METHOD OF CLASSIFYING ANTIBODY, METHOD OF IDENTIFYING ANTIGEN, METHOD OF OBTAINING ANTIBODY OR ANTIBODY SET, METHOD OF CONSTRUCTING ANTIBODY PANEL AND ANTIBODY OR ANTIBODY SET AND USE OF THE SAME

• US 20140235833A1
• Filed: 04/30/2014
• Published: 08/21/2014
• Est. Priority Date: 07/10/2006
• Status: Active Grant

• Current Assignee: Perseus Proteomics Inc.
• Original Assignee: Fujita Health University
• Inventors: SUGIOKA, Atsushi, KUROSAWA, Gene, SUMITOMO, Mariko, KUROSAWA, Yoshikazu
• Granted Patent: US 9,388,249 B2
• Time in Patent Office: Days
• US Class Current: 530/389.7
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07K 16/005 constructed by phage libraries
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/303 Liver or Pancreas
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: G01N 33/57492 involving compounds localized on the membrane of tumor or cancer cells
• CPC Class Codes: G01N 33/6854 Immunoglobulins

Abstract

The present invention relates to an isolated antibody against HER1, an isolated antibody against CD147, an isolated antibody against CD73, and an isolated antibody against EpCAM; reagents and compositions including said antibodies; and uses of said reagents, compositions, and antibodies. The present invention also relates to nucleic acids and vectors expressing said antibodies. The invention further relates to transformants comprising said nucleic acids or vectors.

Claims

1-85. -85. (canceled)

86. An isolated antibody having affinity to HER1, comprising:

a heavy chain variable region CDR3 and a light chain variable region CDR3 specified by a combination of SEQ ID NOs (SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR3 and SEQ ID NO showing an amino acid sequence of a light chain variable region CDR3) selected from the group consisting of the following (1) to (3);

heavy chain variable regions CDR2 and CDR3 and light chain variable regions CDR2 and CDR3 specified by a combination of SEQ ID NOs (SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR2, SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR3, SEQ ID NO showing an amino acid sequence of a light chain variable region CDR2, and SEQ ID NO showing an amino acid sequence of a light chain variable region CDR3) selected from the group consisting of the following (4) to (6);

heavy chain variable regions CDR1 to CDR3 and light chain variable regions CDR1 to CDR3 specified by a combination of SEQ ID NOs (SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR1, SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR2, SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR3, SEQ ID NO showing an amino acid sequence of a light chain variable region CDR1, SEQ ID NO showing an amino acid sequence of a light chain variable region CDR2, and SEQ ID NO showing an amino acid sequence of a light chain variable region CDR3) selected from the group consisting of the following (7) to (9) and (13) to (18);

or

a heavy chain variable region and a light chain variable region specified by a combination of SEQ ID NOs (SEQ ID NO showing an amino acid sequence of a heavy chain variable region and SEQ ID NO showing an amino acid sequence of a light chain variable region) selected from the group consisting of the following (10) to (12) and (19) to (24);

(1) SEQ ID NO;

4 and SEQ ID NO;

8

(2) SEQ ID NO;

12 and SEQ ID NO;

16

(3) SEQ ID NO;

20 and SEQ ID NO;

24

(4) SEQ ID NO;

3, SEQ ID NO;

4, SEQ ID NO;

7, and SEQ ID NO;

8

(5) SEQ ID NO;

11, SEQ ID NO;

12, SEQ ID NO;

15, and SEQ ID NO;

16

(6) SEQ ID NO;

19, SEQ ID NO;

20, SEQ ID NO;

23, and SEQ ID NO;

24

(7) SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

4, SEQ ID NO;

6, SEQ ID NO;

7, and SEQ ID NO;

8

(8) SEQ ID NO;

10, SEQ ID NO;

11, SEQ ID NO;

12, SEQ ID NO;

14, SEQ ID NO;

15, and SEQ ID NO;

16

(9) SEQ ID NO;

18, SEQ ID NO;

19, SEQ ID NO;

20, SEQ ID NO;

22, SEQ ID NO;

23, and SEQ ID NO;

24

(10) SEQ ID NO;

1, and SEQ ID NO;

5

(11) SEQ ID NO;

9, and SEQ ID NO;

13

(12) SEQ ID NO;

17, and SEQ ID NO;

21

(13) SEQ ID NO;

484 (VH CDR1), SEQ ID NO;

485 (VH CDR2), SEQ ID NO;

486 (VH CDR3), SEQ ID NO;

488 (VL CDR1), SEQ ID NO;

489 (VL CDR2), and SEQ ID NO;

490 (VL CDR3)

(14) SEQ ID NO;

492 (VH CDR1), SEQ ID NO;

493 (VH CDR2), SEQ ID NO;

494 (VH CDR3), SEQ ID NO;

496 (VL CDR1), SEQ ID NO;

497 (VL CDR2), and SEQ ID NO;

498 (VL CDR3)

(15) SEQ ID NO;

500 (VH CDR1), SEQ ID NO;

501 (VH CDR2), SEQ ID NO;

502 (VH CDR3), SEQ ID NO;

504 (VL CDR1), SEQ ID NO;

505 (VL CDR2), and SEQ ID NO;

506 (VL CDR3)

(16) SEQ ID NO;

508 (VH CDR1), SEQ ID NO;

509 (VH CDR2), SEQ ID NO;

510 (VH CDR3), SEQ ID NO;

512 (VL CDR1), SEQ ID NO;

513 (VL CDR2), and SEQ ID NO;

514(VL CDR3)

(17) SEQ ID NO;

516 (VH CDR1), SEQ ID NO;

517 (VH CDR2), SEQ ID NO;

518 (VH CDR3), SEQ ID NO;

520 (VL CDR1), SEQ ID NO;

521 (VL CDR2), and SEQ ID NO;

522 (VL CDR3)

(18) SEQ ID NO;

524 (VH CDR1), SEQ ID NO;

525 (VH CDR2), SEQ ID NO;

526 (VH CDR3), SEQ ID NO;

528 (VL CDR1), SEQ ID NO;

529 (VL CDR2), and SEQ ID NO;

530(VL CDR3)

(19) SEQ ID NO;

483 (VH), and SEQ ID NO;

487 (VL)

(20) SEQ ID NO;

491 (VH), and SEQ ID NO;

495 (VL)

(21) SEQ ID NO;

499 (VH), and SEQ ID NO;

503 (VL)

(22) SEQ ID NO;

507 (VH), and SEQ ID NO;

511 (VL)

(23) SEQ ID NO;

515 (VH), and SEQ ID NO;

519 (VL), and

(24) SEQ ID NO;

523 (VH), and SEQ ID NO;

527 (VL)

90. An isolated nucleic acid molecule, which encodes the heavy chain variable region and/or the light chain variable region of the antibody according to claim 86.

91. A vector including the nucleic acid molecule according to claim 90 in a form capable of being expressed.

92. A transformant into which the nucleic acid molecule according to claim 90 is introduced.

93. A cancer therapeutic agent comprising the antibody according to claim 86 as an effective ingredient.

94. A reagent for examining or studying cancer comprising the antibody according to claim 86.

87. An isolated antibody having affinity to CD147 antigen, comprising:

a heavy chain variable region CDR3 and a light chain variable region CDR3 specified by a combination of SEQ ID NOs (SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR3 and SEQ ID NO showing an amino acid sequence of a light chain variable region CDR3) shown in the following (1);

heavy chain variable regions CDR2 and CDR3 and light chain variable regions CDR2 and CDR3 specified by a combination of SEQ ID NOs (SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR2, SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR3, SEQ ID NO showing an amino acid sequence of a light chain variable region CDR2, and SEQ ID NO showing an amino acid sequence of a light chain variable region CDR3) shown in the following (2);

heavy chain variable regions CDR1 to CDR3 and light chain variable regions CDR1 to CDR3 specified by a combination of SEQ ID NOs (SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR1, SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR2, SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR3, SEQ ID NO showing an amino acid sequence of a light chain variable region CDR1, SEQ ID NO showing an amino acid sequence of a light chain variable region CDR2, and SEQ ID NO showing an amino acid sequence of a light chain variable region CDR3) shown in the following (3);

or

a heavy chain variable region and a light chain variable region specified by a combination of SEQ ID NOs (SEQ ID NO showing an amino acid sequence of a heavy chain variable region and SEQ ID NO showing an amino acid sequence of a light chain variable region) shown in the following (4);

(1) SEQ ID NO;

180, and SEQ ID NO;

184

(2) SEQ ID NO;

179, SEQ ID NO;

180, SEQ ID NO;

183, and SEQ ID NO;

184

(3) SEQ ID NO;

178, SEQ ID NO;

179, SEQ ID NO;

180, SEQ ID NO;

182, SEQ ID NO;

183, and SEQ ID NO;

184, and

(4) SEQ ID NO;

177, and SEQ ID NO;

181

95. An isolated nucleic acid molecule, which encodes the heavy chain variable region and/or the light chain variable region of the antibody according to claim 87.

96. A vector including the nucleic acid molecule according to claim 95 in a form capable of being expressed.

97. A transformant into which the nucleic acid molecule according to claim 95 is introduced.

98. A cancer therapeutic agent comprising the antibody according to claim 87 as an effective ingredient.

99. A reagent for examining or studying cancer comprising the antibody according to claim 87.

88. An isolated antibody having affinity to CD73, comprising:

heavy chain variable regions CDR1 to CDR3 and light chain variable regions CDR1 to CDR3 specified by a combination of SEQ ID NOs (SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR1, SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR2, SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR3, SEQ ID NO showing an amino acid sequence of a light chain variable region CDR1, SEQ ID NO showing an amino acid sequence of a light chain variable region CDR2, and SEQ ID NO showing an amino acid sequence of a light chain variable region CDR3) shown in the following (1);

or

a heavy chain variable region and a light chain variable region specified by a combination of SEQ ID NOs (SEQ ID NO showing an amino acid sequence of a heavy chain variable region and SEQ ID NO showing an amino acid sequence of a light chain variable region) shown in the following (2);

(1) SEQ ID NO;

468 (VH CDR1), SEQ ID NO;

469 (VH CDR2), SEQ ID NO;

470 (VH CDR3), SEQ ID NO;

472 (VL CDR1), SEQ ID NO;

473 (VL CDR2), and SEQ ID NO;

474 (VL CDR3), and

(2) SEQ ID NO;

467 (VH), and SEQ ID NO;

471 (VL)

100. An isolated nucleic acid molecule, which encodes the heavy chain variable region and/or the light chain variable region of the antibody according to claim 88.

101. A vector including the nucleic acid molecule according to claim 100 in a form capable of being expressed.

102. A transformant into which the nucleic acid molecule according to claim 100 is introduced.

103. A cancer therapeutic agent comprising the antibody according to claim 88 as an effective ingredient.

104. A reagent for examining or studying cancer comprising the antibody according to claim 88.

89. An isolated antibody having affinity to EpCAM, comprising:

heavy chain variable regions CDR1 to CDR3 and light chain variable regions CDR1 to CDR3 specified by a combination of SEQ ID NOs (SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR1, SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR2, SEQ ID NO showing an amino acid sequence of a heavy chain variable region CDR3, SEQ ID NO showing an amino acid sequence of a light chain variable region CDR1, SEQ ID NO showing an amino acid sequence of a light chain variable region CDR2, and SEQ ID NO showing an amino acid sequence of a light chain variable region CDR3) shown in the following (1);

or

a heavy chain variable region and a light chain variable region specified by a combination of SEQ ID NOs (SEQ ID NO showing an amino acid sequence of a heavy chain variable region and SEQ ID NO showing an amino acid sequence of a light chain variable region) shown in the following (2);

(1) SEQ ID NO;

476 (VH CDR1), SEQ ID NO;

477 (VH CDR2), SEQ ID NO;

478 (VH CDR3), SEQ ID NO;

480 (VL CDR1), SEQ ID NO;

481 (VL CDR2), and SEQ ID NO;

482 (VL CDR3), and

(2) SEQ ID NO;

475(VH), and SEQ ID NO;

479(VL)

105. An isolated nucleic acid molecule, which encodes the heavy chain variable region and/or the light chain variable region of the antibody according to claim 89.

106. A vector including the nucleic acid molecule according to claim 105 in a form capable of being expressed.

107. A transformant into which the nucleic acid molecule according to claim 105 is introduced.

108. A cancer therapeutic agent comprising the antibody according to claim 89 as an effective ingredient.

109. A reagent for examining or studying cancer comprising the antibody according to claim 89.