IP Library › Granted Patent US 10,697,975

Granted Patent B2

US 10,697,975 · App. 15/630,751 · Granted Jun 30, 2020

Methods for identifying, diagnosing, and predicting survival of lymphomas

Inventors: Louis M. Staudt (Bethesda, MD); George Wright (Rockville, MD); Sandeep Dave (Chapel Hill, NC); Bruce Tan (Chicago, IL); John I. Powell (Ijamsville, MD); Wyndham Wilson (Washington, DC); Elaine S. Jaffe (Great Falls, VA); Wing C. Chan (Pasadena, CA); Timothy C. Greiner (Council Bluffs, IA); Dennis Weisenburger (Glendora, CA); James Armitage (Omaha, NE); Kai Fu (Omaha, NE); Richard I. Fisher (Pittsford, NY); Lisa M. Rimsza (Scottsdale, AZ); Thomas Miller (Tucson, AZ); Thomas Grogan (Tucson, AZ); Elias Campo Guerri (Barcelona, ES); Silvia M. Bea (Sabadell, ES); Itziar Salaverria (Barcelona, ES); Armando Lopez-Guillermo (Barcelona, ES); Emilio Montserrat (Barcelona, ES); Victor Moreno (Barcelona, ES); Andreas Zettl (Wurzburg, DE); German Ott (Bietigheim-Bissingen, DE); Hans-Konrad Muller-Hermelink (Wurzburg, DE); Andreas Rosenwald (Wurzburg, DE); Julie Vose (Omaha, NE); Randy Gascoyne (North Vancouver, CA); Joseph Connors (Vancouver, CA); Erlend B. Smeland (Oslo, NO); Stein Kvaloy (Oslo, NO); Harald Holte (Oslo, NO); Jan Delabie (Toronto, CA); T. Andrew Lister (London, GB)

Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services; Board of Regents of the University of Nebraska; University of Rochester; Arizona Board of Regents on behalf of the University of Arizona; Universitat de Barcelona; Fundacio Clinic; Hospital Clinic de Barcelona; Julius-Maximilians-University of Würzburg; British Columbia Cancer Agency Branch; Oslo University Hospital HF; Queen Mary and Westfield College, University of London

G01N33/6842 C12Q1/6886 G16B25/00 C12Q2600/112 C12Q2600/118 C12Q2600/158 G01N2333/51 G16B40/00 Y02A90/26

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Quick Facts

Patent No.: US 10,697,975
App. No.: 15/630,751
Granted: Jun 30, 2020
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

Gene expression data provides a basis for more accurate identification and diagnosis of lymphoproliferative disorders. In addition, gene expression data can be used to develop more accurate predictors of survival. The present invention discloses methods for identifying, diagnosing, and predicting survival in a lymphoma or lymphoproliferative disorder on the basis of gene expression patterns. The invention discloses a novel microarray, the Lymph Dx microarray, for obtaining gene expression data from a lymphoma sample. The invention also discloses a variety of methods for utilizing lymphoma gene expression data to determine the identity of a particular lymphoma and to predict survival in a subject diagnosed with a particular lymphoma. This information will be useful in developing the therapeutic approach to be used with a particular subject.

Claims (199)

1. A method for treating a diffuse large B cell lymphoma (DLBCL) in a subject comprising:

(a) isolating gene expression product from a DLBCL biopsy sample from a subject with DLBCL;

(b) determining an average gene expression level of genes set forth below

Unigene ID

Signature

UNIQID

Build 167

Gene symbol

Germinal center B-cell

1099686

117721

Germinal center B-cell

1099711

243596

Germinal center B-cell

1103390

271752

BPNT1

Germinal center B-cell

1106025

49500

KIAA0746

Germinal center B-cell

1128287

300063

ASB13

Germinal center B-cell

1132520

283063

LMO2

Germinal center B-cell

1138192

126608

NR3C1

Germinal center B-cell

1529318

291954

Germinal center B-cell

1529344

317970

SERPINA11

Germinal center B-cell

1529352

446195

Germinal center B-cell

1096570

409813

ANUBL

Germinal center B-cell

1097897

266175

PAG

Germinal center B-cell

1097901

266175

PAG

Germinal center B-cell

1098611

433611

PDK1

Germinal center B-cell

1100581

155024

BCL6

Germinal center B-cell

1115034

387222

NEK6

Germinal center B-cell

1120090

155024

BCL6

Germinal center B-cell

1120946

25209

MAPK 10

Germinal center B-cell

1121248

54089

BARD1

Germinal center B-cell

1123105

434281

PTK2

Germinal center B-cell

1125456

300592

MYBL1

Germinal center B-cell

1128694

171466

ELL3

Germinal center B-cell

1128787

114611

C7orf10

Germinal center B-cell

1132122

307734

MME

Germinal center B-cell

1136269

101474

MAST2

Germinal center B-cell

1136702

155584

KIAA0121

Germinal center B-cell

1139230

29724

PLEKHF2

Germinal center B-cell

1529292

Germinal center B-cell

1529295

116441

Lymph node

1097126

274520

ANTXR1

Lymph node

1099028

334838

ENDC1

Lymph node

1099358

93135

Lymph node

1101478

146246

MGC45780

Lymph node

1103497

50115

Lymph node

1121029

412999

CSTA

Lymph node

1124429

409602

SULF1

Lymph node

1135068

71719

PDLIM3

Lymph node

1136051

520937

CSF2RA

Lymph node

1136172

38084

SULT1C1

MHC class II

1136777

387679

HLA-DQA1

MHC class II

1136877

409934

HLA-DQB1

Proliferation

1096903

437460

FLJ10385

Proliferation

1120583

153768

RNU3IP2

Proliferation

1123289

5409

POLR1C

Proliferation

1131808

75447

RALBP1

Proliferation

1133102

360041

FRDA

Proliferation

1136595

404814

VDAC1

for the proliferation gene expression signature to obtain a proliferation gene expression signature value;

(c) determining an average gene expression level of genes set forth in the table of (b) for the germinal center B cell gene expression signature to obtain a germinal center B cell gene expression signature value;

(d) determining an average gene expression level of genes set forth in the table of (b) for the MHC class II gene expression signature to obtain an MHC class II gene expression signature value;

(e) determining an average gene expression level of genes set forth in the table of (b) for the lymph node gene expression signature to obtain a lymph node gene expression signature value;

(f) measuring the expression level of BMP6 to obtain a BMP6 expression value;

(g) determining a survival predictor score calculated as [0.241*(proliferation gene expression signature value)]+[0.310*(BMP6 expression value)]−[0.290*(germinal center B cell gene expression signature value)]−[0.311*(MHC class II gene expression signature value)]−[0.249*(lymph node gene expression signature value)], wherein a higher survival predictor score indicates worse survival; and

(h) administering cyclophosphamide, doxorubicine, vincristine, and prednisone to the subject to treat DLBCL in the subject, wherein the intensity of administration is directly related to the survival predictor score.

2. The method of claim 1 , wherein the method further comprises performing comparative genomic hybridization on a DLBCL biopsy sample from the subject to analyze for a gain or amplification in the 3p11-p12 region of chromosome 3.

3. The method of claim 1 , wherein the method further comprises performing cytogenetic analysis of bands in the 3p11-p12 region of chromosome 3 on a DLBCL biopsy sample from the subject to analyze for a gain or amplification in the 3p11-p12 region of chromosome 3.

4. The method of claim 1 , wherein the method further comprises performing polymerase chain reaction (PCR) on a DLBCL biopsy sample from the subject to analyze for a gain or amplification in the 3p11-p12 region of chromosome 3.

5. The method of claim 4 , wherein the PCR is real-time quantitative PCR.

Assignments (6)

RELEASE OF SECURITY INTEREST Recorded May 16, 2024

From: U.S. BANK TRUST COMPANY, NATIONAL ASSOCIATION

To: NANOSTRING TECHNOLOGIES, INC.

Reel/Frame 067453/0565 →

RELEASE OF SECURITY INTEREST Recorded May 16, 2024

From: WILMINGTON TRUST, NATIONAL ASSOCIATION

To: NANOSTRING TECHNOLOGIES, INC.

Reel/Frame 067453/0577 →

SECURITY INTEREST Recorded Feb 8, 2024

From: NANOSTRING TECHNOLOGIES, INC.