IP Library Granted Patent US 8,778,620
Granted Patent B2
US 8,778,620 · App. 13/473,829 · Granted Jul 15, 2014

Methods for diagnosis, prognosis and methods of treatment

Inventors: Wendy J. Fantl (San Francisco, CA); David B. Rosen (San Francisco, CA); Alessandra Cesano (Redwood City, CA); Santosh K. Putta (Foster City, CA); Garry Nolan (San Francisco, CA); Aileen Cohen (Palo Alto, CA); Erik Evensen (Foster City, CA)
Assignee: Nodality, Inc.
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Quick Facts
Patent No.
US 8,778,620
App. No.
13/473,829
Granted
Jul 15, 2014
Kind
B2
Abstract

The present invention provides an approach for the determination of the activation states of a plurality of proteins in single cells. This approach permits the rapid detection of heterogeneity in a complex cell population based on activation states, expression markers and other criteria, and the identification of cellular subsets that exhibit correlated changes in activation within the cell population. Moreover, this approach allows the correlation of cellular activities or properties. In addition, the use of modulators of cellular activation allows for characterization of pathways and cell populations. Several exemplary diseases that can be analyzed using the invention include AML, MDS, and MPN.

Claims (12)

1. A kit comprising

a) at least two modulators selected from the group consisting of Etoposide, Mylotarg, Daunorubicin, AraC, SCF, SDF1a, LPS, Thapsigargin, cyclosporine A, decitibine, azacitadine, Vorinostat, valproic acid, bortezomib, and clofarabine; and

b) at least three binding elements specific to a compound selected from the group consisting of p-Slp-76, p-Plcg2, p-Creb, cleaved Parp, p-Chk2, p-p65/Rel-A, p-S6, Cleaved Caspase 3, Cleaved Caspase 8, Cytoplasmic Cytochrome C, p-H2AX, p-4EBP-1, and p21.

2. The kit of claim 1 further comprising a binding element specific for a cytokine receptor, growth factor receptor or drug transporter selected from the group consisting of MDR1, ABCG2, MRP, P-Glycoprotein, and c-kit.

3. The kit of claim 1 further comprising a binding element specific for CD 34, CD11, or CD 38.

4. The kit of claim 1 further comprising a binding element specific for CD33, CD45, HLA-DR, or CD11b.

5. The kit of claim 1 further comprising one or more modulators selected from the group consisting of: G-CSF, IFN-gamma, IFN-alpha, IL-27, IL-3, IL-6, IL-10, FLT3L, and PMA.

6. The kit of claim 1 further comprising one or more binding elements specific to a particular activation state of an activatable element selected from the group consisting of: p-Stat3, p-Stat5, p-Stat1, p-Stat6, p-Akt, p-Erk, and p38.

7. The kit of claim 1 further comprising one or more binding elements specific to CXCR4 or FLT3.

8. The kit of claim 1 further comprising one or more antibodies specific for one or more proteins, in their phosphorylated or unphosphorlyated states, selected from the group consisting of PI3-Kinase (p85, p110a, p110b, p110d), Jak1, Jak2, SOCs, Rac, Rho, Cdc42, Ras-GAP, Vav, Tiam, Sos, Dbl, Nck, Gab, PRK, SHP1, SHP2, SHIP1, SHIP2, sSHIP, PTEN, Shc, Grb2, PDK1, SGK, Akt1, Akt2, Akt3, TSC1,2, Rheb, mTor, 4EBP-1, p70S6Kinase, S6, LKB-1, AMPK, PFK, Acetyl-CoAa Carboxylase, DokS, Rafs, Mos, Tpl2, MEK1/2, MLK3, TAK, DLK, MKK3/6, MEKK1,4, MLK3, ASK1, MKK4/7, SAPK/JNK1,2,3, p38s, Erk1/2, Syk, Btk, BLNK, LAT, ZAP70, Lck, Cbl, SLP-76, PLCγ1, PLCγ2, STAT1, STAT 3, STAT 4, STAT 5, STAT 6, FAK, p130CAS, PAKs, LIMK1/2, Hsp90, Hsp70, Hsp27, SMADs, Rel-A (p65-NFKB), CREB, Histone H2B, HATs, HDACs, PKR, Rb, Cyclin D, Cyclin E, Cyclin A, Cyclin B, P16, p14Arf, p27KIP, p21CIP, Cdk4, Cdk6, Cdk7, Cdk1, Cdk2, Cdk9, Cdc25, A/B/C, Abl, E2F, FADD, TRADD, TRAF2, RIP, Myd88, BAD, Bcl-2, Mcl-1, Bcl-XL, Caspase 2, Caspase 3, Caspase 6, Caspase 7, Caspase 8, Caspase 9, IAPs, Smac, Fodrin, Actin, Src, Lyn, Fyn, Lck, NIK, IκB, p65(RelA), IKKα, PKA, PKCα, PKCβ, PKCθ, PKCδ, CAMK, Elk, AFT, Myc, Egr-1, NFAT, ATF-2, Mdm2, p53, DNA-PK, Chk1, Chk2, ATM, ATR, βcatenin, CrkL, GSK3α, GSK3β, and FOXO.

9. The kit of claim 1 further comprising a compound selected from the group consisting of aloisine A, alsterpaullone, aminogenistein, API-2, apigenin, arctigenin, AY-22989, BAY 61-3606, Azacitidine bisindolylmaleimide IX, chelerythrine, bevacizumab, 10-[4′-(N,N-Diethylamino)butyl]-2-chlorophenoxazine hydrochloride, dasatinib, 2-Dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole, 5,7-Dimethoxy-3-(4-pyridinyl)quinoline dihydrochloride, decitibine, edelfosine, ellagic acid, enzastaurin, ER 27319 maleate, erlotinib, ET180CH3, ezatiostat, fasudil, flavopiridol, gefitinib, gemtuzumab ozogamicin, GW 5074, H-7, H-8, H-89, HA-100, HA-1004, HA-1077, HA-1100, hydroxyfasudil, indirubin-3′-oxime, 5-Iodotubercidin, kenpaullone, KN-62, KY12420, LFM-A13, lavendustin A, lonafarnib, luteolin, LY-294002, LY294002, mallotoxin, ML-9, NSC-154020, NSC-226080, NSC-231634, NSC-664704, NSC-680410, NU6102, olomoucine, oxindole I, PD-153035, PD-98059, PD 169316, phloretin, phloridzin, piceatannol, picropodophyllin, PKI, PP1, PP2, purvalanol A, quercetin, R406, R788, rapamune, rapamycin, Ro 31-8220, roscovitine, rottlerin, SB202190, SB203580, sirolimus, sorafenib, SL327, SP600125, staurosporine, STI-571, SU-11274, SU4312, SU6656, 4,5,6,7-Tetrabromotriazole, TG101348, tipifarnib, Triciribine, Tyrphostin AG 490, Tyrphostin AG 825, Tyrphostin AG 957, Tyrphostin AG 1024, Tyrphostin SU1498, U0126, VX-509, VX-667, VX-680, W-7, wortmannin, XL-019, XL-147, XL-184, XL-228, XL-281, XL-518, XL-647, XL-765, XL-820, XL-844, XL-880, Y-27632, ZD-1839, ZM-252868, ZM-447439, H202, siRNA, miRNA, Cantharidin, (−)-p-Bromotetramisole, Microcystin LR, Sodium Orthovanadate, Sodium Pervanadate, Vanadyl sulfate, Sodium oxodiperoxo(1,10-phenanthroline)vanadate, bis(maltolato)oxovanadium(IV), Sodium Molybdate, Sodium Permolybdate, Sodium Tartrate, Imidazole, Sodium Fluoride, β-Glycerophosphate, Sodium Pyrophosphate Decahydrate, Calyculin A, Discodermia calyx, bpV(phen), mpV(pic), DMHV, Cypermethrin, Dephostatin, Okadaic Acid, NIPP-1, N-(9,10-Dioxo-9,10-dihydro-phenanthren-2-yl)-2,2-dimethyl-propionamide, α-Bromo-4-hydroxyacetophenone, 4-Hydroxyphenacyl Br, α-Bromo-4-methoxyacetophenone, 4-Methoxyphenacyl Br, α-Bromo-4-(carboxymethoxy)acetophenone, 4-(Carboxymethoxy)phenacyl Br, bis(4-Trifluoromethylsulfonamidophenyl)-1,4-diisopropylbenzene, phenyarsine oxide, Pyrrolidine Dithiocarbamate, and Aluminum fluoride.

10. The kit of claim 1 , further comprising instructions for diagnosis, prognosis, determining acute myeloid leukemia progression, predicting response to a treatment and/or choosing a treatment for acute myeloid leukemia, myelodysplastic syndrome or myeloproliferative neoplasms in an individual.

Assignments (2)
SECURITY INTEREST Recorded Nov 16, 2015
From: NODALITY, INC.
To: ARES CAPITAL CORPORATION
Reel/Frame 037046/0316 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 27, 2012
From: FANTL, WENDY J.; ROSEN, DAVID B.; CESANO, ALESSANDRA; PUTTA, SANTOSH K.; NOLAN, GARRY; COHEN, AILEEN; EVENSEN, ERIK
To: NODALITY, INC.
Reel/Frame 029040/0533 →
Continuity (6)
Division 12460029 · Jul 10, 2009
Provisional Application 61120320 · Dec 5, 2008
Provisional Application 61104666 · Oct 10, 2008
Provisional Application 61085789 · Aug 1, 2008
Provisional Application 61079766 · Jul 10, 2008
Related Publication 20130130279A1 · May 23, 2013