NZ751481B2 - Metabolite biomarkers for diseases associated with the contact activation system - Google Patents

Metabolite biomarkers for diseases associated with the contact activation system Download PDF

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Publication number
NZ751481B2
NZ751481B2 NZ751481A NZ75148117A NZ751481B2 NZ 751481 B2 NZ751481 B2 NZ 751481B2 NZ 751481 A NZ751481 A NZ 751481A NZ 75148117 A NZ75148117 A NZ 75148117A NZ 751481 B2 NZ751481 B2 NZ 751481B2
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NZ
New Zealand
Prior art keywords
acid
diol
metabolite
monosulfate
sulfate
Prior art date
Application number
NZ751481A
Other versions
NZ751481A (en
Inventor
Ryan Faucette
Tripti Gaur
Daniel J Sexton
Malini Viswanathan
Original Assignee
Takeda Pharmaceutical Company Limited
Filing date
Publication date
Application filed by Takeda Pharmaceutical Company Limited filed Critical Takeda Pharmaceutical Company Limited
Priority claimed from PCT/US2017/051755 external-priority patent/WO2018053247A1/en
Publication of NZ751481A publication Critical patent/NZ751481A/en
Publication of NZ751481B2 publication Critical patent/NZ751481B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/22—Haematology
    • G01N2800/224—Haemostasis or coagulation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/50—Determining the risk of developing a disease
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/70—Mechanisms involved in disease identification
    • G01N2800/7095—Inflammation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G01N33/6806—Determination of free amino acids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
    • G01N33/743—Steroid hormones
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/82—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving vitamins or their receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/92—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving lipids, e.g. cholesterol, lipoproteins, or their receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/94—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors
    • G01N33/9406—Neurotransmitters
    • G01N33/942—Serotonin, i.e. 5-hydroxy-tryptamine

Abstract

Provided herein are methods and kits for analyzing a biological sample obtained from a subject having, suspected of having, or being at risk for hereditary angioedema based on a set of metabolite biomarkers.

Claims (33)

WHAT IS CLAIMED IS:
1. A method for analyzing a sample, comprising: (i) providing a biological sample obtained from a subject having, suspected of 5 , or being at risk for hereditary angioedema (HAE); (ii) measuring the level of a metabolite biomarker set, which comprises at least one metabolite biomarker selected from the group ting of: serotonin, tryptophan, indolelactate, indolepropionate, gamma-/beta-tocopherol, ascorbate, palmitic amide, oleamide, linoleamide, 9- hydroxyoctadecadienoic acid (9-HODE), 13-hydroxyoctadecadienoic acid (13-HODE), 9,10-di- 10 hydroxy-12z-octadecenoic acid, (9,10-DiHOME), 12,13-dihydroxy-9z-octadecenoic acid, (12,13-DiHOME), 19,20-dihydroxy-4z,7z,10z,13z,16z, docosapentaenoic acid (19,20 DiHDPA), ylmethionin, methionine sulfone, s-adenosylhomocysteine, cysteine, cysteine sulfinic acid, pregnenolone sulfate, 5 alpha-pregnan-3beta,20beta-diol monosulfate, pregnen-diol disulfate; pregn steroid monosulfate, prenanediolglucuronide, cortisol, corticosterone, cortisone, 15 dehydroisoandrosterone sulfate S), 16a-hydroxy DHEA 3-sulfate, epiandrosterone sulfate, androsterone sulfate, 4-androsten-3beta, 17beta-diol monosulfate, osten-3alpha, 17alpha-diol monosulfate, 4-androsten-3beta, 17beta-diol ate, 5alpha-androstan- 3alpha,17alpha-diol monosulfate, 5alpha-androstan-3beta,17-beta-diol disulfate, andro steroid monosulfate, olanolone glucuronide, pregnanolone/alloprenanolone sulfate, 20 eicosapentaenoate, mead acid, donate, nicotinamide, or pantothenate, or a combination thereof; and (iii) identifying the subject as having HAE, if the level of the metabolite biomarker set of the subject deviates from the level of the same metabolite biomarker set of a control subject. 25
2. A method for analyzing a sample, comprising: (i) providing a biological sample obtained from a subject having, suspected of having, or being at risk for hereditary dema (HAE); (ii) measuring the level of a metabolite biomarker set, which comprises at least one metabolite biomarker ed from the group consisting of: serotonin, tryptophan, indolelactate, 30 propionate, gamma-/beta-tocopherol, ate, palmitic amide, oleamide, amide, 9- hydroxyoctadecadienoic acid (9-HODE), 13-hydroxyoctadecadienoic acid (13-HODE), 9,10-di- y-12z-octadecenoic acid, (9,10-DiHOME), 12,13-dihydroxy-9z-octadecenoic acid, (12,13-DiHOME), 19,20-dihydroxy-4z,7z,10z,13z,16z, docosapentaenoic acid (19,20 DiHDPA), n-acetylmethionin, methionine sulfone, s-adenosylhomocysteine, cysteine, cysteine sulfinic acid, pregnenolone e, 5 alpha-pregnan-3beta,20beta-diol monosulfate, n-diol disulfate; 5 pregn steroid monosulfate, prenanediolglucuronide, cortisol, corticosterone, cortisone, dehydroisoandrosterone sulfate (DHEA-S), 16a-hydroxy DHEA 3-sulfate, epiandrosterone sulfate, androsterone sulfate, 4-androsten-3beta, 17beta-diol monosulfate, 4-androsten-3alpha, 17alpha-diol lfate, 4-androsten-3beta, 17beta-diol disulfate, 5alpha-androstan- 3alpha,17alpha-diol monosulfate, -androstan-3beta,17-beta-diol disulfate, andro steroid 10 monosulfate, etiocholanolone glucuronide, nolone/alloprenanolone sulfate, eicosapentaenoate, mead acid, stearidonate, nicotinamide, or pantothenate, or a ation thereof; and (iii) identifying a suitable ent for the subject based on the level of the biomarker set or identifying the subject as a candidate for a treatment for HAE based on the level of the 15 ker set.
3. The method of claim 1 or 2, wherein the biomarker set consists of 2-10 metabolite biomarkers. 20
4. The method of any one of claims 1-3, wherein the biological sample is a serum sample or a plasma sample.
5. The method of any one of claims 1-4, wherein the HAE is type I HAE or type II HAE. 25
6. The method of any one of claims 1-5, wherein the at least one metabolite biomarker is serotonin.
7. The method of any one of claims 1-5, wherein the at least one metabolite biomarker is a metabolite associated with fatty acid amide hydrolase activity.
8. The method of claim 7, wherein the metabolite biomarker associated with fatty acid amide hydrolase activity is palmitic amide, oleamide, or linoleamide.
9. The method of any one of claims 1-5, wherein the at least one metabolite is a lipid 5 de.
10. The method of claim 9, wherein the lipid peroxide is 9-hydroxyoctadecadienoic acid (9- HODE), 13-hydroxyoctadecadienoic acid (13-HODE), 9,10-di-hdroxy-12Z-octadecenoic acid (9,10-DiHOME), 12,13-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME), or 19,20-dihydroxy- 10 10Z,13Z,16Z-docosapentaenoic acid (19,20 DiHDPA).
11. The method of any one of claims 1-5, wherein the at least one metabolite biomarker is a metabolite involved in sulfur metabolism. 15
12. The method of claim 11, wherein the metabolite involved in sulfur metabolism is N- acetylmethionin, nine sulfone, S-adenosylhomocysteine, cystine, or cysteine sulfinic acid.
13. The method of any one of claims 1-5, wherein the at least one metabolite biomarker is a metabolite involved in steroid metabolism.
14. The method of claim 13, n the metabolite involved in steroid metabolism is ed from the group consisting of pregnenolone sulfate; 5 alpha-pregnan-3beta,20beta-diol monosulfate; pregnen-diol ate; pregn steroid monosulfate; prenanediolglucuronide; cortisol; corticosterone; cortisone; dehydroisoandrosterone sulfate (DHEA-S); 16a-hydroxy 25 DHEA ate; epiandrosterone e; androsterone sulfate; 4-androsten-3beta, 17beta-diol monosulfate; 4-androsten-3alpha, 17alpha-diol monosulfate; 4-androsten-3beta, 17beta-diol disulfate; 5alpha-androstan-3alpha,17alpha-diol monosulfate; 5alpha-androstan-3beta,17-betadiol disulfate; andro steroid monosulfate, etiocholanolone onide; and pregnanolone/alloprenanolone sulfate.
15. The method of any one of claims 1-5, wherein the at least one metabolite biomarker is a fatty acid.
16. The method of claim 15, wherein the fatty acid is eicosapentaenoate (EPA), mead acid, or 5 stearidonate.
17. The method of any one of claims 1-5, wherein the at least one lite biomarker is a cofactor precursor. 10
18. The method of claim 17, wherein the cofactor precursor is nicotinamide or pantothenate.
19. The method of any one of claims 1-18, wherein step (ii) es mass spectrometry, chromatography, or an immunoassay. 15
20. The method of claim 19, wherein step (ii) involves mass spectrometry and wherein the biological sample is subjected to a tion step prior to the mass spectrometry.
21. The method of claim 20, wherein the separation step comprises gas chromatography, liquid chromatography, or capillary electrophoresis.
22. The method of any one of claims 1-21, wherein the subject is a human patient.
23. Use of a therapeutic agent in the manufacture of a medicament for treating HAE, wherein the medicament is to be administered at an effective amount if the t is identified as having 25 HAE according to the method of any one of claims 1 and 3-22.
24. The use of claim 23, wherein therapeutic agent is a plasma kallikrein (pKal) inhibitor, a inin 2 receptor (B2R) inhibitor, and/or a C1 esterase inhibitor. 30
25. The use of claim 24, wherein the pKal inhibitor is an anti-pKal dy or an inhibitory peptide.
26. The use of claim 25, n the therapeutic agent is lanadelumab, ntide, icatibant, or human plasma-derived C1-INH. 5
27. The method of any one of claims 1, or 3-22 or the use of any one of claims 23-26, wherein the metabolite biomarker set comprises one or more metabolite biomarkers selected from the group consisting of cortisterone, eicosapentaenoate, mead acid, stearidonate, nicotinamide, and henate. 10
28. The method or use of claim 27, further comprising assessing the risk of HAE attack in the t based on the level of the metabolite biomarker set, a ion of the metabolite biomarker set level of the t from that of a control subject being indicative of the risk of HAE attack. 15
29. Use of a therapeutic agent in the manufacture of a medicament for treating HAE, wherein the medicament is to be administered if the subject is assessed as at risk of HAE attack according to the method of claim 28.
30. A kit when used for analyzing a sample of a subject having, suspected of having, or at 20 risk for hereditary angioedema, the kit comprising: (i) a first binding agent specific to a first metabolite biomarker, wherein the first metabolite biomarker is selected from the group consisting of: serotonin, tryptophan, indolelactate, indolepropionate, gamma-/beta-tocopherol, ascorbate, palmitic amide, oleamide, linoleamide, 9-hydroxyoctadecadienoic acid (9-HODE), 13-hydroxyoctadecadienoic acid (13- 25 HODE), 9,10-di-hydroxy-12z-octadecenoic acid, (9,10-DiHOME), 12,13-dihydroxy-9zoctadecenoic acid, (12,13-DiHOME), dihydroxy-4z,7z,10z,13z,16z, docosapentaenoic acid (19,20 DiHDPA), n-acetylmethionin, methionine sulfone, s-adenosylhomocysteine, cysteine, cysteine sulfinic acid, pregnenolone sulfate, 5 alpha-pregnan-3beta,20beta-diol monosulfate, pregnen-diol disulfate; pregn steroid monosulfate, prenanediolglucuronide, 30 cortisol, corticosterone, cortisone, oisoandrosterone sulfate (DHEA-S), 16a-hydroxy
31.DHEA ate, epiandrosterone sulfate, androsterone e, 4-androsten-3beta, 17beta-diol monosulfate, 4-androsten-3alpha, 17alpha-diol monosulfate, 4-androsten-3beta, -diol disulfate, -androstan-3alpha,17alpha-diol monosulfate, 5alpha-androstan-3beta,17-betadiol disulfate, andro d monosulfate, etiocholanolone glucuronide, pregnanolone/alloprenanolone sulfate, eicosapentaenoate, mead acid, stearidonate, nicotinamide, 5 or pantothenate, or a combination f; and (ii) a second binding agent specific to a second metabolite biomarker ed from the same group as the first metabolite biomarker in (i); wherein the first metabolite biomarker and the second metabolite biomarker are different. 10 31. The kit of claim 30, further comprising a first detection agent that binds to the first binding agent and a second detection agent that binds the second binding agent.
32. The kit of claim 30 or 31, wherein the first binding agent is an antibody specific to the first metabolite biomarker, and/or the second binding agent is an antibody specific to the second 15 metabolite biomarker.
33. The kit of any one of claims 30-32, wherein the first binding agent and the second binding agent are immobilized on a support member. 20 Takeda Pharmaceutical Company d By the Attorneys for the Applicant SPRUSON & FERGUSON mmEEZ wm 593094 M Wmmmm $8me mmmwa mm $22 . . .mmmmw . _ _ _ _ _ . _ . . . N33 3&1 $me $55.3 my: :er New: 33m mmmvm mam: 3%Eom Sum: + A3,“: Xmmw 2%: ‘ ,x x .EmEmEmmaEmS_m-mEEmm {$39mex -x EmE?am - ‘ x x 92%23 - - mggcmx xcm?oa? Améanms - , - i xma?woééimcammg?m x. x 5N Bmwmiag?mg? www.mmubm 2&3 omcommoa?égcmn? mmemm?SE E9???x x Egogaiwaggmf mamwomc?gm mwmam?mmamoég Q 893%:ié?ga-w wwmwocmiaooam mohmgzmaowgma; SUBSTITUTE SHEET (RULE 26) QmDZELZOU Emmm mumhsuuxx w> w xumwg mmm?umm m Egg .ccwémmwm .Amumzoumz mgmcaaémagz ??mg?a?mei? Ev S m m :emmmr 83 3m agmwm $3 mg: $3 mmNmm 0mm: g?m m SHkw wmwm awmmw 8v? - , - - - “OE? agmumm x x x $32823 mw?moasmg-mx x 4% mwmxaaaagm? - - , , x x x x mwmwohoewémn $53ng mumxommm 83w - - - - - - x x x mwmom?cmacxo,m,_§wc§ xmEOImmé ngaEEE mwmhmmhmgx x 0&4?meTEQEXEv m5 m m?mmmmooou SUBSTITUTE SHEET (RULE 26) ?coE\NA gum?m Ecoekza m> stack? ECOERIH ECOERA N £53me 0 I 4 :EoEEv mMDUE L!) O L” 0 Ln N N H H m mg pageas Q Q Q Q waw?g v33? smug 2239mm S x ST \m x \\\\\\\\\\\\§ .83 353$ q\\\w\W\.\\\\\§ 3323.9 6%.: >5.me < mm 8 B. S. o Au. S Um W. pm.mS SUBSTITUTE SHEET (RULE 26)
NZ751481A 2017-09-15 Metabolite biomarkers for diseases associated with the contact activation system NZ751481B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662395770P 2016-09-16 2016-09-16
US201762518367P 2017-06-12 2017-06-12
PCT/US2017/051755 WO2018053247A1 (en) 2016-09-16 2017-09-15 Metabolite biomarkers for diseases associated with the contact activation system

Publications (2)

Publication Number Publication Date
NZ751481A NZ751481A (en) 2024-02-23
NZ751481B2 true NZ751481B2 (en) 2024-05-24

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