# US 12,006,548 B2 · Treating or inhibiting severe sepsis based on measuring defensin alpha 4 (DEFA4) expression

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- Number: US 12,006,548 B2
- Document ID: US12006548B2
- Status: Granted
- Kind: B2
- Application number: 16/951,758
- Filed: 2020-11-18
- Published: 2021-05-13
- Granted: 2024-06-11
- Earliest claimed: 2014-06-18
- Assignees: Immunexpress Pty Ltd
- Applicants: ImmuneXpress Pty Ltd
- Inventors: Richard Bruce Brandon; Leo Charles McHugh
- Web page: https://patentgrep.com/patent/US12006548B2

## CPC

- C12Q 1/6883: for diseases caused by alterations of genetic material
- C12Q 1/689: for bacteria
- G16B 25/00: ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
- G16B 25/10: Gene or protein expression profiling; Expression-ratio estimation or normalisation
- C12Q 2600/112: Disease subtyping, staging or classification
- C12Q 2600/118: Prognosis of disease development
- C12Q 2600/158: Expression markers
- Y02A 90/10: Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Disclosed is a method for treating or inhibiting the development of severe sepsis in a subject based on measuring the level of a defensin alpha 4 (DEFA4) polynucleotide expression product.

## Claims

### Claim 1

A method for treating or inhibiting the development of severe sepsis in a subject, the method comprising:
(1) determining a biomarker profile for a peripheral blood sample taken from the subject, wherein the determining comprises measuring the level of a defensin alpha 4 (DEFA4) polynucleotide expression product in the peripheral blood sample;
(2) comparing the sample biomarker profile to a reference biomarker profile that correlates presence or absence of severe sepsis specifically with a reference level of the DEFA4 polynucleotide expression product, wherein the level of the DEFA4 polynucleotide expression product in the sample biomarker profile is compared to the level of the DEFA4 polynucleotide expression product in the reference biomarker profile;
(3) determining whether the subject has an increased likelihood of the presence of severe sepsis based on the comparison of the sample biomarker profile to the reference biomarker profile; and
(4) administering to the subject a therapy for treating severe sepsis if the subject is determined to have an increased likelihood of the presence of severe sepsis.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the therapy is selected from an antibiotic, an anti-inflammatory agent, an anti-pyretic agent, an anti-tumor necrosis factor agent, recombinant protein C, oxygen support, a vasoactive compound, a corticosteroid, an antibody to endotoxin and a therapy for restoring or protecting organ function.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the reference biomarker profile correlates presence or absence of severe sepsis specifically with a reference level of another polynucleotide expression product, and the method further comprises measuring the level of the other polynucleotide expression product in the sample, comparing the level of the other polynucleotide expression product in the sample biomarker profile to the level of the other polynucleotide expression product in the reference biomarker profile and determining whether the subject has an increased likelihood of the presence or absence of severe sepsis based on the comparison of the sample biomarker profile to the reference biomarker profile, wherein the other polynucleotide expression product is an expression product of a gene selected from the group consisting of ABCG1, ACER3, AIF1, ANKRD34B, AP3B2, ARL17P1, ATF7, ATP5L, ATP6V0D1, B3GNT5, BMX, BPI, C22orf37, C4orf3, C7orf53, CALM2, CAMK4, CD24, CD63, CEACAM6, CEACAM8, CENPK, CEP97, CLU, CYP4F3, DLEU2, DNAJC9, E2F6, ECHDC3, EFCAB2, EIF1AX, EXOSC4, FAIM3, FAM118A, FAR2, FBXL13, FOLR3, FSD1L, GIMAP7, GK3P, GNLY, GOT2, GPR56, GPR65, GSR, HINT1, HIST1H2AA, HIST1H2AJ, HIST1H3B, HIST2H2BF, HLA-DPA1, HLA-DPB1, HLA-DRA, HPGD, HSP90AB1, IFI44, IL18R1, IL1RL1, IMP3, IRF4, ITGA4, ITK, JKAMP, JUP, KIAA0746, KIAA1324, KLHL5, KLRD1, KLRF1, KLRK1, KPNA5, LCN2, LOC284757, LRRC70, LRRFIP1, LRRN3, MINPP1, MKI67, MPO, MTHFS, NF-E4, NPCDR1, ODZ1, OLAH, OLFM4, OMG, PCOLCE2, PICALM, PLEKHA3, PLEKHF2, PMAIP1, POLE2, PPIF, PPP1R2, RETN, RFESD, RPIA, S100B, SEC24A, a gene having the sequence set forth in any one of SEQ ID NO:110, 132, 199 and 232, SFRS9, SGMS2, SH3PXD2B, SLC15A2, SLC1A3, SLC39A8, SLC39A9, SMPDL3A, SON, TAF13, TCN1, TDRD9, TGFBR1, TLR5, TPX2, TRIM21, TSHZ2, TYMS, VAMP2, VNN1, ZNF28 and ZNF587.

### Claim 4 (depends on 1)

The method according to claim 1, wherein, if the subject is determined to have an increased likelihood of the presence of severe sepsis, the method further comprises administration to the subject of an adjunctive or palliative therapy to increase oxygen supply to major organs, increase blood flow to major organs or reduce the inflammatory response.

### Claim 5 (depends on 4)

The method according to claim 4, wherein the adjunctive or palliative therapy is selected from the group consisting of non-steroidal anti-inflammatory drugs, intravenous fluids and oxygen.