IP Library › Granted Patent US 12,230,398
Granted Patent B2
US 12,230,398 · App. 17/119,200 · Granted Feb 18, 2025

Predictive test for patient benefit from antibody drug blocking ligand activation of the T-cell programmed cell death 1 (PD-1) checkpoint protein and classifier development methods

Inventors: Joanna Roder (Steamboat Springs, CO); Krista Meyer (Steamboat Springs, CO); Julia Grigorieva (Steamboat Springs, CO); Maxim Tsypin (Steamboat Springs, CO); Carlos Oliveira (Steamboat Springs, CO); Ami Steingrimsson (Steamboat Springs, CO); Heinrich Roder (Steamboat Springs, CO); Senait Asmellash (Denver, CO); Kevin Sayers (Denver, CO); Caroline Maher (Denver, CO)
Assignee: BIODESIX, INC.
G16H50/20G01N33/5743G01N33/6851G16B40/00G16B40/10G16B40/20G16H10/40G16H20/10G16H20/30G16H40/63G01N2333/70532G01N2800/52
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Quick Facts
Patent No.
US 12,230,398
App. No.
17/119,200
Granted
Feb 18, 2025
Kind
B2
Abstract

A method is disclosed of predicting cancer patient response to immune checkpoint inhibitors, e.g., an antibody drug blocking ligand activation of programmed cell death 1 (PD-1) or CTLA4. The method includes obtaining mass spectrometry data from a blood-based sample of the patient, obtaining integrated intensity values in the mass spectrometry data of a multitude of pre-determined mass-spectral features; and operating on the mass spectral data with a programmed computer implementing a classifier. The classifier compares the integrated intensity values with feature values of a training set of class-labeled mass spectral data obtained from a multitude of melanoma patients with a classification algorithm and generates a class label for the sample. A class label “early” or the equivalent predicts the patient is likely to obtain relatively less benefit from the antibody drug and the class label “late” or the equivalent indicates the patient is likely to obtain relatively greater benefit from the antibody drug.

Claims (1619)

1. A method of detecting an overall class label in an ovarian cancer patient, comprising:

(a) conducting mass spectrometry on a blood-based sample of the ovarian cancer patient and obtaining mass spectral data;

(b) obtaining integrated intensity values in the mass spectral data of a multitude of mass-spectral features,

(c) operating on the mass spectral data with a programmed computer implementing an ensemble of classifiers;

wherein in the operating step each classifier in the ensemble of classifiers compares the integrated intensity values with feature values of a reference set of class-labeled mass spectral data obtained from blood-based samples of sets of patient samples, each set having different clinical characteristics with a classification algorithm; wherein each classifier in the ensemble of classifiers detects a class label for the sample, and wherein each of the class labels is used to define an overall label classification.

2. The method of claim 1 , wherein the ensemble of classifiers is combined in a hierarchical manner.

3. The method of claim 1 , wherein the blood-based samples of sets of patient samples are samples from cancer patients.

4. The method of claim 1 , wherein the clinical characteristic is tumor size.

5. The method of claim 1 , wherein the clinical characteristic is at least one of age or age group, smoker status, disease stage, level of a serum or tissue protein or gene expression, mutation status, performance status, surgical resection status, menopausal status, number of lines or kinds of prior therapy received, response to prior lines of therapy, tumor size, and histology class or grade.

6. The method of claim 1 , wherein the ensemble of classifiers is IS6.

7. The method of claim 1 , wherein the mass-spectral features include a multitude of features selected from Table A, B, or C:

TABLE A

Left

Center

Right

3073.625

3085.665

3097.705

3098.586

3109.891

3121.197

3123.546

3138.669

3153.793

3190.793

3210.615

3230.436

3230.73

3242.623

3254.516

3255.103

3264.647

3274.191

3296.802

3316.77

3336.739

3349.072

3363.608

3378.144

3380.2

3391.946

3403.692

3405.16

3420.283

3435.407

3435.7

3445.097

3454.494

3454.788

3465.359

3475.931

3531.431

3553.896

3576.36

3581.059

3593.099

3605.138

3665.631

3679.286

3692.941

3693.235

3702.631

3712.028

3712.616

3723.334

3734.052

3745.211

3754.755

3764.299

3764.592

3775.604

3786.616

3804.529

3817.744

3830.958

3831.545

3841.53

3851.514

3876.474

3887.486

3898.499

3914.356

3928.158

3941.959

3942.253

3953.412

3964.571

3994.23

4008.619

4023.008

4024.182

4031.67

4039.159

4039.452

4050.464

4061.476

4086.437

4098.77

4111.104

4111.308

4118.525

4125.742

4126.043

4133.109

4140.176

4198.812

4209.788

4220.764

4255.194

4264.44

4273.687

4273.837

4286.166

4298.495

4328.264

4340.217

4352.17

4352.32

4360.815

4369.31

4369.611

4380.962

4392.314

4393.817

4408.627

4423.436

4424.789

4431.179

4437.569

4437.87

4459.22

4480.57

4496.507

4506.58

4516.654

4538.304

4545.07

4551.836

4552.738

4564.991

4577.245

4577.997

4590.1

4602.203

4616.938

4625.282

4633.627

4633.927

4643.324

4652.721

4664.148

4675.274

4686.4

4690.609

4717.673

4744.736

4746.54

4756.162

4765.785

4766.386

4773.152

4779.918

4780.218

4791.194

4802.17

4802.621

4817.881

4833.142

4836.299

4855.995

4875.691

4880.953

4891.177

4901.401

4909.52

4918.316

4927.111

4927.261

4937.636

4948.01

4948.16

4963.045

4977.93

4987.552

4998.979

5010.405

5011.007

5020.103

5029.199

5029.65

5041.077

5052.504

5053.556

5067.839

5082.123

5087.535

5104.074

5120.613

5120.913

5129.182

5137.452

5137.602

5144.819

5152.036

5152.487

5157.824

5163.162

5163.312

5168.123

5172.935

5173.085

5179.776

5186.466

5187.218

5197.818

5208.417

5209.77

5223.753

5237.736

5238.036

5247.734

5257.432

5275.624

5289.757

5303.89

5347.191

5358.543

5369.894

5370.646

5377.186

5383.726

5383.877

5389.815

5395.754

5395.905

5403.422

5410.94

5411.09

5416.277

5421.464

5421.615

5429.809

5438.003

5439.807

5449.204

5458.601

5463.713

5472.057

5480.402

5481.454

5495.813

5510.171

5510.472

5521.222

5531.972

5538.738

5549.939

5561.14

5561.29

5570.011

5578.731

5666.235

5673.903

5681.571

5685.017

5691.464

5697.911

5698.296

5705.753

5713.211

5713.499

5720.428

5727.356

5727.548

5733.899

5740.25

5740.923

5748.044

5755.165

5756.127

5762.381

5768.636

5769.502

5776.671

5783.84

5787.496

5795.483

5803.469

5803.95

5815.979

5828.007

5828.68

5842.055

5855.431

5856.297

5867.218

5878.14

5879.39

5889.157

5898.924

5899.02

5910.808

5922.595

5930.871

5950.212

5969.553

5978.694

5997.458

6016.222

6016.895

6026.806

6036.717

6082.713

6090.94

6099.167

6099.552

6108.597

6117.642

6117.738

6122.213

6126.687

6145.74

6153.101

6160.462

6161.136

6170.373

6179.611

6184.807

6192.938

6201.069

6201.261

6209.585

6217.908

6218.004

6226.039

6234.074

6244.081

6252.693

6261.305

6262.46

6267.993

6273.526

6273.718

6283.244

6292.771

6292.867

6301.238

6309.61

6309.706

6315.48

6321.253

6321.927

6331.742

6341.556

6349.736

6357.77

6365.805

6379.18

6386.108

6393.037

6393.229

6399.965

6406.7

6408.625

6437.829

6467.033

6467.129

6485.171

6503.214

6519.476

6534.342

6549.209

6560.275

6567.684

6575.093

6577.691

6589.431

6601.17

6603.961

6611.61

6619.26

6620.319

6634.319

6648.32

6648.512

6657.076

6665.64

6668.623

6680.651

6692.68

6719.237

6731.65

6744.063

6754.648

6761.047

6767.446

6767.638

6773.171

6778.704

6778.8

6788.952

6799.104

6799.97

6808.919

6817.868

6824.892

6836.679

6848.467

6848.948

6859.629

6870.31

6873.797

6881.433

6889.07

6890.609

6897.599

6904.589

6914.565

6921.586

6928.606

6933.102

6941.477

6949.853

6950.469

6956.75

6963.032

6963.34

6970.545

6977.75

6978.92

6992.222

7005.524

7014.269

7022.06

7029.85

7029.912

7034.592

7039.272

7039.395

7045.154

7050.912

7067.293

7073.79

7080.287

7119.824

7147.228

7174.633

7177.589

7188.951

7200.314

7235.047

7244.438

7253.83

7254.384

7260.204

7266.023

7266.085

7273.598

7281.111

7281.173

7286.839

7292.504

7292.812

7300.633

7308.454

7310.117

7318.369

7326.622

7326.991

7333.581

7340.17

7352.179

7359.261

7366.343

7379.768

7393.009

7406.249

7406.742

7419.613

7432.484

7432.607

7441.075

7449.543

7449.604

7456.44

7463.276

7463.584

7474.361

7485.138

7497.824

7510.356

7522.889

7523.751

7535.975

7548.2

7731.041

7738.801

7746.561

7761.341

7779.077

7796.813

7874.347

7882.876

7891.405

7904.954

7912.836

7920.719

8007.424

8015.07

8022.717

8134.845

8146.885

8158.925

8173.99

8183.91

8193.83

8195.752

8206.991

8218.23

8238.737

8253.917

8269.098

8308.327

8315.347

8322.368

8322.784

8330.844

8338.904

8353.406

8363.536

8373.667

8380.133

8391.495

8402.857

8404.767

8413.388

8422.01

8422.133

8430.231

8438.33

8457.421

8464.072

8470.723

8470.846

8477.558

8484.271

8485.195

8492.061

8498.928

8506.934

8513.585

8520.236

8520.544

8531.198

8541.852

8554.723

8564.761

8574.799

8575.476

8585.268

8595.06

8618.77

8631.702

8644.635

8649.87

8660.554

8671.239

8671.855

8696.119

8720.383

8720.568

8728.512

8736.456

8736.518

8745.817

8755.116

8756.348

8770.604

8784.861

8791.574

8796.962

8802.351

8802.474

8822.181

8841.887

8861.964

8871.848

8881.732

8883.826

8890.538

8897.251

8897.436

8901.654

8905.873

8905.934

8928.258

8950.582

8967.272

8974.415

8981.559

8988.149

8997.971

9007.794

9010.011

9020.295

9030.58

9030.764

9038.216

9045.668

9067.961

9077.198

9086.436

9091.547

9097.798

9104.049

9105.613

9109.456

9113.299

9115.171

9134.336

9153.501

9175.08

9187.076

9199.073

9199.122

9208.31

9217.498

9217.991

9226.317

9234.643

9234.742

9244.546

9254.35

9254.941

9263.932

9272.924

9273.899

9284.974

9296.05

9310.761

9318.865

9326.969

9344.962

9359.289

9373.615

9387.662

9395.293

9402.923

9410.817

9430.014

9449.211

9475.524

9484.41

9493.296

9494.536

9504.042

9513.549

9520.898

9534.803

9548.707

9559.484

9576.179

9592.874

9615.006

9641.179

9667.352

9689.387

9720.901

9752.414

9784.265

9793.021

9801.777

9840.895

9862.594

9884.294

9908.49

9918.931

9929.371

9929.66

9941.495

9953.331

10002.41

10012.36

10022.32

10066.88

10079.24

10091.61

10091.7

10102.24

10112.77

10120.09

10135.29

10150.49

10150.78

10162.62

10174.45

10174.65

10185.23

10195.82

10195.91

10210.35

10224.78

10225.16

10236.04

10246.91

10250.09

10263.03

10275.97

10276.55

10285.11

10293.68

10294.45

10304.31

10314.17

10314.27

10321.34

10328.41

10333.03

10346.26

10359.49

10359.69

10365.85

10372

10409.53

10418.53

10427.52

10436.76

10448.55

10460.34

10465.73

10476.5

10487.28

10487.47

10493.58

10499.69

10500.46

10508.4

10516.34

10517.4

10533.61

10549.83

10568.97

10588.56

10608.14

10615.84

10636.81

10657.79

10705.55

10734.07

10762.59

10773.07

10782.59

10792.12

10792.22

10801.79

10811.36

10827.72

10846.77

10865.83

10912.98

10923.56

10934.15

10934.82

10944.01

10953.2

10953.3

10961.23

10969.17

11032.68

11044.95

11057.22

11057.51

11067.08

11076.66

11091.28

11103.93

11116.59

11137.08

11149.06

11161.04

11187.6

11197.22

11206.85

11217.43

11228.06

11238.7

11288.09

11306.44

11324.78

11357.26

11375.9

11394.54

11426.18

11445.9

11465.63

11465.99

11480.52

11495.05

11498.47

11526.91

11555.36

11560.53

11576.4

11592.27

11602.51

11632.22

11661.93

11662.77

11686.28

11709.8

11712.08

11733.43

11754.78

11756.23

11786.66

11817.09

11817.93

11834.77

11851.61

11868.93

11898.52

11928.11

11928.7

11952.25

11975.8

11976.8

12002.53

12028.25

12219.68

12232.71

12245.74

12271.47

12290.85

12310.22

12310.89

12321.25

12331.6

12340.29

12351.31

12362.34

12400.43

12412.62

12424.81

12433.83

12457.39

12480.94

12536.4

12565.8

12595.2

12597.2

12613.41

12629.61

12647.98

12674.21

12700.44

12716.47

12738.02

12759.57

12761.24

12785.79

12810.35

12829.73

12873.16

12916.59

12935.63

12967.54

12999.44

13051.23

13080.96

13110.69

13117.71

13134.41

13151.12

13258.69

13274.73

13290.77

13304.46

13323.17

13341.88

13347.56

13364.6

13381.64

13510.26

13524.96

13539.66

13551.35

13567.72

13584.09

13595.12

13614.66

13634.21

13703.7

13721.07

13738.44

13740.45

13762.16

13783.88

13784.55

13798.24

13811.94

13826.64

13842.84

13859.05

13864.06

13882.93

13901.81

13903.15

13916.01

13928.87

13929.87

13943.07

13956.27

13958.61

13983.66

14008.72

14015.73

14042.8

14069.86

14076.2

14097.59

14118.97

14124.31

14149.03

14173.76

14178.77

14198.98

14219.19

14231.55

14254.61

14277.66

14281.33

14306.56

14331.78

14405.61

14433.68

14461.74

14462.41

14488.47

14514.53

14515.19

14540.58

14565.97

14567.31

14594.54

14621.77

14751.73

14784.47

14817.21

14857.63

14884.53

14911.42

15002.96

15026.68

15050.4

15527.48

15563.22

15598.97

15613

15629.04

15645.07

15719.58

15751.48

15783.39

16465.93

16502.17

16538.42

16610.92

16630.13

16649.34

16999.46

17032.54

17065.61

17104.03

17148.13

17192.23

17225.64

17270.91

17316.18

17344.57

17394.52

17444.47

17445.13

17476.37

17507.61

17569.08

17604.33

17639.57

17774.54

17815.47

17856.39

17982.34

18031.12

18079.9

18232.58

18275.34

18318.1

18593.72

18636.99

18680.25

18704.31

18728.69

18753.08

18816.22

18850.13

18884.04

19339.07

19373.15

19407.22

19407.56

19463.85

19520.15

19522.82

19575.27

19627.72

19843.56

19992.15

20140.74

20482.31

20562.33

20642.34

20886.89

20945.69

21004.49

21005.16

21061.95

21118.75

21119.42

21170.37

21221.31

21221.98

21275.44

21328.89

21330.89

21377.17

21423.44

21436.13

21485.91

21535.69

21642.26

21687.7

21733.13

21733.47

21760.7

21787.93

21788.93

21816.49

21844.05

22967.23

23036.05

23104.87

23106.91

23146.16

23185.42

23187.46

23249.14

23310.82

23311.84

23356.7

23401.56

23407.68

23468.85

23530.03

27874.33

27944.17

28014.01

28015.03

28082.32

28149.61

TABLE B

Whole

Whole

Set

Set

Approach

Approach

Approach

Approach

Approach

Approach

1

2

3

4

1

2

3445

3265

3243

3110

3243

3110

3465

3554

3703

3364

3703

3703

3703

3703

3723

3593

3723

3723

3928

3723

3928

3703

3755

3755

4050

3755

4381

3723

3842

3776

4133

3776

4409

3776

3928

3928

4286

3928

5416

3928

3953

3953

4565

3953

5472

4133

4050

4050

4718

4050

5496

4264

4409

4133

4818

4133

5550

4381

4545

4756

5020

4264

5762

4409

4590

4791

5168

4381

5777

4431

5020

5020

5180

4409

5816

4545

5145

5068

5449

4590

5842

4590

5168

5104

5472

5020

5867

4756

5449

5145

5521

5068

5889

4791

5550

5550

5550

5104

5911

4999

5706

5570

5674

5129

5950

5020

5777

5734

5748

5168

5997

5068

5816

5762

5777

5390

6027

5104

5842

5842

5867

5449

7045

5145

5867

5867

5889

5472

7274

5472

5889

5889

5911

5550

7301

5521

5911

5911

5950

5570

7318

5550

5950

5950

5997

5762

7739

5570

5997

5997

6027

5777

7883

5706

6027

6091

6091

5816

8254

5734

6091

6109

6210

5842

8661

5762

6153

6170

6568

5867

8696

5777

6210

6210

6860

5889

8729

5795

6568

6568

6881

5911

8771

5816

6860

6860

6941

5950

8872

5842

6992

6881

6971

5997

8891

5867

7260

7318

7045

6091

8998

5889

7274

8391

7287

6170

9020

5911

7287

8531

7441

6210

9038

5950

7318

9109

7779

6789

9098

5997

8771

11446

8771

6860

9226

6091

9098

11481

9134

6941

10163

6210

9134

11527

9187

7045

10285

6634

9319

11686

9226

7318

10346

6681

9430

11733

9285

7883

10847

6732

10210

11787

9319

7913

11067

6761

11446

11835

9430

8391

11104

6837

11481

11899

9641

8413

11376

6881

11527

11952

9941

8492

11446

6898

11632

12003

10102

8771

11481

6957

11686

13134

10185

9020

11527

7074

11733

13323

10210

9109

11576

7318

11787

13721

10285

9187

11632

7334

11835

13762

10346

9226

11686

7739

11899

13843

10449

9535

11733

7883

11952

17033

10734

10135

11787

8391

12003

18275

11045

10285

11835

8413

12413

18637

11104

11045

11899

8565

12873

18729

11197

11067

11952

8661

13134

18850

11835

11197

12003

8696

13323

19992

11952

11446

13568

8729

13568

23357

12003

11481

13615

8771

13615

23469

12351

11527

13721

8797

13721

12413

11576

13883

8872

14541

12674

11632

13916

8891

14784

13134

11686

18275

8998

17033

13323

11733

23357

9098

17148

13365

11787

23469

9109

18275

13568

11835

9226

18637

13615

11899

9504

18729

13721

11952

10102

21170

13762

12003

11067

21486

14255

12351

11104

23036

15629

12968

11376

23146

17033

13134

11446

23357

17148

13323

11481

23469

17271

13365

11527

17476

13568

11576

18275

13615

11632

18637

13721

11686

18729

13762

11733

19992

13883

11787

21062

15629

11835

21170

17033

11899

21486

17476

11952

23036

18031

12003

23146

18275

12413

18637

13134

18729

13615

18850

13721

19992

13762

20946

13984

21062

18275

21170

18637

21275

18729

23357

18850

23469

19992

21062

23357

23469

TABLE C

3086

3317

3755

3776

3818

3928

3953

4264

4545

4675

4756

4773

5068

5104

5198

5403

5472

5674

5706

5795

6301

6400

6534

6612

6634

6681

6789

6837

6898

6941

6957

7420

8315

8464

8531

8565

8797

8891

8998

9098

9187

9226

9245

9319

9395

9504

9941

10079

10263

10346

10961

12457

13798

13883

13916

13984

14098

17033

17604

17815

23249.

Assignments (2)
SECURITY AGREEMENT Recorded Nov 22, 2022
From: BIODESIX, INC.
To: PERCEPTIVE CREDIT HOLDINGS IV, LP
Reel/Frame 061977/0919 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 19, 2021
From: RODER, JOANNA; MEYER, KRISTA; GRIGORIEVA, JULIA; TSYPIN, MAXIM; OLIVEIRA, CARLOS; STEINGRIMSSON, ARNI; RODER, HEINRICH; ASMELLASH, SENAIT; SAYERS, KEVIN; MAHER, CAROLINE
To: BIODESIX, INC.
Reel/Frame 054947/0863 →
Continuity (7)
Continuation 15991601 · May 29, 2018
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References Cited (173)
US 7736905B2 · Roder et al. · 2010 [cited by applicant]
US 7858389B2 · Roder et al. · 2010 [cited by applicant]
US 7858390B2 · Roder et al. · 2010 [cited by applicant]
US 7867775B2 · Roder et al. · 2011 [cited by applicant]
US 7879620B2 · Roder et al. · 2011 [cited by applicant]
US 7906342B2 · Roeder et al. · 2011 [cited by applicant]
US 8024282B2 · Tsypin et al. · 2011 [cited by applicant]
US 8097469B2 · Roder et al. · 2012 [cited by applicant]
US 8119417B2 · Roeder et al. · 2012 [cited by applicant]
US 8119418B2 · Roeder et al. · 2012 [cited by applicant]
US 8467988B1 · Roder et al. · 2013 [cited by applicant]
US 8586379B2 · Roeder et al. · 2013 [cited by applicant]
US 8586380B2 · Roeder et al. · 2013 [cited by applicant]
US 8718996B2 · Brauns et al. · 2014 [cited by applicant]
US 8914238B2 · Roder et al. · 2014 [cited by applicant]
US 9152758B2 · Roder et al. · 2015 [cited by applicant]
US 9211314B2 · Roder et al. · 2015 [cited by applicant]
US 9254120B2 · Roeder et al. · 2016 [cited by applicant]
US 9279798B2 · Roder et al. · 2016 [cited by applicant]
US 9477906B2 · Roder et al. · 2016 [cited by applicant]
US 9563744B1 · Roder et al. · 2017 [cited by applicant]
US 9606101B2 · Roder et al. · 2017 [cited by applicant]
US 9724413B2 · Maecker et al. · 2017 [cited by applicant]
US 9779204B2 · Roder et al. · 2017 [cited by applicant]
US 9824182B2 · Roder et al. · 2017 [cited by applicant]
US 10007766B2 · Roder et al. · 2018 [cited by applicant]
US 10037874B2 · Roder et al. · 2018 [cited by applicant]
US 10217620B2 · Roder et al. · 2019 [cited by applicant]
US 10489550B2 · Roder et al. · 2019 [cited by applicant]
US 10713590B2 · Roder et al. · 2020 [cited by applicant]
US 20030225526A1 · Golub et al. · 2003 [cited by applicant]
US 20050149269A1 · Thomas et al. · 2005 [cited by applicant]
US 20070178526A1 · Kountakis et al. · 2007 [cited by applicant]
US 20070231921A1 · Heinrich et al. · 2007 [cited by applicant]
US 20070254295A1 · Harvey et al. · 2007 [cited by applicant]
US 20070269804A1 · Liew et al. · 2007 [cited by applicant]
US 20080032299A1 · Burczynski et al. · 2008 [cited by applicant]
US 20080306898A1 · Tsypin et al. · 2008 [cited by applicant]
US 20100174492A1 · Heinrich et al. · 2010 [cited by applicant]
US 20100204061A1 · Heinrich et al. · 2010 [cited by applicant]
US 20100221722A1 · Perou · 2010 [cited by examiner]
US 20100240546A1 · Lo · 2010 [cited by applicant]
US 20100305868A1 · Heinrich et al. · 2010 [cited by applicant]
US 20110208433A1 · Grigorieva et al. · 2011 [cited by applicant]
US 20110271358A1 · Freeman et al. · 2011 [cited by applicant]
US 20120089341A1 · Heinrich et al. · 2012 [cited by applicant]
US 20120191370A1 · Heinrich et al. · 2012 [cited by applicant]
US 20130131996A1 · Roder et al. · 2013 [cited by applicant]
US 20130330925A1 · Cogswell et al. · 2013 [cited by applicant]
US 20130344111A1 · Roder et al. · 2013 [cited by applicant]
US 20140012514A1 · Röder et al. · 2014 [cited by applicant]
US 20140044673A1 · Caprioli · 2014 [cited by applicant]
US 20140200825A1 · Roder et al. · 2014 [cited by applicant]
US 20140243433A1 · Li et al. · 2014 [cited by applicant]
US 20140284468A1 · Grigorieva et al. · 2014 [cited by applicant]
US 20140341902A1 · Maecker et al. · 2014 [cited by applicant]
US 20150071910A1 · Kowanetz et al. · 2015 [cited by applicant]
US 20150102216A1 · Roder et al. · 2015 [cited by applicant]
US 20150125463A1 · Cogswell et al. · 2015 [cited by applicant]
US 20150285817A1 · Roder et al. · 2015 [cited by applicant]
US 20160019342A1 · Roder et al. · 2016 [cited by applicant]
US 20160090417A1 · Cogswell et al. · 2016 [cited by applicant]
US 20160098514A1 · Roder et al. · 2016 [cited by applicant]
US 20160163522A1 · Roder et al. · 2016 [cited by applicant]
US 20160018410A1 · Roder et al. · 2016 [cited by applicant]
US 20160299146A1 · Garraway et al. · 2016 [cited by applicant]
US 20170039345A1 · Röder et al. · 2017 [cited by applicant]
US 20170271136A1 · Roder et al. · 2017 [cited by applicant]
US 20180021431A1 · Maecker et al. · 2018 [cited by applicant]
US 20180312590A1 · Cogswell et al. · 2018 [cited by applicant]
US 20180282413A1 · Cogswell et al. · 2018 [cited by applicant]
US 20180282414A1 · Cogswell et al. · 2018 [cited by applicant]
US 20180027249A1 · Roder et al. · 2018 [cited by applicant]
US 20180273624A1 · Cogswell et al. · 2018 [cited by applicant]
US 20180319887A1 · Cogswell et al. · 2018 [cited by applicant]
US 20190018929A1 · Steingrimsson et al. · 2019 [cited by applicant]
US 20190092863A1 · Cogswell et al. · 2019 [cited by applicant]
US 20190100589A1 · Cogswell et al. · 2019 [cited by applicant]
US 20190100590A1 · Cogswell et al. · 2019 [cited by applicant]
US 20190112376A1 · Cogswell et al. · 2019 [cited by applicant]
US 20190112377A1 · Cogswell et al. · 2019 [cited by applicant]
US 20190135920A1 · Cogswell et al. · 2019 [cited by applicant]
US 20190153099A1 · Cogswell et al. · 2019 [cited by applicant]
US 20190035364A1 · Oliveira et al. · 2019 [cited by applicant]
US 20200308282A1 · Cogswell et al. · 2020 [cited by applicant]
AU 2011203119A1 · 2011 [cited by applicant]
CN 102770760A · 2012 [cited by applicant]
CN 103339509A · 2013 [cited by applicant]
CN 103384827A · 2013 [cited by applicant]
CN 103842030A · 2014 [cited by applicant]
CN 104470949A · 2015 [cited by applicant]
CN 104685360A · 2015 [cited by applicant]
CN 105512669A · 2016 [cited by applicant]
CN 105745659A · 2016 [cited by applicant]
EP 1043676A2 · 2000 [cited by applicant]
EP 1426766A1 · 2004 [cited by applicant]
EP 2241335A1 · 2010 [cited by applicant]
EP 2251044A1 · 2010 [cited by applicant]
WO 2010085234A1 · 2010 [cited by applicant]
WO 2012069462A1 · 2012 [cited by applicant]
WO 2013173223A1 · 2013 [cited by applicant]
WO 2014003853A1 · 2014 [cited by applicant]
WO 2014007859A1 · 2014 [cited by applicant]
WO 2014055543A2 · 2014 [cited by applicant]
WO 2014149629A1 · 2014 [cited by applicant]
WO 2015039021A2 · 2015 [cited by applicant]
WO 2015153991A1 · 2015 [cited by applicant]
WO 2015157109A1 · 2015 [cited by applicant]
WO 2015176033A1 · 2015 [cited by applicant]
WO 2016049385A1 · 2016 [cited by applicant]
WO 2016054031A1 · 2016 [cited by applicant]
WO 2016089553A1 · 2016 [cited by applicant]
WO 2017011439A1 · 2017 [cited by applicant]
International Application No. 20198389.7-1126, Extended European Search Report, dated Dec. 21, 2020, 12 pages. [cited by applicant]
Blanco et al, “Feature selection in Bayesian classifiers for the prognosis of survival of cirrhotic patients treated with TIPS”, Journal of Biomedical Informatics, vol. 38, pp. 376-388, (2005). [cited by applicant]
Carvajal-Hausdorf et al, “Quantitative Measurement of Cancer Tissue Biomarkers in the Lab and in the Clinic”, Lab Invest, vol. 95, No. 4, pp. 385-396, (2015). [cited by applicant]
European Search Report for corresponding European application No. EP16825027, dated Feb. 8, 2019. [cited by applicant]
Giroi et al, “Regularization Theory and Neural Networks Architectures”, Neural Computation, vol. 7, pp. 219-269, (1995). [cited by applicant]
Grivennikov et al, “Immunity, Inflammation, and cancer”, Cell, vol. 140, pp. 883-899, (2010). [cited by applicant]
Gunn et al, “Opposing roles for complement component C5a in tumor progression and the tumor microenvironment”, J Immunol, vol. 189, pp. 2985-2994, (2012). [cited by applicant]
International Search Report and Written Opinion for corresponding PCT Application No. PCT/US2016/041860 dated Oct. 6, 2016. [cited by applicant]
Janelle et al, “Role of the complement system in NK cell-mediated antitumor T-cell responses”, Oncoimmunology, vol. 3, e27897, (2014). [cited by applicant]
Janelle et al, “Transient complement inhibition promotes a tumor-specific immune response through the implication of natural killer cells”, Cancer Immunol Res, vol. 2, pp. 200-206, (2014). [cited by applicant]
Kani et al, “Quantitative Proteomic profiling identifies protein correlates to EGFR kinase inhibition”, Mol Cancer Ther., vol. 11, No. 5, pp. 1071-1081, (2012). [cited by applicant]
Karpievtich et al, “Liquid Chromatography Mass Spectrometry-Based Proteomics: Biological and Technological Aspects”, Ann Appl Stat., vol. 4, No. 4, pp. 1797-1823, (2010). [cited by applicant]
Kennedy-Crispin et al, “Human keratinocytes' response to injury upregulates CCL20 and other genes linking innate and adaptive immunity”, J Invest Dermatol., vol. 132, No. 1, pp. 105-113, (2012). [cited by applicant]
Larkin et al, “Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma”, The New England Journal of Medicine, vol. 373, No. 1, pp. 23-34, (2015). [cited by applicant]
Mantovani et al, “Cancer-related inflammation”, Nature, vol. 454, pp. 436-444, (2008). [cited by applicant]
Markiewski et al, “Modulation of the antitumor immune response by complement”, Natl Immunol, vol. 9, pp. 1225-1235, (2008). [cited by applicant]
Mathem et al, “Molecules Great and Small: The Complement System”, Clin J Am Soc Nephrol, vol. 10, pp. 1636-1650, (2015). [cited by applicant]
Mootha et al, “PGC-1 α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes”, Nat Genet., vol. 34, No. 3, pp. 267-273, (2003). [cited by applicant]
Pio et al, “The role of complement in tumor growth”, Adv Exp Med Biol, vol. 772, pp. 229-262, (2014). [cited by applicant]
Porta et al, “Cellular and molecular pathways linking inflammation and cancer”, Immunobiology, vol. 214, pp. 761-777. (2009). [cited by applicant]
Postow et al, “Peripheral and tumor immune correlates in patients with advanced melanoma treated with nivolumab (aniti-PD-1, BMS-936558, ONO-4538) monotherapy or in combination with ipilimumab”, Journal of Translational… [cited by applicant]
Qi et al, “Advances in the study of serum tumor markers of lung cancer”, Journal of Cancer and Therapeutics, vol. 10, No. 2, pp. C95-C101, (2014). [cited by applicant]
Redman et al, “Advances in immunotherapy for melanoma”, BNC Medicine, vol. 14, No. 1, pp. 1-11, (2016). [cited by applicant]
Romano et al, “The therapeutic promise of disrupting the PD-1/PD-L1 immunie checkpoint in cancer: unleashing the CD8 cell mediated anti-tumor activity results in significant, unprecedented clinical efficacy in various s… [cited by applicant]
Shrivastava et al, “Improving Neural Networks with Dropout”, Master's Thesis, Graduate Department of Computer Science, University of Toronto (2013). [cited by applicant]
Subramanian et al, “Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles”, Proc Natl Acad Sci USA, vol. 102, No. 43, pp. 15545-15550, (2005). [cited by applicant]
Taguchi et al, “Mass Spectrometry to Classify Non-Small-Cell Lung Cancer Patients for Clinical Outcome after Treatment with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Multicohort Cross-Institutional … [cited by applicant]
Taneja et al, “Markers of Small Cell Lung Cancer”, World Journal of Surgical Oncology, vol. 2. No. 10, 5 pages, May 5, 2004. [cited by applicant]
Tibshirani et al, “Regression shrinkage and selection via the lasso”, J. Royal. Statist. B., vol. 58, No. 1, pp. (1996). [cited by applicant]
Tikhonov, “O6 ” [On the stability of inverse problems]. Doklady Akademii Mauk SSSr, vol. 39, No. 5, pp. 195-198, (1943). [cited by applicant]
Vadrevu et al, “Complement c5a receptor facilities cancer metastasis by altering T-cell responses in the metastatic niche”, Cancer Res. vol. 74, pp. 3454-3565, (2014). [cited by applicant]
Vu et al, “RAC1 P29S regulates PD-L 1 expression in melanoma”, Pigment Cell Melanoma Res., vol. 28, No. 5, pp. 590-598, (2015). [cited by applicant]
Weber et al, “A Serum Protein Signature Associated with Outcome After Anti-PD-1 Therapy in Metastatic Melanoma”, ACCR Special Conference on Tumor Immunology and Immunotherapy, Boston, MA, vol. 6, No. 1, pp. 79-86, (2016… [cited by applicant]
Weber et al, “A test identifying advanced melanoma patients with long survival outcomes on nivolumab shows potential for selection for benefit from combination checkpoint blockade”, 31st Annual Meeting and Associated Pr… [cited by applicant]
Weber et al, “Safety, Efficacy, Biomarkers of Nivoluamb With Vaccine in Ipilimumab or -Naïve Melanoma”, J. Clin. Oncol., vol. 31, pp. 4311-4318, (2013). [cited by applicant]
Zang et al, “Progress in immunotherapy of melanoma”, Chinese Journal of Cancer Biotherapy, vol. 20, No. 3, Jun. 30, 2013. [cited by applicant]
Zhang et al, “A Protective Role for C5a in the Development of Allergic Asthma Associated with Altered Levels of B7-H1 and B7-DC on Plasmacytoid Dendritic Cells”, J. Immunol., vol. 182, pp. 5123-5130, (2009). [cited by applicant]
Zhang et al, “Simultaneous blocking of PD-1 and CTLA-4 increases in T cell infiltration in melanoma and reduces the number of Treg and bone-marrow derived suppressor cells”, Progress in Physiological Sciences, vol. 43, … [cited by applicant]
Althammer et al, “Biomarkers and Immune Monitoring”, Journal for Immunotherapy of Caner, vol. 4, No. 91, pp. 223-242, Dec. 8, 2016. [cited by applicant]
Biodesix's Diagnostic Cortex™ Platform Used in Three Studies Presented at SITC, Nov. 15, 2016, Retrieved from the Internet Oct. 26, 2020, URL: https://www.biodesix.com/press-releases/biodesixs-diagnostic-cortex-platform… [cited by applicant]
Bruno et al, “Overexpression of PD-1 and PD-L 1 in Penal Cell Carcinoma is associated with poor prognosis in metastatic patients treated with subtinib”, Annals of Oncology, vol. 26, No. 2, Annual Meeting Poster, (2015). [cited by applicant]
Girosi et al, “Regularization Theory and Neural Architectures”, Neural Computation, vol. 7, pp. 219-269, (1995). [cited by applicant]
International Search Report and Written Opinion for PCT Application No. PCT/US2016/041860 dated Oct. 6, 2016. [cited by applicant]
International Search Report for PCT application No. PCT/US17/13920, dated May 19, 2017. [cited by applicant]
International Search Report for PCT application No. PCT/US2018/12564, dated Mar. 26, 2018. [cited by applicant]
International Search Report for PCT application No. PCT/US2019/021641, dated Jul. 3, 2019, 7 pages. [cited by applicant]
Kani et al, “Quantitative Proteomic profiling identifies protein correlates to EGFR kinase inhibition”, Mol Cancer Ther., Vo. 11, No. 5, pp. 1071-1081, (2012). [cited by applicant]
Karpievitch et al, “Liquid Chromatography Mass Spectrometry-Based Proteomics: Biological and Technological Aspects”, Ann Appl Stat., vol. 4, No. 4, pp. 1797-1823, (2010). [cited by applicant]
Kennedy-Crispin et al, “Human keratinocytes' response to injury upregulates CCI20 and other genes linking innate and adaptive immunity”, J Invest Dermatol., vol. 132, No. 1, pp. 105-113, (2012). [cited by applicant]
Lundqvist et al, “Adoptive Cellular Therapy”, Journal for Immunotherapy of Cancer, vol. 4, No. 82, pp. 1-221, Nov. 16, 2016. [cited by applicant]
Mathern et al, “Molecules Great and Small: The Complement System”, Clin J Am Soc Nephrol, vol. 10, pp. 1636-1650, (2015). [cited by applicant]
McDeromott et al, “Durable benefit and the potential for long-term survival with immunotherapy in advanced melanoma”, Cancer Treatment, vol. 40, No. 9, pp. 1056-1064, Apr. 8, 2014. [cited by applicant]
Pearson et al, J. Clinical Oncology, vol. 34, No. 15, Meeting Abstract, May 2016. [cited by applicant]
Porta et al, “Cellular and molecular pathways linking inflammation and cancer”, Immunobiology, vol. 214, pp. 461-777, (2009). [cited by applicant]
Romano et al, “The therapeutic promise of disrupting the PD-1/PD-L1 immune checkpoint in cancer: unleashing the CD8 cell mediated anti-tumor activity results in significant, unprecedented clinical efficacy in various so… [cited by applicant]
Shrivastava, “Improving Neural Networks with Dropout”, Master's Thesis, Graduate Department of Computer Science, University of Toronto, (2013). [cited by applicant]
Tibshirani, “Regression shrinkage and selection via the lasso”, J. Royal. Statist. Soc B, vol. 58, No. 1, pp. 267-288, (1996). [cited by applicant]
Tikhonov, “On the stability of inverse problems”, Doklady Akademii Nauk SSSR, vol. 39, No. 5, pp. 195-198, (1943). [cited by applicant]
Weber et al, “Pre-treatment selection for nivolumab benefit based on serum mass spectra”, Journal for Immunotherapy of Cancer, No. 3, pp. 1-2, Nov. 4, 2015. [cited by applicant]
Written Opinion of the International Searching Authority for PCT/US219/021641, dated Jul. 3, 2019, 12 pages. [cited by applicant]