Claims for Patent: 8,778,620

Summary for Patent: 8,778,620

Title:	Methods for diagnosis, prognosis and methods of treatment
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.
Inventor(s):	Fantl; Wendy J. (San Francisco, CA), Rosen; David B. (San Francisco, CA), Cesano; Alessandra (Redwood City, CA), Putta; Santosh K. (Foster City, CA), Nolan; Garry (San Francisco, CA), Cohen; Aileen (Palo Alto, CA), Evensen; Erik (Foster City, CA)
Assignee:	Nodality, Inc. (South San Francisco, CA)
Application Number:	13/473,829
Patent Claims:	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, PLC.gamma.1, PLC.gamma.2, 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, I.kappa.B, p65(RelA), IKK.alpha., PKA, PKC.alpha., PKC.beta., PKC.theta., PKC.delta., CAMK, Elk, AFT, Myc, Egr-1, NFAT, ATF-2, Mdm2, p53, DNA-PK, Chk1, Chk2, ATM, ATR, .beta.catenin, CrkL, GSK3.alpha., GSK3.beta., 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, .beta.-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-propion- amide, .alpha.-Bromo-4-hydroxyacetophenone, 4-Hydroxyphenacyl Br, .alpha.-Bromo-4-methoxyacetophenone, 4-Methoxyphenacyl Br, .alpha.-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.

Details for Patent 8,778,620

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2028-07-10
Wyeth Pharmaceuticals Llc	MYLOTARG	gemtuzumab ozogamicin	For Injection	761060	09/01/2017		2028-07-10