C07K14/565

PROPROTEINS AND METHODS OF USE THEREOF

The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask. The disclosure further provides methods of screening for, making, and using these proproteins.

FIBROBLAST ACTIVATION PROTEIN BINDING AGENTS AND USE THEREOF
20220332844 · 2022-10-20 ·

The present invention relates, in part, to agents, chimeric proteins and protein complexes that bind fibroblast activation protein (FAP) and their use as diagnostic and therapeutic agents. The present invention further relates to pharmaceutical compositions comprising the FAP binding agents, chimeric proteins and protein complexes and their use in the treatment of various diseases.

FIBROBLAST ACTIVATION PROTEIN BINDING AGENTS AND USE THEREOF
20220332844 · 2022-10-20 ·

The present invention relates, in part, to agents, chimeric proteins and protein complexes that bind fibroblast activation protein (FAP) and their use as diagnostic and therapeutic agents. The present invention further relates to pharmaceutical compositions comprising the FAP binding agents, chimeric proteins and protein complexes and their use in the treatment of various diseases.

Methods and compositions for promoting immune cell function

The present disclosure features, at least in part, methods for conserving cell function, e.g., immune cell function, e.g., after one or more cycles of freezing and/or thawing the nucleated cell. In embodiments, the methods comprise contacting an immune cell with a protein nanoparticle comprising an IL-15 complex.

Methods and compositions for promoting immune cell function

The present disclosure features, at least in part, methods for conserving cell function, e.g., immune cell function, e.g., after one or more cycles of freezing and/or thawing the nucleated cell. In embodiments, the methods comprise contacting an immune cell with a protein nanoparticle comprising an IL-15 complex.

Vesicular stomatitis viruses

This document provides methods and materials related to vesicular stomatitis viruses. For example, vesicular stomatitis viruses, nucleic acid molecules encoding VSV polypeptides, methods for making vesicular stomatitis viruses, and methods for using vesicular stomatitis viruses to treat cancer are provided.

Vesicular stomatitis viruses

This document provides methods and materials related to vesicular stomatitis viruses. For example, vesicular stomatitis viruses, nucleic acid molecules encoding VSV polypeptides, methods for making vesicular stomatitis viruses, and methods for using vesicular stomatitis viruses to treat cancer are provided.

Compositions and Uses for Engineered Therapeutic Microbes and Associated Receptors

Described herein are microbial probiotics that, in response to metabolite extracellular ATP (eATP) produced in the microenvironment of inflamed tissues detected, e.g., via an engineered mammalian P2Y2 receptor, secrete an anti-inflammatory protein, e.g., IL-2, IL-10, or the CD39-like eATP-degrading enzyme apyrase. Thus, provided herein is an isolated Saccharomyces cell (or cells, e.g., a population of such cells) that has been engineered to express one, two, or all three exogenous proteins selected from: (I) a mammalian P2Y purinoceptor 2 (P2Y2) protein, preferably human P2Y2; 15 (ii) a mutant Gpa1 protein comprising at least 5 C-terminal residues from a mammalian G alpha, preferably Gai3, wherein the mutant Gpa1 protein couples the P2Y2 protein to the yeast mating pathway; and (iii) an anti-inflammatory protein.

Compositions and Uses for Engineered Therapeutic Microbes and Associated Receptors

Described herein are microbial probiotics that, in response to metabolite extracellular ATP (eATP) produced in the microenvironment of inflamed tissues detected, e.g., via an engineered mammalian P2Y2 receptor, secrete an anti-inflammatory protein, e.g., IL-2, IL-10, or the CD39-like eATP-degrading enzyme apyrase. Thus, provided herein is an isolated Saccharomyces cell (or cells, e.g., a population of such cells) that has been engineered to express one, two, or all three exogenous proteins selected from: (I) a mammalian P2Y purinoceptor 2 (P2Y2) protein, preferably human P2Y2; 15 (ii) a mutant Gpa1 protein comprising at least 5 C-terminal residues from a mammalian G alpha, preferably Gai3, wherein the mutant Gpa1 protein couples the P2Y2 protein to the yeast mating pathway; and (iii) an anti-inflammatory protein.

HUMAN INTERFERON-BETA VARIANT WITH DOUBLE MUTATION AND METHOD FOR IMPROVING STABILITY OF HUMAN INTERFERON-BETA VARIANT

The present invention relates to a human interferon-beta variant with double mutation and a method for improving stability of a human interferon-beta variant and, more specifically, to a human interferon-beta variant including an amino acid sequence having serine substituted for the 17th amino acid cysteine of human interferon-beta and threonine substituted for the 27th amino acid arginine of the human interferon-beta, and a method for improving stability of human interferon-beta R27T variant, the method comprising a step of substituting serine for the 17th amino acid serine in the human interferon-beta R27T variant in which threonine is substituted for the 27th amino acid arginine of human interferon-beta.