Platelets Grown From Stem Cells and Loaded With Drugs A Donor-Free Delivery Vehicle

This application covers a method for growing blood platelets from induced pluripotent stem cells in the laboratory and loading them with a therapeutic agent, so that the platelet carries a drug to where it is needed. It was filed by Platelet Biogenesis, Inc., names Jonathan N. Thon, Brad Dykstra and Brenden William Smith as inventors, and is a divisional of Australian application 2019291955. Claim 1 is a production and loading method, and later claims reach the resulting cells, lysates and compositions.

The Problem

Platelets are the blood cells that plug wounds and repair vessels. The specification notes that they are made in the bone marrow by parent cells called megakaryocytes, which make up under 0.1 per cent of the cells there, and that every clinical platelet today comes from human volunteer donors. It says demand exceeds supply by about 20 per cent and that stocks run down fast in emergencies.

The second problem is drug delivery. Getting a medicine to the right tissue and not the rest of the body is a long standing aim of targeted drug delivery. The specification says nanoparticle approaches have not managed to package large protein therapeutics such as coagulation factors or antibody drugs, that fewer than about 1 per cent of injected nanoparticles reach most target sites, and that immune responses to components such as PEG can undermine repeated doses. A cell that already circulates, homes to wounds and carries its own cargo is the alternative being proposed.

What This Invention Does

Claim 1 is a method for producing iPSC derived cells that comprise a therapeutic agent. Pluripotent cells are differentiated in a first culture medium into hemogenic endothelial cells. Those are differentiated in a second medium into megakaryocytic progenitors, which are differentiated into mature megakaryocytes, and the mature megakaryocytes are then differentiated under conditions sufficient to produce platelets. The last step is loading platelets, megakaryocytes, megakaryocytic progenitors, or any combination of them, with a therapeutic agent.

The dependent claims fill in how. Claims 2 and 3 expand the starting stem cells in low adherence or non adherence suspension under agitation so that they self aggregate into spheroids. Claims 4 to 7 run the first differentiation step on a matrix, with claim 5 naming laminin, attached to a flat surface or a three dimensional structure. Claims 19 and 20 turn the mature megakaryocytes into platelets by seeding them onto a porous membrane and exposing them to shear forces, which imitates the flow in the bone marrow where proplatelets shed platelets.

On loading, claim 24 offers three routes: receptor mediated loading, passive loading, or covalent conjugation. Passive loading means incubating the drug with a suspension of the cells. Covalent conjugation is claimed through reacting amines on the drug with the crosslinker SMCC (claim 32). The agents themselves run across claims 33 to 38: chemokines, cytokines, growth factors, polypeptides, anti-angiogenic agents, polynucleotides and small molecules. Named examples include the chemotherapy drug doxorubicin, the antibodies atezolizumab, ipilimumab, bevacizumab, cetuximab and trastuzumab, the small molecules aripiprazole, esomeprazole and rosuvastatin, and clotting factors FVII, FVIII and FIX.

Claims 21 to 23 and 39 to 48 characterise the product. The megakaryocytes carry CD42b, CD61 and DNA markers, the platelets are positive for markers such as CD61 and CD42a, and the platelet does not express GPVI. Claim 39 covers a composition of such cells, claim 41 a lysate of them, claim 45 adds a pharmaceutically acceptable excipient, and claim 46 is to a cell comprising an iPSC derived platelet or megakaryocyte with a therapeutic agent.

The worked examples show loading rather than clinical outcomes. For doxorubicin, 100 micromolar drug was incubated with a preparation of 10 million platelets, and the spec reports retention of the drug in washed platelets afterwards. For ipilimumab, the antibody was added to one million iPSC derived platelets in 100 microlitres, and flow cytometry showed a dose dependent increase in encapsulation. On the production side, the description reports that by 3 to 4 days of the third stage, cells co expressing the mature megakaryocyte markers CD42a and CD42b can reach 70 to 90 per cent of nucleated cells in culture, and in a separate run about 75 per cent of released cells co expressed CD43 and CD41 by day 6 plus 2.

Key Features

• A staged route from stem cell to platelet. Pluripotent cells pass through hemogenic endothelium, megakaryocytic progenitors and mature megakaryocytes before platelets are released, each stage in its own culture medium.
• Suspension spheroids and optional matrices. Starting cells can be expanded as agitated spheroids, and differentiation can be done on a laminin matrix on a flat or three dimensional support.
• Shear on a porous membrane. Megakaryocytes are seeded on a porous membrane and exposed to shear to release platelets.
• Three ways to load the cargo. Receptor mediated, passive incubation, or covalent conjugation, for cargoes from small molecules to antibodies.
• Loading at several stages. The claim allows loading into the platelets, the megakaryocytes or the progenitors, so a cargo can be put in before the final platelets are made.
• Product claims. The cells, a lysate of the cells and a formulated composition are all claimed, not only the manufacturing method.

Who Is Behind It

Platelet Biogenesis, Inc. is a Massachusetts company. According to an Amgen press release from 2016, it is a pre clinical biotechnology company spun out of Harvard in 2014 to develop donor independent human platelets from pluripotent stem cells, with Jonathan N. Thon named as chief executive and co founder and a lab bench at LabCentral in Kendall Square, Cambridge. Thon is also a named inventor on this application. The specification itself contains no company description beyond the applicant name, and a short statement that the government has certain rights in the invention.

On priority, the specification states that the application claims the benefit of US Provisional Application 62/692,277 filed 29 June 2018, and its page headers identify the underlying international publication as WO 2020/006539 (PCT/US2019/040021). The priority country is the United States. This Australian filing is a divisional of 2019291955, and the title page lists Wrays Pty Ltd of Perth as agent.

Why It Matters

Using a living cell as the carrier is an old idea, and platelets are an attractive one because they are small, nucleus free and naturally travel to injury and clot sites. The obstacle has been supply: loading a drug into a donor platelet means depending on the same scarce donor pool that clinical transfusion already strains. A manufacturing route from stem cells removes that dependence in principle and lets the cells be engineered before they mature, which is why the application pairs production and loading in one claim.

The document is a laboratory description. It reports marker percentages and loading assays, not animal or human efficacy, and it gives no figures on how much drug a platelet can carry or how long a loaded platelet survives in circulation. The claims also contain visible typing errors in the filed text, such as megakaryoctyes and progentiors in claim 1, which a later amendment will probably tidy. Whether a manufactured platelet behaves like a donor platelet in a patient is a question the specification leaves open.

Related Concepts

• Induced pluripotent stem cell – the reprogrammed adult cell that serves as the starting material for every platelet in this method.
• Megakaryocyte – the bone marrow cell that sheds platelets and that the method grows in culture.
• Platelet transfusion – the donor dependent treatment whose supply limits motivate the work.
• Targeted drug delivery – the field the loaded platelet is intended to serve.
• Doxorubicin – the chemotherapy drug used as a loading example in the specification.

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AU 2026202258 was published in the Australian Official Journal of Patents on 9 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.