Crystal Bioscience Inc.

Alx Oncology Inc.

Trellis Bioscience, Inc.

Tetragenetics, Inc.

William Don Harriman

Robert Etches

Philip A Leighton

Shelley Izquierdo

Tracy Chia-Chien Kuo

Hong Wan

Bang Janet Sim

Ellen J Collarini

Steven Elliot Kauder

Phil Leighton

Lawrence M Kauvar

Jaume Pons

Remy Cromer

Hans De Haard

Paul A Colussi

Christel Iffland

Theodore G Clark

Lore Mariën

Ashot Papoyan

Yelena Bisharyan

Janna Bednenko

Joanna Cardarelli

Douglas Kahn

Bas Van Der Woning

Alka Agrawal

Ellen Collarini

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.

Anti-B7-H3 antibody and methods of use thereof

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.

Transgenic chicken that makes antibodies with long CDR-H3S stabilized by multiple disulfide bridges and diversified by gene conversion

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.

Transgenic animal for producing diversified antibodies that have the same light chain I

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

Antibodies against signal-regulatory protein alpha and methods of use

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.

Camelization of a human variable domain by gene conversion

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.

In vivo method for generating diversity in a protein scaffold

Anti-Kv1.3 antibodies (mAbs), particularly mAbs that specifically bind to Kv1.3 with high affinity and/or inhibit Kv1.3 function, are disclosed. The amino acid sequences of the CDRs of the light chains and the heavy chains, as well as consensus sequences for these CDRs, of these anti-Kv1.3 mAbs are provided. Additionally, canonical structures for CDRs in the VH and VL regions of anti-Kv1.3 antibodies are provided. The disclosure also provides nucleic acid molecules encoding the anti-Kv1.3 mAbs, expression vectors, host cells, methods for making the anti-Kv1.3 mAbs, and methods for expressing the anti-Kv1.3 mAbs. Finally, methods of using the anti-Kv1.3 mAbs as therapeutics, such as for preventing or treating an autoimmune disorder, are disclosed.

Anti-Kv1.3 antibodies, and methods of production and use thereof

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.

Transgenic chicken comprising an inactivated immunoglobulin gene

Provided herein, inter alia, are isolated antibodies that bind an extracellular domain of a human SIRP-&#x3b1; v1 polypeptide (e.g., the D1 domain), an extracellular domain of a human SIRP-&#x3b1; v2 polypeptide, or both. In some embodiments, the antibodies also bind an extracellular domain of a monkey SIRP-&#x3b1; polypeptide, an extracellular domain of a mouse SIRP-&#x3b1; polypeptide, an extracellular domain of a human SIRP-&#x3b2; polypeptide, and/or an extracellular domain of a human SIRP-&#x3b3; polypeptide. In some embodiments, the antibodies block or do not binding between an extracellular domain of a human SIRP-&#x3b1; polypeptide and an IgSF domain of a human CD47 polypeptide, while in some embodiments, the antibodies reduce the affinity of a human SIRP-&#x3b1; polypeptide for binding an IgSF domain of a human CD47 polypeptide. Further provided herein are methods, polynucleotides, vectors, and host cells related thereto.

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.

Transgenic chicken for production of antibodies having a common light chain

A transgenic animal is provided. In certain embodiments, the transgenic animal comprises a genome comprising: an immunoglobulin light chain locus comprising: a) a functional immunoglobulin light chain gene comprising a transcribed variable region encoding: i. light chain CDR1, CDR2 and CDR3 regions that are composed of 2 to 5 different amino acids; and ii. a light chain framework; and, operably linked to the functional immunoglobulin light chain gene: b) a plurality of pseudogene light chain variable regions each encoding: i. light chain CDR1, CDR2 and CDR3 regions that are composed of the same 2 to 5 different amino acids as the CDRs of the functional gene; and ii. a light chain framework that is identical in amino acid sequence to the light chain framework of the transcribed variable region.

Growing community of inventors

Alameda, CA, United States of America

William Don Harriman