PTK7 binding proteins with PH dependent binding and uses thereof

By developing antigen-binding protein constructs of anti-PTK7 antibodies, using the extracellular domain of PTK7 to screen antibody variants, and reducing toxicity through pH engineering, the problems of high toxicity in target cells and narrow therapeutic windows are solved. , achieving more efficient tumor treatment effects.

CN119421894APending Publication Date: 2025-02-11MYTHIC THERAPEUTICS INC
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Patent Information

Application Number
CN202380048992.2
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Priority Date
2022-05-19
Filing Date
2023-05-19
Publication Date
2025-02-11

AI Technical Summary

Technical Problem

The existing anti-PTK7 antibody drugs are highly toxic in target cells, resulting in damage to normal tissues, and have a limited treatment window, making it difficult to effectively target tumors with low PTK7 expression.

Method used

Develop an antigen-binding protein (ABP) construct to screen immune rabbit antibodies using the extracellular domain of PTK7 to generate antibody variants with higher PTK7 specific binding capacity and stronger internalization capacity, and engineer it through pH Reduce the toxicity of "on-target" and broaden the treatment window.

Benefits of technology

It improves the toxin release and cell killing ability of anti-PTK7 drugs in target cells, increases the uptake of drugs by tumor cells, and improves the pharmacokinetic properties of drugs, especially in patients with low PTK7-expressing tumors.

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Abstract

Provided herein are antigen binding protein constructs (ABPC) that bind to PTK7 and uses thereof.
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Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Patent Application Serial No. 63 / 365,005, filed May 19, 2022; the entire contents of which are incorporated herein by reference.

[0003] Sequence Listing

[0004] This application contains a sequence listing, which has been submitted electronically as an XML file named "45395-0057WO1_SL_ST26.XML". The XML file was created on May 15, 2023 and is 1,242,742 bytes in size. The entire contents of the material in the XML file are hereby incorporated by reference into this document.

[0005] Citation of Related Applications

[0006] The present disclosure relates to the field of antigen binding molecules. Technical Field

[0007] The present disclosure relates to the field of antigen binding molecules. Summary of the Invention

[0008] The present invention is based on the concept that antigen binding protein (ABP) constructs can be generated that exhibit enhanced efficacy of toxin release in target mammalian cells, increased cell killing, and increased endolysosomal delivery.

[0009] Protein tyrosine kinase-like 7 (PTK7), also known as colon cancer kinase 4 (CCK4), is a receptor tyrosine kinase encoded by the PTK7 gene in humans. "PTK7" and "CCK4" are used interchangeably herein. PTK7 is overexpressed in many major cancers (e.g., ovarian cancer, breast cancer, non-small cell lung cancer, and colon cancer), and the anti-PTK7 ADC cofetuzumab pelidotin is currently being evaluated in clinical trials. Reasoning that pH engineering of PTK7 antibodies could potentially reduce the uptake of the corresponding ADC in normal tissues, the applicants sought to develop anti-PTK7 binding proteins as disclosed herein. Compared to pH-independent anti-PTK7 ADCs, such anti-PTK7 pH-ADCs have the potential to mitigate "on-target" toxicity and broaden the therapeutic window. The pH-ADCs disclosed herein can also improve efficacy by increasing tumor uptake and improving PK properties, which may be particularly beneficial for patients with tumors characterized by low PTK7 expression.

[0010] As disclosed herein, the applicants performed a de novo antibody screening campaign using the extracellular domain of PTK7 to immunize rabbits. From hundreds of initial clones, the applicants selected a diverse panel of PTK7 binding proteins for subsequent pH engineering. As detailed herein, the applicants have generated over 500 variants of these initial rabbit monoclonal antibody (RabmAb) clones and similarly tested their ability to exhibit greater specific binding to PTK7 at pH 7.4 relative to pH 5.4, as well as increased internalization by PTK7-expressing cancer cells on their surfaces. Thus, provided herein are antigen binding protein constructs (ABPCs) and pharmaceutical compositions comprising an effective amount of such ABPCs, wherein the antigen binding protein constructs comprise: a first antigen binding domain (ABD) capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell, wherein: (a) the first ABD has a faster off-rate at a pH of about 4.0 to about 6.5 than at a pH of about 7.0 to about 8.0; and / or (b) the first ABD has a dissociation constant (K) at a pH of about 4.0 to about 6.5. D ) than K at a pH of about 7.0 to about 8.0 D In a specific embodiment,

[0011] In addition to generating the aforementioned anti-PTK7 antibodies and variants thereof (each disclosed herein for the first time), the present applicants also generated hundreds of variants starting with a parent PTK7 binding protein selected from cofilinumab, 7C8, and 12C6.

[0012] In some embodiments, the first ABD comprises a heavy chain variable domain (HCVD) of cofilotuzumab, 7C8, 12C6, MYT9345, MYT9359, MYT9361, MYT9412, MYT9460, MYT9792, or MYT9797, each HCVD optionally having at least 1 histidine substitution.

[0013] In some embodiments, the first ABD comprises a light chain variable domain (LCVD) of cofilinumab, 7C8, 12C6, MYT9345, MYT9359, MYT9361, MYT9412, MYT9460, MYT9792, or MYT9797, each LCVD optionally having at least 1 histidine substitution.

[0014] In some embodiments, the first ABD comprises one of: (a) HCVD of MYT9345 and / or LCVD of MYT9345; (b) HCVD of MYT9359 and / or LCVD of MYT9359; (c) HCVD of MYT9361 and / or LCVD of MYT9361; (d) HCVD of MYT9412 and / or LCVD of MYT9412; (e) HCVD of MYT9460 and / or LCVD of MYT9460. CVD; (f) HCVD of MYT9792 and / or LCVD of MYT9792; (g) HCVD of MYT9797 and / or LCVD of MYT9797; (h) HCVD of colestipol and / or LCVD of colestipol; (i) HCVD of 7C8 and / or LCVD of 7C8; and (j) HCVD of 12C6 and / or LCVD of 12C6, each HCVD or LCVD optionally having one or more amino acids substituted by histidine.

[0015] In some embodiments, the HCVD comprises one of the following: (a) HCVD comprising MYT9345 of SEQ ID NO:301; (b) HCVD comprising MYT9359 of SEQ ID NO:375; (c) HCVD comprising MYT9361 of SEQ ID NO:459; (d) HCVD comprising MYT9412 of SEQ ID NO:542; (e) HCVD comprising MYT9460 of SEQ ID NO:628; (f) HCVD comprising MYT9792 of SEQ ID NO:710; (g) HCVD comprising MYT9797 of SEQ ID NO:803; (h) HCVD comprising colefeucin of SEQ ID NO:1; (i) HCVD comprising 7C8 of SEQ ID NO:126; and (j) HCVD comprising 12C6 of SEQ ID NO:229.

[0016] In some embodiments, the LCVD comprises one of the following: (a) an LCVD comprising MYT9345 of SEQ ID NO: 302; (b) an LCVD comprising MYT9359 of SEQ ID NO: 376; (c) an LCVD comprising MYT9361 of SEQ ID NO: 460; (d) an LCVD comprising MYT9412 of SEQ ID NO: 543; (e) an LCVD comprising MYT9460 of SEQ ID NO: 629; (f) an LCVD comprising MYT9792 of SEQ ID NO: 711; (g) an LCVD comprising MYT9797 of SEQ ID NO: 804; (h) an LCVD comprising cofetizumab of SEQ ID NO: 1; (i) an LCVD comprising 7C8 of SEQ ID NO: 127; and (j) an LCVD comprising 12C6 of SEQ ID NO: 229.

[0017] In some embodiments, the first ABD comprises an HCVD of one of the following: (a) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 303, 304, and 305, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 303, 304, and 305 are substituted with histidine; (b) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 377, 378, and 379, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 377, 378, and 379 are substituted with histidine; (c) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 461, 462, and 463, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 461, 462, and 463 are substituted with histidine; (d) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 461, 462, and 463, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 461, 462, and 463 are substituted with histidine; (e) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 630, 631 and 632, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 630, 631 and 632 are optionally substituted with histidine; (f) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 712, 713 and 714, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 712, 713 and 714 are optionally substituted with histidine; (g) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 805, 806 and 807, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 807, 808 and 809 are optionally substituted with histidine; (h) an HCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 3, 4 and 5, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 3, 4 and 5 are optionally substituted with histidine; (i) an HCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 128, 129 and 130, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 128, 129 and 130 are optionally substituted with histidine; and (j) an HCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 231, 232 and 233, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 231, 232 and 233 are optionally substituted with histidine.

[0018] In some embodiments, the first ABD comprises an LCVD of one of the following: (a) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 306, 307, and 308, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 306, 307, and 308 are optionally substituted with histidine; (b) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 380, 381, and 382, ​​respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 380, 381, and 382 are optionally substituted with histidine; (c) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 464, 465, and 466, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 464, 465, and 466 are substituted with histidine; (d) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 464, 465, and 466, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 464, 465, and 466 are substituted with histidine; (e) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 633, 634 and 635, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 633, 634 and 635 are substituted with histidine; (f) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 715, 716 and 717, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 715, 716 and 717 are substituted with histidine; (g) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 808, 809 and 810, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: (h) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 6, 7 and 8, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 6, 7 and 8 are optionally substituted with histidine; (i) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 131, 132 and 133, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 131, 132 and 133 are optionally substituted with histidine; and (j) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 234, 235 and 236, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 234, 235 and 236 are optionally substituted with histidine.

[0019] In some embodiments, the first ABD comprises one of the following: (a) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 303, 304, and 305, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 303, 304, and 305 are substituted with histidine; and / or an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 306, 307, and 308, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 306, 307, and 308 are optionally substituted with histidine; (b) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 377, 378, and 379, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 377, 378, and 379 are optionally substituted with histidine; and / or an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 377, 378, and 379, respectively. (c) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 461, 462 and 463, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 461, 462 and 463 are substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 464, 465 and 466, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 464, 465 and 466 are substituted with histidine; (d) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 544, 545 and 546, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 544, 545 and 546 are substituted with histidine. and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 547, 548 and 549, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 547, 548 and 549 are optionally substituted with histidine; (e) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 630, 631 and 632, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 630, 631 and 632 are optionally substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 633, 634 and 635, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 633, 634 and 635 are substituted with histidine;(f) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 712, 713 and 714, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 712, 713 and 714 are substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 715, 716 and 717, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 715, 716 and 717 are substituted with histidine; (g) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 805, 806 and 807, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 805, 806 and 807 are optionally substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 808, 809 and 810, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: (i) an HCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 131, 132 and 133, wherein a total of one or more amino acid positions in SEQ ID NOs: 131, 132 and 133 are optionally substituted with histidine; and / or an LCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 134, 135 and 136, wherein a total of one or more amino acid positions in SEQ ID NOs: 137, 138 and 139 are optionally substituted with histidine; (i) an HCVD comprising the CDR1, CDR2, and CDR3 of SEQ ID NOs: 231, 232, and 233, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 134, 135, and 136 are substituted with histidine; and (ii) an HCVD comprising the CDR1, CDR2, and CDR3 of SEQ ID NOs: 231, 232, and 233, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 231, 232, and 233 are substituted with histidine; and / or an LCVD comprising the CDR1, CDR2, and CDR3 of SEQ ID NOs: 234, 235, and 236, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 234, 235, and 236 are substituted with histidine.

[0020] In some embodiments, the first ABD comprises one of the following: (a) an HCVD having at least 90% identity to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; (b) an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: 375; (c) an HCVD having at least 90% identity to SEQ ID NO: 459, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: NO:459, wherein the HCVD comprises a histidine at one or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111; (d) an HCVD at least 90% identical to SEQ ID NO:542, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 of SEQ ID NO:542; (e) an HCVD at least 90% identical to SEQ ID NO:628, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 of SEQ ID NO:628; (f) an HCVD at least 90% identical to SEQ ID NO:710, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: NO:710, a histidine at one or more positions selected from the group consisting of: 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113; and (g) a HCVD having at least 90% identity to SEQ ID NO:803, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107 in SEQ ID NO:803.

[0021] In some embodiments, the first ABD comprises one of the following: (a) an LCVD having at least 90% identity to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) an LCVD having at least 90% identity to SEQ ID NO: 376, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376; (c) an LCVD having at least 90% identity to SEQ ID NO: 460, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: (d) an LCVD at least 90% identical to SEQ ID NO: 543, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 of SEQ ID NO: 543; (e) an LCVD at least 90% identical to SEQ ID NO: 629, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 of SEQ ID NO: 629; (f) an LCVD at least 90% identical to SEQ ID NO: 711, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: NO:711, a histidine at one or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99; and (g) an LCVD at least 90% identical to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 of SEQ ID NO:804.

[0022] In some embodiments, the first ABD comprises one of the following: (a) an HCVD having at least 90% identity to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; (b) an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: 375; (c) an HCVD having at least 90% identity to SEQ ID NO: 459, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: NO:459, wherein the HCVD comprises a histidine at two or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111; (d) an HCVD at least 90% identical to SEQ ID NO:542, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 of SEQ ID NO:542; (e) an HCVD at least 90% identical to SEQ ID NO:628, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 of SEQ ID NO:628; (f) an HCVD at least 90% identical to SEQ ID NO:710, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: NO:710, a histidine at two or more positions selected from the group consisting of: 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113; and (g) a HCVD at least 90% identical to SEQ ID NO:803, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107 in SEQ ID NO:803.

[0023] In some embodiments, the first ABD comprises one of the following: (a) an LCVD having at least 90% identity to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) an LCVD having at least 90% identity to SEQ ID NO: 376, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376; (c) an LCVD having at least 90% identity to SEQ ID NO: 460, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: NO: 460, wherein the LCVD comprises a histidine at two or more positions selected from the group consisting of: 30, 31, 33, 51, 92, and 95; (d) an LCVD at least 90% identical to SEQ ID NO: 543, wherein the LCVD optionally comprises a histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98; (e) an LCVD at least 90% identical to SEQ ID NO: 629, wherein the LCVD optionally comprises a histidine at two or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100; (f) an LCVD at least 90% identical to SEQ ID NO: 711, wherein the LCVD optionally comprises a histidine at two or more positions selected from the group consisting of: NO:711, a histidine at two or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99; and (g) an LCVD at least 90% identical to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 of SEQ ID NO:804.

[0024] In some embodiments, the first ABD comprises one of: (a) a HCVD at least 90% identical to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; and / or a LCVD at least 90% identical to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) a HCVD at least 90% identical to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: NO: 375, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 of SEQ ID NO: 375; and / or an LCVD having at least 90% identity to SEQ ID NO: 376, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 of SEQ ID NO: 376; (c) an HCVD having at least 90% identity to SEQ ID NO: 459, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111 of SEQ ID NO: 459; and / or an LCVD having at least 90% identity to SEQ ID NO: 376 (d) an HCVD at least 90% identical to SEQ ID NO: 542, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 of SEQ ID NO: 542; and / or an LCVD at least 90% identical to SEQ ID NO: 543, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 of SEQ ID NO: 543;(e) a HCVD at least 90% identical to SEQ ID NO: 628, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 in SEQ ID NO: 628; and / or a LCVD at least 90% identical to SEQ ID NO: 629, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 in SEQ ID NO: 629; (f) a HCVD at least 90% identical to SEQ ID NO: 710, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, NO:710, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113; and / or an LCVD at least 90% identical to SEQ ID NO:711, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99 of SEQ ID NO:711; (g) an HCVD at least 90% identical to SEQ ID NO:803, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, NO:803, a histidine at one or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107; and / or an LCVD having at least 90% identity to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 of SEQ ID NO:804.

[0025] In some embodiments, the first ABD comprises one of: (a) an HCVD of one of SEQ ID NO: 301, or 309-342; (b) an HCVD of one of SEQ ID NO: 375, or 383-423; (c) an HCVD of one of SEQ ID NO: 459, or 467-511; (d) an HCVD of one of SEQ ID NO: 542, or 550-592; (e) an HCVD of one of SEQ ID NO: 628, or 636-675; (f) an HCVD of one of SEQ ID NO: 710, or 718-767; and (g) an HCVD of one of SEQ ID NO: 803, or 811-854; and / or the first ABD comprises one of: (a) an LCVD of one of SEQ ID NO: 302, or 343-374; (b) an LCVD of SEQ ID NO: 542, or 550-592. NO: 376, or one of 424-458; (c) an LCVD of SEQ ID NO: 460, or one of 512-541; (d) an LCVD of SEQ ID NO: 543, or one of 593-627; (e) an LCVD of SEQ ID NO: 629, or one of 676-709; (f) an LCVD of SEQ ID NO: 711, or one of 768-802; and (g) an LCVD of SEQ ID NO: 804, or one of 855-892.

[0026] In some embodiments, the first ABD comprises one of:

[0027] (a) an HCVD of one of SEQ ID NOs: 301, 309-342, or 309-342; and / or an LCVD of one of SEQ ID NOs: 302, 343-374, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 301 and an LCVD of SEQ ID NO: 302; (ii) an HCVD of SEQ ID NO: 301 and an LCVD that is not one of SEQ ID NOs: 344, 349-352, 354, 359-361, 363, 366-368, 370, and 373; or (iii) an LCVD of SEQ ID NO: 302 and an HCVD that is not one of SEQ ID NOs: 312, 313, 315, 319-323, 327, 329, 335, 340, and 341;

[0028] (b) an HCVD of SEQ ID NO: 375, or one of 383-423; and / or an LCVD of SEQ ID NO: 376, or one of 424-458, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 375 and an LCVD of SEQ ID NO: 376; (ii) an HCVD of SEQ ID NO: 375 and an LCVD that is not one of SEQ ID NOs: 425, 429, 430, 431, 432, 433, 435, 436, 437, 438, 442, 444, 445, 446, 449, 450, 453, and 455; or (iii) an LCVD of SEQ ID NO: 376 and an LCVD that is not one of SEQ ID NOs: HCVD of one of NO: 383, 384, 387, 389, 391, 394, 395, 398, 401, 402, 406, 410, 412, and 421;

[0029] (c) an HCVD of SEQ ID NO: 459, or one of 467-511; and / or an LCVD of SEQ ID NO: 460, or one of 512-541, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 459 and an LCVD of SEQ ID NO: 460; (ii) an HCVD of SEQ ID NO: 459 and an LCVD that is not one of SEQ ID NOs: 518, 519, 521, 524, 533, and 536; or (iii) an LCVD of SEQ ID NO: 460 and an HCVD that is not one of SEQ ID NOs: 473, 496, 498, 499, 503, and 508;

[0030] (d) an HCVD of SEQ ID NO: 542, or one of 550-592; and / or an LCVD of SEQ ID NO: 543, or one of 593-627, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 542 and an LCVD of SEQ ID NO: 543; (ii) an HCVD of SEQ ID NO: 542 and an LCVD that is not one of SEQ ID NOs: 594, 598, 599, 600, 601, 611, 614, and 620; or (iii) an LCVD of SEQ ID NO: 543 and an HCVD that is not one of SEQ ID NOs: 551, 553, 554, 555, 556, 563, 565, 568, 582, 584, and 585;

[0031] (e) an HCVD of SEQ ID NO: 628, or one of 636-675; and / or an LCVD of SEQ ID NO: 629, or one of 676-709, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 628 and an LCVD of SEQ ID NO: 629; (ii) an HCVD of SEQ ID NO: 628 and an LCVD that is not one of SEQ ID NOs: 677, 678, 680, 681, 685, 688, 692, 694, 696, 700, 701, 702, 703, 704, and 705; or (iii) an LCVD of SEQ ID NO: 629 and an LCVD that is not one of SEQ ID NOs: HCVD of one of ID NOs: 636, 638, 640, 646, 648, 649, 650, 651, 652, 653, 666, 667, 668, and 669;

[0032] (f) an HCVD of SEQ ID NO: 710, or one of 718-767; and / or an LCVD of SEQ ID NO: 711, or one of 768-802, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 710 and an LCVD of SEQ ID NO: 711; (ii) an HCVD of SEQ ID NO: 710 and an LCVD that is not one of SEQ ID NOs: 769, 771, 773, 774, 779, 780, 785, 786, 788, 790, 791, 792, 795, and 796; or (iii) an LCVD of SEQ ID NO: 711 and an LCVD that is not one of SEQ ID NOs: HCVD of one of NO: 721, 722, 723, 725, 727, 728, 731, 735, 736, 743, 744, 745, 746, 748, 749, 751, 753, 755, 756, 757, 758, and 761; and

[0033] (g) an HCVD of SEQ ID NO: 803, or one of 811-854; and / or an LCVD of SEQ ID NO: 804, or one of 855-892, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 803 and an LCVD of SEQ ID NO: 804; (ii) an HCVD of SEQ ID NO: 803 and an LCVD that is not one of SEQ ID NOs: 862, 864-866, 868, 870, 881, and 882; or (iii) an LCVD of SEQ ID NO: 804 and an HCVD that is not one of SEQ ID NOs: 818, 821, 824, 826-829, 835, 841, 848, and 850.

[0034] In some embodiments, the first antigen binding domain (ABD) comprises an HCVD of one of the following: (a) an HCVD having at least 90% identity to SEQ ID NO: 1, wherein the HCVD includes histidine at one or more positions of SEQ ID NO: 1 selected from the group consisting of: 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107; (b) an HCVD having at least 90% identity to SEQ ID NO: 126, wherein the HCVD includes histidine at one or more positions of SEQ ID NO: 126 selected from the group consisting of: 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, and 111; and (c) an HCVD having at least 90% identity to SEQ ID NO: 126, wherein the HCVD includes histidine at one or more positions of SEQ ID NO: 1 NO:229 has an HCVD with at least 90% identity, wherein the HCVD comprises histidine at one or more positions selected from the group consisting of: 27, 32, 33, 34, 35, 51, 54, 56, 58, and 100 in SEQ ID NO:229. In some embodiments, the first ABD comprises an LCVD of one of the following: (a) an LCVD at least 90% identical to SEQ ID NO: 2, wherein the LCVD includes a histidine at one or more positions in SEQ ID NO: 2 selected from the group consisting of: 25, 29, 31, 35, 60, 93, and 94; (b) an LCVD at least 90% identical to SEQ ID NO: 127, wherein the LCVD includes a histidine at one or more positions in SEQ ID NO: 127 selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94; and (c) an LCVD at least 90% identical to SEQ ID NO: 230, wherein the LCVD includes a histidine at one or more positions in SEQ ID NO: 230 selected from the group consisting of: 30, 31, 33, 51, 53, 57, 91, 92, 94, and 99.

[0035] In some embodiments, the first ABD comprises an HCVD of one of the following: (a) an HCVD having at least 90% identity to SEQ ID NO: 1, wherein the HCVD includes histidine at two or more positions in SEQ ID NO: 1 selected from the group consisting of: 27, 29, 31, 34, and 53; and (b) an HCVD having at least 90% identity to SEQ ID NO: 126, wherein the HCVD includes histidine at two or more positions in SEQ ID NO: 126 selected from the group consisting of: 53, 56, 57, 102, and 105. In some embodiments, the first ABD comprises an LCVD of one of the following: (a) an LCVD at least 90% identical to SEQ ID NO: 2, wherein the LCVD includes histidine at two or more positions in SEQ ID NO: 2 selected from the group consisting of: 31, 60, and 93; and (b) an LCVD at least 90% identical to SEQ ID NO: 127, wherein the LCVD includes histidine at two or more positions in SEQ ID NO: 127 from the group consisting of: 28 and 90.

[0036] In some embodiments, the first ABD comprises one of: (a) an HCVD having at least 90% identity to SEQ ID NO: 1, wherein the HCVD includes a histidine at one or more positions selected from the group consisting of: 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107 in SEQ ID NO: 1; and / or an LCVD having at least 90% identity to SEQ ID NO: 2, wherein the LCVD includes a histidine at one or more positions selected from the group consisting of: 25, 29, 31, 35, 60, 93, or 94 in SEQ ID NO: 2; (b) an HCVD having at least 90% identity to SEQ ID NO: 126, wherein the HCVD includes a histidine at one or more positions selected from the group consisting of: 25, 29, 31, 35, 60, 93, or 94 in SEQ ID NO: 2. NO: 126 at one or more positions selected from the group consisting of: 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, and 111; and / or an LCVD having at least 90% identity to SEQ ID NO: 127, wherein the LCVD comprises a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94 of SEQ ID NO: 127; and (c) an HCVD having at least 90% identity to SEQ ID NO: 229, wherein the HCVD comprises a histidine at one or more positions selected from the group consisting of: 27, 32, 33, 34, 35, 51, 54, 56, 58, and 100 of SEQ ID NO: 229; and / or an LCVD having at least 90% identity to SEQ ID NO: 127, wherein the LCVD comprises a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, NO: 230. An LCVD having at least 90% identity, wherein the LCVD comprises histidine at one or more positions selected from the group consisting of 30, 31, 33, 51, 53, 57, 91, 92, 94, and 99 in SEQ ID NO: 230.

[0037] In some embodiments, the first ABD comprises an HCVD of one of the following: (a) an HCVD of SEQ ID NO: 1, 14, 17, 18, 19, 20, 21, 22, 24, 25, 29, 30, 31, 33, 34, 40, 44, 46, 48, 49, 53, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98, 99, 100, 101, 102, 103, 104, or 105; (b) an HCVD of SEQ ID NO: NO:126, 147, 148, 150, 151, 154, 166, 167, 168, 169, 170, 172, 173, 174, 175, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 224, 225, 226 or 227; and (c) an HCVD of SEQ ID NO:229, 238, 243, 244, 245, 246, 248, 251, 253, 255 or 267.

[0038] In some embodiments, the first ABD comprises an LCVD of one of the following: (a) an LCVD of SEQ ID NO: 2, 56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, 122, 123, 124, or 125; (b) an LCVD of SEQ ID NO: 127, 181, 182, 184, 185, 187, 188, 189, 191, 199, 201, 203, or 228; and (c) an LCVD of SEQ ID NO: 230, 275, 276, 278, 281, 283, 287, 289, 290, 292, or 297.

[0039] In some embodiments, the first ABD comprises one of: (a) an HCVD of SEQ ID NO: 14, 17, 18, 19, 20, 21, 22, 24, 25, 29, 30, 31, 33, 34, 40, 44, 46, 48, 49, 53, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98, 99, 100, 101, 102, 103, 104, or 105; and / or an LCVD of SEQ ID NO: 2, 56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, 122, 123, 124, or 125, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 1 and an LCVD of SEQ ID NO: 2. NO:2; (ii) the HCVD of SEQ ID NO:1 and an LCVD that is not one of SEQ ID NO:56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, and 122-125; or (iii) the LCVD of SEQ ID NO:2 and an HCVD that is not one of SEQ ID NO:14, 17-22, 24, 25, 29-31, 33, 34, 40, 44, 46, 48, 49, 53, 86-96, and 98-105; (b) the HCVD of SEQ ID NO:1 NO: 147, 148, 150, 151, 154, 166, 167, 168, 169, 170, 172, 173, 174, 175, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 224, 225, 226 or 227; and / or SEQ ID NO: 127, 181, 182, 184, 185, 187, 188, 189, 191, 199, 201, 203 or 228, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 126 and an LCVD of SEQ ID NO: 127; (ii) an LCVD of SEQ ID NO: (iii) an LCVD of SEQ ID NO: 127 and an HCVD that is not one of SEQ ID NOs: 147, 148, 150, 151, 154, 166-170, 172-175, 208-222, and 224-227;and (c) an HCVD of SEQ ID NO: 238, 243, 244, 245, 246, 248, 251, 253, 255, or 267; and / or an LCVD of SEQ ID NO: 230, 275, 276, 278, 281, 283, 287, 289, 290, 292, or 297, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 229 and an LCVD of SEQ ID NO: 230; (ii) an HCVD of SEQ ID NO: 229 and an LCVD that is not one of SEQ ID NOs: 275, 276, 278, 281, 283, 287, 289, 290, 292, and 297; and (iii) an LCVD of SEQ ID NO: 230 and an LCVD that is not one of SEQ ID NOs: HCVD of one of NOs: 238, 243-246, 248, 251, 253, 255, and 267;

[0040] In some embodiments, the ABPC is degraded in the target mammalian cell after the ABPC is internalized by the target mammalian cell.In some embodiments, the ABPC comprises a conjugated toxin, radioisotope, drug, or small molecule.

[0041] In some embodiments, the composition provides an increase in toxin release in target mammalian cells compared to a composition comprising the same amount of control ABPCs. In some embodiments, the composition provides an increase in toxin release in target mammalian cells by at least 20% compared to a composition comprising the same amount of control ABPCs. In some embodiments, the composition provides an increase in toxin release in target mammalian cells by at least 50% compared to a composition comprising the same amount of control ABPCs. In some embodiments, the composition provides an increase in toxin release in target mammalian cells by at least 2-fold compared to a composition comprising the same amount of control ABPCs. In some embodiments, the composition provides an increase in toxin release in target mammalian cells by at least 5-fold compared to a composition comprising the same amount of control ABPCs.

[0042] In some embodiments, the composition provides an increase in killing of target mammalian cells compared to a composition comprising the same amount of control ABPCs. In some embodiments, the composition provides an increase in killing of target mammalian cells by at least 20% or 50% compared to a composition comprising the same amount of control ABPCs. In some embodiments, the composition provides an increase in killing of target mammalian cells by at least 2-fold or 5-fold compared to a composition comprising the same amount of control ABPCs.

[0043] In some embodiments, the composition provides an increase in endolysosomal delivery in target mammalian cells compared to a composition comprising the same amount of control ABPCs. In some embodiments, the composition provides an increase in endolysosomal delivery in target mammalian cells compared to a composition comprising the same amount of control ABPCs by at least 20% or 50%. In some embodiments, the composition provides an increase in endolysosomal delivery in target mammalian cells by at least 2-fold or 5-fold compared to a composition comprising the same amount of control ABPCs.

[0044] In some embodiments, the composition causes less of a decrease in the level of PTK7 presented on the surface of a target mammalian cell than a composition comprising the same amount of a control ABPC. In some embodiments, the composition does not cause a detectable decrease in the level of PTK7 presented on the surface of a target mammalian cell.

[0045] Also provided herein are pharmaceutical compositions comprising an effective amount of an antigen binding protein construct (ABPC) comprising: a first ABD capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, wherein (a) the first ABD has a faster off-rate at a pH of about 4.0 to about 6.5 than at a pH of about 7.0 to about 8.0 or the dissociation constant (K) of the first ABD at a pH of about 4.0 to about 6.5 is greater than that at a pH of about 7.0 to about 8.0. D ) than K at a pH of about 7.0 to about 8.0 D and (b) the composition provides one or more of: an increase in toxin release in the target mammalian cells compared to a composition comprising the same amount of a control ABPC; an increase in target mammalian cell killing compared to a composition comprising the same amount of a control ABPC; and an increase in endolysosomal delivery in the target mammalian cells compared to a composition comprising the same amount of a control ABPC.

[0046] In some embodiments, the first ABD comprises an HCVD of one of the following: (a) an HCVD of MYT9345; (b) an HCVD of MYT9359; (c) an HCVD of MYT9361; (d) an HCVD of MYT9412; (e) an HCVD of MYT9460; (f) an HCVD of MYT9792; and (g) an HCVD of MYT9797, each HCVD optionally having one or more histidine substitutions. In some embodiments, the first ABD comprises an LCVD of one of the following: (a) an LCVD of MYT9345; (b) an LCVD of MYT9359; (c) an LCVD of MYT9361; (d) an LCVD of MYT9412; (e) an LCVD of MYT9460; (f) an LCVD of MYT9792; and (g) an LCVD of MYT9797, each LCVD optionally having one or more histidine substitutions.

[0047] In some embodiments, the first ABD comprises one of: (a) HCVD of MYT9345 and / or LCVD of MYT9345; (b) HCVD of MYT9359 and / or LCVD of MYT9359; (c) HCVD of MYT9361 and / or LCVD of MYT9361; (d) HCVD of MYT9412 and / or LCVD of MYT9412; (e) HCVD of MYT9460 and / or LCVD of MYT9460; (f) HCVD of MYT9792 and / or LCVD of MYT9792; and (g) HCVD of MYT9797 and / or LCVD of MYT9797; each HCVD or LCVD optionally having one or more histidine substitutions.

[0048] In some embodiments, the HCVD comprises one of: (a) an HCVD comprising MYT9345 of SEQ ID NO:301; (b) an HCVD comprising MYT9359 of SEQ ID NO:375; (c) an HCVD comprising MYT9361 of SEQ ID NO:459; (d) an HCVD comprising MYT9412 of SEQ ID NO:542; (e) an HCVD comprising MYT9460 of SEQ ID NO:628; (f) an HCVD comprising MYT9792 of SEQ ID NO:710; and (g) an HCVD comprising MYT9797 of SEQ ID NO:803. In some embodiments, the LCVD comprises one of the following: (a) an LCVD comprising MYT9345 of SEQ ID NO: 302; (b) an LCVD comprising MYT9359 of SEQ ID NO: 376; (c) an LCVD comprising MYT9361 of SEQ ID NO: 460; (d) an LCVD comprising MYT9412 of SEQ ID NO: 543; (e) an LCVD comprising MYT9460 of SEQ ID NO: 629; (f) an LCVD comprising MYT9792 of SEQ ID NO: 711; and (g) an LCVD comprising MYT9797 of SEQ ID NO: 804.

[0049] In some embodiments, the first ABD comprises an HCVD comprising one of the following: (a) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 303, 304, and 305, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 303, 304, and 305 are substituted with histidine; (b) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 377, 378, and 379, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 377, 378, and 379 are optionally substituted with histidine; (c) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 461, 462, and 463, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 461, 462, and 463 are substituted with histidine; (d) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 461, 462, and 463, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 461, 462, and 463 are substituted with histidine; (e) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 630, 631 and 632, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 630, 631 and 632 are optionally substituted with histidine; (f) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 712, 713 and 714, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 712, 713 and 714 are optionally substituted with histidine; and (g) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 805, 806 and 807, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 807 and 808 are optionally substituted with histidine. In total, one or more amino acid positions in NO:805, 806 and 807 are substituted with histidine.

[0050] In some embodiments, the first ABD comprises an LCVD of one of the following: (a) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 306, 307, and 308, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 306, 307, and 308 are optionally substituted with histidine; (b) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 380, 381, and 382, ​​respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 380, 381, and 382 are optionally substituted with histidine; (c) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 464, 465, and 466, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 464, 465, and 466 are optionally substituted with histidine; (d) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 464, 465, and 466, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 464, 465, and 466 are optionally substituted with histidine; (e) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 633, 634 and 635, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 633, 634 and 635 are substituted with histidine; (f) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 715, 716 and 717, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 715, 716 and 717 are substituted with histidine; and (g) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 808, 809 and 810, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 808, 809 and 810 are substituted with histidine. In total, one or more amino acid positions in NO:808, 809 and 810 are substituted with histidine.

[0051] In some embodiments, the first ABD comprises one of the following: (a) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 303, 304, and 305, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 303, 304, and 305 are substituted with histidine; and / or an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 306, 307, and 308, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 306, 307, and 308 are optionally substituted with histidine; (b) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 377, 378, and 379, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 377, 378, and 379 are substituted with histidine; and / or an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 380, 381, and 382, ​​respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 383, 384, and 385 are optionally substituted with histidine. (c) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 461, 462 and 463, respectively, wherein one or more amino acid positions in total are substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 464, 465 and 466, respectively, wherein one or more amino acid positions in total are substituted with histidine; (d) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 544, 545 and 546, respectively, wherein one or more amino acid positions in total are optionally substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 544, 545 and 546, respectively, wherein one or more amino acid positions in total are optionally substituted with histidine; (e) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 630, 631 and 632, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 630, 631 and 632 are substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 633, 634 and 635, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 633, 634 and 635 are substituted with histidine;(f) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 712, 713 and 714, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 712, 713 and 714 are substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 715, 716 and 717, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 715, 716 and 717 are substituted with histidine; and (g) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 805, 806 and 807, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 805, 806 and 807 are optionally substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 808, 809 and 810, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 810 One or more amino acid positions in NO:808, 809 and 810 are substituted with histidine.

[0052] In some embodiments, the first ABD comprises an HCVD of one of the following: (a) an HCVD at least 90% identical to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; (b) an HCVD at least 90% identical to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: 375; (c) an HCVD at least 90% identical to SEQ ID NO: 459, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: NO:459, wherein the HCVD comprises a histidine at one or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111; (d) an HCVD at least 90% identical to SEQ ID NO:542, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 of SEQ ID NO:542; (e) an HCVD at least 90% identical to SEQ ID NO:628, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 of SEQ ID NO:628; (f) an HCVD at least 90% identical to SEQ ID NO:710, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: NO:710, a histidine at one or more positions selected from the group consisting of: 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113; and (g) a HCVD having at least 90% identity to SEQ ID NO:803, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107 in SEQ ID NO:803.

[0053] In some embodiments, the first ABD comprises an LCVD of one of the following: (a) an LCVD at least 90% identical to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) an LCVD at least 90% identical to SEQ ID NO: 376, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376; (c) an LCVD at least 90% identical to SEQ ID NO: 460, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: (d) an LCVD at least 90% identical to SEQ ID NO: 543, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 of SEQ ID NO: 543; (e) an LCVD at least 90% identical to SEQ ID NO: 629, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 of SEQ ID NO: 629; (f) an LCVD at least 90% identical to SEQ ID NO: 711, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: NO:711, a histidine at one or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99; and (g) a LCVD at least 90% identical to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 in SEQ ID NO:804.

[0054] In some embodiments, the first ABD comprises an HCVD of one of the following: (a) an HCVD at least 90% identical to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; (b) an HCVD at least 90% identical to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: 375; (c) an HCVD at least 90% identical to SEQ ID NO: 459, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: NO:459, wherein the HCVD comprises a histidine at two or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111; (d) an HCVD at least 90% identical to SEQ ID NO:542, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 of SEQ ID NO:542; (e) an HCVD at least 90% identical to SEQ ID NO:628, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 of SEQ ID NO:628; (f) an HCVD at least 90% identical to SEQ ID NO:710, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: NO:710, a histidine at two or more positions selected from the group consisting of: 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113; and (g) a HCVD at least 90% identical to SEQ ID NO:803, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107 in SEQ ID NO:803.

[0055] In some embodiments, the first ABD comprises an LCVD of one of the following: (a) an LCVD at least 90% identical to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) an LCVD at least 90% identical to SEQ ID NO: 376, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376; (c) an LCVD at least 90% identical to SEQ ID NO: 460, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: (d) an LCVD at least 90% identical to SEQ ID NO: 543, wherein the LCVD optionally includes histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 in SEQ ID NO: 543; (e) an LCVD at least 90% identical to SEQ ID NO: 629, wherein the LCVD optionally includes histidine at two or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 in SEQ ID NO: 629; (f) an LCVD at least 90% identical to SEQ ID NO: 711, wherein the LCVD optionally includes histidine at two or more positions selected from the group consisting of: NO:711, a histidine at two or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99; and (g) a LCVD at least 90% identical to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 of SEQ ID NO:804.

[0056] In some embodiments, the first ABD comprises one of the following: (a) a HCVD having at least 90% identity to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301, and / or a LCVD having at least 90% identity to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) a HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: NO: 375, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 of SEQ ID NO: 375, and / or a LCVD with at least 90% identity to SEQ ID NO: 376, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 of SEQ ID NO: 376; (c) an HCVD with at least 90% identity to SEQ ID NO: 459, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111 of SEQ ID NO: 459, and / or a LCVD with at least 90% identity to SEQ ID NO: 376 (d) an HCVD at least 90% identical to SEQ ID NO: 542, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 of SEQ ID NO: 542, and / or an LCVD at least 90% identical to SEQ ID NO: 543, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 of SEQ ID NO: 543;(e) a HCVD at least 90% identical to SEQ ID NO: 628, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 of SEQ ID NO: 628, and / or a LCVD at least 90% identical to SEQ ID NO: 629, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 of SEQ ID NO: 629; (f) a HCVD at least 90% identical to SEQ ID NO: 710, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 of SEQ ID NO: NO: 710, and / or an LCVD at least 90% identical to SEQ ID NO: 711, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99 of SEQ ID NO: 711; and (g) an HCVD at least 90% identical to SEQ ID NO: 803, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99 of SEQ ID NO: 803. NO:803, a histidine at one or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107, and / or an LCVD having at least 90% identity to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99, in SEQ ID NO:804.

[0057] In some embodiments, the first ABD comprises one of: (a) an HCVD of SEQ ID NO: 301, or one of 309-342; (b) an HCVD of SEQ ID NO: 375, or one of 383-423; (c) an HCVD of SEQ ID NO: 459, or one of 467-511; (d) an HCVD of SEQ ID NO: 542, or one of 550-592; (e) an HCVD of SEQ ID NO: 628, or one of 636-675; (f) an HCVD of SEQ ID NO: 710, or one of 718-767; and (g) an HCVD of SEQ ID NO: 803, or one of 811-854. In some embodiments, the first ABD comprises one of: (a) an LCVD of SEQ ID NO: 302, or one of 343-374; (b) an LCVD of SEQ ID NO: 376, or one of 424-458; (c) an LCVD of SEQ ID NO: 460, or one of 512-541; (d) an LCVD of SEQ ID NO: 543, or one of 593-627; (e) an LCVD of SEQ ID NO: 629, or one of 676-709; (f) an LCVD of SEQ ID NO: 711, or one of 768-802; and (g) an LCVD of SEQ ID NO: 804, or one of 855-892.

[0058] In some embodiments, the first ABD comprises one of:

[0059] (a) an HCVD of any one of SEQ ID NOs: 301, 309, 342, or 309-342; and / or an LCVD of any one of SEQ ID NOs: 302, 343, 374, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 301 and an LCVD of SEQ ID NO: 302; (ii) an HCVD of SEQ ID NO: 301 and an LCVD that is not one of SEQ ID NOs: 344, 349-352, 354, 359-361, 363, 366-368, 370, and 373; or (iii) an HCVD that is not one of SEQ ID NOs: 312, 313, 315, 319-323, 327, 329, 335, 340, and 341 and an LCVD of SEQ ID NO: 302;

[0060] (b) an HCVD of any one of SEQ ID NO: 375, or one of 383-423; and / or an LCVD of any one of SEQ ID NO: 376, or one of 424-458, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 375 and an LCVD of SEQ ID NO: 376; (ii) an HCVD of SEQ ID NO: 375 and an LCVD that is not one of SEQ ID NOs: 425, 429, 430, 431, 432, 433, 435, 436, 437, 438, 442, 444, 445, 446, 449, 450, 453, and 455; or (iii) an LCVD that is not one of SEQ ID NOs: an HCVD of one of NOs: 383, 384, 387, 389, 391, 394, 395, 398, 401, 402, 406, 410, 412, and 421 and an LCVD of SEQ ID NO: 376;

[0061] (c) the HCVD of any one of SEQ ID NO: 459, or one of 467-511; and / or the LCVD of any one of SEQ ID NO: 460, or one of 512-541, wherein the first ABD does not comprise (i) the HCVD of SEQ ID NO: 459 and the LCVD of SEQ ID NO: 460; (ii) the HCVD of SEQ ID NO: 459 and an LCVD that is not one of SEQ ID NOs: 518, 519, 521, 524, 533, and 536; or (iii) an HCVD that is not one of SEQ ID NOs: 473, 496, 498, 499, 503, and 508 and an LCVD of SEQ ID NO: 460;

[0062] (d) the HCVD of any one of SEQ ID NO: 542, or one of 550-592; and / or the LCVD of any one of SEQ ID NO: 543, or one of 593-627, wherein the first ABD does not comprise (i) the HCVD of SEQ ID NO: 542 and the LCVD of SEQ ID NO: 543; (ii) the HCVD of SEQ ID NO: 542 and an LCVD that is not one of SEQ ID NOs: 594, 598, 599, 600, 601, 611, 614, and 620; or (iii) an HCVD that is not one of SEQ ID NOs: 551, 553, 554, 555, 556, 563, 565, 568, 582, 584, and 585 and an LCVD of SEQ ID NO: 543;

[0063] (e) an HCVD of any one of SEQ ID NO: 628, or one of 636-675; and / or an LCVD of any one of SEQ ID NO: 629, or one of 676-709, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 628 and an LCVD of SEQ ID NO: 629; (ii) an HCVD of SEQ ID NO: 628 and an LCVD that is not one of SEQ ID NOs: 677, 678, 680, 681, 685, 688, 692, 694, 696, 700, 701, 702, 703, 704, and 705; or (iii) an LCVD that is not one of SEQ ID NOs: an HCVD of one of NOs: 636, 638, 640, 646, 648, 649, 650, 651, 652, 653, 666, 667, 668, and 669 and an LCVD of SEQ ID NO: 629;

[0064] (f) an HCVD of any one of SEQ ID NO: 710, or one of 718-767; and / or an LCVD of any one of SEQ ID NO: 711, or one of 768-802, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 710 and an LCVD of SEQ ID NO: 711; (ii) an HCVD of SEQ ID NO: 710 and an LCVD that is not one of SEQ ID NOs: 769, 771, 773, 774, 779, 780, 785, 786, 788, 790, 791, 792, 795, and 796; or (iii) an LCVD that is not one of SEQ ID NOs: HCVD of one of NOs: 721, 722, 723, 725, 727, 728, 731, 735, 736, 743, 744, 745, 746, 748, 749, 751, 753, 755, 756, 757, 758, and 761 and the LCVD of SEQ ID NO: 711; and

[0065] (g) an HCVD of any one of SEQ ID NO: 803, or one of 811-854; and / or an LCVD of any one of SEQ ID NO: 804, or one of 855-892, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 803 and an LCVD of SEQ ID NO: 804; (ii) an HCVD of SEQ ID NO: 803 and an LCVD that is not one of SEQ ID NOs: 862, 864-866, 868, 870, 881, and 882; or (iii) an HCVD that is not one of SEQ ID NOs: 818, 821, 824, 826-829, 835, 841, 848, and 850, and an LCVD of SEQ ID NO: 804.

[0066] In some embodiments, the composition provides an increase in toxin release in target mammalian cells compared to a composition comprising the same amount of control ABPCs. In some embodiments, the composition provides an increase in toxin release in target mammalian cells by at least 20% or 50% compared to a composition comprising the same amount of control ABPCs. In some embodiments, the composition provides an increase in toxin release in target mammalian cells by at least 2-fold or 5-fold compared to a composition comprising the same amount of control ABPCs.

[0067] In some embodiments, the composition provides an increase in killing of target mammalian cells compared to a composition comprising the same amount of control ABPCs. In some embodiments, the composition provides an increase in killing of target mammalian cells by at least 20% or 50% compared to a composition comprising the same amount of control ABPCs. In some embodiments, the composition provides an increase in killing of target mammalian cells by at least 2-fold or 5-fold compared to a composition comprising the same amount of control ABPCs.

[0068] In some embodiments, the composition provides an increase in endolysosomal delivery compared to a composition comprising the same amount of control ABPCs, including an increase in endolysosomal delivery of at least 20% or 50%. In some embodiments, the composition provides an increase in endolysosomal delivery of at least 2-fold or 5-fold in target mammalian cells compared to a composition comprising the same amount of control ABPCs.

[0069] In some embodiments, the composition provides for less reduction in the level of PTK7 presented on the surface of a target mammalian cell than a composition comprising the same amount of a control ABPC. In some embodiments, the composition does not cause a detectable reduction in the level of PTK7 presented on the surface of a target mammalian cell. In some embodiments, the target mammalian cell is a cancer cell.

[0070] In some embodiments, the off-rate of ABD at a pH of about 4.0 to about 6.5 is at least 10% faster than the off-rate of ABD at a pH of about 7.0 to about 8.0. In some embodiments, the off-rate of ABD at a pH of about 4.0 to about 6.5 is at least 3 times faster than the off-rate of ABD at a pH of about 7.0 to about 8.0. In some embodiments, the off-rate of ABD at a pH of about 4.0 to about 6.5 is at least 10 times faster than the off-rate of ABD at a pH of about 7.0 to about 8.0. In some embodiments, the K of ABD at a pH of about 4.0 to about 6.5 is at least 10% faster than the off-rate of ABD at a pH of about 7.0 to about 8.0. D The K of ABD at a pH of about 7.0 to about 8.0 D In some embodiments, the K of the ABD at a pH of about 4.0 to about 6.5 is greater than that of the ABD at a pH of about 4.0 to about 6.5. D The K of ABD at a pH of about 7.0 to about 8.0 D In some embodiments, the K of the ABD at a pH of about 4.0 to about 6.5 is at least 3 times greater. D The K of ABD at a pH of about 7.0 to about 8.0 D Bigger, at least 10 times.

[0071] In some embodiments, the ABPC is cytotoxic or cytostatic to target mammalian cells.

[0072] In some embodiments, the ABPC is cross-reactive with non-human primate PTK7 and human PTK7. In some embodiments, the ABPC is cross-reactive with non-human primate PTK7, human PTK7, and one or both of rat PTK7 and mouse PTK7. In some embodiments, the ABPC is cross-reactive with non-human primate PTK7, human PTK7, rat PTK7, and mouse PTK7. In some embodiments, the ABD binds to an epitope of PTK7 present on the surface of cells from Old World monkeys.

[0073] In some embodiments, the ABPC comprises a single polypeptide. In some embodiments, the ABD is selected from a VH domain, a VHH domain, a VNAR domain, and a scFv. In some embodiments, the ABPC is a BiTe, (scFv)2, a nanobody, a nanobody-HSA, a DART, a TandAb, a scDiabody, a scDiabody-CH3, a scFv-CH-CL-scFv, an HSAbody, a scDiabody-HSA, or a tandem-scFv.

[0074] In some embodiments, the ABPC comprises two or more polypeptides. In some embodiments, the ABPC is selected from the group consisting of antibodies, VHH-scAb, VHH-Fab, double scFab, F(ab')2, double-chain antibodies, cross-Mab, DAF (two-in-one), DAF (four-in-one), DutaMab, DT-IgG, common light chain of knobs-in-hole, knobs-in-hole assembly, charge pair, Fab arm exchange, SEEDBody, LUZ-Y, Fcab, kappa lambda body, orthogonal Fab, DVD-IgG, IgG(H)-scFv, scFv-(H)IgG, IgG(L)-scFv, scFv-(L)IgG, IgG(L,H)-Fv, IgG(H)-V, V(H)-IgG, IgG(L)-V, V(L)-IgG, KIH IgG-scFab, 2scFv-IgG, IgG-2scFv, scFv4-Ig, Zybody, DVI-IgG, diabody-CH3, triabody, minibody, minibody, TriBi minibody, scFv-CH3 KIH, Fab-scFv, F(ab')2-scFv2, scFv-KIH, Fab-scFv-Fc, tetravalent HCAb, scDiabody-Fc, diabody-Fc, tandem scFv-Fc, VHH-Fc, tandem VHH-Fc, VHH-Fc KiH, Fab-VHH-Fc, Intrabody, docked locked antibody, ImmTAC, IgG-IgG conjugate, Cov-X-Body, scFv1-PEG-scFv2, Adnectin, DARPin, fibronectin, and DEP conjugate.

[0075] In some embodiments, at least one polypeptide of the ABPC is conjugated to a toxin, radioisotope, drug, or small molecule via a cleavable linker. In some embodiments, at least one polypeptide of the ABPC is conjugated to a toxin, radioisotope, drug, or small molecule via a non-cleavable linker.

[0076] In some embodiments, the in vivo half-life of the ABPC is increased compared to the in vivo half-life of a control ABPC. In some embodiments, the in vivo half-life of the ABPC is increased by about 5% to about 95% compared to the in vivo half-life of the control ABPC. In some embodiments, the in vivo half-life of the ABPC is increased by about 10% to about 95% compared to the in vivo half-life of the control ABPC. In some embodiments, the in vivo half-life of the ABPC is increased by about 30% to about 95% compared to the in vivo half-life of the control ABPC. In some embodiments, the in vivo half-life of the ABPC is increased by about 50% to about 95% compared to the in vivo half-life of the control ABPC. In some embodiments, the in vivo half-life of the ABPC is increased by about 70% to about 95% compared to the in vivo half-life of the control ABPC. In other embodiments, the in vivo half-life can be decreased.

[0077] In some embodiments, the control ABPC is capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell, wherein: (a) the control ABPC comprises a first ABD; (b) the off-rate of the first ABD of the control ABPC at a pH of about 4.0 to about 6.5 is no more than 3-fold faster than the off-rate at a pH of about 7.0 to about 8.0; and (c) the dissociation constant (K) of the first ABD of the control ABPC at a pH of about 4.0 to about 6.5 is D ) than K at a pH of about 7.0 to about 8.0 D Larger, no more than 3 times.

[0078] In some embodiments, the control ABPC is capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell, wherein: (a) the control ABPC comprises a first ABD; (b) the off-rate of the first ABD of the control ABPC at a pH of about 4.0 to about 6.5 is no more than 2-fold faster than the off-rate at a pH of about 7.0 to about 8.0; and (c) the dissociation constant (K) of the first ABD of the control ABPC at a pH of about 4.0 to about 6.5 is D ) than K at a pH of about 7.0 to about 8.0 D Larger, no more than 2 times.

[0079] In some embodiments, the control ABPC is capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell, wherein: (a) the control ABPC comprises a first ABD; (b) the off-rate of the first ABD of the control ABPC at a pH of about 4.0 to about 6.5 is no more than 1-fold faster than the off-rate at a pH of about 7.0 to about 8.0; and (c) the dissociation constant (K) of the first ABD of the control ABPC at a pH of about 4.0 to about 6.5 isD ) than K at a pH of about 7.0 to about 8.0 D Large, no more than 1 times.

[0080] In some embodiments, the control ABPC is selected from the group consisting of: MYT9345, MYT9359, MYT9361, MYT9412, MYT9460, MYT9792, MYT9797, cofilinumab, 7C8, and 12C6.

[0081] In some embodiments, the ABPC comprises a second ABD.

[0082] Also provided herein are kits comprising at least one dose of any of the pharmaceutical compositions described herein.

[0083] Also provided herein are antigen binding protein constructs (ABPCs) comprising: a first ABD capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell, wherein: (a) the first ABD has a faster off-rate at a pH of about 4.0 to about 6.5 than at a pH of about 7.0 to about 8.0; or (b) the first ABD has a dissociation constant (K) at a pH of about 4.0 to about 6.5. D ) than K at a pH of about 7.0 to about 8.0 D big.

[0084] In some embodiments, the first ABD comprises one of: (a) HCVD of MYT9345; (b) HCVD of MYT9359; (c) HCVD of MYT9361; (d) HCVD of MYT9412; (e) HCVD of MYT9460; (f) HCVD of MYT9792; (g) HCVD of MYT9797; (h) HCVD of colestipol; (i) HCVD of 7C8; and (j) HCVD of 12C6, each HCVD optionally having one or more amino acids substituted with histidine.

[0085] In some embodiments, the first ABD comprises one of: (a) an LCVD of MYT9345; (b) an LCVD of MYT9359; (c) an LCVD of MYT9361; (d) an LCVD of MYT9412; (e) an LCVD of MYT9460; (f) an LCVD of MYT9792; (g) an LCVD of MYT9797; (h) an LCVD of cofetizumab; (i) an LCVD of 7C8; and (j) an LCVD of 12C6, each LCVD optionally having one or more amino acids substituted with histidine.

[0086] In some embodiments, the first ABD comprises one of the following: (a) HCVD of MYT9345 and / or LCVD of MYT9345, either or both having one or more amino acids optionally substituted with histidine; (b) HCVD of MYT9359 and / or LCVD of MYT9359, either or both having one or more amino acids optionally substituted with histidine; (c) HCVD of MYT9361 and / or LCVD of MYT9361, either or both having one or more amino acids optionally substituted with histidine; (d) HCVD of MYT9412 and and / or LCVD of MYT9412, either or both having one or more amino acids optionally substituted with histidine; (e) HCVD of MYT9460 and / or LCVD of MYT9460, either or both having one or more amino acids optionally substituted with histidine; (f) HCVD of MYT9792 and / or LCVD of MYT9792, either or both having one or more amino acids optionally substituted with histidine; and (g) HCVD of MYT9797 and / or LCVD of MYT9797, either or both having one or more amino acids substituted with histidine.

[0087] In some embodiments, the HCVD comprises one of: (a) an HCVD comprising MYT9345 of SEQ ID NO:301; (b) an HCVD comprising MYT9359 of SEQ ID NO:375; (c) an HCVD comprising MYT9361 of SEQ ID NO:459; (d) an HCVD comprising MYT9412 of SEQ ID NO:542; (e) an HCVD comprising MYT9460 of SEQ ID NO:628; (f) an HCVD comprising MYT9792 of SEQ ID NO:710; and (g) an HCVD comprising MYT9797 of SEQ ID NO:803.

[0088] In some embodiments, the LCVD comprises one of the following: (a) an LCVD comprising MYT9345 of SEQ ID NO: 302; (b) an LCVD comprising MYT9359 of SEQ ID NO: 376; (c) an LCVD comprising MYT9361 of SEQ ID NO: 460; (d) an LCVD comprising MYT9412 of SEQ ID NO: 543; (e) an LCVD comprising MYT9460 of SEQ ID NO: 629; (f) an LCVD comprising MYT9792 of SEQ ID NO: 711; and (g) an LCVD comprising MYT9797 of SEQ ID NO: 804.

[0089] In some embodiments, the first ABD comprises an HCVD of one of the following: (a) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 303, 304, and 305, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 303, 304, and 305 are substituted with histidine; (b) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 377, 378, and 379, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 377, 378, and 379 are optionally substituted with histidine; (c) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 461, 462, and 463, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 461, 462, and 463 are substituted with histidine; (d) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 544, 545, and 546, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 546, 547, and 548 are optionally substituted with histidine. (e) an HCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 630, 631 and 632, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 630, 631 and 632 are optionally substituted with histidine; (f) an HCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 712, 713 and 714, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 712, 713 and 714 are optionally substituted with histidine; and (g) an HCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 805, 806 and 807, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 805, 806 and 807 are optionally substituted with histidine.

[0090] In some embodiments, the first ABD comprises an LCVD of one of the following: (a) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 306, 307, and 308, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 306, 307, and 308 are optionally substituted with histidine; (b) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 380, 381, and 382, ​​respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 380, 381, and 382 are optionally substituted with histidine; (c) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 464, 465, and 466, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 464, 465, and 466 are optionally substituted with histidine; (d) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 464, 465, and 466, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 464, 465, and 466 are optionally substituted with histidine; (e) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 633, 634 and 635, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 633, 634 and 635 are substituted with histidine; (f) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 715, 716 and 717, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 715, 716 and 717 are substituted with histidine; and (g) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 808, 809 and 810, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 808, 809 and 810 are substituted with histidine. In total, one or more amino acid positions in NO:808, 809 and 810 are substituted with histidine.

[0091] In some embodiments, the first ABD comprises one of the following: (a) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 303, 304, and 305, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 303, 304, and 305 are substituted with histidine; and / or an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 306, 307, and 308, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 306, 307, and 308 are optionally substituted with histidine; (b) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 377, 378, and 379, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 377, 378, and 379 are optionally substituted with histidine; and / or an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 380, 381, and 382, ​​respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 383, 384, and 385 are optionally substituted with histidine. (c) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 461, 462 and 463, respectively, wherein one or more amino acid positions in total are substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 464, 465 and 466, respectively, wherein one or more amino acid positions in total are substituted with histidine; (d) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 544, 545 and 546, respectively, wherein one or more amino acid positions in total are optionally substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 544, 545 and 546, respectively, wherein one or more amino acid positions in total are optionally substituted with histidine; (e) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 630, 631 and 632, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 630, 631 and 632 are optionally substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 633, 634 and 635, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 633, 634 and 635 are optionally substituted with histidine;(f) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 712, 713 and 714, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 712, 713 and 714 are substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 715, 716 and 717, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 715, 716 and 717 are substituted with histidine; and (g) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 805, 806 and 807, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 805, 806 and 807 are optionally substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 808, 809 and 810, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 810 One or more amino acid positions in NO:808, 809 and 810 are substituted with histidine.

[0092] In some embodiments, the first ABD comprises an HCVD of one of the following: (a) an HCVD at least 90% identical to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; (b) an HCVD at least 90% identical to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: 375; (c) an HCVD at least 90% identical to SEQ ID NO: 459, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: NO:459, wherein the HCVD comprises a histidine at one or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111; (d) an HCVD at least 90% identical to SEQ ID NO:542, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 of SEQ ID NO:542; (e) an HCVD at least 90% identical to SEQ ID NO:628, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 of SEQ ID NO:628; (f) an HCVD at least 90% identical to SEQ ID NO:710, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: NO:710, a histidine at one or more positions selected from the group consisting of: 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113; and (g) a HCVD having at least 90% identity to SEQ ID NO:803, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107 in SEQ ID NO:803.

[0093] In some embodiments, the first ABD comprises an LCVD that is one of the following: (a) an LCVD at least 90% identical to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) an LCVD at least 90% identical to SEQ ID NO: 376, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376; (c) an LCVD at least 90% identical to SEQ ID NO: 460, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: (d) an LCVD at least 90% identical to SEQ ID NO: 543, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 of SEQ ID NO: 543; (e) an LCVD at least 90% identical to SEQ ID NO: 629, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 of SEQ ID NO: 629; (f) an LCVD at least 90% identical to SEQ ID NO: 711, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: NO:711, a histidine at one or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99; and (g) an LCVD at least 90% identical to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 of SEQ ID NO:804.

[0094] In some embodiments, the first ABD comprises an HCVD of one of the following: (a) an HCVD at least 90% identical to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; (b) an HCVD at least 90% identical to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: 375; (c) an HCVD at least 90% identical to SEQ ID NO: 459, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: NO:459, wherein the HCVD comprises a histidine at two or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111; (d) an HCVD at least 90% identical to SEQ ID NO:542, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 of SEQ ID NO:542; (e) an HCVD at least 90% identical to SEQ ID NO:628, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 of SEQ ID NO:628; (f) an HCVD at least 90% identical to SEQ ID NO:710, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: NO:710, a histidine at two or more positions selected from the group consisting of: 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113; and (g) a HCVD at least 90% identical to SEQ ID NO:803, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107 in SEQ ID NO:803.

[0095] In some embodiments, the first ABD comprises an LCVD that is one of: (a) an LCVD at least 90% identical to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) an LCVD at least 90% identical to SEQ ID NO: 376, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376; (c) an LCVD at least 90% identical to SEQ ID NO: 460, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: NO:460, wherein the LCVD comprises a histidine at two or more positions selected from the group consisting of: 30, 31, 33, 51, 92, and 95; (d) an LCVD at least 90% identical to SEQ ID NO: 543, wherein the LCVD optionally comprises a histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98; (e) an LCVD at least 90% identical to SEQ ID NO: 629, wherein the LCVD optionally comprises a histidine at two or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100; (f) an LCVD at least 90% identical to SEQ ID NO: 711, wherein the LCVD optionally comprises a histidine at two or more positions selected from the group consisting of: NO:711, a histidine at two or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99; and (g) an LCVD at least 90% identical to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 of SEQ ID NO:804.

[0096] In some embodiments, the first ABD comprises one of: (a) a HCVD at least 90% identical to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; and / or a LCVD at least 90% identical to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) a HCVD at least 90% identical to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: NO: 375, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 of SEQ ID NO: 375; and / or an LCVD having at least 90% identity to SEQ ID NO: 376, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 of SEQ ID NO: 376; (c) an HCVD having at least 90% identity to SEQ ID NO: 459, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111 of SEQ ID NO: 459; and / or an LCVD having at least 90% identity to SEQ ID NO: 376 (d) an HCVD at least 90% identical to SEQ ID NO: 542, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 of SEQ ID NO: 542; and / or an LCVD at least 90% identical to SEQ ID NO: 543, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 of SEQ ID NO: 543;(e) a HCVD at least 90% identical to SEQ ID NO: 628, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 in SEQ ID NO: 628; and / or a LCVD at least 90% identical to SEQ ID NO: 629, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 in SEQ ID NO: 629; (f) a HCVD at least 90% identical to SEQ ID NO: 710, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, NO:710, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113; and / or an LCVD at least 90% identical to SEQ ID NO:711, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99 of SEQ ID NO:711; and (g) an HCVD at least 90% identical to SEQ ID NO:803, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, NO:803, a histidine at one or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107; and / or an LCVD having at least 90% identity to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 of SEQ ID NO:804.

[0097] In some embodiments, the first ABD comprises an HCVD of one of the following: (a) an HCVD of SEQ ID NO: 301, or one of 309-342; (b) an HCVD of SEQ ID NO: 375, or one of 383-423; (c) an HCVD of SEQ ID NO: 459, or one of 467-511; (d) an HCVD of SEQ ID NO: 542, or one of 550-592; (e) an HCVD of SEQ ID NO: 628, or one of 636-675; (f) an HCVD of SEQ ID NO: 710, or one of 718-767; and (g) an HCVD of SEQ ID NO: 803, or one of 811-854; and / or the first ABD comprises an LCVD of one of the following: (a) an LCVD of SEQ ID NO: 302, or one of 343-374; (b) an LCVD of SEQ ID NO: NO: 376, or one of 424-458; (c) an LCVD of SEQ ID NO: 460, or one of 512-541; (d) an LCVD of SEQ ID NO: 543, or one of 593-627; (e) an LCVD of SEQ ID NO: 629, or one of 676-709; (f) an LCVD of SEQ ID NO: 711, or one of 768-802; and (g) an LCVD of SEQ ID NO: 804, or one of 855-892.

[0098] In some embodiments, the first ABD comprises one of:

[0099] (a) an HCVD of one of SEQ ID NOs: 301, 309-342, or 309-342; and / or an LCVD of one of SEQ ID NOs: 302, 343-374, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 301 and an LCVD of SEQ ID NO: 302; (ii) an HCVD of SEQ ID NO: 301 and an LCVD that is not one of SEQ ID NOs: 344, 349-352, 354, 359-361, 363, 366-368, 370, and 373; or (iii) an HCVD that is not one of SEQ ID NOs: 312, 313, 315, 319-323, 327, 329, 335, 340, and 341 and an LCVD of SEQ ID NO: 302;

[0100] (b) an HCVD of SEQ ID NO: 375, or one of 383-423; and / or an LCVD of SEQ ID NO: 376, or one of 424-458, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 375 and an LCVD of SEQ ID NO: 376; (ii) an HCVD of SEQ ID NO: 375 and an LCVD that is not one of SEQ ID NOs: 425, 429, 430, 431, 432, 433, 435, 436, 437, 438, 442, 444, 445, 446, 449, 450, 453, and 455; or (iii) an LCVD that is not one of SEQ ID NOs: HCVD of one of NOs: 383, 384, 387, 389, 391, 394, 395, 398, 401, 402, 406, 410, 412, and 421 and LCVD of SEQ ID NO: 376;

[0101] (c) an HCVD of SEQ ID NO: 459, or one of 467-511; and / or an LCVD of SEQ ID NO: 460, or one of 512-541, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 459 and an LCVD of SEQ ID NO: 460; (ii) an HCVD of SEQ ID NO: 459 and an LCVD that is not one of SEQ ID NOs: 518, 519, 521, 524, 533, and 536; or (iii) an HCVD that is not one of SEQ ID NOs: 473, 496, 498, 499, 503, and 508 and an LCVD of SEQ ID NO: 460;

[0102] (d) an HCVD of SEQ ID NO: 542, or one of 550-592; and / or an LCVD of SEQ ID NO: 543, or one of 593-627, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 542 and an LCVD of SEQ ID NO: 543; (ii) an HCVD of SEQ ID NO: 542 and an LCVD that is not one of SEQ ID NOs: 594, 598, 599, 600, 601, 611, 614, and 620; or (iii) an HCVD that is not one of SEQ ID NOs: 551, 553, 554, 555, 556, 563, 565, 568, 582, 584, and 585 and an LCVD of SEQ ID NO: 543;

[0103] (e) an HCVD of SEQ ID NO: 628, or one of 636-675; and / or an LCVD of SEQ ID NO: 629, or one of 676-709, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 628 and an LCVD of SEQ ID NO: 629; (ii) an HCVD of SEQ ID NO: 628 and an LCVD that is not one of SEQ ID NOs: 677, 678, 680, 681, 685, 688, 692, 694, 696, 700, 701, 702, 703, 704, and 705; or (iii) an HCVD that is not one of SEQ ID NOs: 636, 638, 640, 646, 648, 649, 650, 651, 652, 653, 666, 667, 668, and 669 and an LCVD that is not one of SEQ ID NOs: LCVD of NO:629;

[0104] (f) an HCVD of SEQ ID NO: 710, or one of 718-767; and / or an LCVD of SEQ ID NO: 711, or one of 768-802, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 710 and an LCVD of SEQ ID NO: 711; (ii) an HCVD of SEQ ID NO: 710 and an LCVD that is not one of SEQ ID NOs: 769, 771, 773, 774, 779, 780, 785, 786, 788, 790, 791, 792, 795, and 796; or (iii) an LCVD that is not one of SEQ ID NOs: HCVD of one of NOs: 721, 722, 723, 725, 727, 728, 731, 735, 736, 743, 744, 745, 746, 748, 749, 751, 753, 755, 756, 757, 758, and 761 and the LCVD of SEQ ID NO: 711; and

[0105] (g) an HCVD of SEQ ID NO: 803, or one of 811-854; and / or an LCVD of SEQ ID NO: 804, or one of 855-892, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 803 and an LCVD of SEQ ID NO: 804; (ii) an HCVD of SEQ ID NO: 803 and an LCVD that is not one of SEQ ID NOs: 862, 864-866, 868, 870, 881, and 882; or (iii) an HCVD that is not one of SEQ ID NOs: 818, 821, 824, 826-829, 835, 841, 848, and 850 and an LCVD of SEQ ID NO: 804.

[0106] In some embodiments, the first antigen binding domain comprises an HCVD that is one of the following: (a) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 3, 4, and 5, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 3, 4, and 5 are substituted with histidine; (b) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 128, 129, and 130, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 128, 129, and 130 are substituted with histidine; and (c) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 231, 232, and 233, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 231, 232, and 233 are substituted with histidine. In some embodiments, the first CCK4 binding domain comprises an LCVD that is one of the following: (a) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 6, 7, and 8, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 6, 7, and 8 are substituted with histidine; (b) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 131, 132, and 133, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 131, 132, and 133 are substituted with histidine; and (c) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 234, 235, and 236, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 234, 235, and 236 are substituted with histidine.

[0107] In some embodiments, the first CCK4 binding domain comprises one of the following: (a) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 3, 4, and 5, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 3, 4, and 5 are substituted with histidine; and / or an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 6, 7, and 8, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 6, 7, and 8 are substituted with histidine; (b) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 128, 129, and 130, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 128, 129, and 130 are substituted with histidine; and / or an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 131, 132, and 133, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: (c) an HCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 231, 232 and 233, respectively, wherein a total of one or more amino acid positions are optionally substituted with histidine; and / or an LCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 234, 235 and 236, respectively, wherein a total of one or more amino acid positions are substituted with histidine.

[0108] In some embodiments, the first antigen binding domain comprises an HCVD of one of the following: (a) an HCVD at least 90% identical to SEQ ID NO: 1, wherein the HCVD includes a histidine at one or more positions selected from the group consisting of: 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107 in SEQ ID NO: 1; (b) an HCVD at least 90% identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at one or more positions selected from the group consisting of: 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, or 111 in SEQ ID NO: 126; and (c) an HCVD at least 90% identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at one or more positions selected from the group consisting of: 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, or 111 in SEQ ID NO: NO:229 has an HCVD with at least 90% identity, wherein the HCVD comprises histidine at one or more positions selected from the group consisting of: 27, 32, 33, 34, 35, 51, 54, 56, 58, or 100 in SEQ ID NO:229.

[0109] In some embodiments, the first antigen binding domain comprises an LCVD that is one of: (a) an LCVD at least 90% identical to SEQ ID NO: 2, wherein the LCVD comprises a histidine at one or more positions in SEQ ID NO: 2 selected from the group consisting of: 25, 29, 31, 35, 60, 93, or 94; (b) an LCVD at least 90% identical to SEQ ID NO: 127, wherein the LCVD comprises a histidine at one or more positions in SEQ ID NO: 127 selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94; and (c) an LCVD at least 90% identical to SEQ ID NO: 230, wherein the LCVD comprises a histidine at one or more positions in SEQ ID NO: 230 selected from the group consisting of: 30, 31, 33, 51, 53, 57, 91, 92, 94, and 99.

[0110] In some embodiments, the first antigen binding domain comprises an HCVD of one of the following: (a) an HCVD having at least 90% identity to SEQ ID NO: 1, wherein the HCVD includes histidine at two or more positions in SEQ ID NO: 1 selected from the group consisting of: 27, 29, 31, 34, and 53; and (b) an HCVD having at least 90% identity to SEQ ID NO: 126, wherein the HCVD includes histidine at two or more positions in SEQ ID NO: 126 selected from the group consisting of: 53, 56, 57, 102, and 105.

[0111] In some embodiments, the first antigen binding domain comprises one of: (a) an HCVD having at least 90% identity to SEQ ID NO: 1, wherein the HCVD includes a histidine at one or more positions selected from the group consisting of: 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107 in SEQ ID NO: 1; and / or an LCVD having at least 90% identity to SEQ ID NO: 2, wherein the LCVD includes a histidine at one or more positions selected from the group consisting of: 25, 29, 31, 35, 60, 93, or 94 in SEQ ID NO: 2; (b) an HCVD having at least 90% identity to SEQ ID NO: 126, wherein the HCVD includes a histidine at one or more positions selected from the group consisting of: 25, 29, 31, 35, 60, 93, or 94 in SEQ ID NO: 2. NO: 126 at one or more positions selected from the group consisting of: 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, and 111; and / or an LCVD having at least 90% identity to SEQ ID NO: 127, wherein the LCVD includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94 of SEQ ID NO: 127; and (c) an HCVD having at least 90% identity to SEQ ID NO: 229, wherein the HCVD includes a histidine at one or more positions selected from the group consisting of: 27, 32, 33, 34, 35, 51, 54, 56, 58, and 100 of SEQ ID NO: 229; and / or an LCVD having at least 90% identity to SEQ ID NO: 127, wherein the LCVD includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94 of SEQ ID NO: NO: 230. An LCVD having at least 90% identity, wherein the LCVD comprises histidine at one or more positions selected from the group consisting of 30, 31, 33, 51, 53, 57, 91, 92, 94, and 99 in SEQ ID NO: 230.

[0112] In some embodiments, the first antigen binding domain comprises an HCVD of one of the following: (a) an HCVD of SEQ ID NO: 1, 14, 17, 18, 19, 20, 21, 22, 24, 25, 29, 30, 31, 33, 34, 40, 44, 46, 48, 49, 53, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98, 99, 100, 101, 102, 103, 104, or 105; (b) an HCVD of SEQ ID NO: NO:126, 147, 148, 150, 151, 154, 166, 167, 168, 169, 170, 172, 173, 174, 175, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 224, 225, 226 or 227; and (c) SEQ ID NO:229, 238, 243, 244, 245, 246, 248, 251, 253, 255 or 267.

[0113] In some embodiments, the first antigen binding domain comprises an LCVD of one of the following: (a) an LCVD of SEQ ID NO: 2, 56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, 122, 123, 124, or 125; (b) an LCVD of SEQ ID NO: 127, 181, 182, 184, 185, 187, 188, 189, 191, 199, 201, 203, or 228; and (c) an LCVD of SEQ ID NO: 230, 275, 276, 278, 281, 283, 287, 289, 290, 292, or 297.

[0114] In some embodiments, the first antigen binding domain comprises one of: (a) an HCVD of SEQ ID NO: 14, 17, 18, 19, 20, 21, 22, 24, 25, 29, 30, 31, 33, 34, 40, 44, 46, 48, 49, 53, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98, 99, 100, 101, 102, 103, 104, or 105; and / or an LCVD of SEQ ID NO: 2, 56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, 122, 123, 124, or 125, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 1 and an LCVD of SEQ ID NO: 2. NO:2; (ii) the HCVD of SEQ ID NO:1 and an LCVD that is not one of SEQ ID NO:56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, and 122-125; or (iii) the LCVD of SEQ ID NO:2 and an HCVD that is not one of SEQ ID NO:14, 17-22, 24, 25, 29-31, 33, 34, 40, 44, 46, 48, 49, 53, 86-96, and 98-105; (b) the HCVD of SEQ ID NO:1 NO: 147, 148, 150, 151, 154, 166, 167, 168, 169, 170, 172, 173, 174, 175, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 224, 225, 226 or 227; and / or SEQ ID NO: 127, 181, 182, 184, 185, 187, 188, 189, 191, 199, 201, 203 or 228, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 126 and an LCVD of SEQ ID NO: 127; (ii) an LCVD of SEQ ID NO: (iii) an LCVD of SEQ ID NO: 127 and an HCVD that is not one of SEQ ID NOs: 147, 148, 150, 151, 154, 166-170, 172-175, 208-222, and 224-227;and (c) an HCVD of SEQ ID NO: 238, 243, 244, 245, 246, 248, 251, 253, 255, or 267; and / or an LCVD of SEQ ID NO: 230, 275, 276, 278, 281, 283, 287, 289, 290, 292, or 297, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 229 and an LCVD of SEQ ID NO: 230; (ii) an HCVD of SEQ ID NO: 229 and an LCVD that is not one of SEQ ID NO: 275, 276, 278, 281, 283, 287, 289, 290, 292, and 297; and (iii) an LCVD of SEQ ID NO: 230 and an LCVD that is not one of SEQ ID NO: HCVD of one of NOs: 238, 243-246, 248, 251, 253, 255, and 267;

[0115] In some embodiments, the ABPC is degraded in the target mammalian cell after the ABPC is internalized by the target mammalian cell.In some embodiments, the ABPC comprises a conjugated toxin, radioisotope, drug, or small molecule.

[0116] In some embodiments, the composition comprising the ABPCs provides an increase in toxin release in target mammalian cells compared to a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPCs provides an increase in toxin release in target mammalian cells by at least 20% or 50% compared to a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPCs provides an increase in toxin release in target mammalian cells by at least 2-fold or 5-fold compared to a composition comprising the same amount of a control ABPC.

[0117] In some embodiments, the composition comprising the ABPCs provides an increase in killing of target mammalian cells compared to a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPCs provides an increase in killing of target mammalian cells by at least 20% or 50% compared to a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPCs provides an increase in killing of target mammalian cells by at least 2-fold or 5-fold compared to a composition comprising the same amount of a control ABPC.

[0118] In some embodiments, the composition comprising the ABPC provides an increase in endolysosomal delivery in the target mammalian cell compared to a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPC provides an increase in endolysosomal delivery in the target mammalian cell compared to a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPC provides an increase in endolysosomal delivery in the target mammalian cell compared to a composition comprising the same amount of a control ABPC by at least 20%. In some embodiments, the composition comprising the ABPC provides an increase in endolysosomal delivery in the target mammalian cell compared to a composition comprising the same amount of a control ABPC by at least 50%. In some embodiments, the composition comprising the ABPC results in an increase in endolysosomal delivery in the target mammalian cell by at least 2 times compared to a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPC results in an increase in endolysosomal delivery in the target mammalian cell by at least 5 times compared to a composition comprising the same amount of a control ABPC.

[0119] In some embodiments, the composition comprising the ABPCs causes less of a decrease in the level of PTK7 presented on the surface of target mammalian cells than a composition comprising the same amount of control ABPCs. In some embodiments, the composition comprising the ABPCs does not cause a detectable decrease in the level of PTK7 presented on the surface of target mammalian cells.

[0120] Also provided herein are antigen binding protein constructs (ABPCs) comprising: a first ABD capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, wherein (a) the first ABD has a faster off-rate at a pH of about 4.0 to about 6.5 than at a pH of about 7.0 to about 8.0 or the dissociation constant (K) of the first ABD at a pH of about 4.0 to about 6.5 is greater than that at a pH of about 7.0 to about 8.0; D ) than K at a pH of about 7.0 to about 8.0 D and (b) the composition provides one or more of: an increase in toxin release in the target mammalian cells compared to a composition comprising the same amount of a control ABPC; an increase in target mammalian cell killing compared to a composition comprising the same amount of a control ABPC; and an increase in endolysosomal delivery in the target mammalian cells compared to a composition comprising the same amount of a control ABPC.

[0121] In some embodiments, the first ABD comprises one of: (a) HCVD of MYT9345; (b) HCVD of MYT9359; (c) HCVD of MYT9361; (d) HCVD of MYT9412; (e) HCVD of MYT9460; (f) HCVD of MYT9792; (g) HCVD of MYT9797; (h) HCVD of colestipol; (i) HCVD of 7C8; and (j) HCVD of 12C6, each or any one having one or more amino acids optionally substituted with histidine. In some embodiments, the first ABD comprises one of: (a) LCVD of MYT9345; (b) LCVD of MYT9359; (c) LCVD of MYT9361; (d) LCVD of MYT9412; (e) LCVD of MYT9460; (f) LCVD of MYT9792; (g) LCVD of MYT9797; (h) LCVD of cofetizumab; (i) LCVD of 7C8; and (j) LCVD of 12C6, each or any one of which optionally has one or more amino acids substituted with histidine.

[0122] In some embodiments, the first ABD comprises one of: (a) HCVD of MYT9345 and LCVD of MYT9345; (b) HCVD of MYT9359 and LCVD of MYT9359; (c) HCVD of MYT9361 and LCVD of MYT9361; (d) HCVD of MYT9412 and LCVD of MYT9412; (e) HCVD of MYT9460 and LCVD of MYT9460. VD; (f) HCVD of MYT9792 and LCVD of MYT9792; (g) HCVD of MYT9797 and LCVD of MYT9797; (h) HCVD of cofetiuzumab and LCVD of cofetiuzumab; (i) HCVD of 7C8 and LCVD of 7C8; and (j) HCVD of 12C6 and LCVD of 12C6, each or any of these domains optionally having one or more amino acids substituted by histidine.

[0123] In some embodiments, the HCVD comprises one of: (a) an HCVD comprising MYT9345 of SEQ ID NO:301; (b) an HCVD comprising MYT9359 of SEQ ID NO:375; (c) an HCVD comprising MYT9361 of SEQ ID NO:459; (d) an HCVD comprising MYT9412 of SEQ ID NO:542; (e) an HCVD comprising MYT9460 of SEQ ID NO:628; (f) an HCVD comprising MYT9792 of SEQ ID NO:710; and (g) an HCVD comprising MYT9797 of SEQ ID NO:803. In some embodiments, the LCVD comprises one of the following: (a) an LCVD comprising MYT9345 of SEQ ID NO: 302; (b) an LCVD comprising MYT9359 of SEQ ID NO: 376; (c) an LCVD comprising MYT9361 of SEQ ID NO: 460; (d) an LCVD comprising MYT9412 of SEQ ID NO: 543; (e) an LCVD comprising MYT9460 of SEQ ID NO: 629; (f) an LCVD comprising MYT9792 of SEQ ID NO: 711; and (g) an LCVD comprising MYT9797 of SEQ ID NO: 804.

[0124] In some embodiments, the first ABD comprises an HCVD of one of the following: (a) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 303, 304, and 305, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 303, 304, and 305 are substituted with histidine; (b) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 377, 378, and 379, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 377, 378, and 379 are optionally substituted with histidine; (c) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 461, 462, and 463, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 461, 462, and 463 are substituted with histidine; (d) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 544, 545, and 546, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 546, 547, and 548 are optionally substituted with histidine. (e) an HCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 630, 631 and 632, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 630, 631 and 632 are optionally substituted with histidine; (f) an HCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 712, 713 and 714, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 712, 713 and 714 are optionally substituted with histidine; and (g) an HCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 805, 806 and 807, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 805, 806 and 807 are optionally substituted with histidine.

[0125] In some embodiments, the first ABD comprises an LCVD of one of the following: (a) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 306, 307, and 308, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 306, 307, and 308 are optionally substituted with histidine; (b) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 380, 381, and 382, ​​respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 380, 381, and 382 are optionally substituted with histidine; (c) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 464, 465, and 466, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 464, 465, and 466 are optionally substituted with histidine; (d) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 464, 465, and 466, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 464, 465, and 466 are optionally substituted with histidine; (e) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 633, 634 and 635, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 633, 634 and 635 are substituted with histidine; (f) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 715, 716 and 717, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 715, 716 and 717 are substituted with histidine; and (g) an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 808, 809 and 810, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 808, 809 and 810 are substituted with histidine. In total, one or more amino acid positions in NO:808, 809 and 810 are substituted with histidine.

[0126] In some embodiments, the first ABD comprises one of the following: (a) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 303, 304, and 305, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 303, 304, and 305 are substituted with histidine; and / or an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 306, 307, and 308, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 306, 307, and 308 are optionally substituted with histidine; (b) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 377, 378, and 379, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 377, 378, and 379 are optionally substituted with histidine; and / or an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 380, 381, and 382, ​​respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 383, 384, and 385 are optionally substituted with histidine. (c) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 461, 462 and 463, respectively, wherein one or more amino acid positions in total are substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 464, 465 and 466, respectively, wherein one or more amino acid positions in total are substituted with histidine; (d) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 544, 545 and 546, respectively, wherein one or more amino acid positions in total are optionally substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 544, 545 and 546, respectively, wherein one or more amino acid positions in total are optionally substituted with histidine; (e) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 630, 631 and 632, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 630, 631 and 632 are optionally substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 633, 634 and 635, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 633, 634 and 635 are optionally substituted with histidine;(f) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 712, 713 and 714, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 712, 713 and 714 are substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 715, 716 and 717, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 715, 716 and 717 are substituted with histidine; and (g) an HCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 805, 806 and 807, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 805, 806 and 807 are optionally substituted with histidine; and / or an LCVD comprising the CDR1, CDR2 and CDR3 of SEQ ID NOs: 808, 809 and 810, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 810 One or more amino acid positions in NO:808, 809 and 810 are substituted with histidine.

[0127] In some embodiments, the first ABD comprises an HCVD of one of the following: (a) an HCVD at least 90% identical to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; (b) an HCVD at least 90% identical to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: 375; (c) an HCVD at least 90% identical to SEQ ID NO: 459, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: NO:459, wherein the HCVD comprises a histidine at one or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111; (d) an HCVD at least 90% identical to SEQ ID NO:542, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 of SEQ ID NO:542; (e) an HCVD at least 90% identical to SEQ ID NO:628, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 of SEQ ID NO:628; (f) an HCVD at least 90% identical to SEQ ID NO:710, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: NO:710, a histidine at one or more positions selected from the group consisting of: 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113; and (g) a HCVD having at least 90% identity to SEQ ID NO:803, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107 in SEQ ID NO:803.

[0128] In some embodiments, the first ABD comprises an LCVD of one of the following: (a) an LCVD at least 90% identical to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) an LCVD at least 90% identical to SEQ ID NO: 376, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376; (c) an LCVD at least 90% identical to SEQ ID NO: 460, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: (d) an LCVD at least 90% identical to SEQ ID NO: 543, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 of SEQ ID NO: 543; (e) an LCVD at least 90% identical to SEQ ID NO: 629, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 of SEQ ID NO: 629; (f) an LCVD at least 90% identical to SEQ ID NO: 711, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: NO:711, a histidine at one or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99; and (g) a LCVD at least 90% identical to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 in SEQ ID NO:804.

[0129] In some embodiments, the first ABD comprises an HCVD of one of the following: (a) an HCVD at least 90% identical to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; (b) an HCVD at least 90% identical to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: 375; (c) an HCVD at least 90% identical to SEQ ID NO: 459, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: NO:459, wherein the HCVD comprises a histidine at two or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111; (d) an HCVD at least 90% identical to SEQ ID NO:542, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 of SEQ ID NO:542; (e) an HCVD at least 90% identical to SEQ ID NO:628, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 of SEQ ID NO:628; (f) an HCVD at least 90% identical to SEQ ID NO:710, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: NO:710, a histidine at two or more positions selected from the group consisting of: 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113; and (g) a HCVD at least 90% identical to SEQ ID NO:803, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107 in SEQ ID NO:803.

[0130] In some embodiments, the first ABD comprises an LCVD of one of the following: (a) an LCVD at least 90% identical to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) an LCVD at least 90% identical to SEQ ID NO: 376, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376; (c) an LCVD at least 90% identical to SEQ ID NO: 460, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: NO: 460, wherein the LCVD comprises a histidine at two or more positions selected from the group consisting of: 30, 31, 33, 51, 92, and 95; (d) an LCVD at least 90% identical to SEQ ID NO: 543, wherein the LCVD optionally comprises a histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98; (e) an LCVD at least 90% identical to SEQ ID NO: 629, wherein the LCVD optionally comprises a histidine at two or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100; (f) an LCVD at least 90% identical to SEQ ID NO: 711, wherein the LCVD optionally comprises a histidine at two or more positions selected from the group consisting of: NO:711, a histidine at two or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99; and (g) an LCVD at least 90% identical to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 of SEQ ID NO:804.

[0131] In some embodiments, the first ABD comprises one of: (a) a HCVD at least 90% identical to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; and / or a LCVD at least 90% identical to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) a HCVD at least 90% identical to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: NO: 375, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 of SEQ ID NO: 375; and / or an LCVD having at least 90% identity to SEQ ID NO: 376, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 of SEQ ID NO: 376; (c) an HCVD having at least 90% identity to SEQ ID NO: 459, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111 of SEQ ID NO: 459; and / or an LCVD having at least 90% identity to SEQ ID NO: 376 (d) an HCVD at least 90% identical to SEQ ID NO: 542, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 of SEQ ID NO: 542; and / or an LCVD at least 90% identical to SEQ ID NO: 543, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 of SEQ ID NO: 543;(e) a HCVD at least 90% identical to SEQ ID NO: 628, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 in SEQ ID NO: 628; and / or a LCVD at least 90% identical to SEQ ID NO: 629, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 in SEQ ID NO: 629; (f) a HCVD at least 90% identical to SEQ ID NO: 710, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, NO:710, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113; and / or an LCVD at least 90% identical to SEQ ID NO:711, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99 of SEQ ID NO:711; and (g) an HCVD at least 90% identical to SEQ ID NO:803, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, NO:803, a histidine at one or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107; and / or an LCVD having at least 90% identity to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 of SEQ ID NO:804.

[0132] In some embodiments, the first ABD comprises one of: (a) a HCVD at least 90% identical to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; and / or a LCVD at least 90% identical to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) a HCVD at least 90% identical to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: NO: 375, wherein the HCVD optionally comprises a histidine at two or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 of SEQ ID NO: 375; and / or an LCVD having at least 90% identity to SEQ ID NO: 376, wherein the LCVD optionally comprises a histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 of SEQ ID NO: 376; (c) an HCVD having at least 90% identity to SEQ ID NO: 459, wherein the HCVD optionally comprises a histidine at two or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111 of SEQ ID NO: 459; and / or an LCVD having at least 90% identity to SEQ ID NO: 376 (d) an HCVD at least 90% identical to SEQ ID NO: 542, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 of SEQ ID NO: 542; and / or an LCVD at least 90% identical to SEQ ID NO: 543, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 of SEQ ID NO: 543;(e) a HCVD at least 90% identical to SEQ ID NO: 628, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 in SEQ ID NO: 628; and / or a LCVD at least 90% identical to SEQ ID NO: 629, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 in SEQ ID NO: 629; (f) a HCVD at least 90% identical to SEQ ID NO: 710, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 in SEQ ID NO: NO:710; and / or an LCVD at least 90% identical to SEQ ID NO:711, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99 of SEQ ID NO:711; and (g) an HCVD at least 90% identical to SEQ ID NO:803, wherein the HCVD optionally includes a histidine at two or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99 of SEQ ID NO:803. NO:803, a histidine at two or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107; and / or an LCVD having at least 90% identity to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at two or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 of SEQ ID NO:804.

[0133] In some embodiments, the first ABD comprises one of: (a) an HCVD of SEQ ID NO: 301, or one of 309-342; (b) an HCVD of SEQ ID NO: 375, or one of 383-423; (c) an HCVD of SEQ ID NO: 459, or one of 467-511; (d) an HCVD of SEQ ID NO: 542, or one of 550-592; (e) an HCVD of SEQ ID NO: 628, or one of 636-675; (f) an HCVD of SEQ ID NO: 710, or one of 718-767; and (g) an HCVD of SEQ ID NO: 803, or one of 811-854.

[0134] In some embodiments, the first ABD comprises one of: (a) an LCVD of SEQ ID NO: 302, or one of 343-374; (b) an LCVD of SEQ ID NO: 376, or one of 424-458; (c) an LCVD of SEQ ID NO: 460, or one of 512-541; (d) an LCVD of SEQ ID NO: 543, or one of 593-627; (e) an LCVD of SEQ ID NO: 629, or one of 676-709; (f) an LCVD of SEQ ID NO: 711, or one of 768-802; and (g) an LCVD of SEQ ID NO: 804, or one of 855-892.

[0135] In some embodiments, the first ABD comprises one of:

[0136] (a) an HCVD of one of SEQ ID NOs: 301, 309-342, or 309-342; and / or an LCVD of one of SEQ ID NOs: 302, 343-374, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 301 and an LCVD of SEQ ID NO: 302; (ii) an HCVD of SEQ ID NO: 301 and an LCVD that is not one of SEQ ID NOs: 344, 349-352, 354, 359-361, 363, 366-368, 370, and 373; or (iii) an HCVD that is not one of SEQ ID NOs: 312, 313, 315, 319-323, 327, 329, 335, 340, and 341 and an LCVD of SEQ ID NO: 302;

[0137] (b) an HCVD of SEQ ID NO: 375, or one of 383-423; and / or an LCVD of SEQ ID NO: 376, or one of 424-458, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 375 and an LCVD of SEQ ID NO: 376; (ii) an HCVD of SEQ ID NO: 375 and an LCVD that is not one of SEQ ID NOs: 425, 429, 430, 431, 432, 433, 435, 436, 437, 438, 442, 444, 445, 446, 449, 450, 453, and 455; or (iii) an LCVD that is not one of SEQ ID NOs: HCVD of one of NOs: 383, 384, 387, 389, 391, 394, 395, 398, 401, 402, 406, 410, 412, and 421 and LCVD of SEQ ID NO: 376;

[0138] (c) an HCVD of SEQ ID NO: 459, or one of 467-511; and / or an LCVD of SEQ ID NO: 460, or one of 512-541, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 459 and an LCVD of SEQ ID NO: 460; (ii) an HCVD of SEQ ID NO: 459 and an LCVD that is not one of SEQ ID NOs: 518, 519, 521, 524, 533, and 536; or (iii) an HCVD that is not one of SEQ ID NOs: 473, 496, 498, 499, 503, and 508 and an LCVD of SEQ ID NO: 460;

[0139] (d) an HCVD of SEQ ID NO: 542, or one of 550-592; and / or an LCVD of SEQ ID NO: 543, or one of 593-627, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 542 and an LCVD of SEQ ID NO: 543; (ii) an HCVD of SEQ ID NO: 542 and an LCVD that is not one of SEQ ID NOs: 594, 598, 599, 600, 601, 611, 614, and 620; or (iii) an HCVD that is not one of SEQ ID NOs: 551, 553, 554, 555, 556, 563, 565, 568, 582, 584, and 585 and an LCVD of SEQ ID NO: 543;

[0140] (e) an HCVD of SEQ ID NO: 628, or one of 636-675; and / or an LCVD of SEQ ID NO: 629, or one of 676-709, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 628 and an LCVD of SEQ ID NO: 629; (ii) an HCVD of SEQ ID NO: 628 and an LCVD that is not one of SEQ ID NOs: 677, 678, 680, 681, 685, 688, 692, 694, 696, 700, 701, 702, 703, 704, and 705; or (iii) an HCVD that is not one of SEQ ID NOs: 636, 638, 640, 646, 648, 649, 650, 651, 652, 653, 666, 667, 668, and 669 and an LCVD that is not one of SEQ ID NOs: LCVD of NO:629;

[0141] (f) an HCVD of SEQ ID NO: 710, or one of 718-767; and / or an LCVD of SEQ ID NO: 711, or one of 768-802, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 710 and an LCVD of SEQ ID NO: 711; (ii) an HCVD of SEQ ID NO: 710 and an LCVD that is not one of SEQ ID NOs: 769, 771, 773, 774, 779, 780, 785, 786, 788, 790, 791, 792, 795, and 796; or (iii) an LCVD that is not one of SEQ ID NOs: HCVD of one of NOs: 721, 722, 723, 725, 727, 728, 731, 735, 736, 743, 744, 745, 746, 748, 749, 751, 753, 755, 756, 757, 758, and 761 and the LCVD of SEQ ID NO: 711; and

[0142] (g) an HCVD of SEQ ID NO: 803, or one of 811-854; and / or an LCVD of SEQ ID NO: 804, or one of 855-892, wherein the first ABD does not comprise (i) an HCVD of SEQ ID NO: 803 and an LCVD of SEQ ID NO: 804; (ii) an HCVD of SEQ ID NO: 803 and an LCVD that is not one of SEQ ID NOs: 862, 864-866, 868, 870, 881, and 882; or (iii) an HCVD that is not one of SEQ ID NOs: 818, 821, 824, 826-829, 835, 841, 848, and 850 and an LCVD of SEQ ID NO: 804.

[0143] In some embodiments, the first antigen binding domain comprises an HCVD that is one of the following: (a) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 3, 4, and 5, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 3, 4, and 5 are substituted with histidine; (b) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 128, 129, and 130, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 128, 129, and 130 are substituted with histidine; and (c) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 231, 232, and 233, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 231, 232, and 233 are substituted with histidine. In some embodiments, the first CCK4 binding domain comprises an LCVD that is one of the following: (a) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 6, 7, and 8, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 6, 7, and 8 are substituted with histidine; (b) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 131, 132, and 133, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 131, 132, and 133 are substituted with histidine; and (c) an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 234, 235, and 236, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 234, 235, and 236 are substituted with histidine.

[0144] In some embodiments, the first CCK4 binding domain comprises one of the following: (a) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 3, 4, and 5, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 3, 4, and 5 are substituted with histidine; and / or an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 6, 7, and 8, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 6, 7, and 8 are substituted with histidine; (b) an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 128, 129, and 130, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: 128, 129, and 130 are substituted with histidine; and / or an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 131, 132, and 133, respectively, wherein a total of one or more amino acid positions in SEQ ID NOs: (c) an HCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 231, 232 and 233, respectively, wherein a total of one or more amino acid positions are optionally substituted with histidine; and / or an LCVD comprising CDR1, CDR2 and CDR3 of SEQ ID NOs: 234, 235 and 236, respectively, wherein a total of one or more amino acid positions are substituted with histidine.

[0145] In some embodiments, the first antigen binding domain comprises an HCVD of one of the following: (a) an HCVD at least 90% identical to SEQ ID NO: 1, wherein the HCVD includes a histidine at one or more positions selected from the group consisting of: 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107 in SEQ ID NO: 1; (b) an HCVD at least 90% identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at one or more positions selected from the group consisting of: 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, or 111 in SEQ ID NO: 126; and (c) an HCVD at least 90% identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at one or more positions selected from the group consisting of: 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, or 111 in SEQ ID NO: NO:229 has an HCVD with at least 90% identity, wherein the HCVD comprises histidine at one or more positions selected from the group consisting of: 27, 32, 33, 34, 35, 51, 54, 56, 58, or 100 in SEQ ID NO:229. In some embodiments, the first antigen binding domain comprises an LCVD of one of the following: (a) an LCVD at least 90% identical to SEQ ID NO: 2, wherein the LCVD comprises a histidine at one or more positions in SEQ ID NO: 2 selected from the group consisting of: 25, 29, 31, 35, 60, 93, or 94; (b) an LCVD at least 90% identical to SEQ ID NO: 127, wherein the LCVD comprises a histidine at one or more positions in SEQ ID NO: 127 selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94; and (c) an LCVD at least 90% identical to SEQ ID NO: 230, wherein the LCVD comprises a histidine at one or more positions in SEQ ID NO: 230 selected from the group consisting of: 30, 31, 33, 51, 53, 57, 91, 92, 94, and 99.

[0146] In some embodiments, the first antigen binding domain comprises an HCVD of one of the following: (a) an HCVD having at least 90% identity to SEQ ID NO: 1, wherein the HCVD includes histidine at two or more positions in SEQ ID NO: 1 selected from the group consisting of: 27, 29, 31, 34, and 53; and (b) an HCVD having at least 90% identity to SEQ ID NO: 126, wherein the HCVD includes histidine at two or more positions in SEQ ID NO: 126 selected from the group consisting of: 53, 56, 57, 102, and 105.

[0147] In some embodiments, the first antigen binding domain comprises an LCVD of one of the following: (a) an LCVD with at least 90% identity to SEQ ID NO: 2, wherein the LCVD includes histidine at two or more positions in SEQ ID NO: 2 selected from the group consisting of: 31, 60, and 93; and (b) an LCVD with at least 90% identity to SEQ ID NO: 127, wherein the LCVD includes histidine at two or more positions in SEQ ID NO: 127 from the group consisting of: 28 and 90.

[0148] In some embodiments, the first antigen binding domain comprises one of: (a) an HCVD having at least 90% identity to SEQ ID NO: 1, wherein the HCVD includes a histidine at one or more positions selected from the group consisting of: 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107 in SEQ ID NO: 1; and / or an LCVD having at least 90% identity to SEQ ID NO: 2, wherein the LCVD includes a histidine at one or more positions selected from the group consisting of: 25, 29, 31, 35, 60, 93, or 94 in SEQ ID NO: 2; (b) an HCVD having at least 90% identity to SEQ ID NO: 126, wherein the HCVD includes a histidine at one or more positions selected from the group consisting of: 25, 29, 31, 35, 60, 93, or 94 in SEQ ID NO: 2. NO: 126 at one or more positions selected from the group consisting of: 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, and 111; and / or an LCVD having at least 90% identity to SEQ ID NO: 127, wherein the LCVD includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94 of SEQ ID NO: 127; and (c) an HCVD having at least 90% identity to SEQ ID NO: 229, wherein the HCVD includes a histidine at one or more positions selected from the group consisting of: 27, 32, 33, 34, 35, 51, 54, 56, 58, and 100 of SEQ ID NO: 229; and / or an LCVD having at least 90% identity to SEQ ID NO: 127, wherein the LCVD includes a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94 of SEQ ID NO: NO: 230. An LCVD having at least 90% identity, wherein the LCVD comprises histidine at one or more positions selected from the group consisting of 30, 31, 33, 51, 53, 57, 91, 92, 94, and 99 in SEQ ID NO: 230.

[0149] In some embodiments, the first antigen binding domain comprises an HCVD of one of the following SEQ ID NOs: (a) an HCVD of SEQ ID NO: 1, 14, 17, 18, 19, 20, 21, 22, 24, 25, 29, 30, 31, 33, 34, 40, 44, 46, 48, 49, 53, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98, 99, 100, 101, 102, 103, 104, or 105; (b) an HCVD of SEQ ID NO: NO:126, 147, 148, 150, 151, 154, 166, 167, 168, 169, 170, 172, 173, 174, 175, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 224, 225, 226 or 227; and (c) an HCVD of SEQ ID NO:229, 238, 243, 244, 245, 246, 248, 251, 253, 255 or 267. In some embodiments, the first antigen binding domain comprises an LCVD of one of the following SEQ ID NOs: (a) an LCVD of SEQ ID NO: 2, 56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, 122, 123, 124, or 125; (b) an LCVD of SEQ ID NO: 127, 181, 182, 184, 185, 187, 188, 189, 191, 199, 201, 203, or 228; and (c) an LCVD of SEQ ID NO: 230, 275, 276, 278, 281, 283, 287, 289, 290, 292, or 297.

[0150] In some embodiments, the first antigen binding domain comprises one of: (a) an HCVD of SEQ ID NO: 14, 17, 18, 19, 20, 21, 22, 24, 25, 29, 30, 31, 33, 34, 40, 44, 46, 48, 49, 53, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98, 99, 100, 101, 102, 103, 104, or 105; and / or an LCVD of SEQ ID NO: 2, 56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, 122, 123, 124, or 125, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 1 and an LCVD of SEQ ID NO: 2. NO:2; (ii) the HCVD of SEQ ID NO:1 and an LCVD that is not one of SEQ ID NO:56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, and 122-125; or (iii) the LCVD of SEQ ID NO:2 and an HCVD that is not one of SEQ ID NO:14, 17-22, 24, 25, 29-31, 33, 34, 40, 44, 46, 48, 49, 53, 86-96, and 98-105; (b) the HCVD of SEQ ID NO:1 NO: 147, 148, 150, 151, 154, 166, 167, 168, 169, 170, 172, 173, 174, 175, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 224, 225, 226 or 227; and / or SEQ ID NO: 127, 181, 182, 184, 185, 187, 188, 189, 191, 199, 201, 203 or 228, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 126 and an LCVD of SEQ ID NO: 127; (ii) an LCVD of SEQ ID NO: (iii) an LCVD of SEQ ID NO: 127 and an HCVD that is not one of SEQ ID NOs: 147, 148, 150, 151, 154, 166-170, 172-175, 208-222, and 224-227;and (c) an HCVD of SEQ ID NO: 238, 243, 244, 245, 246, 248, 251, 253, 255, or 267; and / or an LCVD of SEQ ID NO: 230, 275, 276, 278, 281, 283, 287, 289, 290, 292, or 297, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 229 and an LCVD of SEQ ID NO: 230; (ii) an HCVD of SEQ ID NO: 229 and an LCVD that is not one of SEQ ID NO: 275, 276, 278, 281, 283, 287, 289, 290, 292, and 297; and (iii) an LCVD of SEQ ID NO: 230 and an LCVD that is not one of SEQ ID NO: HCVD of one of NOs: 238, 243-246, 248, 251, 253, 255, and 267;

[0151] In some embodiments, the composition comprising the ABPC provides an increase in toxin release in the target mammalian cell compared to a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPC provides an increase in toxin release in the target mammalian cell compared to a composition comprising the same amount of a control ABPC by at least 20%. In some embodiments, the composition comprising the ABPC provides an increase in toxin release in the target mammalian cell compared to a composition comprising the same amount of a control ABPC by at least 50%. In some embodiments, the composition comprising the ABPC provides an increase in toxin release in the target mammalian cell by at least 2-fold compared to a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPC provides an increase in toxin release in the target mammalian cell by at least 5-fold compared to a composition comprising the same amount of a control ABPC.

[0152] In some embodiments, the composition comprising the ABPCs provides an increase in killing of target mammalian cells compared to a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPCs provides an increase in killing of target mammalian cells by at least 20% or 50% compared to a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPCs provides an increase in killing of target mammalian cells by at least 2-fold or 5-fold compared to a composition comprising the same amount of a control ABPC.

[0153] In some embodiments, the composition comprising the ABPCs provides an increase in endolysosomal delivery in target mammalian cells compared to a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPCs provides an increase in endolysosomal delivery in target mammalian cells compared to a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPCs provides an increase in endolysosomal delivery in target mammalian cells by at least 20% or 50% compared to a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPCs provides an increase in endolysosomal delivery in target mammalian cells by at least 2-fold or 5-fold compared to a composition comprising the same amount of a control ABPC.

[0154] In some embodiments, the composition comprising the ABPCs provides less of a decrease in the level of PTK7 presented on the surface of a target mammalian cell than a composition comprising the same amount of a control ABPC. In some embodiments, the composition comprising the ABPCs does not cause a detectable decrease in the level of PTK7 presented on the surface of a target mammalian cell. In some embodiments, the target mammalian cell is a cancer cell.

[0155] In some embodiments, the off-rate of ABD at a pH of about 4.0 to about 6.5 is at least 10% faster than the off-rate of ABD at a pH of about 7.0 to about 8.0. In some embodiments, the off-rate of ABD at a pH of about 4.0 to about 6.5 is at least 3 times faster than the off-rate of ABD at a pH of about 7.0 to about 8.0. In some embodiments, the off-rate of ABD at a pH of about 4.0 to about 6.5 is at least 10 times faster than the off-rate of ABD at a pH of about 7.0 to about 8.0. In some embodiments, the K of ABD at a pH of about 4.0 to about 6.5 is at least 10% faster than the off-rate of ABD at a pH of about 7.0 to about 8.0. D The K of ABD at a pH of about 7.0 to about 8.0 D In some embodiments, the K of the ABD at a pH of about 4.0 to about 6.5 is greater than that of the ABD at a pH of about 4.0 to about 6.5. D The K of ABD at a pH of about 7.0 to about 8.0 D In some embodiments, the K of the ABD at a pH of about 4.0 to about 6.5 is at least 3 times greater. D The K of ABD at a pH of about 7.0 to about 8.0 D Bigger, at least 10 times.

[0156] In some embodiments, the ABPC is cytotoxic or cytostatic to target mammalian cells.

[0157] In some embodiments, the ABPCs are cross-reactive with non-human primate PTK7 and human PTK7. In some embodiments, the ABPCs are cross-reactive with non-human primate PTK7, human PTK7, and one or both of rat PTK7 and mouse PTK7. In some embodiments, the ABPCs are cross-reactive with non-human primate PTK7, human PTK7, rat PTK7, and mouse PTK7.

[0158] In some embodiments, the ABD binds to an epitope of PTK7 present on the surface of a cell from an Old World monkey.

[0159] In some embodiments, the ABPC comprises a single polypeptide. In some embodiments, the ABD is selected from a VH domain, a VHH domain, a VNAR domain, and a scFv. In some embodiments, the ABPC is a BiTe, (scFv)2, a nanobody, a nanobody-HSA, a DART, a TandAb, a scDiabody, a scDiabody-CH3, a scFv-CH-CL-scFv, an HSAbody, a scDiabody-HSA, or a tandem-scFv.

[0160] In some embodiments, the ABPC comprises two or more polypeptides. In some embodiments, the ABPC is selected from the group consisting of antibodies, VHH-scAb, VHH-Fab, double scFab, F(ab')2, double-chain antibodies, cross-Mab, DAF (two-in-one), DAF (four-in-one), DutaMab, DT-IgG, common light chain of knobs-in-hole, knobs-in-hole assembly, charge pair, Fab arm exchange, SEEDBody, LUZ-Y, Fcab, kappa lambda body, orthogonal Fab, DVD-IgG, IgG(H)-scFv, scFv-(H)IgG, IgG(L)-scFv, scFv-(L)IgG, IgG(L,H)-Fv, IgG(H)-V, V(H)-IgG, IgG(L)-V, V(L)-IgG, KIH IgG-scFab, 2scFv-IgG, IgG-2scFv, scFv4-Ig, Zybody, DVI-IgG, diabody-CH3, triabody, minibody, minibody, TriBi minibody, scFv-CH3 KIH, Fab-scFv, F(ab')2-scFv2, scFv-KIH, Fab-scFv-Fc, tetravalent HCAb, scDiabody-Fc, diabody-Fc, tandem scFv-Fc, VHH-Fc, tandem VHH-Fc, VHH-Fc KiH, Fab-VHH-Fc, Intrabody, docked locked antibody, ImmTAC, IgG-IgG conjugate, Cov-X-Body, scFv1-PEG-scFv2, Adnectin, DARPin, fibronectin, and DEP conjugate.

[0161] In some embodiments, at least one polypeptide of the ABPC is conjugated to a toxin, radioisotope, drug, or small molecule via a cleavable linker. In some embodiments, at least one polypeptide of the ABPC is conjugated to a toxin, radioisotope, drug, or small molecule via a non-cleavable linker.

[0162] In some embodiments, the half-life of the ABPC in vivo is reduced compared to the half-life of a control ABPC in vivo. In some embodiments, the half-life of the ABPC in vivo is reduced by about 5% to 95% compared to the half-life of the control ABPC in vivo. In some embodiments, the half-life of the ABPC in vivo is reduced by about 10% to 95% compared to the half-life of the control ABPC in vivo. In some embodiments, the half-life of the ABPC in vivo is reduced by about 30% to 95% compared to the half-life of the control ABPC in vivo. In some embodiments, the half-life of the ABPC in vivo is reduced by about 50% to 95% compared to the half-life of the control ABPC in vivo. In some embodiments, the half-life of the ABPC in vivo is reduced by about 70% to 95% compared to the half-life of the control ABPC in vivo.

[0163] In some embodiments, the control ABPC is capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell, wherein: (a) the control ABPC comprises a first ABD; (b) the off-rate of the first ABD of the control ABPC at a pH of about 4.0 to about 6.5 is no more than 3-fold faster than the off-rate at a pH of about 7.0 to about 8.0; and (c) the dissociation constant (K) of the first ABD of the control ABPC at a pH of about 4.0 to about 6.5 is D ) than K at a pH of about 7.0 to about 8.0 D Larger, no more than 3 times.

[0164] In some embodiments, the control ABPC is capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell, wherein: (a) the control ABPC comprises a first ABD; (b) the off-rate of the first ABD of the control ABPC at a pH of about 4.0 to about 6.5 is no more than 2-fold faster than the off-rate at a pH of about 7.0 to about 8.0; and (c) the dissociation constant (K) of the first ABD of the ABPC at a pH of about 4.0 to about 6.5 is D ) than K at a pH of about 7.0 to about 8.0 D Larger, no more than 2 times.

[0165] In some embodiments, the control ABPC is capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell, wherein: (a) the control ABPC comprises a first ABD; (b) the off-rate of the first ABD of the control ABPC at a pH of about 4.0 to about 6.5 is no more than 1-fold faster than the off-rate at a pH of about 7.0 to about 8.0; and (c) the dissociation constant (K) of the first ABD of the control ABPC at a pH of about 4.0 to about 6.5 is D ) than K at a pH of about 7.0 to about 8.0D Large, no more than 1 times.

[0166] In some embodiments, the control ABPC is MYT9345, MYT9359, MYT9361, MYT9412, MYT9460, MYT9792, MYT9797, cofilinumab, 7C8, or 12C6.

[0167] In some embodiments, the ABPC comprises a second ABD.

[0168] Also provided herein are kits comprising at least one dose of any ABPC described herein.

[0169] Also provided herein are methods of treating cancer characterized by a population of cancer cells having PTK7 or an epitope of PTK7 presented on their surface, the method comprising administering a therapeutically effective amount of any pharmaceutical composition described herein or any ABPC described herein to a subject identified as having a cancer characterized by having said population of cancer cells.

[0170] Also provided herein are methods of reducing the volume of a tumor in a subject, wherein the tumor is characterized by a population of cancer cells having PTK7 or an epitope of PTK7 presented on its surface, the method comprising administering a therapeutically effective amount of any pharmaceutical composition described herein or any ABPC described herein to a subject identified as having a cancer characterized by having said population of cancer cells.

[0171] Also provided herein are methods of inducing cell death in cancer cells in a subject, wherein the cancer cells have PTK7 or an epitope of PTK7 presented on their surface, wherein the method comprises administering a therapeutically effective amount of any pharmaceutical composition described herein or any ABPC described herein to a subject identified as having a cancer characterized by having a population of said cancer cells.

[0172] In some embodiments, the cancer is a primary tumor. In some embodiments, the cancer is a metastasis. In some embodiments, the cancer is a non-T cell infiltrated tumor. In some embodiments, the cancer is a T cell infiltrated tumor.

[0173] Also provided herein are methods of reducing the risk of developing metastasis or reducing the risk of developing additional metastases in a subject having cancer, wherein the cancer is characterized by a population of cancer cells having PTK7 or an epitope of PTK7 presented on its surface, the method comprising administering a therapeutically effective amount of any one of the pharmaceutical compositions described herein or any of the ABPCs described herein to a subject identified as having cancer characterized by the population of cancer cells.

[0174] In some embodiments, the cancer is a non-T cell infiltrated tumor. In some embodiments, the cancer is a T cell infiltrated tumor.

[0175] As used herein, the term "antigen-binding protein construct" is (i) a single polypeptide comprising at least one ABD or (ii) a complex of two or more polypeptides (e.g., the same polypeptide or different polypeptides) that together form at least one ABD. Non-limiting examples and aspects of antigen-binding protein constructs are described herein. Additional examples and aspects of antigen-binding protein constructs are known in the art.

[0176] "Multi-specific ABPC" is an ABPC comprising two or more different ABDs that specifically bind to two or more different epitopes in total. The two or more different epitopes can be epitopes on the same antigen (e.g., a single polypeptide present on the cell surface) or different antigens (e.g., different proteins present on the same cell surface or on different cell surfaces). In some aspects, the antigen is present on the cell surface. In some aspects, the multi-specific ABPC binds to two different epitopes (i.e., "bispecific ABPC"). In some aspects, the multi-specific ABPC binds to three different epitopes (i.e., "trispecific ABPC"). In some aspects, the multi-specific ABPC binds to four different epitopes (i.e., "tetraspecific ABPC"). In some aspects, the multi-specific ABPC binds to five different epitopes (i.e., "pentaspecific ABPC"). Each binding specificity can exist at any suitable valence. Non-limiting examples of multi-specific ABPC are described herein.

[0177] An "antigen binding protein" or "ABD" is one or more protein domains (e.g., formed from amino acids from a single polypeptide or formed from amino acids from two or more polypeptides (e.g., the same or different polypeptides)) that are capable of specifically binding to one or more different antigens. In some instances, the ABD may bind to an antigen or epitope with a specificity and affinity similar to that of a naturally occurring antibody. In some embodiments, the ABD may be an antibody or fragment thereof. In some embodiments, the ABD may comprise an alternative scaffold. Non-limiting examples of ABDs are described herein. Other examples of ABDs are known in the art. In some instances, the ABD may bind to a single antigen.

[0178] The term "antibody" is used herein in its broadest sense and includes certain types of immunoglobulin molecules that include one or more ABDs that specifically bind to an antigen or epitope. Antibodies particularly include, for example, complete antibodies (e.g., complete immunoglobulins, such as human IgG (e.g., human IgG1, human IgG2, human IgG3, human IgG4)), antibody fragments, and multispecific antibodies. An example of an ABD is an ABD formed by a VH-VL dimer. Additional examples of antibodies are described herein. Additional examples of antibodies are known in the art.

[0179] The phrase "endosomal / lysosomal pathway" refers to the network of endosomes (early endosomes, multivesicular bodies, late endosomes, and lysosomes) in the cytoplasm of mammalian cells where molecules internalized by cell-mediated internalization processes (e.g., pinocytosis, micropinocytosis, receptor-mediated endocytosis, and / or phagocytosis) are sorted.

[0180] Once the endosomes in the endosomal / lysosomal pathway are purified or isolated, the target protein (e.g., an antigen-binding protein construct described herein) can be assayed using methods known in the art (ELISA, Western blot, immunofluorescence, and immunoprecipitation followed by determination of protein concentration) and can be used to determine the concentration or relative level of the target protein in the endosome. Alternatively, immunofluorescence microscopy can be used using a detectably labeled antibody (e.g., a fluorophore-labeled antibody, a dye-labeled antibody, or a GFP-labeled antibody, e.g., CellLight TM Endosomes in the endosomal / lysosomal pathway can be imaged by combining a fluorescently labeled early endosome-GFP) and a fluorophore-labeled antibody that specifically binds to a target protein (e.g., ABPC), and the target protein level in endosomes can be determined by quantifying the overlap in the fluorescence emission of the two different antibodies.

[0181] The phrase "endolysosomal delivery" refers to the rate of accumulation of an ABPC (e.g., any ABPC described herein) in the endosomal / lysosomal pathway of a mammalian cell (e.g., any exemplary target mammalian cell described herein) over time or the total rate of accumulation at a specific time point.

[0182] An exemplary method for calculating the increase in endosomal delivery of a pH-engineered ABPC variant compared to its corresponding starting ABPC from cellular fluorescence data is to measure the mean fluorescence intensity of the variant minus the mean fluorescence intensity of a non-binding IgG control and then divide the whole by the ratio of the mean fluorescence intensity of the variant's corresponding starting ABPC minus the mean fluorescence intensity of the IgG control.

[0183] Exemplary assays for measuring endosomal delivery of any ABPC described herein include those involving labeling the ABPC with a fluorescent dye, then incubating the labeled ABPC with cells and measuring cell fluorescence as an indicator of ABPC endolysosomal delivery (e.g., as generally described in Wustner, Traffic 7(6):699-715, 2006). Alternatively, a pH-sensitive dye that preferentially fluoresces at acidic pH rather than neutral pH can be used to label any ABPC described herein, which can then be incubated with cells and cell fluorescence measured as an indicator of ABPC delivery to the acidic endolysosomal compartment.

[0184] The term "population" when used before a noun means two or more of the specific noun. For example, the phrase "a population of cancer cells" means "two or more cancer cells." Non-limiting examples of cancer cells are described herein.

[0185] The phrase "cytostatic to a cell" refers to a direct or indirect reduction in the proliferation (cell division) of a cell (e.g., a cancer cell) in vivo or in vitro. When an agent is cytostatic to a cell, the agent can, for example, directly or indirectly cause cell cycle arrest of a cell (e.g., a cancer cell). In some instances, an agent that is cytostatic to a cell can reduce the number of cells in S phase in a cell population (compared to the number of cells in S phase in the cell population prior to contact with the agent). In some instances, an agent that is cytostatic to a cell can reduce the percentage of cells in S phase by at least 20%, at least 40%, at least 60%, or at least 80% (e.g., compared to the percentage of cells in S phase in the cell population prior to contact with the agent).

[0186] The phrase "cytotoxic to cells" refers to inducing, directly or indirectly, cell death (eg, necrosis or apoptosis) of cells (eg, mammalian cells, such as cancer cells).

[0187] "Affinity" refers to the total strength of non-covalent interactions between an antigen binding site and its binding partner (e.g., an antigen or epitope). Unless otherwise indicated, as used herein, "affinity" refers to intrinsic binding affinity, which reflects a 1:1 interaction between a member of an ABD and an antigen or epitope. The affinity of a molecule X for its partner Y can be expressed in terms of the dissociation equilibrium constant (K D ). Affinity can be measured by common methods known in the art, including those described herein. Affinity can be measured, for example, using surface plasmon resonance (SPR) technology (e.g., ) or biofilm interference techniques (e.g. Additional methods for determining affinity for an ABD and its corresponding antigen or epitope are known in the art.

[0188] The term "epitope" means a portion of an antigen that is specifically bound by an ABD through a set of physical interactions between: (i) all monomers on the portion of the ABD that specifically binds to the antigen (e.g., individual amino acid residues, sugar side chains, and post-translationally modified amino acid residues), and (ii) all monomers on the portion of the antigen that is specifically bound by the ABD (e.g., individual amino acid residues, sugar side chains, and post-translationally modified amino acid residues). An epitope can, for example, consist of surface-accessible amino acid residues, sugar side chains, phosphorylated amino acid residues, methylated amino acid residues, and / or acetylated amino acid residues and can have specific three-dimensional structural characteristics and specific charge characteristics. The difference between a conformational epitope and a non-conformational epitope is that binding to the former, rather than binding to the latter, may be lost in the presence of a denaturing solvent. In some embodiments, an epitope is defined by a linear amino acid sequence of at least about 3 to 6 amino acids or about 10 to 15 amino acids. In some embodiments, an epitope refers to a portion of a full-length protein defined by a three-dimensional structure (e.g., protein folding) or a portion thereof. In some embodiments, an epitope is defined by a discontinuous amino acid sequence that is aggregated via protein folding. In some embodiments, an epitope is defined by a discontinuous amino acid sequence held together by a quaternary structure (e.g., a cleft formed by the interaction of two different polypeptide chains). The amino acid sequence between the residues defining the epitope may not be critical to the three-dimensional structure of the epitope. Conformational epitopes can be determined and screened using assays that compare the binding of antigen-binding protein constructs to denatured forms of the antigen in order to generate linear epitopes. An epitope may comprise amino acid residues that are directly involved in binding and other residues that are not directly involved in binding.

[0189] Methods for identifying the epitope to which the ABD specifically binds are known in the art, such as structure-based analysis (e.g., X-ray crystallography, NMR and / or electron microscopy) (e.g., based on the antigen and / or antigen-ABD complex) and / or mutagenesis-based analysis (e.g., alanine scanning mutagenesis, glycine scanning mutagenesis, and homology scanning mutagenesis), wherein mutants are measured in binding assays with the binding partner, many of which are known in the art.

[0190] The term "paratope" means a portion of an ABD that specifically binds to an antigen through a set of physical interactions between: (i) all monomers on the portion of the ABD that specifically binds to the antigen (e.g., a single amino acid residue, a sugar side chain, a post-translationally modified amino acid residue), and (ii) all monomers on the portion of the antigen that is specifically bound by the ABD (e.g., a single amino acid residue, a sugar side chain, a post-translationally modified amino acid residue). A paratope can, for example, consist of surface-accessible amino acid residues and can have specific three-dimensional structural characteristics and specific charge characteristics. In some embodiments, a paratope refers to a portion or a portion of a full-length ABD defined by a three-dimensional structure (e.g., a protein fold). In some embodiments, a paratope is defined by a discontinuous amino acid sequence that is brought together via protein folding. In some embodiments, an epitope is defined by a discontinuous amino acid sequence that is brought together by a quaternary structure (e.g., a cleft formed by the interaction of two different polypeptide chains). The amino acid sequence between the residues that define the paratope may not be critical for the three-dimensional structure of the paratope. A paratope can include amino acid residues that are directly involved in binding and other residues that are not directly involved in binding.

[0191] Methods for identifying the paratope to which the ABD specifically binds are known in the art, such as structure-based analysis (e.g., X-ray crystallography, NMR, and / or electron microscopy) (e.g., based on the ABD and / or the ABD-antigen complex) and / or mutagenesis-based analysis (e.g., alanine scanning mutagenesis, glycine scanning mutagenesis, and homology scanning mutagenesis), wherein mutants are measured in binding assays with the binding partner, many of which are known in the art.

[0192] The phrase "present on the surface of a mammalian cell" means an antigen that is (1) physically attached to or at least partially embedded in the plasma membrane of a mammalian cell (e.g., a transmembrane protein, a peripheral membrane protein, a lipid-anchored protein (e.g., a GPI-anchor), an N-myristoylated protein, or an S-palmitoylated protein) or (2) stably bound to its cognate receptor, wherein the cognate receptor is physically attached to the plasma membrane of the cell (e.g., a ligand that binds to its cognate receptor, wherein the cognate receptor is physically attached to the plasma membrane). Non-limiting methods for determining the presence of an antigen on the surface of a mammalian cell include fluorescence activated cell sorting (FACS), immunohistochemistry, cell fractionation assays, and Western blotting.

[0193] The phrase "control ABPC" or "control antigen binding protein construct" means any of the following: (1) an ABPC capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a mammalian cell (e.g., a target mammalian cell), wherein one or both of the following are true: (a) the off-rate of the first ABD at a pH of about 4.0 to about 6.5 (e.g., any subrange of this range described herein) is greater than the off-rate at a pH of about 7.0 to about 8.0 (e.g., any subrange of this range described herein); or (b) the dissociation constant (K) of the first ABD at a pH of about 4.0 to about 6.5 (e.g., any subrange of this range described herein); D ) than the K at a pH of about 7.0 to about 8.0 (e.g., any subrange of this range described herein). D greater, ≤3-fold (e.g., ≤2.8-fold, ≤2.6-fold, ≤2.5-fold, ≤2.4-fold, ≤2.2-fold, ≤2.0-fold, ≤1.8-fold, ≤1.6-fold, ≤1.5-fold, ≤1.4-fold, ≤1.2-fold, ≤1.0-fold, ≤0.8-fold, ≤0.6-fold, ≤0.5-fold, ≤0.4-fold, ≤0.3-fold, ≤0.2-fold, or ≤0.1-fold); (2) MYT9345; (3) MYT9359; (4) MYT9361; (5) MYT9412; (6) MYT9460; (7) MYT9792; (8) MYT9797; (9) cofetizumab; (10) 7C8; or (11) 12C6.

[0194] The term "extracellular space" refers to the fluid outside the plasma membrane of a mammalian cell. When the mammalian cell is in vitro, the extracellular space can be a liquid culture medium. When the mammalian cell is in vivo, the extracellular space can be, for example, plasma, serum, blood, interstitial fluid, or lymph.

[0195] The term "endolysosomal space" refers to the fluid enclosed by the vesicles and organelles that constitute the endosomal / lysosomal pathway in mammalian cells.

[0196] The phrase "reduced levels" or "decreased levels" can be a decrease or decrease of at least 1% (e.g., ≥2%, ≥4%, ≥6%, ≥8%, ≥10%, ≥12%, ≥14%, ≥16%, ≥18%, ≥20%, ≥22%, ≥24%, ≥26%, ≥30%, ≥35%, ≥40%, ≥45%, ≥50%, ≥55%, ≥60%, ≥65%, ≥70%, ≥75%, ≥80%, ≥85%, ≥90%, ≥95% or ≥99%) compared to a reference level or reference value.

[0197] The term "cell killing efficacy" refers to the ability of an agent (e.g., any ABPC described herein) to directly or indirectly induce apoptosis and / or necrosis of mammalian cells (e.g., cancer cells) as measured over time or at a rate at a relevant time point. Methods for determining the cell killing efficacy of cells are known in the art (e.g., trypan blue staining, microscopy, fluorescence-assisted cell sorting, and assays for detecting apoptosis markers (e.g., annexin V). In a non-limiting example, the cell killing efficacy can be measured by, for example, by killing cells at a single concentration of the agent, by the IC50 of the agent (i.e., the concentration of the agent that achieves half the maximum cell killing efficacy), or by the ratio of the dissociation constant KD of the agent on mammalian cells divided by its IC50. In some non-limiting examples, the IC50 and / or KD ratios described herein are compared to those of a control ABPC (as defined herein), and it is optionally demonstrated that the ABPC described herein has a higher cell killing efficacy than the control ABPC.

[0198] The term "toxin release" refers to the ability of a mammalian cell (e.g., a non-cancerous mammalian cell or a cancer cell) to internalize (e.g., via pinocytosis and / or receptor-mediated endocytosis) any ABPC described herein (e.g., any ABPC described herein or a control ABPC) conjugated to a toxin, as measured over time or at a specific time point, and subsequently release the toxin conjugated to the ABPC. Toxin release can be assessed using a variety of different exemplary assays, such as ELISA, immunofluorescence, cell killing assays, cell cycle arrest assays, DNA damage assays, mass spectrometry, HPLC, and / or isotope-labeled toxins.

[0199] The phrase "target cell" or "target mammalian cell" or "mammalian target cell" means a mammalian cell having at least one PTK7 present on its surface. In some examples, the mammalian target cell can be a cancer cell. In some embodiments, the target mammalian cell can have a total of about the following (each ± ​​about 10%): 1-10E6, 1-9E6, 1-8E6, 1-7E6, 1-6E6, 1-5E6, 1-4E6, 1-3E6, 1-2E6, 1-1E6, 1-800,000, 1-600,000, 1-400,000, 1-200,000, 1-100,000, 1-80,000, 1-80,000, 1-75,000, 1-70,000, 1-65,000, 1-60,000, 1-55 ,000, 1-50,000, 1-45,000, 1-40,000, 1-35,000, 1-30,000, 1-25,000, 1-20,000, 1-15,000, 1-10,000, 1-7,500, 1-5,000, 1-4,000, 1-3,000, 1-2,000, 1-1,000, 1-500, 1-100, 1-50, or 1-10 PTK7s, or any range of values ​​described in US2022 / 0281984, are present on the plasma membrane of the target mammalian cell.

[0200] The phrase "antigen density" means the number of PTK7 present on the surface of a target mammalian cell or the average number of PTK7 present on the surface of a population of target mammalian cells of a particular type. "Antigen density" can be measured using, for example, a Quantibright bead kit or a radiolabel (e.g., BD Biosciences PE Phycoerythrin Fluorescence Quantitation Kit, catalog number 340495).

[0201] The phrase "amino acid is substituted with histidine" means that an amino acid residue in a reference polypeptide sequence that is not histidine is substituted with histidine. Non-limiting methods for substituting amino acid residues in a reference polypeptide with histidine are described herein. Additional methods for substituting amino acid residues in a reference polypeptide with histidine are known in the art.

[0202] The phrase "amino acid is substituted with alanine" means that an amino acid residue in a reference polypeptide sequence that is histidine is replaced with alanine. Non-limiting methods for replacing histidine in a reference polypeptide with alanine are described herein. Additional methods for replacing histidine in a reference polypeptide with alanine are known in the art.

[0203] Unless otherwise defined, 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 invention belongs. Methods and materials for use in the present invention are described herein; other suitable methods and materials known in the art may also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In the event of a conflict, the present specification (including definitions) will prevail.

[0204] Other features and advantages of the invention will be apparent from the following detailed description and drawings, and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0205] Figure 1 SDS PAGE analysis of histidine- and alanine-scanning cofetizumab. Harvested Expi293 cell culture supernatants were loaded onto non-reducing SDS PAGE gels to confirm the expression of cofetizumab and its histidine- and alanine-scanning variants. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT6002 is cofetizumab, and MYT6152–MYT6193 are cofetizumab heavy chain histidine- and alanine-scanning variants.

[0206] Figures 2a to 2aq : Binding of cofetizumab starting ABPC and histidine- and alanine-scan variants to PTK7 as determined by biofilm interferometry. MYT6002 (cofetizumab) and MYT6152-MYT6193 (i.e., heavy chain histidine- and alanine-scan variants) were captured on an anti-human Fc biosensor and associated with PTK7 at pH 7.4. Dissociation was performed at pH 7.4 (black trace) or pH 5.4 (grey trace).

[0207] Figure 3 : Construct identifier to SEQ ID NO correspondence table. Constructs, i.e., heavy chain histidine scan and alanine scan variants, are listed in the first column of the table, the SEQ ID NO is listed and corresponds to the construct on the left and the appropriate heavy and / or light chain class along the top.

[0208] Figure 4SDS PAGE for histidine- and alanine-scanning of cofetizumab. Harvested Expi293 cell culture supernatants were loaded onto non-reducing SDS PAGE gels to confirm expression of histidine- and alanine-scanning variants of cofetizumab. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT6194–MYT6224 are histidine- and alanine-scanning variants of the cofetizumab light chain.

[0209] Figures 5a to 5af : Binding of cofetizumab starting ABPC and histidine- and alanine-scan variants to PTK7 as determined by biofilm interferometry. MYT6002 (cofetizumab) and MYT6194-MYT6224 (i.e., histidine- and alanine-scan light chain variants of cofetizumab) were captured on an anti-human Fc biosensor and associated with PTK7 at pH 7.4. Dissociation was performed at pH 7.4 (black trace) or pH 5.4 (grey trace).

[0210] Figure 6 : Construct identifier to SEQ ID NO correspondence table. Constructs, i.e., light chain histidine scan and alanine scan variants, are listed in the first column of the table, the SEQ ID NO is listed and corresponds to the construct on the left and the appropriate heavy and / or light chain class along the top.

[0211] Figure 7 Figure 2: SDS PAGE of histidine- and alanine-scanned cofetizumab. Harvested Expi293 cell culture supernatants were loaded onto non-reducing SDS PAGE gels to confirm expression of histidine- and alanine-scanned cofetizumab variants. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT7837-MYT7856 are combined histidine- and alanine-scanned cofetizumab heavy chain variants.

[0212] Figures 8a to 8u Binding of histidine-scan and alanine-scan variants of cofetizumab to PTK7 as determined by biofilm interferometry. MYT6002 (cofetizumab) and MYT7837-MYT7856 (i.e., combined histidine-scan and alanine-scan heavy chain variants of cofetizumab) were captured on an anti-human Fc biosensor and associated with PTK7 at pH 7.4. Dissociation was performed at pH 7.4 (black trace) or pH 5.4 (grey trace).

[0213] Figure 9: Construct identifier to SEQ ID NO correspondence table. Constructs, heavy chain combination histidine scan and alanine scan variants are listed in the first column of the table, the SEQ ID NO is listed and corresponds to the construct on the left and the appropriate heavy and / or light chain class along the top.

[0214] Figure 10 Figure 2: SDS PAGE of histidine- and alanine-scanned cofetizumab. Harvested Expi293 cell culture supernatants were loaded onto non-reducing SDS PAGE gels to confirm expression of histidine- and alanine-scanned cofetizumab variants. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT7857-MYT7876 are combined histidine- and alanine-scanned cofetizumab light chain variants.

[0215] Figures 11a to 11u Binding of histidine-scan and alanine-scan variants of cofetizumab to PTK7 as determined by biofilm interferometry. MYT6002 (cofetizumab) and MYT7857-MYT7876 (i.e., combined histidine-scan and alanine-scan light chain variants of cofetizumab) were captured on an anti-human Fc biosensor and associated with PTK7 at pH 7.4. Dissociation was performed at pH 7.4 (black trace) or pH 5.4 (grey trace).

[0216] Figure 12 : Construct identifier to SEQ ID NO correspondence table. Constructs, light chain combination histidine scan and alanine scan variants are listed in the first column of the table, with the SEQ ID NO listed and corresponding to the construct on the left and the appropriate heavy and / or light chain class along the top.

[0217] Figure 13 : SDS PAGE for 7C8 His- and Alanine-scanning. Harvested Expi293 cell culture supernatants were loaded onto non-reducing SDS PAGE gels to confirm expression of 7C8 and histidine- and alanine-scan variants. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT6003 is 7C8, and the remainder of the lane (MYT6225-MYT6270) are 7C8 heavy chain histidine- and alanine-scan variants.

[0218] Figures 14a to 14auBinding of 7C8 starting ABPC and histidine- and alanine-scan variants to PTK7 as determined by biofilm interferometry. MYT6003 (7C8) and MYT6225-MYT6270 (i.e., heavy chain histidine- and alanine-scan variants) were captured on an anti-human Fc biosensor and associated with PTK7 at pH 7.4. Dissociation was performed at pH 7.4 (black trace) or pH 5.4 (grey trace).

[0219] Figure 15 : Construct identifier to SEQ ID NO correspondence table. Constructs, i.e., heavy chain histidine scan and alanine scan variants, are listed in the first column of the table, the SEQ ID NO is listed and corresponds to the construct on the left and the appropriate heavy and / or light chain class along the top.

[0220] Figure 16 : SDS PAGE for 7C8 Histidine and Alanine Scanning. Harvested Expi293 cell culture supernatants were loaded onto non-reducing SDS PAGE gels to confirm expression of 7C8 Histidine and Alanine Scanning variants. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gels. MYT6271-MYT6298 are 7C8 light chain Histidine and Alanine Scanning variants.

[0221] Figures 17a to 17ac : Binding of 7C8 starting ABPC and histidine- and alanine-scan variants to PTK7 as determined by biofilm interferometry. MYT6003 (7C8) and MYT6271-MYT6298 (i.e., histidine- and alanine-scan light chain variants of 7C8) were captured on an anti-human Fc biosensor and associated with PTK7 at pH 7.4. Dissociation was performed at pH 7.4 (black trace) or pH 5.4 (grey trace).

[0222] Figure 18 : Construct identifier to SEQ ID NO correspondence table. Constructs, i.e., light chain histidine scan and alanine scan variants, are listed in the first column of the table, the SEQ ID NO is listed and corresponds to the construct on the left and the appropriate heavy and / or light chain class along the top.

[0223] Figure 19 : SDS PAGE for 7C8 Histidine and Alanine Scanning. Harvested Expi293 cell culture supernatants were loaded onto non-reducing SDS PAGE gels to confirm expression of 7C8 Histidine and Alanine Scanning variants. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT7816-MYT7835 are 7C8 heavy chain variants with combined Histidine and Alanine Scanning.

[0224] Figures 20a to 20u : Histidine- and alanine-scan variants of 7C8 bind to PTK7 by biolayer interferometry. MYT6003 (7C8) and MYT7816-MYT7835 (i.e., combined histidine- and alanine-scan variants of the heavy chain of 7C8) were captured on an anti-human Fc biosensor and associated with PTK7 at pH 7.4. Dissociation was performed at pH 7.4 (black trace) or pH 5.4 (grey trace).

[0225] Figure 21 : Construct identifier to SEQ ID NO correspondence table. Constructs, heavy chain combination histidine scan and alanine scan variants are listed in the first column of the table, the SEQ ID NO is listed and corresponds to the construct on the left and the appropriate heavy and / or light chain class along the top.

[0226] Figure 22 : SDS PAGE for 7C8 Histidine and Alanine Scans. Harvested Expi293 cell culture supernatants were loaded onto non-reducing SDS PAGE gels to confirm expression of 7C8 Histidine and Alanine Scan variants. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gels. MYT7836 is a 7C8 light chain variant with both Histidine and Alanine Scans.

[0227] Figures 23a to 23b : Histidine- and alanine-scan variants of 7C8 bind to PTK7 by biolayer interferometry. MYT6003 (7C8) and MYT7836 (i.e., combined histidine- and alanine-scan light chain variants of 7C8) were captured on an anti-human Fc biosensor and associated with PTK7 at pH 7.4. Dissociation was performed at pH 7.4 (black trace) or pH 5.4 (grey trace).

[0228] Figure 24 : Construct identifier to SEQ ID NO correspondence table. Constructs, light chain combination histidine scan and alanine scan variants are listed in the first column of the table, with the SEQ ID NO listed and corresponding to the construct on the left and the appropriate heavy and / or light chain class along the top.

[0229] Figure 25: SDS PAGE for 12C6 His- and Alanine-scanning. Harvested Expi293 cell culture supernatants were loaded onto non-reducing SDS PAGE gels to confirm expression of 12C6 and histidine- and alanine-scan variants. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gel. MYT7959 is 12C6, and the remainder of the lane (MYT7960-MYT7991) represents the 12C6 heavy chain histidine- and alanine-scan variants.

[0230] Figures 26a to 26ag Binding of 12C6 starting ABPC and histidine- and alanine-scan variants to PTK7 as measured by biofilm interferometry. MYT7959 (12C6) and MYT7960-MYT7991 (i.e., heavy chain histidine- and alanine-scan variants) were captured on an anti-human Fc biosensor and associated with PTK7 at pH 7.4. Dissociation was performed at pH 7.4 (black trace) or pH 5.4 (grey trace).

[0231] Figure 27 : Construct identifier to SEQ ID NO correspondence table. Constructs, i.e., heavy chain histidine scan and alanine scan variants, are listed in the first column of the table, the SEQ ID NO is listed and corresponds to the construct on the left and the appropriate heavy and / or light chain class along the top.

[0232] Figure 28 : SDS PAGE for 12C6 Histidine and Alanine Scanning. Harvested Expi293 cell culture supernatants were loaded onto non-reducing SDS PAGE gels to confirm expression of 12C6 Histidine and Alanine Scanning variants. Arrows indicate the corresponding sizes of IgG on the non-reducing SDS PAGE gels. MYT7992-MYT8020 are 12C6 light chain Histidine and Alanine Scanning variants.

[0233] Figures 29a to 29ad Binding of 12C6 starting ABPC and histidine- and alanine-scan variants to PTK7 as measured by biofilm interferometry. MYT7959 (12C6) and MYT7992-MYT8020 (i.e., histidine- and alanine-scan light chain variants of 12C6) were captured on an anti-human Fc biosensor and associated with PTK7 at pH 7.4. Dissociation was performed at pH 7.4 (black trace) or pH 5.4 (grey trace).

[0234] Figure 30: Construct identifier to SEQ ID NO correspondence table. Constructs, i.e., light chain histidine scan and alanine scan variants, are listed in the first column of the table, the SEQ ID NO is listed and corresponds to the construct on the left and the appropriate heavy and / or light chain class along the top.

[0235] Figures 31a to 31d : Internalization of anti-PTK7 mAbs in cells. Anti-PTK7 pH engineered antibody variants, corresponding starting ABPC antibodies, control IgG1 isotype control (BP0297, Bioxcell) along with vehicle control, as specified in Figure 31, were assayed for internalization and endolysosomal delivery as measured by median fluorescence density on cells at 25 nM after 24 hours. Error bars represent standard deviations (where present). Numbers above the bars represent fold changes relative to the corresponding starting ABPCs.

[0236] Figures 32a to 31b : Internalization of anti-PTK7 mAbs in cells. Anti-PTK7 pH engineered antibody variants, corresponding starting ABPC antibodies, control IgG1 isotype control (BP0297, Bioxcell) along with vehicle control, as specified in Figure 32, were assayed for internalization and endolysosomal delivery as measured by median fluorescence density on cells at 25 nM after 24 hours. Error bars represent standard deviations (where present). Numbers above the bars represent fold changes relative to the corresponding starting ABPCs.

[0237] Figures 33a to 33b : Internalization of anti-PTK7 mAbs in cells. Anti-PTK7 pH engineered antibody variants, corresponding starting ABPC antibodies, control IgG1 isotype control (BP0297, Bioxcell) along with vehicle control, as specified in Figure 33, were assayed for internalization and endolysosomal delivery as measured by median fluorescence density on cells at 25 nM after 24 hours. Error bars represent standard deviations (where present). Numbers above the bars represent fold changes relative to the corresponding starting ABPCs.

[0238] Figures 34a to 34b present octet plots of MYT9345 HC and LC variants. For each of Figures 34-40, the y-axis (nm) array was either (A) fixed or (B) automatically set by the software to maximize the vertical distribution of the data. For each fixed y-axis, the major scale is 0.4 nm and the minor scale is 0.1 nm.

[0239] Figures 35a to 35b: present octet maps of MYT9359 HC and LC variants.

[0240] Figures 36a to 36b: present octet maps of MYT9361 HC and LC variants.

[0241] Figures 37a to 37b: present octet maps of MYT9412 HC and LC variants.

[0242] Figures 38a to 38b: present octet maps of MYT9460 HC and LC variants.

[0243] Figures 39a to 39b: present octet maps of MYT9792 HC and LC variants.

[0244] Figures 40a to 40b: Presents octet maps of MYT9797 HC and LC variants. DETAILED DESCRIPTION

[0245] Provided herein are antigen binding protein constructs (ABPCs) comprising: a first ABD (ABD) capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell, wherein: (a) the first ABD has a faster off-rate at a pH of about 4.0 to about 6.5 than at a pH of about 7.0 to about 8.0; and / or (b) the first ABD has a dissociation constant (K) at a pH of about 4.0 to about 6.5. D ) than K at a pH of about 7.0 to about 8.0 D In some examples of these ABPCs, the ABPC is degraded in the target mammalian cell after the ABPC is internalized by the target mammalian cell. Some examples of any ABPC described herein may also include a conjugated toxin, radioisotope, drug, or small molecule (e.g., fluorophore or dye).

[0246] Also provided are antigen binding protein constructs (ABPCs) comprising: a first ABD capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, wherein: (a) the first ABD has a faster off-rate at a pH of about 4.0 to about 6.5 than at a pH of about 7.0 to about 8.0; and / or the dissociation constant (K) of the first ABD at a pH of about 4.0 to about 6.5 is greater than that of the first ABD. D ) than K at a pH of about 7.0 to about 8.0 Dand (b) the composition comprising the ABPCs provides one or more (e.g., two or three) of the following: an increase (e.g., a detectable increase) in toxin release in target mammalian cells compared to a composition comprising the same amount of a control ABPC; an increase (e.g., a detectable increase) in killing of target mammalian cells compared to a composition comprising the same amount of a control ABPC; and an increase (e.g., a detectable increase) in endolysosomal delivery in target mammalian cells compared to a composition comprising the same amount of a control ABPC.

[0247] In some instances of any ABPCs described herein, the first ABD comprises the HCVD of coleficizumab, wherein one or more amino acids are substituted with histidine. In some instances of any ABPCs described herein, the first ABD comprises the LCVD of coleficizumab, wherein one or more amino acids are substituted with histidine. In some instances of any ABPCs described herein, the first ABD comprises the HCVD of coleficizumab, wherein one or more amino acids are substituted with histidine; and the LCVD of coleficizumab, wherein one or more amino acids are substituted with histidine. In some instances of any ABPCs described herein, the HCVD of coleficizumab comprises SEQ ID NO: 1. In some instances of any ABPCs described herein, the LCVD of coleficizumab comprises SEQ ID NO: 2.

[0248] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO: 3, 4, and 5 are substituted with histidine. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO: 6, 7, and 8 are substituted with histidine. In some examples of any of the ABPCs described herein, the first ABD comprises: an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO: 3, 4, and 5 are substituted with histidine; and an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO: 6, 7, and 8 are substituted with histidine.

[0249] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 1, wherein the HCVD includes histidine at one or more amino acid positions in SEQ ID NO: 1 selected from the group consisting of 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, wherein the LCVD includes histidine at one or more amino acid positions in SEQ ID NO:2 selected from the group consisting of 25, 29, 31, 35, 60, 93, or 94. In some examples of any of the ABPCs described herein, the first ABD comprises: an HCVD having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO: 1, wherein the HCVD includes a histidine at one or more amino acid positions selected from the group consisting of 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107 in SEQ ID NO: 1; and an LCVD having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO: 2, wherein the LCVD includes a histidine at one or more amino acid positions selected from the group consisting of 25, 29, 31, 35, 60, 93, or 94 in SEQ ID NO: 2.

[0250] In some examples of any ABPC described herein, the HCVD comprises an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 1, wherein the HCVD comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 1 listed in Table 1.

[0251] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 1, wherein the HCVD includes an alanine at position 35 in SEQ ID NO: 1.

[0252] In some examples of any of the ABPCs described herein, the first ABD comprises: an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 1, wherein the HCVD includes an alanine at position 35 in SEQ ID NO: 1; and an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 2, wherein the LCVD includes a histidine at one or more amino acid positions selected from the group consisting of: 25, 29, 31, 35, 60, 93, or 94 in SEQ ID NO: 2.

[0253] Table 1. Exemplary combinations of amino acid positions in SEQ ID NO: 1 that can be substituted with histidine

[0254]

[0255]

[0256]

[0257]

[0258]

[0259] In some examples of any of the ABPCs described herein, the LCVD comprises an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 2, wherein the LCVD comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 2 listed in Table 2.

[0260] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, wherein the LCVD includes an alanine at position 38 in SEQ ID NO:2.

[0261] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, wherein the LCVD includes an alanine at position 38 in SEQ ID NO:2; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the HCVD includes a histidine at one or more amino acid positions in SEQ ID NO:1 selected from the group consisting of 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107.

[0262] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:2, wherein the LCVD includes a histidine at one or more amino acid positions in SEQ ID NO:2 selected from the group consisting of 25, 29, 31, 35, 60, 93, or 94, and wherein the LCVD includes an alanine at position 38 in SEQ ID NO:2. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO: 2, wherein the LCVD comprises a histidine at one or more amino acid positions in SEQ ID NO: 2 selected from the group consisting of 25, 29, 31, 35, 60, 93, or 94 and wherein the LCVD comprises an alanine at position 38 in SEQ ID NO: 2; and an HCVD having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO: 1, wherein the HCVD comprises a histidine at one or more amino acid positions in SEQ ID NO: 2 selected from the group consisting of 25, 29, 31, 35, 60, 93, or 94 and wherein the LCVD comprises an alanine at position 38 in SEQ ID NO: 2. Histidine at one or more amino acid positions selected from the group consisting of: 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103 or 107 in NO: 1.

[0263] In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO: 2, wherein the LCVD comprises a histidine at one or more amino acid positions in SEQ ID NO: 2 selected from the group consisting of 25, 29, 31, 35, 60, 93, or 94 and wherein the LCVD comprises an alanine at position 38 in SEQ ID NO: 2; and an HCVD having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO: 1, wherein the HCVD comprises a histidine at one or more amino acid positions in SEQ ID NO: 2 selected from the group consisting of 25, 29, 31, 35, 60, 93, or 94 and wherein the LCVD comprises an alanine at position 38 in SEQ ID NO: 2. NO: 1 at one or more histidine positions selected from the group consisting of: 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107 and wherein the HCVD comprises an alanine at position 35.

[0264] In some examples of any of the ABPCs described herein, the LCVD comprises an LCVD having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO: 2, wherein the LCVD comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 2 listed in Table 2 and wherein the LCVD comprises an alanine at position 38 of SEQ ID NO: 2.

[0265] Table 2. Exemplary combinations of amino acid positions in SEQ ID NO: 2 that can be substituted with histidine

[0266]

[0267]

[0268] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 1, wherein the HCVD includes histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 1 listed in Table 1; and an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 2, wherein the LCVD includes histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 2 listed in Table 2.

[0269] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 2, wherein the LCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 2 listed in Table 2, and wherein the LCVD includes an alanine at position 38 in SEQ ID NO: 2; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 1, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 1 listed in Table 1.

[0270] In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 2; and a HCVD having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO: 1, wherein the HCVD includes histidine at any specific combination of one or more (e.g., two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO: 1 listed in Table 1.

[0271] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO:2, wherein the LCVD includes a histidine at position 25 in SEQ ID NO:2; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0272] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO:2, wherein the LCVD includes a histidine at position 29 in SEQ ID NO:2; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0273] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO:2, wherein the LCVD includes a histidine at position 31 in SEQ ID NO:2; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0274] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO:2, wherein the LCVD includes a histidine at position 35 in SEQ ID NO:2; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0275] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO:2, wherein the LCVD includes a histidine at position 60 in SEQ ID NO:2; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0276] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO:2, wherein the LCVD includes a histidine at position 93 in SEQ ID NO:2; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0277] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO:2, wherein the LCVD includes a histidine at position 94 in SEQ ID NO:2; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:1, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO:1 listed in Table 1.

[0278] In some instances of any ABPCs described herein, the first ABD comprises an HCVD of coleficizumab, wherein one or more histidines are substituted with alanine. In some instances of any ABPCs described herein, the first ABD comprises an LCVD of coleficizumab, wherein one or more histidines are substituted with alanine. In some instances of any ABPCs described herein, the first ABD comprises an HCVD of coleficizumab, wherein one or more histidines are substituted with alanine; and an LCVD of coleficizumab, wherein one or more histidines are substituted with alanine. In some instances of any ABPCs described herein, the HCVD of coleficizumab comprises SEQ ID NO: 1. In some instances of any ABPCs described herein, the LCVD of coleficizumab comprises SEQ ID NO: 2.

[0279] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NO: 3, 4, and 5 are substituted with alanine. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NO: 6, 7, and 8 are substituted with alanine. In some examples of any of the ABPCs described herein, the first ABD comprises: an HCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NO: 3, 4, and 5 are substituted with alanine; and an LCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NO: 6, 7, and 8 are substituted with alanine.

[0280] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD of SEQ ID NO: 1; or one of 13-54; or one of 86- 105. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD of SEQ ID NO: 2; or one of 55-85; or one of 106-125.

[0281] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 2, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 55, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 56, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 57, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 58, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 59, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 60, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 61, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 62, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 63, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105.In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 64, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 65, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 66, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 67, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 68, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 69, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 70, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 71, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 72, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 73, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105.In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 74, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 75, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 76, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 77, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 78, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 79, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 80, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 81, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 82, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 83, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105.In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 84, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 85, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 106, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 107, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 108, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 109, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 110, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 111, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 112, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 113, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105.In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 114, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 115, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 116, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 117, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 118, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 119, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 120, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 121, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 122, and an HCVD comprising SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 123, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105.In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 124, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 125, and an HCVD comprising: SEQ ID NO: 1; or one of 13-54; or one of 86-105.

[0282] In some instances of any ABPCs described herein, the first ABD comprises the HCVD of 7C8, wherein one or more amino acids are substituted with histidine. In some instances of any ABPCs described herein, the first ABD comprises the LCVD of 7C8, wherein one or more amino acids are substituted with histidine. In some instances of any ABPCs described herein, the first ABD comprises: the HCVD of 7C8, wherein one or more amino acids are substituted with histidine; and the LCVD of 7C8, wherein one or more amino acids are substituted with histidine. In some instances of any ABPCs described herein, the HCVD of 7C8 comprises SEQ ID NO: 126. In some instances of any ABPCs described herein, the LCVD of 7C8 comprises SEQ ID NO: 127.

[0283] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 130, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO: 128, 129, and 130 are substituted with histidine. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 131, SEQ ID NO: 132, and SEQ ID NO: 133, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO: 131, 132, and 133 are substituted with histidine. In some examples of any of the ABPCs described herein, the first ABD comprises: an HCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 130, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO: 128, 129, and 130 are substituted with histidine; and an LCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 131, SEQ ID NO: 132, and SEQ ID NO: 133, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO: 131, 132, and 133 are substituted with histidine.

[0284] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 126, wherein the HCVD includes histidine at one or more amino acid positions in SEQ ID NO: 126 selected from the group consisting of: 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, and 111. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 127, wherein the LCVD includes histidine at one or more amino acid positions selected from the group consisting of 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94 in SEQ ID NO: 127. In some examples of any of the ABPCs described herein, the first ABD comprises: an HCVD having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO: 126, wherein the HCVD includes histidine at one or more amino acid positions in SEQ ID NO: 126 selected from the group consisting of 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, and 111; and an LCVD having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO: 127, wherein the LCVD includes a histidine at one or more amino acid positions in SEQ ID NO: 127. Histidine at one or more amino acid positions selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94 of NO: 127.

[0285] In some examples of any of the ABPCs described herein, the HCVD comprises an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 126, wherein the HCVD comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 126 listed in Table 3.

[0286] Table 3. Exemplary combinations of amino acid positions in SEQ ID NO: 126 that can be substituted with histidine

[0287]

[0288]

[0289]

[0290]

[0291] In some examples of any of the ABPCs described herein, the LCVD comprises an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 127, wherein the LCVD comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 127 listed in Table 4.

[0292] Table 4. Exemplary combinations of amino acid positions in SEQ ID NO: 127 that can be substituted with histidine

[0293]

[0294]

[0295] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 126, wherein the HCVD includes histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 126 listed in Table 3; and an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 127, wherein the LCVD includes histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 127 listed in Table 4.

[0296] In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 127, and a HCVD having at least 90% (e.g., ≥92%, ≥94%, ≥96%, ≥98%, ≥99%, or 100%) identity to SEQ ID NO: 126, wherein the HCVD includes histidine at any specific combination of one or more (e.g., two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO: 126 listed in Table 3.

[0297] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 127, wherein the LCVD includes a histidine at position 25 in SEQ ID NO: 127; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 126 listed in Table 3.

[0298] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 127, wherein the LCVD includes a histidine at position 26 in SEQ ID NO: 127; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 126 listed in Table 3.

[0299] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 127, wherein the LCVD includes a histidine at position 28 in SEQ ID NO: 127; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 126 listed in Table 3.

[0300] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 127, wherein the LCVD includes a histidine at position 29 in SEQ ID NO: 127; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 126 listed in Table 3.

[0301] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 127, wherein the LCVD includes a histidine at position 31 in SEQ ID NO: 127; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 126 listed in Table 3.

[0302] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 127, wherein the LCVD includes a histidine at position 32 in SEQ ID NO: 127; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 126 listed in Table 3.

[0303] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 127, wherein the LCVD includes a histidine at position 33 in SEQ ID NO: 127; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 126 listed in Table 3.

[0304] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 127, wherein the LCVD includes a histidine at position 50 in SEQ ID NO: 127; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 126 listed in Table 3.

[0305] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 127, wherein the LCVD includes a histidine at position 90 in SEQ ID NO: 127; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 126 listed in Table 3.

[0306] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 127, wherein the LCVD includes a histidine at position 92 in SEQ ID NO: 127; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 126 listed in Table 3.

[0307] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 127, wherein the LCVD includes a histidine at position 94 in SEQ ID NO: 127; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 126, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 126 listed in Table 3.

[0308] In some instances of any ABPCs described herein, the first ABD comprises an HCVD of 7C8, wherein one or more histidines are substituted with alanine. In some instances of any ABPCs described herein, the first ABD comprises an LCVD of 7C8, wherein one or more histidines are substituted with alanine. In some instances of any ABPCs described herein, the first ABD comprises an HCVD of 7C8, wherein one or more histidines are substituted with alanine; and an LCVD of 7C8, wherein one or more histidines are substituted with alanine. In some instances of any ABPCs described herein, the HCVD of 7C8 comprises SEQ ID NO: 126. In some instances of any ABPCs described herein, the LCVD of 7C8 comprises SEQ ID NO: 127.

[0309] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 130, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NO: 128, 129, and 130 are substituted with alanine. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 131, SEQ ID NO: 132, and SEQ ID NO: 133, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NO: 131, SEQ ID NO: 132, and SEQ ID NO: 133 are substituted with alanine. In some examples of any of the ABPCs described herein, the first ABD comprises: an HCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 128, SEQ ID NO: 129, and SEQ ID NO: 130, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NO: 128, 129, and 130 are substituted with alanine; and an LCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 131, SEQ ID NO: 132, and SEQ ID NO: 133, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NO: 131, 132, and 133 are substituted with alanine.

[0310] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD of SEQ ID NO: 126; or one of 134-179; or one of 208-227.

[0311] In some examples of any of the ABPCs described herein, the first ABD comprises the LCVD of SEQ ID NO: 127; or one of 180-207; or 228.

[0312] In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 127, and an HCVD comprising one of SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 180, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 181, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 182, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 183, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 184, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 185, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 186, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 187, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 188, and an HCVD comprising: SEQ ID NO: 126; or one of 134-179; or one of 208-227.In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 189, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 190, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 191, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 192, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 193, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 194, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 195, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 196, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 197, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 198, and an HCVD comprising: SEQ ID NO: 126; or one of 134-179; or one of 208-227.In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 199, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 200, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 201, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 202, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 203, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 204, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 205, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 206, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 207, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227. In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 228, and an HCVD comprising SEQ ID NO: 126; or one of 134-179; or one of 208-227.

[0313] In some instances of any ABPCs described herein, the first ABD comprises the HCVD of 12C6, wherein one or more amino acids are substituted with histidine. In some instances of any ABPCs described herein, the first ABD comprises the LCVD of 12C6, wherein one or more amino acids are substituted with histidine. In some instances of any ABPCs described herein, the first ABD comprises: the HCVD of 12C6, wherein one or more amino acids are substituted with histidine; and the LCVD of 12C6, wherein one or more amino acids are substituted with histidine. In some instances of any ABPCs described herein, the HCVD of 12C6 comprises SEQ ID NO: 229. In some instances of any ABPCs described herein, the LCVD of 12C6 comprises SEQ ID NO: 230.

[0314] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 231, 232, and 233, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 231, 232, and 233 are substituted with histidine. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 234, 235, and 236, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NOs: 234, 235, and 236 are substituted with histidine. In some examples of any of the ABPCs described herein, the first ABD comprises: an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 231, SEQ ID NO: 232, and SEQ ID NO: 233, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO: 231, 232, and 233 are substituted with histidine; and an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 234, SEQ ID NO: 235, and SEQ ID NO: 236, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO: 234, 235, and 236 are substituted with histidine.

[0315] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 229, wherein the HCVD includes histidine at one or more amino acid positions in SEQ ID NO: 229 selected from the group consisting of 27, 32, 33, 34, 35, 51, 54, 56, 58, and 100. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 230, wherein the LCVD includes histidine at one or more amino acid positions in SEQ ID NO: 230 selected from the group consisting of 30, 31, 33, 51, 53, 57, 91, 92, 94, and 99. In some examples of any of the ABPCs described herein, the first ABD comprises: an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 229, wherein the HCVD includes histidine at one or more amino acid positions selected from the group consisting of 27, 32, 33, 34, 35, 51, 54, 56, 58, and 100 in SEQ ID NO: 229; and an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 230, wherein the LCVD includes histidine at one or more amino acid positions selected from the group consisting of 30, 31, 33, 51, 53, 57, 91, 92, 94, and 99 in SEQ ID NO: 230.

[0316] In some examples of any of the ABPCs described herein, the HCVD comprises an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 229, wherein the HCVD comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 229 listed in Table 5.

[0317] Table 5. Exemplary combinations of amino acid positions in SEQ ID NO: 229 that can be substituted with histidine

[0318]

[0319]

[0320] In some examples of any of the ABPCs described herein, the LCVD comprises an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 230, wherein the LCVD comprises histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 230 listed in Table 6.

[0321] Table 6. Exemplary combinations of amino acid positions in SEQ ID NO: 230 that can be substituted with histidine

[0322]

[0323]

[0324] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 229, wherein the HCVD includes histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 229 listed in Table 5; and an LCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 230, wherein the LCVD includes histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 230 listed in Table 6.

[0325] In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 230, and a HCVD having at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identity to SEQ ID NO: 229, wherein the HCVD includes histidine at any specific combination of one or more (e.g., two, three, four, five, six, seven, eight, nine, or ten) amino acid positions in SEQ ID NO: 229 listed in Table 5.

[0326] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 230, wherein the LCVD includes a histidine at position 30 in SEQ ID NO: 230; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 229, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 229 listed in Table 5.

[0327] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 230, wherein the LCVD includes a histidine at position 31 in SEQ ID NO: 230; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 229, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 229 listed in Table 5.

[0328] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 230, wherein the LCVD includes a histidine at position 33 in SEQ ID NO: 230; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 229, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 229 listed in Table 5.

[0329] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 230, wherein the LCVD includes a histidine at position 51 in SEQ ID NO: 230; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 229, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 229 listed in Table 5.

[0330] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 230, wherein the LCVD includes a histidine at position 53 in SEQ ID NO: 230; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 229, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 229 listed in Table 5.

[0331] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 230, wherein the LCVD includes a histidine at position 57 in SEQ ID NO: 230; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 229, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 229 listed in Table 5.

[0332] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 230, wherein the LCVD includes a histidine at position 91 in SEQ ID NO: 230; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 229, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 229 listed in Table 5.

[0333] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 230, wherein the LCVD includes a histidine at position 92 in SEQ ID NO: 230; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 229, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 229 listed in Table 5.

[0334] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 230, wherein the LCVD includes a histidine at position 94 in SEQ ID NO: 230; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 229, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 229 listed in Table 5.

[0335] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD that is at least 90% identical to SEQ ID NO: 230, wherein the LCVD includes a histidine at position 99 in SEQ ID NO: 230; and an HCVD that is at least 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 229, wherein the HCVD includes a histidine at any specific combination of one or more amino acid positions in SEQ ID NO: 229 listed in Table 5.

[0336] In some instances of any ABPCs described herein, the first ABD comprises the HCVD of 12C6, wherein one or more histidines are substituted with alanine. In some instances of any ABPCs described herein, the first ABD comprises the LCVD of 12C6, wherein one or more histidines are substituted with alanine. In some instances of any ABPCs described herein, the first ABD comprises the HCVD of 12C6, wherein one or more histidines are substituted with alanine; and the LCVD of 12C6, wherein one or more histidines are substituted with alanine. In some instances of any ABPCs described herein, the HCVD of 12C6 comprises SEQ ID NO: 229. In some instances of any ABPCs described herein, the LCVD of 12C6 comprises SEQ ID NO: 230.

[0337] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 231, SEQ ID NO: 232, and SEQ ID NO: 233, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NO: 231, 232, and 233 are substituted with alanine. In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 234, SEQ ID NO: 235, and SEQ ID NO: 236, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NO: 234, 235, and 236 are substituted with alanine. In some examples of any of the ABPCs described herein, the first ABD comprises: an HCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 231, SEQ ID NO: 232, and SEQ ID NO: 233, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NO: 231, 232, and 233 are substituted with alanine; and an LCVD comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 234, SEQ ID NO: 235, and SEQ ID NO: 236, respectively, wherein a total of one or more (e.g., one, two, three, four, five, six, seven, eight, nine, or ten) histidines in SEQ ID NO: 234, 235, and 236 are substituted with alanine.

[0338] In some examples of any of the ABPCs described herein, the first ABD comprises an HCVD of one of SEQ ID NOs: 229; or 237-268.

[0339] In some examples of any of the ABPCs described herein, the first ABD comprises an LCVD of one of SEQ ID NO: 230; or 269-297.

[0340] In some examples of any of the ABPCs described herein, the first ABD comprises: an LCVD comprising SEQ ID NO: 230, and an HCVD comprising one of 237-268.

[0341] In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 269, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 270, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 271, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 272, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 273, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 274, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 275, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 276, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 277, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 278, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 279, and an HCVD comprising SEQ ID NO: 229; or one of 237-268.In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 280, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 281, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 282, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 283, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 284, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 285, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 286, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 287, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 288, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 289, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 290, and an HCVD comprising SEQ ID NO: 229; or one of 237-268.In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 291, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 292, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 293, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 294, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 295, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 296, and an HCVD comprising SEQ ID NO: 229; or one of 237-268. In some instances of any of the ABPCs described herein, the first ABD comprises an LCVD comprising SEQ ID NO: 297, and an HCVD comprising SEQ ID NO: 229; or one of 237-268.

[0342] In some instances, the first ABD comprises the HCVD of MYT9345, optionally wherein one or more amino acids are substituted with histidine. In some instances, the first ABD comprises the LCVD of MYT9345, optionally wherein one or more amino acids are substituted with histidine. In some instances, the first ABD comprises: the HCVD of MYT9345, optionally wherein one or more amino acids are optionally substituted with histidine; and the LCVD of MYT9345, wherein one or more amino acids are substituted with histidine. In some instances, the HCVD of MYT9345 comprises SEQ ID NO: 301. In some instances, the LCVD of MYT9345 comprises SEQ ID NO: 302.

[0343] In some examples, the first ABD comprises: an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 303, 304, and 305, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 303, 304, and 305 are substituted with histidine. In some examples, the first ABD comprises: an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 306, 307, and 308, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 306, 307, and 308 are substituted with histidine. In some examples, the first ABD comprises: an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 303, 304, and 305, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 303, 304, and 305 are substituted with histidine; and an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 306, 307, and 308, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 306, 307, and 308 are substituted with histidine.

[0344] In some examples, the first ABD comprises: an HCVD having at least 90% identity to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301. In some examples, the first ABD comprises: an LCVD having at least 90% identity to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302. In some examples, the first ABD comprises: an HCVD having at least 90% identity to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; and an LCVD having at least 90% identity to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302.

[0345] In some examples, the HCVD includes an HCVD that is at least 90% identical to SEQ ID NO: 301, wherein the HCVD includes histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0346] In some examples, the first ABD comprises an HCVD having ≥90% (e.g., ≥92%, ≥94%, ≥96%, ≥98%, ≥99%, or 100%) identity to SEQ ID NO: 301, wherein the HCVD includes an alanine at position 52 in SEQ ID NO: 301.

[0347] In some examples, the first ABD comprises an HCVD having ≥90% (e.g., ≥92%, ≥94%, ≥96%, ≥98%, ≥99%, or 100%) identity to SEQ ID NO: 301, wherein the HCVD includes an alanine at position 52 in SEQ ID NO: 301; and an LCVD having ≥90% (e.g., ≥92%, ≥94%, ≥96%, ≥98%, ≥99%, or 100%) identity to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302.

[0348] Table 7. Exemplary combinations of amino acid positions in SEQ ID NO: 301 that can be substituted with histidine (or alanine, if indicated).

[0349]

[0350] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 302 listed in Table 8, and / or wherein the LCVD includes an alanine at position 95 of SEQ ID NO: 302.

[0351] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO:302, wherein the LCVD includes an alanine at position 95 in SEQ ID NO:302.

[0352] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes an alanine at position 95 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301.

[0353] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of 25, 30-33, 35, 55-57, 91, 94-96, and 98 of SEQ ID NO: 302, and / or wherein the LCVD includes an alanine at position 95 of SEQ ID NO: 302. In some examples, the first ABD comprises: an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302, and / or wherein the LCVD includes an alanine at position 95 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301.

[0354] In some examples, the first ABD comprises: an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of 25, 30-33, 35, 55-57, 91, 94-96, and 98 of SEQ ID NO: 302, and / or wherein the LCVD includes an alanine at position 95 of SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of 29, 30, 32, 50-54, 58, 60, 96, and 101 of SEQ ID NO: 301, and / or wherein the HCVD includes an alanine at position 52.

[0355] Table 8. Exemplary combinations of amino acid positions in SEQ ID NO: 302 that can be substituted with histidine (or alanine, if indicated).

[0356]

[0357]

[0358] In some examples, the first ABD comprises an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7; and an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 302 listed in Table 8.

[0359] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes histidine at any specific combination of two or more amino acid positions of SEQ ID NO: 302 listed in Table 8, and / or wherein the LCVD includes an alanine at position 95 of SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes histidine at any specific combination of two or more amino acid positions of SEQ ID NO: 301 listed in Table 7. In some examples, the first ABD comprises: an LCVD comprising SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes histidine at any specific combination of two or more amino acid positions of SEQ ID NO: 301 listed in Table 7.

[0360] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at position 25 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0361] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at position 30 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0362] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at position 31 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0363] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes an alanine at position 95 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0364] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at position 32 in SEQ ID NO: 302; and a HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0365] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at position 33 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0366] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at position 35 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0367] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at position 55 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0368] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at position 56 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0369] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at position 57 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0370] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at position 91 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0371] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at position 94 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0372] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at position 95 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0373] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at position 96 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0374] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at position 98 in SEQ ID NO: 302; and an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 301 listed in Table 7.

[0375] In some examples, the first ABD comprises an HCVD having ≥90% identity to SEQ ID NO: 301, wherein the HCVD includes a histidine at any one of positions 29, 30, 32, 50-54, 58, 60, 96, and 101 of SEQ ID NO: 301; and an LCVD having ≥90% identity to SEQ ID NO: 302, wherein the LCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 302 listed in Table 8.

[0376] In some examples, the first ABD comprises an HCVD of SEQ ID NO: 301; or one of 309-342; and / or the first ABD comprises an LCVD of SEQ ID NO: 302; or one of 343-374.

[0377] In some examples of ABPC, the first ABD comprises: an LCVD comprising any one of SEQ ID NO: 302; or one of 343-374; and an HCVD comprising any one of SEQ ID NO: 301; or one of 309-342.

[0378] In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 343 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 344 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 345 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 346 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 347 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 348 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 349 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 350 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 351 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 352 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 353 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 354 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342.In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 355 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 356 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 357 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 358 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 359, and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 360, and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 361, and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 362, and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 363 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 364 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 365 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 366 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342.In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 367 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 368 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 369 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 370 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 371 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 372 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 373 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 374 and an HCVD comprising one of the following: SEQ ID NO: 301; or one of 309-342.

[0379] In some instances, the first ABD comprises the HCVD of MYT9359, wherein one or more amino acids are substituted with histidine. In some instances, the first ABD comprises the LCVD of MYT9359, wherein one or more amino acids are substituted with histidine. In some instances, the first ABD comprises: the HCVD of MYT9359, wherein one or more amino acids are optionally substituted with histidine; and the LCVD of MYT9359, wherein one or more amino acids are substituted with histidine. In some instances, the HCVD of MYT9359 comprises SEQ ID NO: 375. In some instances, the LCVD of MYT9359 comprises SEQ ID NO: 376.

[0380] In some examples, the first ABD comprises: an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 377, 378, and 379, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 377, 378, and 379 are substituted with histidine. In some examples, the first ABD comprises: an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 380, 381, and 382, ​​respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 380, 381, and 382 are substituted with histidine. In some examples, the first ABD comprises: an HCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 377, 378, and 379, respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 377, 378, and 379 are optionally substituted with histidine; and an LCVD comprising CDR1, CDR2, and CDR3 of SEQ ID NOs: 380, 381, and 382, ​​respectively, optionally wherein a total of one or more amino acid positions in SEQ ID NOs: 380, 381, and 382 are substituted with histidine.

[0381] In some examples, the first ABD comprises: an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: 375. In some examples, the first ABD comprises: an LCVD having at least 90% identity to SEQ ID NO: 376, wherein the LCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376. In some examples, the first ABD comprises: an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: 375; and an LCVD having at least 90% identity to SEQ ID NO: 376, wherein the LCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376.

[0382] In some examples, the HCVD includes an HCVD that is at least 90% identical to SEQ ID NO: 375, wherein the HCVD includes histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0383] In some examples, the first ABD comprises an HCVD having ≥90% (e.g., ≥92%, ≥94%, ≥96%, ≥98%, ≥99%, or 100%) identity to SEQ ID NO: 375, wherein the HCVD includes an alanine at position 107 in SEQ ID NO: 375.

[0384] In some examples, the first ABD comprises an HCVD having ≥90% (e.g., ≥92%, ≥94%, ≥96%, ≥98%, ≥99%, or 100%) identity to SEQ ID NO: 375, wherein the HCVD includes an alanine at position 107 in SEQ ID NO: 375; and an LCVD having ≥90% (e.g., ≥92%, ≥94%, ≥96%, ≥98%, ≥99%, or 100%) identity to SEQ ID NO: 376, wherein the LCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: 376.

[0385] Table 9. Exemplary combinations of amino acid positions in SEQ ID NO: 375 that can be substituted with histidine (or alanine, if indicated).

[0386]

[0387] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 376 listed in Table 10, and / or wherein the LCVD includes an alanine at position 98 of SEQ ID NO: 376.

[0388] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes an alanine at position 98 in SEQ ID NO: 376.

[0389] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes an alanine at position 98 in SEQ ID NO: 376; and an HCVD having ≥90% identity to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: 375.

[0390] In some examples, the first ABD comprises: an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 of SEQ ID NO: 376, and / or wherein the LCVD includes an alanine at position 98 of SEQ ID NO: 376. In some examples, the first ABD comprises: an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376, and / or wherein the LCVD includes an alanine at position 98 in SEQ ID NO: 376; and an HCVD having ≥90% identity to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO: 375.

[0391] In some examples, the first ABD comprises: an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 of SEQ ID NO: 376, and / or wherein the LCVD includes an alanine at position 98 of SEQ ID NO: 376; and an HCVD having ≥90% identity to SEQ ID NO: 375, wherein the HCVD optionally includes a histidine at one or more amino acid positions selected from the group consisting of 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 of SEQ ID NO: 375, and / or wherein the HCVD includes an alanine at position 107.

[0392] Table 10. Exemplary combinations of amino acid positions in SEQ ID NO: 376 that can be substituted with histidine (or alanine, if indicated).

[0393]

[0394]

[0395] In some examples, the first ABD comprises an HCVD having ≥90% identity to SEQ ID NO: 375, wherein the HCVD includes histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9; and an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 376 listed in Table 10.

[0396] In some examples, the first ABD comprises an LCVD with ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 376 listed in Table 10, and / or wherein the LCVD includes an alanine at position 98 in SEQ ID NO: 376; and an HCVD with ≥90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0397] In some examples, the first ABD comprises: an LCVD comprising SEQ ID NO: 376; and a HCVD having ≥90% identity to SEQ ID NO: 375, wherein the HCVD includes histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0398] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 25 in SEQ ID NO: 376; and an HCVD having ≥90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0399] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 29 in SEQ ID NO: 376; and an HCVD having ≥90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0400] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 30 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0401] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes an alanine at position 98 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0402] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 31 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0403] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 33 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0404] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 50 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0405] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 51 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0406] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 52 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0407] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 53 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0408] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 89 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0409] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 91 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0410] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 92 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0411] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 93 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0412] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 96 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0413] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 97 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0414] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 100 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0415] In some examples, the first ABD comprises an LCVD having ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at position 102 in SEQ ID NO: 376; and an HCVD having at least 90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 375 listed in Table 9.

[0416] In some examples, the first ABD comprises an HCVD with ≥90% identity to SEQ ID NO: 375, wherein the HCVD includes a histidine at any one of positions 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 of SEQ ID NO: 375; and an LCVD with ≥90% identity to SEQ ID NO: 376, wherein the LCVD includes a histidine at any specific combination of two or more amino acid positions in SEQ ID NO: 376 listed in Table 10.

[0417] In some examples, the first ABD comprises an HCVD of SEQ ID NO: 375; or one of 383-423; and / or the first ABD comprises an LCVD of SEQ ID NO: 376; or one of 424-458. In some examples of ABPCs, the first ABD comprises: an LCVD comprising any one of SEQ ID NO: 376; or one of 424-458; and an HCVD comprising any one of SEQ ID NO: 375; or one of 383-423.

[0418] In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 424 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 425 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 426 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 427 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 428 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 429 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 430 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 431 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 432 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 433 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 434 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 435 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423.In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 436 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 437 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 438 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first ABD comprises an LCVD comprising SEQ ID NO: 439 and an HCVD comprising one of the following: SEQ ID NO: 375; or one of 383-423. In some instances, the first A...

Claims

1. A pharmaceutical composition comprising an effective amount of an antigen binding protein construct (ABPC), the antigen binding protein construct comprising: a first antigen binding domain (ABD) capable of specifically binding to PTK7 or an epitope of PTK7 present on the surface of a target mammalian cell, wherein: The first ABD has a faster dissociation rate at a pH of about 4.0-6.5 than at a pH of about 7.0-8.0; and / or the first ABD has a K of about 1.0 at a pH of about 4.0-6.

5. D At a pH of about 7.0-8.0, the K D and optionally wherein the ABPCs exhibit increased target-specific uptake by cancer cells expressing PTK7 relative to uptake of suitable control ABPCs by the same cells.

2. The composition of claim 1, wherein the first ABD comprises a heavy chain variable domain (HCVD) of MYT9345, MYT9359, MYT9361, MYT9412, MYT9460, MYT9792 or MYT9797, optionally with one or more histidine substitutions; or a HCVD of cofilotuzumab, 7C8 or 12C6, each with at least one histidine substitution.

3. The composition of claim 1, wherein the first ABD comprises a light chain variable domain (LCVD) of MYT9345, MYT9359, MYT9361, MYT9412, MYT9460, MYT9792 or MYT9797, optionally with one or more histidine substitutions; or a LCVD of cofilotuzumab, 7C8 or 12C6, each with at least one histidine substitution.

4. The composition of any one of claims 1, wherein the ABD comprises one of: (a) HCVD of MYT9345 and / or LCVD of MYT9345; (b) HCVD of MYT9359 and / or LCVD of MYT9359; (c) HCVD of MYT9361; and / or LCVD of MYT9361; (d) HCVD of MYT9412 and / or LCVD of MYT9412; (e) HCVD of MYT9460 and / or LCVD of MYT9460; (f) HCVD of MYT9792; and / or or LCVD of MYT9792; and (g) HCVD of MYT9797 and / or LCVD of MYT9797; wherein each HCVD and / or LCVD optionally has one or more histidine substitutions; or, the ABD comprises one of the following: (h) HCVD of cofilotuzumab and / or LCVD of cofilotuzumab; (i) HCVD of 7C8 and / or LCVD of 7C8; and (j) HCVD of 12C6; and / or LCVD of 12C6, wherein each HCVD and / or LCVD of (i), (h) or (j) has at least one histidine substitution.

5. The composition of any one of claims 1 to 4, wherein the HCVD comprises one of the sequences shown in SEQ ID NO: 1, 126, 229, 301, 375, 459, 542, 628, 710 and 803.

6. The composition of any one of claims 1 to 4, wherein the LCVD comprises one of the sequences shown in SEQ ID NO: 2, 127, 230, 302, 376, 460, 543, 629, 711, and 804.

7. The composition of claim 1, wherein the first ABD comprises an HCVD comprising CDR1, 2 and 3 of one of the following: (a) SEQ ID NOs: 303, 304 and 305; (b) SEQ ID NOs: 377, 378 and 379; (c) SEQ ID NOs: 461, 462 and 463; (d) SEQ ID NOs: 544, 545 and 546; (e) SEQ ID NOs: 630, 631 and 632; (f) SEQ ID NOs: 712, 713 and 714; (g) SEQ ID NOs: 805, 806 and 807; (h) SEQ ID NOs: 3, 4 and 5; (i) SEQ ID NOs: 128, 129 and 130; and (j) SEQ ID NOs: NO:231, 232 and 233, wherein for (a) to (g), each group of three CDRs optionally has a total of one or more positions substituted by histidine, and for (h) to (j), each group of three CDRs has a total of at least one or more positions substituted by histidine.

8. The composition of claim 1, wherein the first ABD comprises an LCVD comprising CDR1, 2, and 3 of one of the following: (a) SEQ ID NOs: 306, 307, and 308; (b) SEQ ID NOs: 380, 381, and 382; (c) SEQ ID NOs: 464, 465, and 466; (d) SEQ ID NOs: 547, 548, and 549; (e) SEQ ID NOs: 633, 634, and 635; (f) SEQ ID NOs: 715, 716, and 717; (g) SEQ ID NOs: 808, 809, and 810; (h) SEQ ID NOs: 6, 7, and 8; (i) SEQ ID NOs: 131, 132, and 133; and (j) SEQ ID NOs: 234, 235, and 236; wherein for (a) to (g), each set of three CDRs optionally has one or more positions in total substituted with histidine, and for (h) to (j), each set of three CDRs has at least one or more positions in total substituted with histidine.

9. The composition of claim 1, wherein the first ABD comprises one of: (a) a HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 303, 304 and 305; and / or a LCVD comprising CDR1, 2 and 3 of one of SEQ ID NOs: 306, 307 and 308; (b) a HCVD comprising CDR1, 2 and 3 of one of SEQ ID NOs: 377, 378 and 379; and / or a LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 380, 381 and 382; (c) an HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 461, 462 and 463; and / or an LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 464, 465 and 466; (d) an HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 544, 545 and 546; and / or an LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 547, 548 and 549; (e) a HCVD comprising CDR1, 2 and 3 of one of SEQ ID NOs: 630, 631 and 632; and / or a LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 633, 634 and 635; (f) a HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 712, 713 and 714; and / or a LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 715, 716 and 717; (g) a HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 805, 806 and 807; and / or a LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 808, 809 and 810; (h) an HCVD comprising CDR1, 2 and 3 of one of SEQ ID NOs: 3, 4 and 5; and / or an LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 6, 7 and 8; (i) an HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 128, 129 and 130; and / or an LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 131, 132 and 133; and (j) an HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 231, 232 and 233; and / or an LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 234, 235 and 236; wherein for (a) to (g), any one or both of each set of three CDRs optionally have one or more positions in total substituted with histidine, and wherein for (h) to (j), any one or both of each set of three CDRs have at least one or more positions substituted with histidine in total.

10. The composition of claim 1, 2 or 7, wherein the first ABD comprises one of: (a) a HCVD having at least 90% identity to SEQ ID NO: 301, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; (b) a HCVD having at least 90% identity to SEQ ID NO:375, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO:375; (c) a HCVD having at least 90% identity to SEQ ID NO:459, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111 in SEQ ID NO:459; (d) a HCVD having at least 90% identity to SEQ ID NO:542, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 in SEQ ID NO:542; (e) a HCVD having at least 90% identity to SEQ ID NO:628, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 in SEQ ID NO:628; (f) a HCVD having at least 90% identity to SEQ ID NO:710, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113 in SEQ ID NO:710; (g) a HCVD having at least 90% identity to SEQ ID NO:803, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107 in SEQ ID NO:803; (h) a HCVD having at least 90% identity to SEQ ID NO: 1, wherein the HCVD comprises histidine at one or more positions in SEQ ID NO: 1 selected from the group consisting of: 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107; (i) a HCVD having at least 90% identity to SEQ ID NO: 126, wherein the HCVD comprises histidine at one or more positions in SEQ ID NO: 126 selected from the group consisting of: 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, and 111; and (j) a HCVD having at least 90% identity to SEQ ID NO:229, wherein the HCVD comprises histidine at one or more positions in SEQ ID NO:229 selected from the group consisting of: 27, 32, 33, 34, 35, 51, 54, 56, 58 and 100.

11. The composition of claim 1, 2 or 7, wherein the first ABD comprises one of: (a) an LCVD having at least 90% identity to SEQ ID NO: 302, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) an LCVD having at least 90% identity to SEQ ID NO: 376, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376; (c) an LCVD having at least 90% identity to SEQ ID NO: 460, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 30, 31, 33, 51, 92, and 95 in SEQ ID NO: 460; (d) a LCVD having at least 90% identity to SEQ ID NO:543, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 in SEQ ID NO:543; (e) a LCVD having at least 90% identity to SEQ ID NO: 629, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 in SEQ ID NO: 629; (f) an LCVD having at least 90% identity to SEQ ID NO: 711, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99 in SEQ ID NO: 711; (g) a LCVD having at least 90% identity to SEQ ID NO: 804, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 in SEQ ID NO: 804; (h) an LCVD having at least 90% identity to SEQ ID NO:2, wherein the LCVD comprises histidine at one or more positions in SEQ ID NO:2 selected from the group consisting of: 25, 29, 31, 35, 60, 93, and 94; (i) an LCVD having at least 90% identity to SEQ ID NO: 127, wherein the LCVD comprises histidine at one or more positions in SEQ ID NO: 127 selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94; and (j) an LCVD having at least 90% identity to SEQ ID NO:230, wherein the LCVD comprises histidine at one or more positions in SEQ ID NO:230 selected from the group consisting of: 30, 31, 33, 51, 53, 57, 91, 92, 94 and 99.

12. The composition of claim 1, 2 or 7, wherein the first ABD comprises: (a) a HCVD having at least 90% identity to SEQ ID NO: 301, wherein the HCVD optionally comprises histidine at two or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; (b) a HCVD having at least 90% identity to SEQ ID NO:375, wherein the HCVD optionally comprises histidine at two or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO:375; (c) a HCVD having at least 90% identity to SEQ ID NO:459, wherein the HCVD optionally comprises histidine at two or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111 in SEQ ID NO:459; (d) a HCVD having at least 90% identity to SEQ ID NO:542, wherein the HCVD optionally comprises histidine at two or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 in SEQ ID NO:542; (e) a HCVD having at least 90% identity to SEQ ID NO:628, wherein the HCVD optionally comprises histidine at two or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 in SEQ ID NO:628; (f) a HCVD having at least 90% identity to SEQ ID NO:710, wherein the HCVD optionally comprises histidine at two or more positions selected from the group consisting of: 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113 in SEQ ID NO:710; (g) a HCVD having at least 90% identity to SEQ ID NO:803, wherein the HCVD optionally comprises histidine at two or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107 in SEQ ID NO:803; (h) a HCVD having at least 90% identity to SEQ ID NO: 1, wherein the HCVD comprises histidine at two or more positions in SEQ ID NO: 1 selected from the group consisting of: 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107; (i) a HCVD having at least 90% identity to SEQ ID NO: 126, wherein the HCVD comprises histidine at two or more positions in SEQ ID NO: 126 selected from the group consisting of: 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, and 111; and (j) a HCVD having at least 90% identity to SEQ ID NO:229, wherein the HCVD comprises histidine at two or more positions selected from the group consisting of: 27, 32, 33, 34, 35, 51, 54, 56, 58 and 100 in SEQ ID NO:

229.

13. The composition of claim 1, 3 or 8, wherein the first ABD comprises one of: (a) an LCVD having at least 90% identity to SEQ ID NO: 302, wherein the LCVD optionally comprises histidine at two or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) an LCVD having at least 90% identity to SEQ ID NO: 376, wherein the LCVD optionally comprises histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376; (c) an LCVD having at least 90% identity to SEQ ID NO: 460, wherein the LCVD optionally comprises histidine at two or more positions selected from the group consisting of: 30, 31, 33, 51, 92, and 95 in SEQ ID NO: 460; (d) a LCVD having at least 90% identity to SEQ ID NO:543, wherein the LCVD optionally comprises histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 in SEQ ID NO:543; (e) a LCVD having at least 90% identity to SEQ ID NO: 629, wherein the LCVD optionally comprises histidine at two or more positions selected from the group consisting of 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 in SEQ ID NO: 629; (f) an LCVD having at least 90% identity to SEQ ID NO: 711, wherein the LCVD optionally comprises histidine at two or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99 in SEQ ID NO: 711; (g) a LCVD having at least 90% identity to SEQ ID NO: 804, wherein the LCVD optionally comprises histidine at two or more positions in SEQ ID NO: 804 selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99; (h) a LCVD having at least 90% identity to SEQ ID NO:2, wherein the LCVD comprises histidine at two or more positions in SEQ ID NO:2 selected from the group consisting of: 25, 29, 31, 35, 60, 93, and 94; (i) an LCVD having at least 90% identity to SEQ ID NO: 127, wherein the LCVD comprises histidine at two or more positions in SEQ ID NO: 127 selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94; and (j) a LCVD having at least 90% identity to SEQ ID NO:230, wherein the LCVD comprises histidine at two or more positions in SEQ ID NO:230 selected from the group consisting of: 30, 31, 33, 51, 53, 57, 91, 92, 94 and 99.

14. The composition of claim 1, 4 or 9, wherein the first ABD comprises one of: (a) a HCVD having at least 90% identity to SEQ ID NO: 301, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; and / or a LCVD having at least 90% identity to SEQ ID NO: 302, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) a HCVD having at least 90% identity to SEQ ID NO:375, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO:375; and / or a LCVD having at least 90% identity to SEQ ID NO:376, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO:376; (c) a HCVD having at least 90% identity to SEQ ID NO: 459, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111 in SEQ ID NO: 459; and / or a LCVD having at least 90% identity to SEQ ID NO: 460, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 30, 31, 33, 51, 92, and 95 in SEQ ID NO: 460; (d) a HCVD having at least 90% identity to SEQ ID NO:542, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 in SEQ ID NO:542; and / or a LCVD having at least 90% identity to SEQ ID NO:543, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of 25, 29, 30, 31, 32, 89, 92, and 98 in SEQ ID NO:543; (e) a HCVD having at least 90% identity to SEQ ID NO:628, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 in SEQ ID NO:628; and / or a LCVD having at least 90% identity to SEQ ID NO:629, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 in SEQ ID NO:629; (f) a HCVD having at least 90% identity to SEQ ID NO:710, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113 in SEQ ID NO:710; and / or a LCVD having at least 90% identity to SEQ ID NO:711, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99 in SEQ ID NO:711; (g) a HCVD having at least 90% identity to SEQ ID NO:803, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107 in SEQ ID NO:803; and / or a LCVD having at least 90% identity to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 in SEQ ID NO:

804.

15. The composition of claim 1, wherein the first ABD comprises an HCVD comprising a sequence of one of: SEQ ID NO: 301, or one of 309-342; SEQ ID NO: 375, or one of 383-423; SEQ ID NO: 459, or one of 467-511; SEQ ID NO: 542, or one of 550-592; SEQ ID NO: 628, or one of 636-675; SEQ ID NO: 710, or one of 718-767; and SEQ ID NO: 803, or one of 811-854; or wherein the HCVD comprises one of: (a) SEQ ID NO: 1, 14, 17, 18, 19, 20, 21, 22, 24, 25, 29, 30, 31, 33, 34, 40, 44, 46, 48, 49, 53, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98, 99, 100, 101, 102, 103, 104 or 105 HCVD; (b) SEQ ID NO:126, 147, 148, 150, 151, 154, 166, 167, 168, 169, 170, 172, 173, 174, 175, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 224, 225, 226 or 227; and (c) an HCVD of SEQ ID NO:229, 238, 243, 244, 245, 246, 248, 251, 253, 255 or 267.

16. The composition of claim 1 or 15, wherein the first ABD comprises a LCVD comprising a sequence of one of: SEQ ID NO: 302, or one of 343-374; SEQ ID NO: 376, or one of 424-458; SEQ ID NO: 460, or one of 512-541; SEQ ID NO: 543, or one of 593-627; SEQ ID NO: 629, or one of 676-709; SEQ ID NO: 711, or one of 768-854; and SEQ ID NO: 804, or one of 855-892; or wherein the LCVD comprises one of: (a) SEQ ID NO:2, 56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, 122, 123, 124 or 125; (b) an LCVD of SEQ ID NO:127, 181, 182, 184, 185, 187, 188, 189, 191, 199, 201, 203 or 228; and (c) an LCVD of SEQ ID NO:230, 275, 276, 278, 281, 283, 287, 289, 290, 292 or 297.

17. The composition of claim 1, wherein the first ABD comprises one of: (a) an HCVD of one of SEQ ID NOs: 301, or one of 309-342; and / or an LCVD of one of SEQ ID NOs: 302, or one of 343-374, wherein the first ABD does not comprise (i) SEQ ID NOs: 301 and 5; (ii) an HCVD of SEQ ID NO: 301 and an LCVD that is not one of SEQ ID NOs: 344, 349-352, 354, 359-361, 363, 366-368, 370, and 373; or (iii) an LCVD of SEQ ID NO: 302 and an HCVD that is not one of SEQ ID NOs: 312, 313, 315, 319-323, 327, 329, 335, 340, and 341; (b) an HCVD of one of SEQ ID NO: 375, or one of 383-423; and / or an LCVD of one of SEQ ID NO: 376, or one of 424-458, wherein the first ABD does not comprise (i) SEQ ID NO: 375 and 79; (ii) an HCVD of SEQ ID NO: 375 and an LCVD that is not one of SEQ ID NO: 425, 429, 430, 431, 432, 433, 435, 436, 437, 438, 442, 444, 445, 446, 449, 450, 453, and 455; or (iii) an LCVD of SEQ ID NO: 376 and an LCVD that is not one of SEQ ID NO: HCVD of one of NO: 383, 384, 387, 389, 391, 394, 395, 398, 401, 402, 406, 410, 412 and 421; (c) an HCVD of one of SEQ ID NOs: 459, or one of 467-511; and / or an LCVD of one of SEQ ID NOs: 460, or one of 512-541, wherein the first ABD does not comprise (i) SEQ ID NOs: 459 and 163; (ii) an HCVD of SEQ ID NO: 459 and an LCVD that is not one of SEQ ID NOs: 518, 519, 521, 524, 533, and 536; or (iii) an LCVD of SEQ ID NO: 460 and an HCVD that is not one of SEQ ID NOs: 473, 496, 498, 499, 503, and 508; (d) an HCVD of one of SEQ ID NOs: 542, or one of 550-592; and / or an LCVD of one of SEQ ID NOs: 543, or one of 593-627, wherein the first ABD does not comprise (i) SEQ ID NOs: 542 and 246; (ii) an HCVD of SEQ ID NO: 542 and an LCVD that is not one of SEQ ID NOs: 594, 598, 599, 600, 601, 611, 614, and 620; or (iii) an LCVD of SEQ ID NO: 543 and an HCVD that is not one of SEQ ID NOs: 551, 553, 554, 555, 556, 563, 565, 568, 582, 584, and 585; (e) an HCVD of one of SEQ ID NOs: 628, or one of 636-675; and / or an LCVD of one of SEQ ID NOs: 629, or one of 676-709, wherein the first ABD does not comprise (i) SEQ ID NOs: 628 and 332; (ii) an HCVD of SEQ ID NO: 628 and an LCVD that is not one of SEQ ID NOs: 677, 678, 680, 681, 685, 688, 692, 694, 696, 700, 701, 702, 703, 704, and 705; or (iii) an LCVD of SEQ ID NO: 629 and an LCVD that is not one of SEQ ID NOs: HCVD of one of NO: 636, 638, 640, 646, 648, 649, 650, 651, 652, 653, 666, 667, 668 and 669; (f) an HCVD of one of the following: SEQ ID NO: 710, or one of 718-767; and / or an LCVD of one of the following: SEQ ID NO: 711, or one of 768-802, wherein the first ABD does not comprise (i) SEQ ID NO: 710 and 414; (ii) an HCVD of SEQ ID NO: 710 and an LCVD that is not one of SEQ ID NO: 769, 771, 773, 774, 779, 780, 785, 786, 788, 790, 791, 792, 795, and 796; or (iii) an LCVD of SEQ ID NO: 711 and an LCVD that is not one of SEQ ID NO: HCVD of one of IDNO: 721, 722, 723, 725, 727, 728, 731, 735, 736, 743, 744, 745, 746, 748, 749, 751, 753, 755, 756, 757, 758 and 761; (g) an HCVD of one of SEQ ID NOs: 803, or one of 811-854; and / or an LCVD of one of SEQ ID NOs: 804, or one of 855-892, wherein the first ABD does not comprise (i) SEQ ID NOs: 803 and 507; (ii) an HCVD of SEQ ID NO: 803 and an LCVD that is not one of SEQ ID NOs: 862, 864-866, 868, 870, 881, and 882; or (iii) an LCVD of SEQ ID NO: 804 and an HCVD that is not one of SEQ ID NOs: 818, 821, 824, 826-829, 835, 841, 848, and 850; (h) an HCVD of SEQ ID NO: 14, 17, 18, 19, 20, 21, 22, 24, 25, 29, 30, 31, 33, 34, 40, 44, 46, 48, 49, 53, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98, 99, 100, 101, 102, 103, 104, or 105; and / or an LCVD of SEQ ID NO: 2, 56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, 122, 123, 124, or 125, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 1 and an LCVD of SEQ ID NO: 2; (ii) an HCVD of SEQ ID NO: 2 NO:1 and an LCVD that is not one of SEQ ID NO:56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, and 122-125; or (iii) an LCVD that is SEQ ID NO:2 and an HCVD that is not one of SEQ ID NO:14, 17-22, 24, 25, 29-31, 33, 34, 40, 44, 46, 48, 49, 53, 86-96, and 98-105; (i) an HCVD of SEQ ID NO: 147, 148, 150, 151, 154, 166, 167, 168, 169, 170, 172, 173, 174, 175, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 224, 225, 226, or 227; and / or an LCVD of SEQ ID NO: 127, 181, 182, 184, 185, 187, 188, 189, 191, 199, 201, 203, or 228, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 126 and an LCVD of SEQ ID NO: 127; (ii) an HCVD of SEQ ID NO: 1 (iii) an LCVD of SEQ ID NO: 127 and an HCVD that is not one of SEQ ID NOs: 147, 148, 150, 151, 154, 166-170, 172-175, 208-222, and 224-227; and (j) an HCVD of SEQ ID NO: 238, 243, 244, 245, 246, 248, 251, 253, 255 or 267; and / or an LCVD of SEQ ID NO: 230, 275, 276, 278, 281, 283, 287, 289, 290, 292 or 297, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 229 and an LCVD of SEQ ID NO: 230; (ii) an HCVD of SEQ ID NO: 229 and an LCVD that is not one of SEQ ID NO: 275, 276, 278, 281, 283, 287, 289, 290, 292 and 297; and (iii) an LCVD of SEQ ID NO: 230 and an LCVD that is not one of SEQ ID NO: HCVD of one of NO: 238, 243-246, 248, 251, 253, 255 and 267.

18. The composition of any one of claims 1-17, wherein the ABPC is degraded in the target mammalian cell after the ABPC is internalized by the target mammalian cell.

19. The composition of any one of claims 1-18, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule.

20. The composition of claim 19, wherein the composition provides an increase in toxin release in the target mammalian cells compared to a composition comprising the same amount of a control ABPC.

21. The composition of claim 20, wherein the composition increases toxin release in the target mammalian cells by at least 20%, 50%, 2-fold, or 5-fold compared to a composition comprising the same amount of a control ABPC.

22. The composition of any one of claims 19-21, wherein the composition provides increased killing of target mammalian cells compared to a composition comprising the same amount of control ABPCs.

23. The composition of claim 22, wherein the composition increases the killing of target mammalian cells by at least 20%, 50%, 2-fold, or 5-fold compared to a composition comprising the same amount of control ABPCs.

24. The composition of any one of claims 1-23, wherein the composition provides an increase in endolysosomal delivery in the target mammalian cell compared to a composition comprising the same amount of control ABPCs.

25. The composition of claim 24, wherein the composition increases endolysosomal delivery in the target mammalian cell by at least 20%, 50%, 2-fold, or 5-fold compared to a composition comprising the same amount of a control ABPC.

26. The composition of any one of claims 1-25, wherein the composition causes less or no detectable decrease in the level of PTK7 presented on the surface of the target mammalian cell compared to a composition comprising the same amount of a control ABPC.

27. A composition comprising an effective amount of an antigen binding protein construct (ABPC), wherein the antigen binding protein construct comprises: a first ABD capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug or small molecule, in: (a) the dissociation rate of the first ABD at a pH of about 4.0-6.5 is faster than the dissociation rate at a pH of about 7.0-8.0; or the dissociation constant (K) of the first ABD at a pH of about 4.0-6.5 is D ) than K at a pH of about 7.0-8.0 D Large; and (b) the composition provides one or more of the following: (i) an increase in toxin release in the target mammalian cells compared to a composition comprising the same amount of a control ABPC; (ii) an increase in target mammalian cell killing compared to a composition comprising the same amount of a control ABPC; or (iii) an increase in endolysosomal delivery in the target mammalian cells compared to a composition comprising the same amount of a control ABPC.

28. The composition of claim 27, wherein the ABD comprises a heavy chain variable domain (HCVD) of MYT9345, MYT9359, MYT9361, MYT9412, MYT9460, MYT9792, or MYT9797, optionally with one or more histidine substitutions; or a HCVD of cofilotuzumab, 7C8, or 12C6, each with at least one histidine substitution.

29. The composition of claim 27, wherein the first ABD comprises a light chain variable domain (LCVD) of MYT9345, MYT9359, MYT9361, MYT9412, MYT9460, MYT9792, or MYT9797, optionally with one or more histidine substitutions; or a LCVD of cofilotuzumab, 7C8, or 12C6, each with at least one histidine substitution.

30. The composition of claim 27, wherein the ABD comprises one of: (a) HCVD of MYT9345 and / or LCVD of MYT9345; (b) HCVD of MYT9359 and / or LCVD of MYT9359; (c) HCVD of MYT9361; and / or LCVD of MYT9361; (d) HCVD of MYT9412 and / or LCVD of MYT9412; (e) HCVD of MYT9460 and / or LCVD of MYT9460; (f) HCVD of MYT9792; and / or LCVD of MYT9792; and (g) HCVD of MYT9797 and / or LCVD of MYT9797; wherein each HCVD and / or LCVD optionally has one or more histidine substitutions; alternatively, the ABD comprises one of the following: (h) HCVD of cofilotuzumab and / or LCVD of cofilotuzumab; (i) HCVD of 7C8 and / or LCVD of 7C8; and (j) HCVD of 12C6; and / or LCVD of 12C6, wherein each HCVD and / or LCVD of (i), (h) or (j) has at least one histidine substitution.

31. The composition of claim 28 or 30, wherein the HCVD comprises one of the following: (a) an HCVD comprising MYT9345 of SEQ ID NO: 301; (b) an HCVD comprising MYT9359 of SEQ ID NO: 375; (c) an HCVD comprising MYT9361 of SEQ ID NO: 459; (d) an HCVD comprising MYT9412 of SEQ ID NO: 542; (e) an HCVD comprising MYT9460 of SEQ ID NO: 628; (f) an HCVD comprising MYT9792 of SEQ ID NO: 710; (g) an HCVD comprising MYT9797 of SEQ ID NO: 803; (h) an HCVD comprising cofiltizumab of SEQ ID NO: 1; (i) an HCVD comprising 7C8 of SEQ ID NO: 126; and (j) an HCVD comprising SEQ ID NO:

134. NO:229's 12C6's HCVD.

32. The composition of claim 29 or 30, wherein the LCVD comprises one of the following: (a) an LCVD comprising MYT9345 of SEQ ID NO: 302; (b) an LCVD comprising MYT9359 of SEQ ID NO: 376; (c) an LCVD comprising MYT9361 of SEQ ID NO: 460; (d) an LCVD comprising MYT9412 of SEQ ID NO: 543; (e) an LCVD comprising MYT9460 of SEQ ID NO: 629; (f) an LCVD comprising MYT9792 of SEQ ID NO: 711; (g) an LCVD comprising MYT9797 of SEQ ID NO: 804; (h) an LCVD comprising cofiltizumab of SEQ ID NO: 2; (i) an LCVD comprising 7C8 of SEQ ID NO: 127; and (j) an LCVD comprising SEQ ID NO: NO:23012C6LCVD.

33. The composition of claim 27, wherein the first ABD comprises an HCVD comprising CDR1, 2 and 3 of one of the following: (a) SEQ ID NOs: 303, 304 and 305; (b) SEQ ID NOs: 377, 378 and 379; (c) SEQ ID NOs: 461, 462 and 463; (d) SEQ ID NOs: 544, 545 and 546; (e) SEQ ID NOs: 630, 631 and 632; (f) SEQ ID NOs: 712, 713 and 714; (g) SEQ ID NOs: 805, 806 and 807; (h) SEQ ID NOs: 3, 4 and 5; (i) SEQ ID NOs: 128, 129 and 130; and (j) SEQ ID NOs: NO:231, 232 and 233, wherein for (a) to (g), each group of three CDRs optionally has a total of one or more positions substituted by histidine, and for (h) to (j), each group of three CDRs has a total of at least one or more positions substituted by histidine.

34. The composition of claim 27, wherein the first ABD comprises a LCVD comprising CDR1, 2, and 3 of one of the following: (a) SEQ ID NOs: 306, 307, and 308; (b) SEQ ID NOs: 380, 381, and 382; (c) SEQ ID NOs: 464, 465, and 466; (d) SEQ ID NOs: 547, 548, and 549; (e) SEQ ID NOs: 633, 634, and 635; (f) SEQ ID NOs: 715, 716, and 717; (g) SEQ ID NOs: 808, 809, and 810; (h) SEQ ID NOs: 6, 7, and 8; (i) SEQ ID NOs: 131, 132, and 133; and (j) SEQ ID NOs: 234, 235, and 236; wherein for (a) to (g), each set of three CDRs optionally has one or more positions in total substituted with histidine, and for (h) to (j), each set of three CDRs has at least one or more positions in total substituted with histidine.

35. The composition of claim 27, wherein the first ABD comprises one of: (a) an HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 303, 304 and 305; and / or an LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 306, 307 and 308; (b) an HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 377, 378 and 379; and / or an LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 380, 381 and 382; (c) an HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 461, 462 and 463; and / or an LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 464, 465 and 466; (d) an HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 544, 545 and 546; and / or an LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 547, 548 and 549; (e) a HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 630, 631 and 632; and / or a LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 633, 634 and 635; (f) a HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 712, 713 and 714; and / or a LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 715, 716 and 717; (g) a HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 805, 806 and 807; and / or a LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 808, 809 and 810; (h) an HCVD comprising CDR1, 2 and 3 of one of SEQ ID NOs: 3, 4 and 5; and / or an LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 6, 7 and 8; (i) an HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 128, 129 and 130; and / or an LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 131, 132 and 133; and (j) an HCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 231, 232 and 233; and / or an LCVD comprising CDR1, 2 and 3 of SEQ ID NOs: 234, 235 and 236; wherein for (a) to (g), any one or both of each set of three CDRs optionally have one or more positions in total substituted with histidine, and wherein for (h) to (j), any one or both of each set of three CDRs have at least one or more positions substituted with histidine in total.

36. The composition of claim 27, 28 or 33, wherein the first ABD comprises one of: (a) an LCVD having at least 90% identity to SEQ ID NO: 302, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) an LCVD having at least 90% identity to SEQ ID NO: 376, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376; (c) an LCVD having at least 90% identity to SEQ ID NO: 460, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 30, 31, 33, 51, 92, and 95 in SEQ ID NO: 460; (d) a LCVD having at least 90% identity to SEQ ID NO:543, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 in SEQ ID NO:543; (e) a LCVD having at least 90% identity to SEQ ID NO: 629, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 in SEQ ID NO: 629; (f) an LCVD having at least 90% identity to SEQ ID NO: 711, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99 in SEQ ID NO: 711; (g) a LCVD having at least 90% identity to SEQ ID NO: 804, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 in SEQ ID NO: 804; (h) an LCVD having at least 90% identity to SEQ ID NO:2, wherein the LCVD comprises histidine at one or more positions in SEQ ID NO:2 selected from the group consisting of: 25, 29, 31, 35, 60, 93, and 94; (i) an LCVD having at least 90% identity to SEQ ID NO: 127, wherein the LCVD comprises histidine at one or more positions in SEQ ID NO: 127 selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94; and (j) an LCVD having at least 90% identity to SEQ ID NO:230, wherein the LCVD comprises histidine at one or more positions in SEQ ID NO:230 selected from the group consisting of: 30, 31, 33, 51, 53, 57, 91, 92, 94 and 99.

37. The composition of claim 27, 29 or 34, wherein the first ABD comprises one of: (a) a HCVD having at least 90% identity to SEQ ID NO: 301, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; (b) a HCVD having at least 90% identity to SEQ ID NO:375, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO:375; (c) a HCVD having at least 90% identity to SEQ ID NO:459, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111 in SEQ ID NO:459; (d) a HCVD having at least 90% identity to SEQ ID NO:542, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 in SEQ ID NO:542; (e) a HCVD having at least 90% identity to SEQ ID NO:628, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 in SEQ ID NO:628; (f) a HCVD having at least 90% identity to SEQ ID NO:710, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113 in SEQ ID NO:710; (g) a HCVD having at least 90% identity to SEQ ID NO:803, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107 in SEQ ID NO:803; (h) a HCVD having at least 90% identity to SEQ ID NO: 1, wherein the HCVD comprises histidine at two or more positions in SEQ ID NO: 1 selected from the group consisting of: 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107; (i) a HCVD having at least 90% identity to SEQ ID NO: 126, wherein the HCVD comprises histidine at two or more positions in SEQ ID NO: 126 selected from the group consisting of: 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, and 111; and (j) a HCVD having at least 90% identity to SEQ ID NO:229, wherein the HCVD comprises histidine at two or more positions selected from the group consisting of: 27, 32, 33, 34, 35, 51, 54, 56, 58 and 100 in SEQ ID NO:

229.

38. The composition of claim 27, 28 or 33, wherein the first ABD comprises one of: (a) an LCVD having at least 90% identity to SEQ ID NO: 302, wherein the LCVD optionally comprises histidine at two or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) an LCVD having at least 90% identity to SEQ ID NO: 376, wherein the LCVD optionally comprises histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376; (c) an LCVD having at least 90% identity to SEQ ID NO: 460, wherein the LCVD optionally comprises histidine at two or more positions selected from the group consisting of: 30, 31, 33, 51, 92, and 95 in SEQ ID NO: 460; (d) a LCVD having at least 90% identity to SEQ ID NO:543, wherein the LCVD optionally comprises histidine at two or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 in SEQ ID NO:543; (e) a LCVD having at least 90% identity to SEQ ID NO: 629, wherein the LCVD optionally comprises histidine at two or more positions selected from the group consisting of 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 in SEQ ID NO: 629; (f) an LCVD having at least 90% identity to SEQ ID NO: 711, wherein the LCVD optionally comprises histidine at two or more positions selected from the group consisting of: 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99 in SEQ ID NO: 711; (g) a LCVD having at least 90% identity to SEQ ID NO: 804, wherein the LCVD optionally comprises histidine at two or more positions in SEQ ID NO: 804 selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99; (h) a LCVD having at least 90% identity to SEQ ID NO:2, wherein the LCVD comprises histidine at two or more positions in SEQ ID NO:2 selected from the group consisting of: 25, 29, 31, 35, 60, 93, and 94; (i) an LCVD having at least 90% identity to SEQ ID NO: 127, wherein the LCVD comprises histidine at two or more positions in SEQ ID NO: 127 selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94; and (j) a LCVD having at least 90% identity to SEQ ID NO:230, wherein the LCVD comprises histidine at two or more positions in SEQ ID NO:230 selected from the group consisting of: 30, 31, 33, 51, 53, 57, 91, 92, 94 and 99.

39. The composition of claims 27, 29, 34, wherein the first ABD comprises one of: (a) a HCVD having at least 90% identity to SEQ ID NO: 301, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; and / or a LCVD having at least 90% identity to SEQ ID NO: 302, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) a HCVD having at least 90% identity to SEQ ID NO:375, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO:375; and / or a LCVD having at least 90% identity to SEQ ID NO:376, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO:376; (c) a HCVD having at least 90% identity to SEQ ID NO: 459, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111 in SEQ ID NO: 459; and / or a LCVD having at least 90% identity to SEQ ID NO: 460, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 30, 31, 33, 51, 92, and 95 in SEQ ID NO: 460; (d) a HCVD having at least 90% identity to SEQ ID NO:542, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 in SEQ ID NO:542; and / or a LCVD having at least 90% identity to SEQ ID NO:543, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of 25, 29, 30, 31, 32, 89, 92, and 98 in SEQ ID NO:543; (e) a HCVD having at least 90% identity to SEQ ID NO:628, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 in SEQ ID NO:628; and / or a LCVD having at least 90% identity to SEQ ID NO:629, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 in SEQ ID NO:629; (f) a HCVD having at least 90% identity to SEQ ID NO: 710, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113 in SEQ ID NO: 710; and / or a LCVD having at least 90% identity to SEQ ID NO: 711, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99 in SEQ ID NO: 711; and (g) a HCVD having at least 90% identity to SEQ ID NO:803, wherein the HCVD optionally includes a histidine at one or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107 in SEQ ID NO:803; and / or a LCVD having at least 90% identity to SEQ ID NO:804, wherein the LCVD optionally includes a histidine at one or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 in SEQ ID NO:

804. (h) a HCVD having at least 90% identity to SEQ ID NO: 1, wherein the HCVD comprises histidine at one or more positions in SEQ ID NO: 1 selected from the group consisting of: 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107; (i) a HCVD having at least 90% identity to SEQ ID NO: 126, wherein the HCVD comprises histidine at one or more positions in SEQ ID NO: 126 selected from the group consisting of: 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, and 111; and (j) a HCVD having at least 90% identity to SEQ ID NO:229, wherein the HCVD comprises histidine at one or more positions in SEQ ID NO:229 selected from the group consisting of: 27, 32, 33, 34, 35, 51, 54, 56, 58 and 100.

40. The composition of claim 27, 30 or 35, wherein the first ABD comprises an HCVD comprising a sequence of one of: SEQ ID NO: 301, or one of 309-342; SEQ ID NO: 375, or one of 383-423; SEQ ID NO: 459, or one of 467-511; SEQ ID NO: 542, or one of 550-592; SEQ ID NO: 628, or one of 636-675; SEQ ID NO: 710, or one of 718-767; and SEQ ID NO: 803, or one of 811-854; or Wherein the HCVD comprises one of the following: (a) an HCVD of SEQ ID NO: 1, 14, 17, 18, 19, 20, 21, 22, 24, 25, 29, 30, 31, 33, 34, 40, 44, 46, 48, 49, 53, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98, 99, 100, 101, 102, 103, 104 or 105; (b) an HCVD of SEQ ID NO: 126, 147, 148, 150, 151, 154, 166, 167, 168, 169, 170, 172, 173, 174, 175, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 224, 225, 226, or 227; and (c) HCVD of SEQ ID NO: 229, 238, 243, 244, 245, 246, 248, 251, 253, 255 or 267.

41. The composition of claim 27, wherein the first ABD comprises a LCVD comprising a sequence of one of: SEQ ID NO: 302, or one of 343-374; SEQ ID NO: 376, or one of 424-458; SEQ ID NO: 460, or one of 512-541; SEQ ID NO: 543, or one of 593-627; SEQ ID NO: 629, or one of 676-709; SEQ ID NO: 711, or one of 768-854; and SEQ ID NO: 804, or one of 855-892; or Wherein the LCVD comprises one of the following: (a) an LCVD of SEQ ID NO: 2, 56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, 122, 123, 124 or 125; (b) an LCVD of SEQ ID NO: 127, 181, 182, 184, 185, 187, 188, 189, 191, 199, 201, 203 or 228; and (c) LCVD of SEQ ID NO: 230, 275, 276, 278, 281, 283, 287, 289, 290, 292 or 297.

42. The composition of claim 27 or 41, wherein the first ABD comprises: (a) an HCVD of one of SEQ ID NOs: 301, or one of 309-342; and / or an LCVD of one of SEQ ID NOs: 302, or one of 343-374, wherein the first ABD does not comprise (i) SEQ ID NOs: 301 and 5; (ii) an HCVD of SEQ ID NO: 301 and an LCVD that is not one of SEQ ID NOs: 344, 349-352, 354, 359-361, 363, 366-368, 370, and 373; or (iii) an LCVD of SEQ ID NO: 302 and an HCVD that is not one of SEQ ID NOs: 312, 313, 315, 319-323, 327, 329, 335, 340, and 341; (b) an HCVD of one of SEQ ID NO: 375, or one of 383-423; and / or an LCVD of one of SEQ ID NO: 376, or one of 424-458, wherein the first ABD does not comprise (i) SEQ ID NO: 375 and 79; (ii) an HCVD of SEQ ID NO: 375 and an LCVD that is not one of SEQ ID NO: 425, 429, 430, 431, 432, 433, 435, 436, 437, 438, 442, 444, 445, 446, 449, 450, 453, and 455; or (iii) an LCVD of SEQ ID NO: 376 and an LCVD that is not one of SEQ ID NO: HCVD of one of NO: 383, 384, 387, 389, 391, 394, 395, 398, 401, 402, 406, 410, 412 and 421; (c) an HCVD of one of SEQ ID NOs: 459, or one of 467-511; and / or an LCVD of one of SEQ ID NOs: 460, or one of 512-541, wherein the first ABD does not comprise (i) SEQ ID NOs: 459 and 163; (ii) an HCVD of SEQ ID NO: 459 and an LCVD that is not one of SEQ ID NOs: 518, 519, 521, 524, 533, and 536; or (iii) an LCVD of SEQ ID NO: 460 and an HCVD that is not one of SEQ ID NOs: 473, 496, 498, 499, 503, and 508; and (d) an HCVD of one of SEQ ID NOs: 542, or one of 550-592; and / or an LCVD of one of SEQ ID NOs: 543, or one of 593-627, wherein the first ABD does not comprise (i) SEQ ID NOs: 542 and 246; (ii) an HCVD of SEQ ID NO: 542 and an LCVD that is not one of SEQ ID NOs: 594, 598, 599, 600, 601, 611, 614, and 620; or (iii) an LCVD of SEQ ID NO: 543 and an HCVD that is not one of SEQ ID NOs: 551, 553, 554, 555, 556, 563, 565, 568, 582, 584, and 585; (e) an HCVD of one of SEQ ID NOs: 628, or one of 636-675; and / or an LCVD of one of SEQ ID NOs: 629, or one of 676-709, wherein the first ABD does not comprise (i) SEQ ID NOs: 628 and 332; (ii) an HCVD of SEQ ID NO: 628 and an LCVD that is not one of SEQ ID NOs: 677, 678, 680, 681, 685, 688, 692, 694, 696, 700, 701, 702, 703, 704, and 705; or (iii) an LCVD of SEQ ID NO: 629 and an LCVD that is not one of SEQ ID NOs: HCVD of one of NO: 636, 638, 640, 646, 648, 649, 650, 651, 652, 653, 666, 667, 668 and 669; (f) an HCVD of one of the following: SEQ ID NO: 710, or one of 718-767; and / or an LCVD of one of the following: SEQ ID NO: 711, or one of 768-802, wherein the first ABD does not comprise (i) SEQ ID NO: 710 and 414; (ii) an HCVD of SEQ ID NO: 710 and an LCVD that is not one of SEQ ID NO: 769, 771, 773, 774, 779, 780, 785, 786, 788, 790, 791, 792, 795, and 796; or (iii) an LCVD of SEQ ID NO: 711 and an LCVD that is not one of SEQ ID NO: HCVD of one of IDNO: 721, 722, 723, 725, 727, 728, 731, 735, 736, 743, 744, 745, 746, 748, 749, 751, 753, 755, 756, 757, 758 and 761; (g) an HCVD of one of SEQ ID NOs: 803, or one of 811-854; and / or an LCVD of one of SEQ ID NOs: 804, or one of 855-892, wherein the first ABD does not comprise (i) SEQ ID NOs: 803 and 507; (ii) an HCVD of SEQ ID NO: 803 and an LCVD that is not one of SEQ ID NOs: 862, 864-866, 868, 870, 881, and 882; or (iii) an LCVD of SEQ ID NO: 804 and an HCVD that is not one of SEQ ID NOs: 818, 821, 824, 826-829, 835, 841, 848, and 850; (h) an HCVD of SEQ ID NO: 14, 17, 18, 19, 20, 21, 22, 24, 25, 29, 30, 31, 33, 34, 40, 44, 46, 48, 49, 53, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98, 99, 100, 101, 102, 103, 104, or 105; and / or an LCVD of SEQ ID NO: 2, 56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, 122, 123, 124, or 125, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 1 and an LCVD of SEQ ID NO: 2; (ii) an HCVD of SEQ ID NO: 2 NO:1 and an LCVD that is not one of SEQ ID NO:56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, and 122-125; or (iii) an LCVD that is SEQ ID NO:2 and an HCVD that is not one of SEQ ID NO:14, 17-22, 24, 25, 29-31, 33, 34, 40, 44, 46, 48, 49, 53, 86-96, and 98-105; (i) an HCVD of SEQ ID NO: 147, 148, 150, 151, 154, 166, 167, 168, 169, 170, 172, 173, 174, 175, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 224, 225, 226, or 227; and / or an LCVD of SEQ ID NO: 127, 181, 182, 184, 185, 187, 188, 189, 191, 199, 201, 203, or 228, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 126 and an LCVD of SEQ ID NO: 127; (ii) an HCVD of SEQ ID NO: 1 (iii) an LCVD of SEQ ID NO: 127 and an HCVD that is not one of SEQ ID NOs: 147, 148, 150, 151, 154, 166-170, 172-175, 208-222, and 224-227; and (j) an HCVD of SEQ ID NO: 238, 243, 244, 245, 246, 248, 251, 253, 255 or 267; and / or an LCVD of SEQ ID NO: 230, 275, 276, 278, 281, 283, 287, 289, 290, 292 or 297, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 229 and an LCVD of SEQ ID NO: 230; (ii) an HCVD of SEQ ID NO: 229 and an LCVD that is not one of SEQ ID NO: 275, 276, 278, 281, 283, 287, 289, 290, 292 and 297; and (iii) an LCVD of SEQ ID NO: 230 and an LCVD that is not one of SEQ ID NO: HCVD of one of NO: 238, 243-246, 248, 251, 253, 255 and 267.

43. A composition as described in any of claims 27-42, wherein the composition causes at least a 20%, 50%, 2-fold or 5-fold increase in toxin release in the target mammalian cells, and / or cell killing, and / or at least a 20%, 50%, 2-fold or 5-fold increase in endolysosomal delivery compared to a composition comprising the same amount of control ABPCs.

44. The composition of any one of claims 1-43, wherein the dissociation rate of the ABD at a pH of about 4.0-6.5 is at least 10%, 3 times, or 10 times faster than the dissociation rate of the ABD at a pH of about 7.0-8.0; and / or the K of the ABD at a pH of about 4.0-6.5 is at least 10%, 3 times, or 10 times faster than the K of the ABD at a pH of about 4.0-6.

5. D than the K of the ABD at a pH of about 7.0-8.0 D At least 10%, 3 times or 10 times larger.

45. A composition as described in any of claims 1-44, wherein the ABPC comprises a single polypeptide, optionally wherein the ABD is selected from a VH domain, a VHH domain, a VNAR domain and a scFv; and / or wherein the ABPC is a BiTe, (scFv)2, a nanobody, a nanobody-HSA, a DART, a TandAb, a scDiabody, a scDiabody-CH3, a scFv-CH-CL-scFv, a HSAbody, a scDiabody-HSA or a tandem-scFv.

46. ​​The composition of any one of claims 1-45, wherein the ABPC comprises two or more polypeptides.

47. The composition of any one of claims 17-46, wherein at least one polypeptide of the ABPC is conjugated to a toxin, a radioisotope, a drug, or a small molecule via a cleavable linker or a non-cleavable linker.

48. The composition of any of claims 1-47, wherein the half-life of the ABPC in vivo is increased compared to the half-life of a control ABPC in vivo, optionally wherein the half-life is increased by about 5%-95%, about 10%-95%, about 30%-95%, about 50%-95%, or about 70%-95% compared to the half-life of a control ABPC in vivo.

49. The composition of any one of claims 17-48, wherein the control ABPC is capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell, wherein: (a) the control ABPC comprises a first ABD; (b) the first ABD of the control ABPC has an off-rate at a pH of about 4.0-6.5 that is no more than 2-fold or 3-fold faster than the off-rate at a pH of about 7.0-8.0; and (c) the dissociation constant (K) of the first ABD of the control ABPC at a pH of about 4.0-6.5 D ) than K at a pH of about 7.0-8.0 D Larger, no more than 2 or 3 times.

50. The composition of any one of claims 20-49, wherein the control ABPC is MYT9345, MYT9359, MYT9361, MYT9412, MYT9460, MYT9792, MYT9797, cofilotuzumab, 7C8, or 12C6.

51. The composition of any one of claims 1-50, wherein the ABPC further comprises a second ABD.

52. A kit comprising at least one dose of the composition of any one of claims 1-51.

53. An antigen binding protein construct (ABPC), comprising: a first antigen binding domain (ABD) capable of specifically binding to PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell, wherein: The first ABD has a faster dissociation rate at a pH of about 4.0-6.5 than at a pH of about 7.0-8.0; or the first ABD has a K at a pH of about 4.0-6.5 than at a pH of about 7.0-8.

0. D At a pH of about 7.0-8.0, the K D big.

54. The ABPC of claim 53, wherein the first ABD comprises a HCVD of one of the following: MYT9345, MYT9359, MYT9361, MYT9412, MYT9460, MYT9792, MYT9797, cofilotuzumab, 7C8, and 12C6; and / or a LCVD of one of the following: MYT9345, MYT9359, MYT9361, MYT9412, MYT9460, MYT9792, MYT9797, cofilotuzumab, 7C8, and 12C6, each HCVD or LCVD having one or more amino acids substituted with histidine.

55. The ABPC of claim 54, wherein the HCVD comprises one of the following: (a1) HCVD comprising MYT9345 of SEQ ID NO: 301; (b1) HCVD comprising MYT9359 of SEQ ID NO: 375; (c1) HCVD comprising MYT9361 of SEQ ID NO: 459; (d1) HCVD comprising MYT9412 of SEQ ID NO: 542; (e1) HCVD comprising MYT9460 of SEQ ID NO: 628; (f1) HCVD comprising MYT9792 of SEQ ID NO: 710; (g1) HCVD comprising MYT9797 of SEQ ID NO: 803; (h1) HCVD comprising colefeucin of SEQ ID NO: 1; (i1) HCVD comprising 7C8 of SEQ ID NO: 126; and (j1) HCVD comprising SEQ ID NO: NO:229 of 12C6; and one of the corresponding following: (a2) LCVD comprising MYT9345 of SEQ ID NO:302; (b2) LCVD comprising MYT9359 of SEQ ID NO:376; (c2) LCVD comprising MYT9361 of SEQ ID NO:460; (d2) LCVD comprising MYT9412 of SEQ ID NO:543; (e2) LCVD comprising MYT9460 of SEQ ID NO:629; (f2) LCVD comprising MYT9792 of SEQ ID NO:711; (g2) LCVD comprising MYT9797 of SEQ ID NO:804; (h2) LCVD comprising colefeucin of SEQ ID NO:2; (i2) LCVD comprising 7C8 of SEQ ID NO:127; and (j2) LCVD comprising SEQ ID The LCVD of 12C6 of NO:230; wherein each HCVD and / or LCVD has one or more histidine substitutions.

56. The ABPC of claim 55, wherein the first ABD comprises an HCVD comprising CDRs 1, 2, and 3 of one of the following: (a) SEQ ID NOs: 303, 304, and 305; (b) SEQ ID NOs: 377, 378, and 379; (c) SEQ ID NOs: 461, 462, and 463; (d) SEQ ID NOs: 544, 545, and 546; (e) SEQ ID NOs: 630, 631, and 632; (f) SEQ ID NOs: 712, 713, and 714; (g) SEQ ID NOs: 805, 806, and 807; (h) SEQ ID NOs: 3, 4, and 5; (i) SEQ ID NOs: 128, 129, and 130; and (j) SEQ ID NOs: NO: 231, 232 and 233, wherein for (a) to (g), each group of three CDRs optionally has one or more positions in total substituted with histidine, and for (h) to (j), each group of three CDRs has at least one or more positions in total substituted with histidine; and / or wherein the first ABD comprises an LCVD comprising CDR1, 2 and 3 of one of the following: (a) SEQ ID NOs: 306, 307 and 308; (b) SEQ ID NOs: 380, 381 and 382; (c) SEQ ID NOs: 464, 465 and 466; (d) SEQ ID NOs: 547, 548 and 549; (e) SEQ ID NOs: 633, 634 and 635; (f) SEQ ID NOs: 715, 716 and 717; (g) SEQ ID NOs: 808, 809 and 810; (h) SEQ ID NOs: 6, 7 and 8; (i) SEQ ID NOs: 131, 132 and 133; and (j) SEQ ID NOs: 133, 134 and 135. NO:234, 235 and 236; wherein for (a) to (g), each group of three CDRs optionally has a total of one or more positions substituted by histidine, and for (h) to (j), each group of three CDRs has a total of at least one or more positions substituted by histidine.

57. The ABPC of any one of claims 54-56, comprising an HCVD of one of: (a) a HCVD having at least 90% identity to SEQ ID NO: 301, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 29, 30, 32, 50-54, 58, 60, 96, and 101 in SEQ ID NO: 301; (b) a HCVD having at least 90% identity to SEQ ID NO:375, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 26, 27, 30, 32, 34, 51, 52, 55, 58, 59, 63, 97, 99, and 108 in SEQ ID NO:375; (c) a HCVD having at least 90% identity to SEQ ID NO:459, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 32, 99, 101, 102, 106, and 111 in SEQ ID NO:459; (d) a HCVD having at least 90% identity to SEQ ID NO:542, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 27, 29, 30, 31, 32, 53, 55, 58, 102, 104, and 105 in SEQ ID NO:542; (e) a HCVD having at least 90% identity to SEQ ID NO:628, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 26, 28, 30, 50, 52, 53, 54, 55, 56, 57, 100, 101, 102, and 103 in SEQ ID NO:628; (f) a HCVD having at least 90% identity to SEQ ID NO:710, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of 29, 30, 31, 33, 35, 50, 53, 57, 58, 65, 96, 97, 98, 100, 101, 103, 105, 107, 108, 109, 110, and 113 in SEQ ID NO:710; and (g) a HCVD having at least 90% identity to SEQ ID NO:803, wherein the HCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 33, 50, 53, 55-58, 64, 100, and 107 in SEQ ID NO:803; (h) a HCVD having at least 90% identity to SEQ ID NO: 1, wherein the HCVD comprises histidine at one or more positions in SEQ ID NO: 1 selected from the group consisting of: 24, 27, 28, 29, 30, 31, 32, 34, 53, 54, 55, 57, 58, 64, 98, 100, 102, 103, and 107; (i) a HCVD having at least 90% identity to SEQ ID NO: 126, wherein the HCVD comprises histidine at one or more positions in SEQ ID NO: 126 selected from the group consisting of: 53, 54, 56, 57, 60, 102, 103, 104, 105, 106, 108, 109, 110, and 111; and (j) a HCVD having at least 90% identity to SEQ ID NO:229, wherein the HCVD comprises histidine at one or more positions in SEQ ID NO:229 selected from the group consisting of: 27, 32, 33, 34, 35, 51, 54, 56, 58 and 100.

58. The ABPC of any one of claims 54-56, comprising an LCVD of one of: (a) an LCVD having at least 90% identity to SEQ ID NO: 302, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 30-33, 35, 55-57, 91, 94-96, and 98 in SEQ ID NO: 302; (b) an LCVD having at least 90% identity to SEQ ID NO: 376, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 33, 50, 51, 52, 53, 89, 91, 92, 93, 96, 97, 100, and 102 in SEQ ID NO: 376; (c) an LCVD having at least 90% identity to SEQ ID NO: 460, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 30, 31, 33, 51, 92, and 95 in SEQ ID NO: 460; (d) a LCVD having at least 90% identity to SEQ ID NO:543, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 29, 30, 31, 32, 89, 92, and 98 in SEQ ID NO:543; (e) a LCVD having at least 90% identity to SEQ ID NO: 629, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 25, 26, 28, 29, 33, 51, 55, 89, 91, 95, 96, 97, 98, 99, and 100 in SEQ ID NO: 629; (f) an LCVD having at least 90% identity to SEQ ID NO: 711, wherein the LCVD optionally comprises histidine at one or more positions selected from the group consisting of 25, 27, 29, 30, 35, 36, 56, 57, 91, 93, 94, 95, 98, and 99 in SEQ ID NO: 711; and (g) a LCVD having at least 90% identity to SEQ ID NO: 804, wherein the LCVD optionally comprises a histidine at one or more positions selected from the group consisting of: 31, 33-35, 52, 54, 98, and 99 in SEQ ID NO: 804; (h) an LCVD having at least 90% identity to SEQ ID NO:2, wherein the LCVD comprises histidine at one or more positions in SEQ ID NO:2 selected from the group consisting of: 25, 29, 31, 35, 60, 93, and 94; (i) an LCVD having at least 90% identity to SEQ ID NO: 127, wherein the LCVD comprises histidine at one or more positions in SEQ ID NO: 127 selected from the group consisting of: 25, 26, 28, 29, 31, 32, 33, 50, 90, 92, and 94; and (j) an LCVD having at least 90% identity to SEQ ID NO:230, wherein the LCVD comprises histidine at one or more positions in SEQ ID NO:230 selected from the group consisting of: 30, 31, 33, 51, 53, 57, 91, 92, 94 and 99.

59. The ABPC of 57 or 58, wherein the HCVD and / or LCVD optionally comprises histidine at two or more positions in its defining SEQ ID NO.

60. The ABPC of claim 53, wherein the first ABD comprises an HCVD comprising a sequence of one of: SEQ ID NO: 301, or one of 309-342; SEQ ID NO: 375, or one of 383-423; SEQ ID NO: 459, or one of 467-511; SEQ ID NO: 542, or one of 550-592; SEQ ID NO: 628, or one of 636-675; SEQ ID NO: 710, or one of 718-767; and SEQ ID NO: 803, or one of 811-854; or wherein the HCVD comprises one of: (a) SEQ ID NO: 1, 14, 17, 18, 19, 20, 21, 22, 24, 25, 29, 30, 31, 33, 34, 40, 44, 46, 48, 49, 53, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98, 99, 100, 101, 102, 103, 104 or 105 HCVD; (b) SEQ ID NO:126, 147, 148, 150, 151, 154, 166, 167, 168, 169, 170, 172, 173, 174, 175, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 224, 225, 226 or 227; and (c) an HCVD of SEQ ID NO:229, 238, 243, 244, 245, 246, 248, 251, 253, 255 or 267.

61. The ABPC of claim 53, wherein the first ABD comprises one of: (a) an HCVD of one of SEQ ID NOs: 301, or one of 309-342; and / or an LCVD of one of SEQ ID NOs: 302, or one of 343-374, wherein the first ABD does not comprise (i) SEQ ID NOs: 301 and 5; (ii) an HCVD of SEQ ID NO: 301 and an LCVD that is not one of SEQ ID NOs: 344, 349-352, 354, 359-361, 363, 366-368, 370, and 373; or (iii) an LCVD of SEQ ID NO: 302 and an HCVD that is not one of SEQ ID NOs: 312, 313, 315, 319-323, 327, 329, 335, 340, and 341; (b) an HCVD of one of SEQ ID NO: 375, or one of 383-423; and / or an LCVD of one of SEQ ID NO: 376, or one of 424-458, wherein the first ABD does not comprise (i) SEQ ID NO: 375 and 79; (ii) an HCVD of SEQ ID NO: 375 and an LCVD that is not one of SEQ ID NO: 425, 429, 430, 431, 432, 433, 435, 436, 437, 438, 442, 444, 445, 446, 449, 450, 453, and 455; or (iii) an LCVD of SEQ ID NO: 376 and an LCVD that is not one of SEQ ID NO: HCVD of one of NO: 383, 384, 387, 389, 391, 394, 395, 398, 401, 402, 406, 410, 412 and 421; (c) an HCVD of one of SEQ ID NOs: 459, or one of 467-511; and / or an LCVD of one of SEQ ID NOs: 460, or one of 512-541, wherein the first ABD does not comprise (i) SEQ ID NOs: 459 and 163; (ii) an HCVD of SEQ ID NO: 459 and an LCVD that is not one of SEQ ID NOs: 518, 519, 521, 524, 533, and 536; or (iii) an LCVD of SEQ ID NO: 460 and an HCVD that is not one of SEQ ID NOs: 473, 496, 498, 499, 503, and 508; (d) an HCVD of one of SEQ ID NOs: 542, or one of 550-592; and / or an LCVD of one of SEQ ID NOs: 543, or one of 593-627, wherein the first ABD does not comprise (i) SEQ ID NOs: 542 and 246; (ii) an HCVD of SEQ ID NO: 542 and an LCVD that is not one of SEQ ID NOs: 594, 598, 599, 600, 601, 611, 614, and 620; or (iii) an LCVD of SEQ ID NO: 543 and an HCVD that is not one of SEQ ID NOs: 551, 553, 554, 555, 556, 563, 565, 568, 582, 584, and 585; (e) an HCVD of one of SEQ ID NOs: 628, or one of 636-675; and / or an LCVD of one of SEQ ID NOs: 629, or one of 676-709, wherein the first ABD does not comprise (i) SEQ ID NOs: 628 and 332; (ii) an HCVD of SEQ ID NO: 628 and an LCVD that is not one of SEQ ID NOs: 677, 678, 680, 681, 685, 688, 692, 694, 696, 700, 701, 702, 703, 704, and 705; or (iii) an LCVD of SEQ ID NO: 629 and an LCVD that is not one of SEQ ID NOs: HCVD of one of NO: 636, 638, 640, 646, 648, 649, 650, 651, 652, 653, 666, 667, 668 and 669; (f) an HCVD of one of the following: SEQ ID NO: 710, or one of 718-767; and / or an LCVD of one of the following: SEQ ID NO: 711, or one of 768-802, wherein the first ABD does not comprise (i) SEQ ID NO: 710 and 414; (ii) an HCVD of SEQ ID NO: 710 and an LCVD that is not one of SEQ ID NO: 769, 771, 773, 774, 779, 780, 785, 786, 788, 790, 791, 792, 795, and 796; or (iii) an LCVD of SEQ ID NO: 711 and an LCVD that is not one of SEQ ID NO: HCVD of one of IDNO: 721, 722, 723, 725, 727, 728, 731, 735, 736, 743, 744, 745, 746, 748, 749, 751, 753, 755, 756, 757, 758 and 761; (g) an HCVD of one of SEQ ID NOs: 803, or one of 811-854; and / or an LCVD of one of SEQ ID NOs: 804, or one of 855-892, wherein the first ABD does not comprise (i) SEQ ID NOs: 803 and 507; (ii) an HCVD of SEQ ID NO: 803 and an LCVD that is not one of SEQ ID NOs: 862, 864-866, 868, 870, 881, and 882; or (iii) an LCVD of SEQ ID NO: 804 and an HCVD that is not one of SEQ ID NOs: 818, 821, 824, 826-829, 835, 841, 848, and 850; (h) an HCVD of SEQ ID NO: 14, 17, 18, 19, 20, 21, 22, 24, 25, 29, 30, 31, 33, 34, 40, 44, 46, 48, 49, 53, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98, 99, 100, 101, 102, 103, 104, or 105; and / or an LCVD of SEQ ID NO: 2, 56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, 122, 123, 124, or 125, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 1 and an LCVD of SEQ ID NO: 2; (ii) an HCVD of SEQ ID NO: 2 NO:1 and an LCVD that is not one of SEQ ID NO:56, 60, 62, 66, 69, 76, 77, 78, 110, 113, 114, 119, and 122-125; or (iii) an LCVD that is SEQ ID NO:2 and an HCVD that is not one of SEQ ID NO:14, 17-22, 24, 25, 29-31, 33, 34, 40, 44, 46, 48, 49, 53, 86-96, and 98-105; (i) an HCVD of SEQ ID NO: 147, 148, 150, 151, 154, 166, 167, 168, 169, 170, 172, 173, 174, 175, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 224, 225, 226, or 227; and / or an LCVD of SEQ ID NO: 127, 181, 182, 184, 185, 187, 188, 189, 191, 199, 201, 203, or 228, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 126 and an LCVD of SEQ ID NO: 127; (ii) an HCVD of SEQ ID NO: 1 (iii) an LCVD of SEQ ID NO: 127 and an HCVD that is not one of SEQ ID NOs: 147, 148, 150, 151, 154, 166-170, 172-175, 208-222, and 224-227; and (j) an HCVD of SEQ ID NO: 238, 243, 244, 245, 246, 248, 251, 253, 255 or 267; and / or an LCVD of SEQ ID NO: 230, 275, 276, 278, 281, 283, 287, 289, 290, 292 or 297, wherein the first antigen binding domain does not comprise (i) an HCVD of SEQ ID NO: 229 and an LCVD of SEQ ID NO: 230; (ii) an HCVD of SEQ ID NO: 229 and an LCVD that is not one of SEQ ID NO: 275, 276, 278, 281, 283, 287, 289, 290, 292 and 297; and (iii) an LCVD of SEQ ID NO: 230 and an LCVD that is not one of SEQ ID NO: HCVD of one of NO: 238, 243-246, 248, 251, 253, 255 and 267.

62. The ABPC of any one of claims 53-61, wherein the ABPC is degraded in the target mammalian cell after the ABPC is internalized by the cell; and / or wherein the ABPC further comprises a conjugated toxin, a radioisotope, a drug or a small molecule; and / or wherein the ABPC provides an increase in toxin release from the cell compared to the same amount of a control ABPC.

63. The ABPC of claim 62, wherein the ABPC increases toxin release by at least 20%, 50%, 2-fold, or 5-fold; and / or wherein the ABPC increases killing of target mammalian cells compared to the same amount of a control ABPC.

64. The ABPC of claim 63, wherein the composition increases killing of target mammalian cells by at least 20%, 50%, 2-fold, or 5-fold compared to the same amount of control ABPC.

65. The ABPC of any one of claims 53-64, wherein the ABPC causes an increase in endolysosomal delivery in the target mammalian cell compared to the same amount of control ABPC; optionally wherein the increase is at least 20%, 50%, 2-fold or 5-fold.

66. The ABPC of any one of claims 53-65, wherein the ABPC causes less or no detectable decrease in the level of PTK7 presented on the surface of the target mammalian cell compared to the same amount of a control ABPC.

67. The ABPC of any one of claims 53-66, wherein the ABPC further comprises a second ABD, and / or wherein the ABPC is conjugated to a drug.

68. A kit comprising at least one dose of the ABPC of any one of claims 53-67.

69. A method for treating cancer characterized by a population of cancer cells having a predetermined level of PTK7 or an epitope of PTK7 presented on the surface, the method comprising administering a therapeutically effective amount of a composition as described in any one of claims 1-51 or an ABPC as described in any one of claims 53-68 to a subject identified as having cancer characterized by having the population of cancer cells.

70. A method of reducing the volume of a tumor in a subject, wherein the tumor is characterized by having PTK7-positive cancer cells, the method comprising administering a therapeutically effective amount of a composition as described in any one of claims 1-51 or an ABPC as described in any one of claims 53-67 to a subject identified as having cancer characterized by the cancer cells.

71. A method of inducing cell death of PTK7-positive cancer cells in a subject, the method comprising administering a therapeutically effective amount of the composition of any one of claims 1-51 or the ABPC of any one of claims 53-67 to a subject identified as having cancer.

72. A method of reducing the risk of developing metastasis or additional metastasis in a subject having a PTK7-positive cancer, the method comprising administering a therapeutically effective amount of the composition of any of claims 1-51 or the ABPC of any of claims 53-67 to a subject identified as having cancer.

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