Alx Oncology Inc.

Tallac Therapeutics, Inc.

Bang Janet Sim

Tracy Chia-Chien Kuo

Jaume Pons

Hong Wan

Steven Elliot Kauder

William Don Harriman

Shelley Izquierdo

Sukumar Sakamuri

Son Lam

Curt W Bradshaw

Laura Deming

Corey Goodman

Hong I Wan

Edward HyungSuk Ha

Marija Vrljic

Sophia Randolph

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

Provided are methods of treating cancer that comprise administering a polypeptide (e.g. a fusion polypeptide) that comprises a SIRPα D1 domain variant and an Fc domain variant in combination with at least one chemotherapy agent and/or at least one therapeutic antibody. Also provided are related kits.

Combination therapies for treating cancer

Provided herein, inter alia, are isolated, humanized antibodies that bind an extracellular domain of a human SIRP-α polypeptide. Also provided are polynucleotides, vectors, host cells, and methods of production and use related thereto.

The present disclosure provides for antibody-oligonucleotide conjugates, methods of preparation thereof, and methods of use thereof. Also provided are related compounds, compositions and kits.

Transglutaminase-mediated conjugation

The present disclosure features signal-regulatory protein &#x3b1; (SIRP-&#x3b1;) polypeptides and constructs that are useful, e.g., to target a cell (e.g., a cancer cell or a cell of the immune system), to increase phagocytosis of the target cell, to eliminate immune cells such as regulatory T-cells, to kill cancer cells, to treat a disease (e.g., cancer) in a subject, or any combinations thereof. The SIRP-&#x3b1; constructs include a high affinity SIRP-&#x3b1; D1 domain or variant thereof that binds CD47 with higher affinity than a wild-type SIRP-&#x3b1;. The SIRP-&#x3b1; polypeptides or constructs include a SIRP-&#x3b1; D1 variant fused to an Fc domain monomer, a human serum albumin (HSA), an albumin-binding peptide, or a polyethylene glycol (PEG) polymer. Compositions provided herein include (i) a polypeptide including a signal-regulatory protein &#x3b1; (SIRP-&#x3b1;) D1 variant and (ii) an antibody.

Constructs having a SIRP-&#x3b1; domain or variant thereof

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.

Provided herein, inter alia, are isolated, humanized antibodies that bind an extracellular domain of a human SIRP-&#x3b1; polypeptide. Also provided are polynucleotides, vectors, host cells, and methods of production and use related thereto.

Antibodies against signal-regulatory protein &#x3b1; and methods of use

Constructs having a SIRP-alpha domain or variant thereof

The present disclosure features signal-regulatory protein &#x3b1; (SIRP&#x3b1;) polypeptides and constructs that are useful, e.g., to target a cell (e.g., a cancer cell or a cell of the immune system), to increase phagocytosis of the target cell, to eliminate immune cells such as regulatory T-cells, to kill cancer cells, to treat a disease (e.g., cancer) in a subject, or any combinations thereof. The SIRP-&#x3b1; constructs include a high affinity SIRP-&#x3b1; D1 domain or variant thereof that binds CD47 with higher affinity than a wild-type SIRP-&#x3b1;. The SIRP-&#x3b1; polypeptides or constructs include a SIRP-&#x3b1; D1 variant fused to an Fc domain monomer, a human serum albumin (HSA), an albumin-binding peptide, or a polyethylene glycol (PEG) polymer. Compositions provided herein include (i) a polypeptide including a signal-regulatory protein &#x3b1; (SIRP-&#x3b1;) D1 variant and (ii) an antibody.

Growing community of inventors

Brisbane, CA, United States of America

Bang Janet Sim