City of Hope

Other

Yuelong Ma

David A Horne

John C Williams

Heng Wei Chang

Jun Xie

Cindy Zer

Joshua Michael Donaldson

Kendra Nicole Avery

Krzysztof Bzymek

Yang Su

Yuan Chen

Yi-Jia Li

Hua Yu

Angela L Perkins-Harki

Rajiv Nallu

Provided herein are solution formulations of CX-011 and related methods for making solution formulations of CX-011. Also provided are methods of treating an inflammatory disorder, such as osteoarthritis, or cancer in a subject in need thereof by administering an effective amount of the solution formulations of CX-011.

Solution formulations of CX-011

Antibodies and meditopes that bind to the antibodies are provided, as well as complexes, compositions and combinations containing the meditopes and antibodies, and methods of producing, using, testing, and screening the same, including therapeutic and diagnostic methods and uses.

Meditopes and meditope-binding antibodies and uses thereof

According to some embodiments, methods for covalently or non-covalently conjugating an antibody (e.g., hu3S193 or other humanized antibody) or functional fragment thereof with an siRNA molecule (e.g., anti-STAT3 siRNA) is provided. Such methods may include (1) modifying an antibody or functional fragment thereof with a linker to provide a linker-modified antibody, combining a target siRNA with a disulfide containing aldehyde linker to provide a linker-modified target siRNA and combining the linker-modified target siRNA with linker-modified antibody to form an antibody-siRNA complex; or (2) modifying an antibody or functional fragment thereof with a (Arginine)peptide to form an antibody-9R complex and associating an siRNA molecule with the antibody-9R complex to form an electrostatic antibody-9R:siRNA complex. In another embodiment, an antibody-siRNA conjugate may be used in methods for suppressing or silencing STAT3 protein expression in a cancer cell.

Humanized lewis-Y specific antibody-based delivery of dicer substrate siRNA (D-siRNA) against STAT3

A composition used to develop a reagent for investigating Ubl-modifications in cellular functions and in the treatment of cancer is provided. The composition comprises gold nanoparticle (AuNP)-ligand conjugates that include at least two components: gold nanoparticles (AuNPs) and modified ubiquitin- or ubiquitin-like interacting motif (UIM or ULIM) mimetics. In one embodiment, the modified ULM mimetic is a modified SUMO interaction motif (SIM) mimetic. According to the embodiments described herein, the compound inhibits ubiquitin- or ubiquitin-like protein (Ubl)-mediated protein-protein interactions and sensitizes cells to ionizing radiation. The modified UIM and ULIM mimetics may be conjugated to the AuNP such that each AuNP is conjugated to a plurality of modified UIM or ULIM mimetics. The modified ULIM mimetics may be conjugated to the AuNP via a thiol group.

Multi-valent poly-Ubl chain inhibitors and methods of use

Meditope variants and methods for their use are provided herein. A meditope variant as described herein comprises a peptide having a sequence CQFDLSTRRLKC (SEQ ID NO:1) or CQYNLSSRALKC (SEQ ID NO:2) that has one or more modifications at of least one amino acid residue of the sequence. Multivalent meditope variant tethering entities are also provided. Such entities may include two or more meditopes coupled via a long linker, multivalent scaffold, biotin-streptavidin, or IgG Fc domain. Further, methods of treating, imaging or diagnosing a disease or condition are provided. Such methods may include administering a therapeutically effective amount of a pharmaceutical composition to a subject, the pharmaceutical compound comprising an antibody-meditope complex; a multivalent tethering agent in combination with a monoclonal antibody or functional fragment thereof; or a combination thereof.

Meditopes and related meditope-monoclonal antibody delivery systems, synthesis and therapeutic uses thereof

Growing community of inventors

Duarte, CA, United States of America

Yuelong Ma