Medical countermeasures for unwanted CBRN exposures: part II radiological and nuclear threats with review of recent countermeasure patents

Figures & data

Figure 1. US FDA-approved countermeasures for RN threats following the Animal Rule and other promising agents. In 2002, the FDA issued the Animal Rule to expedite the development of medical countermeasures against CBRN threats. Since then, 2 countermeasures (*) have been approved by the FDA following the Animal Rule.

Table 1. Patents of countermeasures for ionizing radiation.

Patent number*	Year of publication	Inventor(s)	Molecule/Compound details	Properties
US9017658B2	2015	Burt	Stem cells	Assist in tissue repair
EP2245056 B1	2015	Cerami et al.	Tissue protective peptides	Contain pyroglutamate
US9198914B2	2015	Connell et al.	RAD51 modulator	Enhances DNA repair
US8980574B2	2015	Crapo et al.	Alpha-1 antitrypsin	Prevents and treats radiation-induced necrosis and mucosal injury
US9186406B2	2015	Daly et al.	Purine or pyrimidine nucleosides with antioxidant	Preserve protein function
US8951522B2	2015	Demopulos et al.	MASP-2 inhibitory agent	Blocks/Reduces inflammation
EP2468275B1	2015	Denisenko et al.	Heterocyclic compound	Protects DNA and antimicrobial properties
EP1812555B1	2015	Fong et al.	Myeloid cells	Reconstitutes hematopoiesis
EP2488202B1	2015	Fox et al.	Anti-TNF antibody	Treats GI inflammation
US9216162B2	2015	Goldstein	N-acetylcysteine amide	Counteracts oxidative stress and free radical formation
EP2185581B1	2015	Hesson et al.	Serum amyloid P polypeptide	Treats inflammation and mucositis
EP2578598B1	2015	Hipler et al.	Novel normuramyl glycopeptide compound	Induces certain cytokines and growth factors
JP5777821B2	2015	Inufusa	Composed of Vitamin C, l-glutamine, l-cystine or l-cysteine, riboflavin, succinic acid, fumaric acid, coenzyme Q10, and niacin	Free-radical scavenger
US8951527B2	2015	Isenberg et al.	Antisense molecules, peptides, and antibodies	Increase cell survival, inhibit TSP-1 and CD47 interaction
CN102821605B	2015	Maniar	α,β-Unsaturated aryl sulfone	Protects normal cells from radiation-induced damage
US8734804B2	2015	Mariusz et al.	Pluripotent stem cells	Rescue hematopoietic and immune systems
CA2673417C	2015	Martin et al.	Benzimidazole	Protects from DNA strand breaks
US8975224B2	2015	Mogelsvang et al.	Serpin molecule	Potent anti-inflammatory agent
EP2310035B1	2015	Okunieff et al.	Fibroblast growth factor	Stimulates hematopoietic stem cell proliferation
EP1539801B1	2015	Pena et al.	Peptides and analogs of heparin-binding growth factors	Induce growth factors/hematopoietic recovery
US9173860B2	2015	Perrine et al.	Compositions comprising S-isomer of α-methyl-hydrocinnamic acid	Stimulate multi-lineage hematopoietic cell production
US9018176B2	2015	Perrine et al.	Benserazide or desloratadine	Treats neutropenia and thrombocytopenia
JP5823486B2	2015	Rodgers	Novel peptide (Nle A(1–7)	Treats combined injury
US9000147B2	2015	Sauve et al.	Nicotinoyl ribosides and nicotinamide riboside derivatives	May inhibit apoptosis
US9045474B2	2015	Schiestl et al.	Two compounds, one is selected from amifostine, growth factors, immune modulators, and antiapoptotic agents	Mitigate radiation-induced tissue damage
US9006183B2	2015	Shakhov et al.	Lipopeptides	Induce NF-κB
US9173922B2	2015	Tingchao et al.	IL-12	Hematopoiesis stimulant
US9120843B2	2015	Turdiev	Tortoise spleen protein extract	Enhances hematopoietic reconstruction
CN103153298B	2015	Vidyasagar et al.	Free amino acids	Treat radiation-induced GI symptoms
US9200035B2	2015	Wipf et al.	Novel oxetane-substituted sulfoxide, sulfide, and sulfone compounds	Radiation mitigator
US9216976B2	2015	Wipf et al.	Nitroxide agents	Free-radical scavenger
CA2668923C	2015	Richter et al.	Tri-substituted glycerol compounds	Cytoprotective
CN103501803B	2015	Xiao-Jing et al.	Smad7	Reduces inflammation
US8734804B2	2014	Marcus	PF4-interacting heparinoids	Promote thrombopoiesis and neutrophil production
US8900635B2	2014	Elder et al.	Nanoparticle isoflavone compositions	Protect DNA
US8784840B2	2014	Gudkov	Recombinant flagellin	Induces NF-κB, modulates apoptosis
JP5389666B2	2014	Shakhov et al.	Lipopeptide	Hematopoietic stem cell mobilizer
US8648042B2	2014	Wang et al.	Pharmaceutical polymer comprising a glycopeptide and an amifostine	Quenches free radicals
US8921315B1	2014	Basile	IL-12 formulation	Preserves bone marrow function
US8916712B2	2014	Basnakian et al.	Zinc chelate	Quenches reactive oxygen species
JP5498940B2	2014	Bemis et al.	Sirtuin-modulating compounds	DNA protectant
CA2645550C	2014	Benner et al.	Novel peptide	Scavenges activated oxygen free radicals and antioxidizing activity
US8765193B2	2014	Djang	Composition of Gynostemma pentaphyllum, Crataegus pinnatifida, and Camellia sinensis	Antioxidant, protects from DNA damage
US8883852B2	2014	Epperly et al.	Glyburide or other sulfonylurea hypoglycemic compounds or potassium channel inhibitors	Protects against cell death resulting from oxidative stress
US8796336B2	2014	Schellenberg et al.	Methoxypolyethylene glycol chelate	Quenches free radicals and removes heavy metals
US8906965B2	2014	Yates et al.	Quinic or shikimic acids	Anti-inflammatory agent
EP2245056 B1	2015	Cerami et al.	Tissue protective peptides	Contain pyroglutamate

*Radiation countermeasure patents from 2014 to 2015. Previously, some of the patents have been filed with another country or region; however, their most recent versions are described above.

All patent references are not provided in this manuscript due to space restrictions. Due to the references limit for this article, citations for each patent presented in this table have not been included in the list of references. Only references that have been cited within the manuscript text have been included in the list of references.

Beginning letters in patent number signifies which patent office approved this property: US: United States Patent and Trademark Office; EP: European Patent Office; CN: China Patent & Trademark Office; JP: Japan Patent Office; CA: Canadian Intellectual Property Office.

GI: Gastrointestinal; IL: interleukin; TNF: tumor necrosis factor.