said Fc1 operably linked to a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a third heavy chain region of a third Fab (“Fab3”) operably linked to a second Fc domain (“Fc2”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”); and e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); wherein f) ABD1 and ABD2 bind to a capsid of an AAV particle; g) ABD3 binds to TfR; h) Fc1 comprises the amino acid sequence of SEQ ID NO: 1365, or a variant thereof; i) Fc2 comprises the amino acid sequence of SEQ ID NO: 1345, or a variant thereof; and, j) the first light chain, the second light chain, and the third light chain comprise the same amino acid sequence.

56. The multispecific antibody or multispecific antigen-binding fragment of claim 55, wherein the first light chain, the second light chain, and the third light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof.

57. The multispecific antibody or multispecific antigen-binding fragment of claim 55 or 56, wherein the second heavy chain region is linked to the Fc domain via a linker. ^ ^Attorney Docket No.250298.000954 58. The multispecific antibody or multispecific antigen-binding fragment of claim 57, wherein the linker is G4Sx3 (SEQ ID NO: 1115).

59. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 55-58, wherein ABD1 and ABD2 bind to the capsid of the AAV particle, and wherein ABD1 and ABD2 comprises: k) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 803, or a variant thereof; or l) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 71, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 803, or a variant thereof.

60. The multispecific antibody or multispecific antigen-binding fragment of claim 59, wherein ABD1 and ABD2 bind to the capsid of the AAV particle, and wherein ABD1 and ABD2 comprises: m) an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or n) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 71, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof.

61. The multispecific antibody or multispecific antigen-binding fragment of claim 59 or 60, wherein ABD1 and ABD2 bind to the capsid of the AAV particle, and wherein ABD1 and ABD2 comprises: o) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or p) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 73, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 75, and an HCDR3 comprising the amino acid ^ ^Attorney Docket No.250298.000954 sequence of SEQ ID NO: 77; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

62. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 55-61, wherein ABD3 binds to TfR, and wherein ABD3 comprises: q) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; r) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 511, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; s) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 531, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or t) an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 552, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

63. The multispecific antibody or multispecific antigen-binding fragment of claim 62, wherein ABD3 binds to TfR, and wherein ABD3 comprises: u) an HCVR that comprises the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; v) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 511, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof; w) an HCVR that comprises the amino acid sequence of SEQ ID NO: 531, or a variant thereof and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof; or x) an HCVR that comprises the amino acid sequence set forth in SEQ ID NO: 552, or a variant thereof, and an LCVR that comprises the amino acid sequence set forth in SEQ ID NO: 10, or a variant thereof. ^ ^Attorney Docket No.250298.000954 64. The multispecific antibody or multispecific antigen-binding fragment of claim 62 or 63, wherein ABD3 binds to TfR, and wherein ABD3 comprises: y) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; z) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 512, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 513, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 514; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; aa) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 532, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 533, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 534; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or bb) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 553, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 554, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 555; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

65. A multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”), said Fc1 operably linked to a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a third heavy chain region of a third Fab (“Fab3”) operably linked to a second Fc domain (“Fc2”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”); and ^ ^Attorney Docket No.250298.000954 e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); wherein f) ABD1 and ABD2 bind to a capsid of an AAV particle; g) ABD3 binds to CACNG1; h) Fc1 comprises the amino acid sequence of SEQ ID NO: 1365, or a variant thereof; i) Fc2 comprises the amino acid sequence of SEQ ID NO: 1345, or a variant thereof; and j) the first light chain and the second light chain comprise the same amino acid sequence and the third light chain comprises an different amino acid sequence.

66. The multispecific antibody or multispecific antigen-binding fragment of claim 65, wherein^ the first light chain and the second light chain comprise the amino acidsequence of SEQ ID NO: 20, or a variant thereof.

67. The multispecific antibody or multispecific antigen-binding fragment of claim 65 or 66, wherein^the third light chain comprises the amino acid sequence of SEQ ID NO: 813, or a variant thereof.

68. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 65-67, wherein the second heavy chain region is linked to the Fc domain via a linker.

69. The multispecific antibody or multispecific antigen-binding fragment of claim 68, wherein the linker is G4Sx3 (SEQ ID NO: 1115).

70. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 65-69, wherein ABD1 and ABD2 bind to the capsid of the AAV particle, and wherein ABD1 and ABD2 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO:

10.

71. The multispecific antibody or multispecific antigen-binding fragment of claim 70, wherein ABD1 and ABD2 bind to the capsid of the AAV particle, and wherein ABD1 and ABD2 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, ^ ^Attorney Docket No.250298.000954 and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

72. The multispecific antibody or multispecific antigen-binding fragment of claim 70 or 71, wherein ABD1 and ABD2 bind to the capsid of the AAV particle, and wherein ABD1 and ABD2 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

73. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 65-72, wherein ABD3 binds to CACNG1, and wherein ABD3 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

74. The multispecific antibody or multispecific antigen-binding fragment of claim 73, wherein ABD3 binds to CACNG1, and wherein ABD3 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

75. The multispecific antibody or multispecific antigen-binding fragment of claim 73 or 74 wherein ABD3 binds CACNG1, and wherein ABD3 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 801; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

809.

76. A multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”), said Fc1 operably linked to a second heavy chain region of a second Fab (“Fab2”); ^ ^Attorney Docket No.250298.000954 b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a third heavy chain region of a third Fab (“Fab3”) operably linked to a second Fc domain (“Fc2”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”); and e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); wherein f) ABD1 and ABD2 bind to a capsid of an AAV particle; g) ABD3 binds to CACNG1; h) Fc1 comprises the amino acid sequence of SEQ ID NO: 1365, or a variant thereof; i) Fc2 comprises the amino acid sequence of SEQ ID NO: 1345, or a variant thereof; and j) the first light chain, the second light chain, and the third light chain comprise the same amino acid sequence.

77. The multispecific antibody or multispecific antigen-binding fragment of claim 76, wherein the first light chain, the second light chain, and the third light chain comprise the amino acid sequence of SEQ ID NO: 813, or a variant thereof.

78. The multispecific antibody or multispecific antigen-binding fragment of claim 76 or 77, wherein the second heavy chain region is linked to the Fc domain via a linker.

79. The multispecific antibody or multispecific antigen-binding fragment of claim 78, wherein the linker is G4Sx3 (SEQ ID NO: 1115).

80. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 76-79, wherein ABD1 and ABD2 bind to the capsid of the AAV particle, and wherein ABD1 and ABD2 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

81. The multispecific antibody or multispecific antigen-binding fragment of claim 80, ^ ^Attorney Docket No.250298.000954 wherein ABD1 and ABD2 bind to the capsid of the AAV particle, and wherein ABD1 and ABD2 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

82. The multispecific antibody or multispecific antigen-binding fragment of claim 80 or 81, wherein ABD1 and ABD2 bind to the capsid of the AAV particle, and wherein ABD1 and ABD2 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

809.

83. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 76-82, wherein ABD3 binds to CACNG1, and wherein ABD3 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

84. The multispecific antibody or multispecific antigen-binding fragment of claim 83, wherein ABD3 binds to CACNG1, and wherein ABD3 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

85. The multispecific antibody or multispecific antigen-binding fragment of claim 83 or 84 wherein ABD3 binds CACNG1, and wherein ABD3 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 801; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

809.

86. A multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: ^ ^Attorney Docket No.250298.000954 a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to an Fc domain, said Fc domain operably linked to a first scFv comprising a first antigen-binding domain (“ABD1”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a second heavy chain region of a second Fab (“Fab2”) operably linked to an Fc domain, said Fc domain operably linked to a second scFv comprising a second antigen-binding domain (“ABD2”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a third antigen-binding domain (“ABD3”); and d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a fourth antigen-binding domain (“ABD4”); wherein e) at least one of ABD1, ABD2, ABD3, and ABD4 binds to a capsid of an AAV particle, and the other(s) of ABD1, ABD2, ABD3, and ABD4 bind to CACNG1; f) the Fc domain is derived from an IgG4 heavy chain constant region; and g) the first light chain and the second light chain comprise the same amino acid sequence.

87. The multispecific antibody or multispecific antigen-binding fragment of claim 86, wherein two of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and two of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1.

88. The multispecific antibody or multispecific antigen-binding fragment of claim 87, wherein ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD3 and ABD4 binds to CACNG1.

89. The multispecific antibody or multispecific antigen-binding fragment of claim 87, wherein ABD3 and ABD4 bind to the capsid of the AAV particle, and ABD1 and ABD2 binds to CACNG1.

90. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 86-89, wherein the Fc domain comprises the amino acid sequence of SEQ ID NO: 1397, or a variant thereof.

91. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 86-90, wherein the first light chain and the second light chain comprise the amino acid sequence of SEQ ID NO: 813, or a variant thereof. ^ ^Attorney Docket No.250298.000954 92. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 86-91, wherein the first scFv and / or the second scFv are linked to the Fc domain via a linker.

93. The multispecific antibody or multispecific antigen-binding fragment of claim 92, wherein the linker is or comprises a multimer of GnS (SEQ ID NO: 239) or SGn (SEQ ID NO: 240), wherein n is an integer from 1 to 10.

94. The multispecific antibody or multispecific antigen-binding fragment of claim 92, wherein the linker is or comprises a multimer of G4S (SEQ ID NO: 242).

95. The multispecific antibody or multispecific antigen-binding fragment of claim 94, wherein the linker is G4Sx3 (SEQ ID NO: 1115).

96. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 86-87 and 90-95, wherein at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 1159, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 1157, or a variant thereof.

97. The multispecific antibody or multispecific antigen-binding fragment of claim 96, wherein at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 1159, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 1157, or a variant thereof.

98. The multispecific antibody or multispecific antigen-binding fragment of claim 96 or 97, wherein at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ^ ^Attorney Docket No.250298.000954 ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

99. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 86-87 and 90-98, wherein the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

100. The multispecific antibody or multispecific antigen-binding fragment of claim 99, wherein the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

101. The multispecific antibody or multispecific antigen-binding fragment of claim 99 or 100, wherein the other(s) of ABD1, ABD2, ABD3, and ABD4 binds CACNG1, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 801; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

809.

102. A multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first scFv comprising a first antigen-binding domain (“ABD1”) operably linked to an Fc domain, said Fc domain operably linked to a first heavy chain region of a first Fab (“Fab1”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a second scFv comprising a second antigen-binding domain (“ABD2”) operably linked to an Fc domain, said Fc domain operably linked to a second heavy chain region of a second Fab (“Fab2”) ; c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a third antigen-binding domain (“ABD3”); and ^ ^Attorney Docket No.250298.000954 d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a fourth antigen-binding domain (“ABD4”); wherein e) at least one of ABD1, ABD2, ABD3, and ABD4 binds to a capsid of an AAV particle, and the other(s) of ABD1, ABD2, ABD3, and ABD4 bind to CACNG1; f) the Fc domain is derived from an IgG4 heavy chain constant region; and g) the first light chain and the second light chain comprise the same amino acid sequence.

103. The multispecific antibody or multispecific antigen-binding fragment of claim 102, wherein two of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and two of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1.

104. The multispecific antibody or multispecific antigen-binding fragment of claim 103, wherein ABD1 and ABD2 bind to the capsid of the AAV particle, and ABD3 and ABD4 binds to CACNG1.

105. The multispecific antibody or multispecific antigen-binding fragment of claim 103, wherein ABD3 and ABD4 bind to the capsid of the AAV particle, and ABD1 and ABD2 binds to CACNG1.

106. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 102-105, wherein the Fc domain comprises the amino acid sequence of SEQ ID NO: 1397, or a variant thereof.

107. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 102-106, wherein the first light chain and the second light chain comprise the sequence of SEQ ID NO: 20 or 813, or a variant thereof.

108. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 102-107, wherein the first Fab and / or the second Fab is linked to the Fc domain via a linker.

109. The multispecific antibody or multispecific antigen-binding fragment of claim 108, wherein the linker is or comprises a multimer of GnS (SEQ ID NO: 239) or SGn (SEQ ID NO: 240), wherein n is an integer from 1 to 10. ^ ^Attorney Docket No.250298.000954 110. The multispecific antibody or multispecific antigen-binding fragment of claim 108, wherein the linker is or comprises a multimer of G4S (SEQ ID NO: 242).

111. The multispecific antibody or multispecific antigen-binding fragment of claim 110, wherein the linker is G4Sx3 (SEQ ID NO: 1115).

112. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 102-103 and 106-111, wherein at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10 or 1157, or a variant thereof.

113. The multispecific antibody or multispecific antigen-binding fragment of claim 112, wherein at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10 or 1157, or a variant thereof.

114. The multispecific antibody or multispecific antigen-binding fragment of claim 112 or 113, wherein at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

115. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 102-103 and 106-114, wherein the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and / or an LCVR that comprises an ^ ^Attorney Docket No.250298.000954 LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

116. The multispecific antibody or multispecific antigen-binding fragment of claim 115, wherein the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803 or 1352, or a variant thereof.

117. The multispecific antibody or multispecific antigen-binding fragment of claim 115 or 116, wherein the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 801; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

809.

118. A multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to an Fc domain, said Fc domain operably linked to a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a third heavy chain region of a third Fab (“Fab3”) operable liked to an Fc domain, said Fc domain operably linked to a fourth heavy chain region of a fourth Fab (“Fab4”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ADB2”); e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); and f) a sixth polypeptide chain comprising a fourth light chain that pairs with the fourth heavy chain region to form Fab4, wherein Fab4 comprises a fourth antigen-binding domain (“ABD4”); ^ ^Attorney Docket No.250298.000954 wherein g) at least one of ABD1, ABD2, ABD3, and ABD4 binds to a capsid of an AAV particle, and the other(s) of ABD1, ABD2, ABD3, and ABD4 bind to CACNG1; h) the Fc domain is derived from an IgG4 heavy chain constant region; and i) the first light chain, the second light chain, the third light chain, and the fourth light chain comprise the same amino acid sequence.

119. The multispecific antibody or multispecific antigen-binding fragment of claim 118, wherein two of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and two of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1.

120. The multispecific antibody or multispecific antigen-binding fragment of claim 119, wherein ABD1 and ABD3 bind to the capsid of the AAV particle, and ABD2 and ABD4 binds to CACNG1.

121. The multispecific antibody or multispecific antigen-binding fragment of claim 119, wherein ABD2 and ABD4 bind to the capsid of the AAV particle, and ABD1 and ABD3 binds to CACNG1.

122. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 118-121, wherein the first light chain, the second light chain, the third light chain, and the fourth light chain comprise the amino acid sequence of SEQ ID NO: 813, or a variant thereof.

123. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 118-122, wherein the Fc domain is linked to the second heavy chain region and the fourth heavy chain region via a linker.

124. The multispecific antibody or multispecific antigen-binding fragment of claim 123, wherein the linker is or comprises a multimer of GnS (SEQ ID NO: 239) or SGn (SEQ ID NO: 240), wherein n is an integer from 1 to 10.

125. The multispecific antibody or multispecific antigen-binding fragment of claim 123, wherein the linker is or comprises a multimer of G4S (SEQ ID NO: 242).

126. The multispecific antibody or multispecific antigen-binding fragment of claim 125, ^ ^Attorney Docket No.250298.000954 wherein the linker is G4Sx3 (SEQ ID NO: 1115).

127. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 118-119 and 122-126, wherein at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

128. The multispecific antibody or multispecific antigen-binding fragment of claim 127, wherein at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

129. The multispecific antibody or multispecific antigen-binding fragment of claim 127 or 128, wherein at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

809.

130. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 118-119 and 122-129, wherein the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

131. The multispecific antibody or multispecific antigen-binding fragment of claim 130, wherein the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and wherein ^ ^Attorney Docket No.250298.000954 ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 1351, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 803, or a variant thereof.

132. The multispecific antibody or multispecific antigen-binding fragment of claim 130 or 131, wherein the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to CACNG1, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 797, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 799, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 801; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 805, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 807, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

809.

133. A multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to an Fc domain, said Fc domain operably linked to a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a third heavy chain region of a third Fab (“Fab3”) operable liked to an Fc domain, said Fc domain operably linked to a fourth heavy chain region of a fourth Fab (“Fab4”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ADB2”); e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); and f) a sixth polypeptide chain comprising a fourth light chain that pairs with the fourth heavy chain region to form Fab4, wherein Fab4 comprises a fourth antigen-binding domain (“ABD4”); wherein g) at least one of ABD1, ABD2, ABD3, and ABD4 binds to a capsid of an AAV particle, and the other(s) of ABD1, ABD2, ABD3, and ABD4 bind to TfR; h) the Fc domain is derived from an IgG4 heavy chain constant region; and i) the first light chain, the second light chain, the third light chain, and the fourth light chain comprise the same amino acid sequence. ^ ^Attorney Docket No.250298.000954 134. The multispecific antibody or multispecific antigen-binding fragment of claim 133, wherein two of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and two of ABD1, ABD2, ABD3, and ABD4 binds to TfR.

135. The multispecific antibody or multispecific antigen-binding fragment of claim 134, wherein ABD1 and ABD3 bind to TfR, and ABD2 and ABD4 binds to the capsid of the AAV particle.

136. The multispecific antibody or multispecific antigen-binding fragment of claim 134, wherein ABD2 and ABD4 bind to TfR, and ABD1 and ABD3 binds to the capsid of the AAV particle.

137. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 133-136, wherein the first light chain, the second light chain, the third light chain, and the fourth light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof.

138. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 133-137, wherein the Fc domain is linked to the second heavy chain region and the fourth heavy chain region via a linker.

139. The multispecific antibody or multispecific antigen-binding fragment of claim 138, wherein the linker is or comprises a multimer of GnS (SEQ ID NO: 239) or SGn (SEQ ID NO: 240), wherein n is an integer from 1 to 10.

140. The multispecific antibody or multispecific antigen-binding fragment of claim 138, wherein the linker is or comprises a multimer of G4S (SEQ ID NO: 242).

141. The multispecific antibody or multispecific antigen-binding fragment of claim 140, wherein the linker is G4Sx3 (SEQ ID NO: 1115).

142. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 133-134 and 137-141, wherein at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: ^ ^Attorney Docket No.250298.000954 an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

143. The multispecific antibody or multispecific antigen-binding fragment of claim 142, wherein at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

144. The multispecific antibody or multispecific antigen-binding fragment of claim 142 or 143, wherein at least one of ABD1, ABD2, ABD3, and ABD4 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

145. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 133-134 and 137-144, wherein the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to TfR, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

146. The multispecific antibody or multispecific antigen-binding fragment of claim 145, wherein the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to TfR, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

147. The multispecific antibody or multispecific antigen-binding fragment of claim 145 or 146, wherein the other(s) of ABD1, ABD2, ABD3, and ABD4 binds to TfR, and wherein ^ ^Attorney Docket No.250298.000954 ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

148. A multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”), said Fc1 operably linked to a second heavy chain region of a second Fab (“Fab2”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a second Fc domain (“Fc2”), said Fc2 operably linked to a third heavy chain region of a third Fab (“Fab3”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ADB2”); and e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); wherein f) at least one of ABD1, ABD2, and ABD3 binds to a capsid of an AAV particle, and the other(s) of ABD1, ABD2, and ABD3 bind to TfR; g) Fc1 and / or Fc2 are derived from an IgG4 heavy chain constant region; and h) the first light chain, the second light chain, and the third light chain comprise the same amino acid sequence.

149. The multispecific antibody or multispecific antigen-binding fragment of claim 148, wherein two of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and one of ABD1, ABD2, and ABD3 binds to TfR.

150. The multispecific antibody or multispecific antigen-binding fragment of claim 148, wherein two of ABD1, ABD2, and ABD3 bind to TfR, and one of ABD1, ABD2, and ABD3 binds to the capsid of the AAV particle. ^ ^Attorney Docket No.250298.000954 151. The multispecific antibody or multispecific antigen-binding fragment of claim 149, wherein ABD1 binds to TfR, and ABD2 and ABD3 binds to the capsid of the AAV particle.

152. The multispecific antibody or multispecific antigen-binding fragment of claim 150, wherein ABD1 binds to the capsid of the AAV particle, and ABD2 and ABD3 binds to TfR.

153. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 148-152, wherein Fc1 and Fc2 form an Fc heterodimer.

154. The multispecific antibody or multispecific antigen-binding fragment of claim 153, wherein the Fc1 and / or Fc2 in the Fc heterodimer comprise a knob-in-hole mutation as compared to a wild type Fc domain.

155. The multispecific antibody or multispecific antigen-binding fragment of claim 153 or 154, wherein one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions S354C and T366W (according to EU numbering) as compared to a wild type Fc domain, and the other of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions Y349C, T366S, L368A, and Y407V (according to EU numbering) as compared to a wild type Fc domain.

156. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 153-155, wherein at least one of Fc1 and Fc2 in the Fc heterodimer comprises a star mutation as compared to a wild type Fc domain.

157. The multispecific antibody or multispecific antigen-binding fragment of claim 156, wherein one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid mutations H435R and / or Y436F (according to EU numbering) as compared to a wild type Fc domain.

158. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 148-157, wherein Fc1 and / or Fc2 comprises the amino acid sequence of SEQ ID NO: 1397 or 1511, or a variant thereof.

159. The multispecific antibody or multispecific antigen-binding fragment of any one of ^ ^Attorney Docket No.250298.000954 claims 148-158, wherein the first light chain, the second light chain, and the third light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof.

160. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 148-159, wherein Fc1 and / or Fc2 is linked to the second heavy chain region and the third heavy chain region via a linker.

161. The multispecific antibody or multispecific antigen-binding fragment of claim 160, wherein the linker is or comprises a multimer of GnS (SEQ ID NO: 239) or SGn (SEQ ID NO: 240), wherein n is an integer from 1 to 10.

162. The multispecific antibody or multispecific antigen-binding fragment of claim 160, wherein the linker is or comprises a multimer of G4S (SEQ ID NO: 242).

163. The multispecific antibody or multispecific antigen-binding fragment of claim 162, wherein the linker is G4Sx3 (SEQ ID NO: 1115).

164. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 148-150 and 153-163, wherein at least one of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, and / or ABD3 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

165. The multispecific antibody or multispecific antigen-binding fragment of claim 164, wherein at least one of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, and / or ABD3 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

166. The multispecific antibody or multispecific antigen-binding fragment of claim 164 or 165, wherein at least one of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, and / or ABD3 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid ^ ^Attorney Docket No.250298.000954 sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

167. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 148-150 and 153-166, wherein the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and wherein ABD1, ABD2, and / or ABD3 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

168. The multispecific antibody or multispecific antigen-binding fragment of claim 167, wherein the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and wherein ABD1, ABD2, ABD3, and / or ABD4 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

169. The multispecific antibody or multispecific antigen-binding fragment of claim 167 or 168, wherein the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and wherein ABD1, ABD2, and / or ABD3 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

14.

170. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 151 and 153-169, wherein: i) ABD1 binds to TfR; j) ABD2 and ABD3 bind to the capsid of the AAV particle; k) Fc1 comprises the amino acid sequence of SEQ ID NO: 1397, or a variant thereof; and l) Fc2 comprises the amino acid sequence of SEQ ID NO: 1511, or a variant thereof.

171. A multispecific antibody, or a multispecific antigen-binding fragment thereof, comprising: ^ ^Attorney Docket No.250298.000954 a) a first polypeptide chain comprising, in an N- to C-terminal orientation: a first heavy chain region of a first Fab (“Fab1”) operably linked to a first Fc domain (“Fc1”); b) a second polypeptide chain comprising, in an N- to C-terminal orientation: a second heavy chain region of a second Fab (“Fab2”) operably linked to a second Fc domain (“Fc2”), said Fc2 operably linked to a third heavy chain region of a third Fab (“Fab3”); c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form Fab1, wherein Fab1 comprises a first antigen-binding domain (“ABD1”); d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form Fab2, wherein Fab2 comprises a second antigen-binding domain (“ABD2”); and e) a fifth polypeptide chain comprising a third light chain that pairs with the third heavy chain region to form Fab3, wherein Fab3 comprises a third antigen-binding domain (“ABD3”); wherein f) at least one of ABD1, ABD2, and ABD3 binds to a capsid of an AAV particle, and the other(s) of ABD1, ABD2, and ABD3 bind to TfR; g) Fc1 and / or Fc2 are derived from an IgG4 heavy chain constant region; and h) the first light chain, the second light chain, and the third light chain comprise the same amino acid sequence.

172. The multispecific antibody or multispecific antigen-binding fragment of claim 171, wherein two of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and one of ABD1, ABD2, and ABD3 binds to TfR.

173. The multispecific antibody or multispecific antigen-binding fragment of claim 171, wherein two of ABD1, ABD2, and ABD3 bind to TfR, and one of ABD1, ABD2, and ABD3 binds to the capsid of the AAV particle.

174. The multispecific antibody or multispecific antigen-binding fragment of claim 172, wherein ABD2 and ABD3 bind to the capsid of the AAV particle, and ABD1 binds to TfR.

175. The multispecific antibody or multispecific antigen-binding fragment of claim 173, wherein ABD2 and ABD3 bind to TfR, and ABD1 binds to the capsid of the AAV particle.

176. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 171-175, wherein Fc1 and Fc2 form an Fc heterodimer. ^ ^Attorney Docket No.250298.000954 177. The multispecific antibody or multispecific antigen-binding fragment of claim 176, wherein the Fc1 and / or Fc2 in the Fc heterodimer comprise a knob-in-hole mutation as compared to a wild type Fc domain.

178. The multispecific antibody or multispecific antigen-binding fragment of claim 176 or 177, wherein one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions S354C and T366W (according to EU numbering) as compared to a wild type Fc domain, and the other of Fc1 and Fc2 in the Fc heterodimer comprises amino acid substitutions Y349C, T366S, L368A, and Y407V (according to EU numbering) as compared to a wild type Fc domain.

179. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 176-178, wherein at least one of Fc1 and Fc2 in the Fc heterodimer comprises a star mutation as compared to a wild type Fc domain.

180. The multispecific antibody or multispecific antigen-binding fragment of claim 179, wherein one of Fc1 and Fc2 in the Fc heterodimer comprises amino acid mutations H435R and / or Y436F (according to EU numbering) as compared to a wild type Fc domain.

181. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 171-180, wherein Fc1 and / or Fc2 comprises the amino acid sequence of SEQ ID NO: 1397 or 1511, or a variant thereof.

182. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 171-181, wherein the first light chain, the second light chain, and the third light chain comprise the amino acid sequence of SEQ ID NO: 20, or a variant thereof.

183. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 171-182, wherein Fc2 is linked to the third heavy chain region via a linker.

184. The multispecific antibody or multispecific antigen-binding fragment of claim 183, wherein the linker is or comprises a multimer of GnS (SEQ ID NO: 239) or SGn (SEQ ID NO: 240), wherein n is an integer from 1 to 10. ^ ^Attorney Docket No.250298.000954 185. The multispecific antibody or multispecific antigen-binding fragment of claim 183, wherein the linker is or comprises a multimer of G4S (SEQ ID NO: 242).

186. The multispecific antibody or multispecific antigen-binding fragment of claim 185, wherein the linker is G4Sx3 (SEQ ID NO: 1115).

187. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 171-173 and 176-186, wherein at least one of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, and / or ABD3 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

188. The multispecific antibody or multispecific antigen-binding fragment of claim 187, wherein at least one of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, and / or ABD3 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 52, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

189. The multispecific antibody or multispecific antigen-binding fragment of claim 187 or 188, wherein at least one of ABD1, ABD2, and ABD3 bind to the capsid of the AAV particle, and wherein ABD1, ABD2, and / or ABD3 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 54, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 58; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

190. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 171-173 and 176-189, wherein the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and wherein ABD1, ABD2, and / or ABD3 comprises: an HCVR that comprises an HCDR1, HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and / or an LCVR that comprises an LCDR1, LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence of SEQ ID NO: 10, or a variant thereof. ^ ^Attorney Docket No.250298.000954 191. The multispecific antibody or multispecific antigen-binding fragment of claim 190, wherein the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and wherein ABD1, ABD2, and / or ABD3 comprises: an HCVR that comprises the amino acid sequence of SEQ ID NO: 501, or a variant thereof, and an LCVR that comprises the amino acid sequence of SEQ ID NO: 10, or a variant thereof.

192. The multispecific antibody or multispecific antigen-binding fragment of claim 190 or 191, wherein the other(s) of ABD1, ABD2, and ABD3 binds to TfR, and wherein ABD1, ABD2, and / or ABD3 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 502, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 503, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 504; and / or an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

14.

193. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 174 and 176-192, wherein: i) ABD1 binds to TfR; j) ABD2 and ABD3 bind to the capsid of the AAV particle; k) Fc1 comprises the amino acid sequence of SEQ ID NO: 1397, or a variant thereof; and l) Fc2 comprises the amino acid sequence of SEQ ID NO: 1511, or a variant thereof.

194. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 1-193, wherein the AAV is wild type.

195. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 1-193, wherein the AAV particle comprises one or more mutations in one or more AAV capsid proteins inhibiting the natural tropism of said AAV particle.

196. The multispecific antibody or multispecific antigen-binding fragment of any one of claims 1-195, wherein the multispecific antibody or multispecific antigen-binding fragment is a bispecific antibody or bispecific antigen-binding fragment thereof.

197. A pharmaceutical composition comprising the multispecific antibody or multispecific antigen-binding fragment of any one of claims 1-196, and a pharmaceutically ^ ^Attorney Docket No.250298.000954 acceptable carrier or excipient.

198. A molecular complex comprising an AAV particle bound to one or more multispecific antibodies and / or multispecific antigen-binding fragments of any one of claims 1-196.

199. The molecular complex of claim 198, wherein said AAV particle comprises one or more mutations in one or more AAV capsid proteins inhibiting the natural tropism of said AAV particle.

200. A pharmaceutical composition comprising the molecular complex of claim 198 or 199 and a pharmaceutically acceptable carrier or excipient.

201. A method of preparing the molecular complex of claim 198 or 199, comprising incubating said AAV particle in the presence of said one or more multispecific antibodies and / or multispecific antigen-binding fragments under conditions allowing specific binding of said one or more multispecific antibodies and / or multispecific antigen-binding fragments to said AAV particle capsid.

202. A method for targeting an AAV particle to a cell expressing a molecule on the cell surface, comprising contacting the cell with the molecular complex of claim 198 or 199, or the pharmaceutical composition of claim 200, wherein said molecular complex comprises one or more multispecific antibodies and / or multispecific antigen-binding fragments which bind to said molecule on the cell surface.

203. A method for delivering a polynucleotide to a cell expressing a molecule on the cell surface, comprising contacting the cell with the molecular complex of claim 198 or 199 or the pharmaceutical composition of claim 200, wherein said molecular complex comprises the AAV particle comprising said polynucleotide and bound to one or more multispecific antibodies and / or multispecific antigen-binding fragments which bind to said molecule on the cell surface.

204. The method of claim 202 or 203, wherein said cell is in a subject and said molecular complex is administered to the subject.

205. The method of any one of claims 202-204, wherein said AAV particle does not target said cell in the absence of said one or more multispecific antibodies and / or ^ ^Attorney Docket No.250298.000954 multispecific antigen-binding fragments. ^ ^

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