Abstract: The present disclosure provides antibodies that specifically bind to TIGIT. The antibodies find use in a variety of treatment, diagnostic, and monitoring applications, which are also described. For example, the antibody may be used to treat a patient for cancer, particularly a patient is also being treated or has been treated with an immune checkpoint inhibitor, e.g., a PD-1/PD-L1 inhibitor.

Abstract: A transgenic non-human animal is provided. In certain embodiments, the animal comprises a genome comprising an immunoglobulin heavy chain locus comprising: a) a transcribed gene encoding a fusion protein comprising, from N-terminus to C-terminus: i. a scaffold comprising a first binding domain; and ii. a heavy chain constant region operably linked to the scaffold; wherein the scaffold is capable of specifically binding to a target in the absence of additional polypeptides; and b) a plurality of pseudogenes that are operably linked to the transcribed gene and that donate, by gene conversion, nucleotide sequence to the part of the transcribed gene that encodes the binding domain.

Abstract: A transgenic non-human animal is provided. In certain embodiments, the animal comprises a genome comprising an immunoglobulin heavy chain locus comprising: a) a transcribed gene encoding a fusion protein comprising, from N-terminus to C-terminus: i. a scaffold comprising a first binding domain; and ii. a heavy chain constant region operably linked to the scaffold; wherein the scaffold is capable of specifically binding to a target in the absence of additional polypeptides; and b) a plurality of pseudogenes that are operably linked to the transcribed gene and that donate, by gene conversion, nucleotide sequence to the part of the transcribed gene that encodes the binding domain.

Abstract: Provided herein, inter alia, are isolated antibodies that bind an extracellular domain of a human SIRP-? v1 polypeptide (e.g., the D1 domain), an extracellular domain of a human SIRP-? v2 polypeptide, or both. In some embodiments, the antibodies also bind an extracellular domain of a monkey SIRP-? polypeptide, an extracellular domain of a mouse SIRP-? polypeptide, an extracellular domain of a human SIRP-? polypeptide, and/or an extracellular domain of a human SIRP-? polypeptide. In some embodiments, the antibodies block or do not binding between an extracellular domain of a human SIRP-? polypeptide and an IgSF domain of a human CD47 polypeptide, while in some embodiments, the antibodies reduce the affinity of a human SIRP-? polypeptide for binding an IgSF domain of a human CD47 polypeptide. Further provided herein are methods, polynucleotides, vectors, and host cells related thereto.

Abstract: A transgenic chicken comprising an inactivated heavy immunoglobulin gene and/or inactivated light chain immunoglobulin gene is provided, as well as cells and targeting vectors for making the same.

Abstract: The present disclosure provides antibodies that specifically bind to CD38. The antibodies find use in a variety of treatment, diagnostic, and monitoring applications, which are also described. The present disclosure provides antibodies that specifically bind to, and in some embodiments, inhibit CD38. A subject antibody specifically binds CD38 from humans and other mammals, e.g., monkey and mouse.

Abstract: The present disclosure provides antibodies that specifically bind to B7-H3. The antibodies find use in a variety of treatment, diagnostic, and monitoring applications, which are also described. The present disclosure provides antibodies that specifically bind to B7-H3. A subject antibody specifically binds B7-H3 from humans and other mammals, e.g., monkey and mouse.

Abstract: This disclosure provides, among other things, strategies for minimizing antibody diversification in a transgenic animal that uses gene conversion for antibody diversification. In some embodiments, the animal may comprise a genome comprising an endogenous immunoglobulin light chain locus comprising: (a) a functional immunoglobulin light chain gene comprising a nucleic acid encoding a light chain variable region; and (b) a plurality of pseudogenes that are operably linked to the functional immunoglobulin light chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding a light chain variable region, wherein the pseudogenes are upstream or downstream of the functional immunoglobulin light chain gene and encode the same amino acid sequence as the light chain variable region of the functional immunoglobulin light chain gene of (a). In other embodiments, the locus may have a tandem array of coding sequences for the light chain.

Abstract: Provided herein, inter alia, are isolated antibodies that bind an extracellular domain of a human SIRP-? v1 polypeptide (e.g., the D1 domain), an extracellular domain of a human SIRP-? v2 polypeptide, or both. In some embodiments, the antibodies also bind an extracellular domain of a monkey SIRP-? polypeptide, an extracellular domain of a mouse SIRP-? polypeptide, an extracellular domain of a human SIRP-? polypeptide, and/or an extracellular domain of a human SIRP-? polypeptide. In some embodiments, the antibodies block or do not binding between an extracellular domain of a human SIRP-? polypeptide and an IgSF domain of a human CD47 polypeptide, while in some embodiments, the antibodies reduce the affinity of a human SIRP-? polypeptide for binding an IgSF domain of a human CD47 polypeptide. Further provided herein are methods, polynucleotides, vectors, and host cells related thereto.

Abstract: This disclosure provides, among other things, strategies for minimizing antibody diversification in a transgenic animal that uses gene conversion for antibody diversification. In some embodiments, the animal may comprise a genome comprising an endogenous immunoglobulin light chain locus comprising: (a) a functional immunoglobulin light chain gene comprising a nucleic acid encoding a light chain variable region; and (b) a plurality of pseudogenes that are operably linked to the functional immunoglobulin light chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding a light chain variable region, wherein the pseudogenes are upstream or downstream of the functional immunoglobulin light chain gene and encode the same amino acid sequence as the light chain variable region of the functional immunoglobulin light chain gene of (a). In other embodiments, the locus may have a tandem array of coding sequences for the light chain.

Abstract: Provided herein, inter alia, are isolated antibodies that bind an extracellular domain of a human SIRP-? v1 polypeptide (e.g., the D1 domain), an extracellular domain of a human SIRP-? v2 polypeptide, or both. In some embodiments, the antibodies also bind an extracellular domain of a monkey SIRP-? polypeptide, an extracellular domain of a mouse SIRP-? polypeptide, an extracellular domain of a human SIRP-? polypeptide, and/or an extracellular domain of a human SIRP-? polypeptide. In some embodiments, the antibodies block or do not binding between an extracellular domain of a human SIRP-? polypeptide and an IgSF domain of a human CD47 polypeptide, while in some embodiments, the antibodies reduce the affinity of a human SIRP-? polypeptide for binding an IgSF domain of a human CD47 polypeptide. Further provided herein are methods, polynucleotides, vectors, and host cells related thereto.

Abstract: Provided herein, inter alia, are isolated antibodies that bind an extracellular domain of a human SIRP-? v1 polypeptide (e.g., the D1 domain), an extracellular domain of a human SIRP-? v2 polypeptide, or both. In some embodiments, the antibodies also bind an extracellular domain of a monkey SIRP-? polypeptide, an extracellular domain of a mouse SIRP-? polypeptide, an extracellular domain of a human SIRP-? polypeptide, and/or an extracellular domain of a human SIRP-? polypeptide. In some embodiments, the antibodies block or do not binding between an extracellular domain of a human SIRP-? polypeptide and an IgSF domain of a human CD47 polypeptide, while in some embodiments, the antibodies reduce the affinity of a human SIRP-? polypeptide for binding an IgSF domain of a human CD47 polypeptide. Further provided herein are methods, polynucleotides, vectors, and host cells related thereto.

Abstract: Provided herein, inter alia, are isolated antibodies that bind an extracellular domain of a human SIRP-? v1 polypeptide (e.g., the D1 domain), an extracellular domain of a human SIRP-? v2 polypeptide or both. In some embodiments, the antibodies also bind an extracellular domain of a monkey SIRP-? polypeptide, an extracellular domain of a SIRP-? polypeptide, an extracellular domain of a human SIRP-? polypeptide, and/or an extracellular domain of a human SIRP-? polypeptide. In some embodiments, the antibodies block or do not binding between an extracellular domain of a human SIRP-? polypeptide and an IgSF domain of a human CD47 polypeptide, while in some embodiments, the antibodies reduce the affinity of a human SIRP-? polypeptide for binding an IgSF domain of a human CD47 polypeptide. Further provided herein are methods, polynucleotides, vectors, and host cells related thereto.

Abstract: Provided herein is a transgenic chicken comprising a genome having an endogenous immunoglobulin heavy chain gene in which the IgY CH1 coding sequence is functionally deleted. In certain embodiments, in B cells of the chicken the endogenous immunoglobulin heavy chain gene comprises: (a) a functional immunoglobulin heavy chain gene comprising, in operable linkage, a nucleic acid encoding an antibody heavy chain variable domain and a constant region coding sequence in which the IgY CH1 coding sequence is functionally deleted; and (b) a plurality of pseudogenes that are operably linked to said functional immunoglobulin heavy chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding the variable domain of (a), wherein the pseudogenes are upstream of the nucleic acid encoding an antibody heavy chain variable domain of (a).

Abstract: This disclosure provides, among other things, a transgenic animal that uses gene conversion for antibody diversification comprising B cells in which the endogenous immunoglobulin heavy chain locus comprises: (a) a functional immunoglobulin heavy chain gene comprising a nucleic acid encoding a human heavy chain variable domain; and (b) a plurality of pseudogenes that are operably linked to the functional immunoglobulin heavy chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding the human heavy chain variable domain of (a), wherein the pseudogenes are upstream or downstream of the functional immunoglobulin heavy chain gene and encode variable domains that have camelizing amino acid substitutions.

Abstract: This disclosure provides, among other things, a transgenic chicken. In some embodiments, the transgenic chicken comprises B cells in which the endogenous immunoglobulin heavy chain locus comprises: (a) a functional immunoglobulin heavy chain gene comprising a nucleic acid encoding a heavy chain variable domain in which the CDR3 is in the range of 30-60 amino acids in length and comprises at least 2 cysteine residues; and (b) a plurality of pseudogenes that are operably linked to said functional immunoglobulin heavy chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding the heavy chain variable domain of (a), wherein the pseudogenes are upstream or downstream of the functional immunoglobulin heavy chain gene.

Abstract: This disclosure provides, among other things, a transgenic animal that uses gene conversion for antibody diversification, comprising B cells in which the endogenous immunoglobulin heavy chain locus comprises: (a) a functional immunoglobulin heavy chain gene comprising a nucleic acid encoding an autonomous heavy chain (AHC) variable domain; and (b) a plurality of pseudogenes that are operably linked to said functional immunoglobulin heavy chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding the AHC variable domain of (a), wherein the pseudogenes are upstream or downstream of the functional immunoglobulin heavy chain gene.

Abstract: This disclosure provides, among other things, a transgenic animal and a method of using the same to make antibodies that have a common light chain. In certain embodiments, the transgenic animal may comprising a genome comprising a common light chain transgene, wherein the common light chain transgene comprises a non-immunoglobulin light-chain promoter and a common light-chain coding sequence. In certain embodiments, the common light chain is constitutively expressed.

Abstract: This disclosure provides, among other things, strategies for minimizing antibody diversification in a transgenic animal that uses gene conversion for antibody diversification. In some embodiments, the animal may comprise a genome comprising an endogenous immunoglobulin light chain locus comprising: (a) a functional immunoglobulin light chain gene comprising a nucleic acid encoding a light chain variable region; and (b) a plurality of pseudogenes that are operably linked to the functional immunoglobulin light chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding a light chain variable region, wherein the pseudogenes are upstream or downstream of the functional immunoglobulin light chain gene and encode the same amino acid sequence as the light chain variable region of the functional immunoglobulin light chain gene of (a). In other embodiments, the locus may have a tandem array of coding sequences for the light chain.

Abstract: This disclosure provides, among other things, strategies for minimizing antibody diversification in a transgenic animal that uses gene conversion for antibody diversification. In some embodiments, the animal may comprise a genome comprising an endogenous immunoglobulin light chain locus comprising: (a) a functional immunoglobulin light chain gene comprising a nucleic acid encoding a light chain variable region; and (b) a plurality of pseudogenes that are operably linked to the functional immunoglobulin light chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding a light chain variable region, wherein the pseudogenes are upstream or downstream of the functional immunoglobulin light chain gene and encode the same amino acid sequence as the light chain variable region of the functional immunoglobulin light chain gene of (a). In other embodiments, the locus may have a tandem array of coding sequences for the light chain.