Building a Sugar Nanogel That Steers Itself to Immune Cells A Step by Step Recipe for Mannan Carriers

This application covers a manufacturing recipe for a tiny gel particle made from mannan, a sugar polymer, which is meant to carry peptides or RNA to immune cells that carry the mannose receptor CD206. It was filed by ImmunityBio, Inc., names Philip T. Liu, Wendy Higashide, Wade Nichols Richardson and Clifford Anders Olson as inventors, and is a divisional of Australian application 2022405521. The title talks about a neoepitope vaccine delivery vehicle, but the claims are not to a vaccine. They are to a seven step method of making the nanogel and loading it with a thiol-containing cargo.

The Problem

Vaccines that rely on short protein fragments, peptides, have a delivery problem. A bare peptide is fragile in the body and is not steered to the cells that can teach the immune system to recognise it. The background describes the attraction of a synthetic nanoscale carrier: it can be designed from the bottom up, can protect sensitive cargo such as peptides, and can be made at scale in a reproducible way. It also says that several nanoparticle vaccine platforms are under development in a race to deliver a first priming dose as quickly as possible.

The specification points at one particular target. Dendritic cells are the immune cells that pick up antigens and show them to T cells, and they display the mannose receptor, also known as CD206, on their surface. Binding to it triggers uptake into the cell, which the specification describes as ideal for processing antigen cargo. A carrier coated in the right sugar should be drawn in. The difficulty is making particles that stick to CD206 cells and not to everything else.

What This Invention Does

Claim 1 is a method of making a self-assembling mannan nanogel for delivery of therapeutic agents to mannose-binding C-type lectin-expressing cells. Mannan is a polysaccharide of mannose sugar, with a figure in the description showing the structure of mannan from the yeast S. cerevisiae. The claim lists seven steps:

1. Oxidise the mannan with sodium periodate, which opens sugar rings and creates reactive aldehyde groups. 2. Purify the oxidised mannan. 3. Add aniline, which attaches water-repelling phenylimine groups. These cause the mannan to clump together on its own into a nanogel. 4. Lock the gel together by reacting it with cystamine and ethylenediamine dihydrochloride, then sodium cyanoborohydride, which adds diamine crosslinkers. 5. Coat the particles with more periodate-oxidised mannan and react with sodium cyanoborohydride, forming a secondary mannan shell. 6. Reduce the disulfide bonds in the crosslinkers with TCEP, leaving free thiols, and activate those thiols with 2,2-dithiopyridine. 7. Load a thiol-containing cargo onto the activated thiols.

Claim 10 is the same method by a different route. In step 4 it uses succinate dihydrazide and 3,3′-dithiobis(propanoic dihydrazide) as crosslinkers, and the shell is applied without the cyanoborohydride reaction. The dependent claims say the lectin is CD206, that the shell gives specificity for CD206-expressing cells in the body or in culture, that those cells are dendritic cells or engineered HEK-293T cells, and that the cargo is a thiol-modified RNA or one or more peptides.

The description gives working quantities. Mannan is oxidised at 10 mg/mL with sodium periodate at a final concentration of 60 mM for the core and 1 mM for the secondary shell, for 30 minutes. A 500 microgram batch of oxidised mannan gets 5 microlitres of aniline, about 10 seconds in a bath sonicator, and an overnight rest. The dihydrazide route uses 50 mM of each crosslinker in a 2:1 acetonitrile to acetate buffer mix overnight. The diamine route uses 50 mM each of EDA and cystamine in PBS for one hour, then overnight with the reducing agent. Activation uses 100 mM TCEP for one hour and 100 mM dithiopyridine for four hours, and cargo is added as 100 microlitres of a 20 mM solution. For RNA, a weight ratio of about 25 parts nanogel to 1 part RNA gave the highest expression in the examples.

The performance results are in figures, not in text, so this article does not quote them. What the written description does say is that low-oxidation mannan gives a surface with fewer reactive groups prone to non-specific sticking but less stable gels with lower cargo capacity, and that adding a secondary low-oxidation mannan shell reduces non-specific uptake and imparts CD206 specificity. That is the reasoning behind step 5 of claim 1.

Key Features

• Self-assembly from an oxidised sugar. The core forms when aniline groups on oxidised mannan clump together in water, with no separate polymer or lipid needed.
• Two crosslinking routes. The diamine route is water soluble and adds a positive charge to the gel. The dihydrazide route needs organic solvent and adds no charge at body pH, according to the description.
• A secondary mannan shell. A second coat of lightly oxidised mannan is claimed as the step that imparts CD206 specificity, as the description explains it.
• Cleavable cargo attachment. Cargo is joined to the gel through disulfide bonds, which break in the reducing conditions inside a cell. The description uses this for peptides and for RNA with a thiolated 3′ end.
• A cell line for testing uptake. The description sets out a CD206-expressing HEK-293T line, made by transfecting with a CD206 plasmid and selecting with puromycin for two weeks, used to measure nanogel uptake. The claims themselves mention engineered HEK-293T cells only in dependent claims 7 and 16.

Who Is Behind It

The applicant is ImmunityBio, a California immunotherapy company that describes itself as vertically integrated and building immunotherapies and vaccines against cancer and infectious disease. It was formed through a 2021 merger of NantKwest and NantCell, two companies founded by Patrick Soon-Shiong, according to Fierce Pharma, which also reports that the FDA approved its IL-15 superagonist Anktiva on 22 April 2024 for BCG-unresponsive non-muscle-invasive bladder cancer. The nanogel in this application is a separate, earlier stage platform and the specification does not link it to Anktiva or to any clinical programme.

On priority, the specification states that it claims the benefit of U.S. Provisional Patent Application No. 63/287,176, filed 8 December 2021, and the title page records it as a divisional of Australian application 2022405521. The page headers of the specification carry the publication number WO 2023/107951 and PCT/US2022/081025, which identify the international application behind the family.

Why It Matters

The idea that sugar-coated particles can find immune cells is not new, and CD206 has been a target for years. The difficulty has been in the chemistry: making particles of consistent size, cross-linked firmly enough to survive, but still able to release cargo inside the cell, and clean enough on the outside that they do not bind to everything. The claims here are a sequence of operations that tries to do all of that, with each reagent named.

That makes this a process patent more than a product patent. A competitor making a different particle would not infringe, but anyone following this order of steps with these reagents to prepare a mannan carrier would be inside it. The title promises a neoepitope vaccine, and the background speaks of particles decorated with cleavable neoepitope peptides, but the working examples use a model peptide from cytomegalovirus and a reporter RNA. The specification is silent on neoepitope vaccination results, so the vaccine is a stated aim and the claim is the carrier chemistry.

Related Concepts

• Neoantigen – the tumour-specific peptide targets that the title says the carrier is meant to deliver.
• Cancer vaccine – the broader approach of training the immune system against tumours, which the nanogel is intended to serve.
• Nanogel – a nanoscale crosslinked polymer particle that holds water and can carry cargo.
• C-type lectin – the family of sugar-binding receptors, including CD206, that the claimed particles are designed to engage.
• Reductive amination – the chemistry used with cyanoborohydride to fix amines onto the oxidised sugar.
• Periodate – the oxidising agent that opens mannan’s sugar rings to expose reactive aldehydes.

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AU 2026202277 was published in the Australian Official Journal of Patents on 16 April 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.