Method of producing an immunoligand/payload conjugate
Inventors
Grawunder, Ulf • BEERLI, Roger Renzo
Assignees
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Publication Number
US-11364301-B2
Publication Date
2022-06-21
Expiration Date
Abstract
The present invention relates to a method of producing an immunoligand/payload conjugate, which method encompasses conjugating a payload to an immunoligand by means of a sequence-specific transpeptidase, or a catalytic domain thereof (FIG. 6B).
Core Innovation
The invention relates to a method of treating a pathologic condition in a subject in need thereof by administering an immunoligand/payload conjugate produced by enzymatically conjugating at least one glycine-modified payload to an immunoligand with a sequence-specific sortase or a catalytic domain thereof. The conjugation is sequence-specific and enzymatic, and it couples a payload to a target-binding immunoligand in a controlled, conjugate-producing manner.
The immunoligand is selected from an antibody, an antibody-based binding protein containing at least one antibody-derived VH, VL, or CH immunoglobulin domain, an antibody fragment binding to a receptor, antigen, growth factor, cytokine, or hormone, or an antibody mimetic selected from DARPins, C-type lectins, A-domain proteins of S. aureus, transferrins, lipocalins, fibronectin type III domains, Kunitz domain protease inhibitors, affilins, gamma crystallin derived binders, cysteine knots or knottins, thioredoxin A scaffold based binders, nucleic acid aptamers, artificial antibodies produced by molecular imprinting of polymers, and stradobodies.
The payload is selected from cytokines, radioactive agents, anti-inflammatory drugs, toxins, and chemotherapeutic agents. The background problem addressed is that chemical conjugation approaches for lysine/cysteine-based attachment are stochastic and can lead to heterogeneity and batch variability, and therefore can require extensive purification to obtain desired conjugate populations.
Claims Coverage
One independent claim is provided in the partial content, centered on enzymatic, sequence-specific sortase conjugation of a glycine-modified payload to a selected immunoligand, followed by treatment of a pathologic condition.
Treating a pathologic condition with a sortase-produced immunoligand/payload conjugate
A method of treating a pathologic condition in a subject in need thereof by administering an effective amount of an immunoligand/payload conjugate produced by enzymatically conjugating at least one glycine-modified payload to the immunoligand with a sequence-specific sortase or a catalytic domain thereof.
Immunoligand selection across antibody formats and antibody mimetics
The immunoligand is selected from an antibody; an antibody-based binding protein containing at least one antibody-derived VH, VL, or CH immunoglobulin domain; an antibody fragment binding to a receptor, antigen, growth factor, cytokine, or hormone; and an antibody mimetic selected from DARPins, C-type lectins, A-domain proteins of S. aureus, transferrins, lipocalins, fibronectin type III domains, Kunitz domain protease inhibitors, affilins, gamma crystallin derived binders, cysteine knots or knottins, thioredoxin A scaffold based binders, nucleic acid aptamers, artificial antibodies produced by molecular imprinting of polymers, and stradobodies.
Payload selection for immunoligand/payload conjugate therapy
The payload is selected from a cytokine, a radioactive agent, an anti-inflammatory drug, a toxin, and a chemotherapeutic agent.
The claim coverage is anchored by a sortase-produced immunoligand/payload conjugate made by enzymatically conjugating glycine-modified payloads to an immunoligand. The therapy is defined by the immunoligand format and by the payload classes.
Stated Advantages
Produces immunoligand/payload conjugates by sequence-specific enzymatic conjugation using a glycine-modified payload and a sequence-specific sortase or a catalytic domain thereof.
Addresses problems associated with stochastic lysine/cysteine chemical conjugation approaches, including conjugate heterogeneity and batch variability, and reduces the need for extensive purification to obtain desired conjugate populations.
Documented Applications
Treating a pathologic condition in a subject in need thereof using an immunoligand/payload conjugate produced by enzymatic, sequence-specific sortase conjugation.
Neoplastic disease, including ovarian cancer.
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