Kite Pharma, Inc.

University of California

University of Washington

Stuart A Sievers

Jed Wiltzius

Jed J W Wiltzius

Arianne Perez Garcia

David Baker

David S Eisenberg

Jonathan Belk

Ruben Alvarez Rodriguez

Arianne Perez

John Karanicolas

Stephanie Astrow

Jed JW Wiltzius

The disclosure provides a chimeric antigen receptor (CAR) comprising a modified hinge, transmembrane and/or intracellular domain disclosed herein. Some aspects of the disclosure relate to a polynucleotide encoding a chimeric antigen receptor (CAR) comprising the costimulatory domain disclosed herein. Other aspects of the disclosure relate to cells comprising the CAR and use in a T cell therapy.

Modified chimeric antigen receptors and methods of use

The invention provides novel peptides (e.g., linkers) and polypeptide compositions comprising the linkers (e.g., fusion proteins) and methods of using the polypeptide compositions. Peptides (e.g., linkers) are useful as tags and for engineering fusion proteins (e.g., antigen binding molecules, scFv). Polypeptide linkers described herein facilitate flexibility of linked peptides allowing for proper folding, conformation and reduced immunogenicity.

Chimeric polypeptides and uses thereof

Isolated antigen binding molecules that specifically bind to an anti-CD19 scFv comprising SEQ ID NO: 1 are provided. The antigen binding molecules can be used in the methods provided herein.

Antigen binding molecules specific for an anti-CD19 scFV

Isolated antigen binding molecules that specifically binds to a molecule comprising an amino acid sequence selected from the group consisting of GGGS (SEQ ID NO: 1), GGGGS (SEQ ID NO: 46) and related sequences are provided. The antigen binding molecules may be used in the methods provided herein.

Antigen binding molecules and methods of use thereof

Isolated antigen binding molecules that specifically bind to a polypeptide comprising the alpha chain of the constant region of a T cell receptor (TCR) are provided. The antigen binding molecules may be used in the methods provided herein.

T cell receptor antigen binding molecules and methods of use thereof

Provided is a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising one or more of the antigen binding motifs disclosed herein. Aspects of the disclosure relate to a polynucleotide encoding a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising one or more of the antigen binding motifs. Provided are antibodies and antigen binding systems that comprise a binding motif that binds CD20 and optionally a binding motif that binds CD19, and methods of producing and using the same. Antibodies and antigen binding systems of the present disclosure comprise CARs that comprise an anti-CD20 binding motif and an anti-CD19 binding motif. Provided are compositions, such as antibodies and CARs that are or comprise an anti-CD20/anti-CD19 antigen binding system of the present disclosure, and cell therapies comprising the same, are useful, e.g., in the treatment of cancer.

Chimeric antigen and T cell receptors and methods of use

Isolated antigen binding molecules that specifically binds to a molecule comprising an amino acid sequence selected from the group consisting of GSTSGSGKPGSGEGSTKG (SEQ ID NO: 1), GSGKPGSGEG (SEQ ID NO: 2), GKPGSGEG (SEQ ID NO: 3), SGKPGSGE (SEQ ID NO: 499) and KPGSG (SEQ ID NO: 500) are provided. The antigen binding molecules can be used in the methods provided herein.

Antigen binding molecules specific for an anti-CD19 scFv

The invention provides a humanized anti-CD19 antibody or antigen binding fragment thereof comprising a light chain variable (VL) region and a heavy chain variable (VH) region in which the humanized VL and VL regions are derived from the mouse anti-CD19 clone FMC63 antibody; the humanized VL and/or humanized VH region comprise one or more amino acid substitutions in the framework region. The humanized anti-CD19 antibody or antigen binding fragment may be part of a single chain variable fragment (scFv), a chimeric antigen receptor (CAR) or a T cell receptor (TCR). Other aspects of the invention relate to cells comprising the CAR or the TCR and their use in a T cell therapy.

Humanized antigen-binding domains and methods of use

The invention provides methods for designing peptides that inhibit aggregation in target polypeptides. The candidate inhibitory peptidic compounds have an oligomeric sequence that forms energetically-favorable interactions with the amino acid sequence of the steric zipper region of the target protein, and also possess a zipper-disrupting feature that disrupt the peptide stacking at the steric zipper region. This method can be used to obtain inhibitory peptides to disrupt fibril formation involving any protein for which a steric zipper sequence can be identified. The invention also provides inhibitory peptidic compounds, which can be used in pharmaceutical compositions and methods for treating polypeptide aggregation-associated diseases or conditions.

Growing community of inventors

Van Nuys, CA, United States of America

Stuart A Sievers