Title:
THERAPEUTIC AGENT COMPRISING HUMANIZED ANTI-EPIREGULIN ANTIBODY AS ACTIVE INGREDIENT FOR NON-SMALL-CELL LUNG CARCINOMA EXCLUDING ADENOCARCINOMA
Document Type and Number:
WIPO Patent Application WO/2014/208482
Kind Code:
A1
Abstract:
The present inventors succeeded in producing: an anti-Epiregulin antibody exhibiting a cross-species reactivity between a non-human animal crab-eating monkey and a human animal; an anti-Epiregulin antibody with suppressed chemical decomposition; an anti-Epiregulin antibody having a lowered isoelectric point; an anti-Epiregulin antibody having an elevated thermal denaturation midpoint temperature; and an anti-Epiregulin antibody having a reduced amount of aggregates, by appropriately substituting an amino acid residue in the variable region sequence of a humanized EP27 antibody that is capable of exhibiting a cytotoxic activity and neutralization activity on a cancer cell, said cancer cell expressing human Epiregulin, to thereby inhibit the proliferation of the cancer cell. Also, the present inventors succeeded in creating a therapeutic agent for non-small-cell lung carcinoma excluding adenocarcinoma, said therapeutic agent comprising one of the aforesaid antibodies as an active ingredient.
Inventors:
SUZUKI MASAMI (JP)
KATO ATSUHIKO (JP)
TAKEIRI ETSUKO (JP)
HASHIMOTO ERI (JP)
OUCHI KAORI (JP)
SATOH KENNICHI (JP)
KATO ATSUHIKO (JP)
TAKEIRI ETSUKO (JP)
HASHIMOTO ERI (JP)
OUCHI KAORI (JP)
SATOH KENNICHI (JP)
Application Number:
PCT/JP2014/066512
Publication Date:
December 31, 2014
Filing Date:
June 23, 2014
Export Citation:
Assignee:
CHUGAI PHARMACEUTICAL CO LTD (JP)
MIYAGI CANCER CT RES INST (JP)
MIYAGI CANCER CT RES INST (JP)
International Classes:
A61K39/395; A61P35/00; A61P43/00; C07K16/30; C07K16/46; C12N15/09; C12P21/08
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CANCER RES., vol. 53, 1993, pages 851 - 856
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CURR. OPIN. BIOTECHNOL., vol. 20, no. 6, 2009, pages 708 - 714
J. PHARM SCI., vol. 100, no. 4, 2010, pages 1306 - 1315
JUNG ET AL., J. MOL. BIOL., vol. 309, no. 3, 2001, pages 701 - 716
XIANG ET AL., J. MOL. BIOL., vol. 253, no. 3, 1995, pages 385 - 390
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VARGAS-MADRAZO ET AL., J. MOL. RECOGNIT., vol. 16, no. 3, 2003, pages 113 - 120
MOREA ET AL., J. MOL. BIOL., vol. 275, 1998, pages 269 - 294
GEIGER ET AL., J. BIOL. CHEM., vol. 262, 1987, pages 785 - 794
SEGALAS ET AL., FEBS LETTERS, vol. 371, 1995, pages 171 - 175
VAISITTI ET AL., J. BIOL. REGUL. HOMEOST. AGENTS., vol. 19, no. 3-4, 2005, pages 105 - 112
PARDRIDGE ET AL., J. PHARMACOL. EXP. THER., vol. 286, no. 1, 1998, pages 548 - 554
BJELLQVIST ET AL., ELECTROPHORESIS, vol. 14, 1993, pages 1023
BIOPHYS. J., vol. 78, 2000, pages 394 - 404
COLLOIDS SURFACES A: PHYSICOCHEM. ENG. ASPECTS., vol. 161, 2000, pages 139 - 150
J. COLLOID INTERFACE SCI., vol. 225, 2000, pages 394 - 397
BIOPHYS. J., vol. 79, 2000, pages 2150 - 2154
VERMEER ET AL., BIOPHYS. J., vol. 79, 2000, pages 2150 - 2154
VERMEER ET AL., BIOCHIM. BIOPHYS. ACTA, vol. 1425, 1988, pages 1 - 12
FASMAN ET AL.: "Circular Dichroism and the Confonnational Analysis of Biomolecules", 1996, PLENUM PRESS
BIOCHEMISTRY, vol. 33, 1994, pages 14521 - 14528
BASHFORD ET AL.: "Spectrophotometry and Spectrofluorometry: A Practical Approach", 1987, IRL PRESS LTD., pages: 91 - 114
BELL, J. E.: "Spectroscopy in Biocheinistry", vol. I, 1981, CRC PRESS, pages: 155 - 194
BRAND ET AL., ANN. REV. BIOCHEM., vol. 41, 1972, pages 843
WANG ET AL., J. PARENTERAL SCIENCE & TECHNOLOGY, vol. 42, pages S4 - S26
ANAL. BIOCHEM., vol. 360, no. 1, 2007, pages 75 - 83
WANG ET AL., J. PARENTERAL SCIENCE & TECHNOLOGY, vol. 42, 1988, pages S4 - S26
"Current protocols in Immunology", 1993, JOHN WILEY & SONS, INC., article "Chapter 7"
J. BIOL. CHEM., vol. 278, 2003, pages 3466 - 3473
J. PHARM. SCI., vol. 83, no. 12, 1994, pages 1670 - 1675
J. CLIN. INVEST., vol. 108, no. 11, 2001, pages 1687 - 1695
ANAL. BIOCHEM., vol. 230, no. 2, 1995, pages 229 - 238
IMMUNOLOGY LETTERS, vol. 143, 2012, pages 60 - 69
TROUET ET AL., PROC. NATL. ACAD. SCI. USA, vol. 79, 1982, pages 626 - 629
UMEMOTO ET AL., INT. J. CANCER, vol. 43, 1989, pages 677 - 684
LANGONE ET AL., METHODS IN ENZYMOLOGY, vol. 93, 1993, pages 307 - 308
PAI ET AL., NAT. MED., vol. 2, no. 3, 1996, pages 350 - 353
FULTON ET AL., J. BIOL. CHEM., vol. 261, 1986, pages 5314 - 5319
SIVAM ET AL., CANCER RES., vol. 47, 1987, pages 3169 - 3173
CUMBER ET AL., J. IMMUNOL. METHODS, vol. 135, 1990, pages 15 - 24
WAWRZYNCZAK ET AL., CANCER RES., vol. 50, 1990, pages 7519 - 7562
GHEEITE ET AL., J. IMMUNOL. METHODS, vol. 142, 1991, pages 223 - 230
THORPE ET AL., CANCER RES., vol. 47, 1987, pages 5924 - 5931
WAWRZYNCZAK ET AL., BR. J. CANCER, vol. 66, 1992, pages 361 - 366
WAWRZYNCZAK ET AL., CANCER RES, vol. 50, 1990, pages 7519 - 7562
BOLOGNESI ET AL., CLIN. EXP. IMMUNOL., vol. 89, 1992, pages 341 - 346
STIRPE ET AL., FEBS LET., vol. 195, 1986, pages 1 - 8
CASELLAS ET AL., EUR. J. BIOCHEM., vol. 176, 1988, pages 581 - 588
ANTICANCER RESEARCH, vol. 13, 1993, pages 2207 - 2212
CO ET AL., J. IMMUNOL., vol. 152, 1994, pages 2968 - 2976
BETTER ET AL., METHODS IN ENZYMOLOGY, vol. 178, 1989, pages 476 - 496
PLUECKTHUN ET AL., METHODS IN ENZYMOLOGY, vol. 178, 1989, pages 476 - 496
LAMOYI, METHODS IN ENZYMOLOGY, vol. 121, 1989, pages 652 - 663
ROUSSEAUX ET AL., METHODS IN ENZYMOLOGY, vol. 121, 1989, pages 663 - 669
BIRD ET AL., TIBTECH, vol. 9, 1991, pages 132 - 137
HOLLINGER ET AL., PROC. NATL. ACAD. SCI. USA, vol. 90, 1993, pages 6444 - 6448
HUSTON ET AL., PROC. NATL. ACAD. SCI. U.S.A., vol. 85, 1988, pages 5879 - 5883
HUDSON ET AL., J. IMMUNOL. METHODS, vol. 231, 1999, pages 177 - 189
REMINGTON'S: "Pharmaceutical Science", MARK PUBLISHING COMPANY
EWERT ET AL., METHODS, vol. 34, no. 2, October 2004 (2004-10-01), pages 184 - 199
HONEGGER ET AL., J. MOL. BIOL., vol. 309, 2001, pages 657 - 670
ANAL BIOCHEM., vol. 360, no. 1, 1 January 2007 (2007-01-01), pages 75 - 83
JEFFERIS ET AL., MABS 1, vol. 4, July 2009 (2009-07-01), pages 1 - 7
PROTEIN SCIENCE, vol. 4, 1995, pages 2411 - 2423
HETEROGENEITY OF MONOCLONAL ANTIBODIES: JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 97, no. 7, pages 2426 - 2447
J. PHARM. SCI., vol. 100, no. 4, 2010, pages 1306 - 1315
CHAPMAN ET AL., NAT. REV. DRUG DISCOV., vol. 6, 2007, pages 120 - 126
FARADY ET AL., BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 19, 2009, pages 3744 - 3747
BAKER ET AL., CURR. DRUG SAF., vol. 5, no. 4, 2010, pages 308 - 313
BRYSON ET AL., BIODRUGS, vol. 24, no. 1, 2010, pages 1 - 8
GROOT ET AL., CURR. OPIN. PHARMACOL., vol. 8, no. 5, 2008, pages 620 - 626
RODOLFO ET AL., IMMUNOLOGY LETTERS, 1999, pages 47 - 52
FERRARA ET AL., BIOTECHNOL. BIOENG., vol. 93, no. 5, 2006, pages 851 - 861
EXPERT OPIN BIOL THER., vol. 7, no. 3, March 2007 (2007-03-01), pages 405 - 418
See also references of EP 3015115A4
CLIN.CANCER RES., vol. 18, 2012, pages 3002 - 3007
PLOS ONE, vol. 7, 2012, pages E40109
J.THORAC.ONCOL., vol. 5, 2010, pages 1416 - 1423
J.CLIN.ONCOL., vol. 28, 2010, pages 5311 - 5320
CLEVE.CLIN.J.MED., vol. 79, no. 1, 2012, pages ES46 - 50
J.MED.PRIMATOL., vol. 15, 1986, pages 441 - 451
J.MED.PRIMATOL., vol. 40, 2001, pages 141 - 147
CANCER IMMUNOL. IMMUNOTHER., vol. 20, 2005, pages 1 - 12
HUM.EXP.TOXICOL., vol. 19, 2000, pages 230 - 243
"Epitope Mapping Protocols in Methods in Molecular Biology", vol. 66, 1996
"Antibodies: A Laboratory Manual", 1988, COLD SPRING HARBOR LABORATORY, pages: 359 - 420
SAMBROOK, J ET AL.: "Molecular Cloning", 1989, COLD SPRING HARBOR LAB. PRESS, article "Molecular Cloning", pages: 9.47 - 9.58
J. IMMUNOL., vol. 123, no. 4, 1979, pages 1548 - 1550
CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY, vol. 81, 1978, pages 1 - 7
C. EUR. J. IMMUNOL., vol. 6, no. 7, 1976, pages 511 - 519
CELL, vol. 8, no. 3, 1976, pages 405 - 415
NATURE, vol. 276, no. 5685, 1978, pages 269 - 270
J. IMMUNOL. METHODS, vol. 35, no. 1-2, 1980, pages 1 - 21
J. EXP. MED., vol. 148, no. 1, 1978, pages 313 - 323
NATURE, vol. 277, no. 5692, 1979, pages 131 - 133
MILSTEIN ET AL., METHODS ENZYMOL., vol. 73, 1981, pages 3 - 46
VANDAMME ET AL., EUR. J. BIOCHEM., vol. 192, no. 3, 1990, pages 767 - 775
BIOCHEMISTRY, vol. 18, no. 24, 1979, pages 5294 - 5299
ANAL. BIOCHEM., vol. 162, no. 1, 1987, pages 156 - 159
PROC. NATL. ACAD. SCI. USA, vol. 85, no. 23, 1988, pages 8998 - 9002
NUCLEIC ACIDS RES., vol. 17, no. 8, 1989, pages 2919 - 2932
BIO/TECHNOLOGY, vol. 12, no. 7, 1994, pages 699 - 702
CANCER RES., vol. 53, 1993, pages 851 - 856
BERNASCONI ET AL., SCIENCE, vol. 298, 2002, pages 2199 - 2202
"Sequences of Proteins of Immunological Interest", 1987, NATIONAL INSTITUTE OF HEALTH, BETHESDA, MD.
KUNKEL ET AL., PROC. NATL. ACAD. SCI. USA, vol. 82, 1985, pages 488 - 492
ANNU. REV. BIOPHYS. BIOMOL. STRUCT., vol. 35, 2006, pages 225 - 249
PROC. NATL. ACAD. SCI. U.S.A., vol. 100, no. 11, 2003, pages 6353 - 6357
FLOWER ET AL., DRUG DISCOV. TODAY, vol. 9, no. 2, 2004, pages 82 - 90
HAMMER J ET AL., J. EXP. MED., vol. 180, 1994, pages 2353 - 2358
GENES AND IMMUNITY, vol. 12, 2011, pages 213 - 221
CURR. OPIN. BIOTECHNOL., vol. 20, no. 6, 2009, pages 708 - 714
J. PHARM SCI., vol. 100, no. 4, 2010, pages 1306 - 1315
JUNG ET AL., J. MOL. BIOL., vol. 309, no. 3, 2001, pages 701 - 716
XIANG ET AL., J. MOL. BIOL., vol. 253, no. 3, 1995, pages 385 - 390
EWERT ET AL., METHODS, vol. 34, no. 2, 2004, pages 184 - 199
VARGAS-MADRAZO ET AL., J. MOL. RECOGNIT., vol. 16, no. 3, 2003, pages 113 - 120
MOREA ET AL., J. MOL. BIOL., vol. 275, 1998, pages 269 - 294
GEIGER ET AL., J. BIOL. CHEM., vol. 262, 1987, pages 785 - 794
SEGALAS ET AL., FEBS LETTERS, vol. 371, 1995, pages 171 - 175
VAISITTI ET AL., J. BIOL. REGUL. HOMEOST. AGENTS., vol. 19, no. 3-4, 2005, pages 105 - 112
PARDRIDGE ET AL., J. PHARMACOL. EXP. THER., vol. 286, no. 1, 1998, pages 548 - 554
BJELLQVIST ET AL., ELECTROPHORESIS, vol. 14, 1993, pages 1023
BIOPHYS. J., vol. 78, 2000, pages 394 - 404
COLLOIDS SURFACES A: PHYSICOCHEM. ENG. ASPECTS., vol. 161, 2000, pages 139 - 150
J. COLLOID INTERFACE SCI., vol. 225, 2000, pages 394 - 397
BIOPHYS. J., vol. 79, 2000, pages 2150 - 2154
VERMEER ET AL., BIOPHYS. J., vol. 79, 2000, pages 2150 - 2154
VERMEER ET AL., BIOCHIM. BIOPHYS. ACTA, vol. 1425, 1988, pages 1 - 12
FASMAN ET AL.: "Circular Dichroism and the Confonnational Analysis of Biomolecules", 1996, PLENUM PRESS
BIOCHEMISTRY, vol. 33, 1994, pages 14521 - 14528
BASHFORD ET AL.: "Spectrophotometry and Spectrofluorometry: A Practical Approach", 1987, IRL PRESS LTD., pages: 91 - 114
BELL, J. E.: "Spectroscopy in Biocheinistry", vol. I, 1981, CRC PRESS, pages: 155 - 194
BRAND ET AL., ANN. REV. BIOCHEM., vol. 41, 1972, pages 843
WANG ET AL., J. PARENTERAL SCIENCE & TECHNOLOGY, vol. 42, pages S4 - S26
ANAL. BIOCHEM., vol. 360, no. 1, 2007, pages 75 - 83
WANG ET AL., J. PARENTERAL SCIENCE & TECHNOLOGY, vol. 42, 1988, pages S4 - S26
"Current protocols in Immunology", 1993, JOHN WILEY & SONS, INC., article "Chapter 7"
J. BIOL. CHEM., vol. 278, 2003, pages 3466 - 3473
J. PHARM. SCI., vol. 83, no. 12, 1994, pages 1670 - 1675
J. CLIN. INVEST., vol. 108, no. 11, 2001, pages 1687 - 1695
ANAL. BIOCHEM., vol. 230, no. 2, 1995, pages 229 - 238
IMMUNOLOGY LETTERS, vol. 143, 2012, pages 60 - 69
TROUET ET AL., PROC. NATL. ACAD. SCI. USA, vol. 79, 1982, pages 626 - 629
UMEMOTO ET AL., INT. J. CANCER, vol. 43, 1989, pages 677 - 684
LANGONE ET AL., METHODS IN ENZYMOLOGY, vol. 93, 1993, pages 307 - 308
PAI ET AL., NAT. MED., vol. 2, no. 3, 1996, pages 350 - 353
FULTON ET AL., J. BIOL. CHEM., vol. 261, 1986, pages 5314 - 5319
SIVAM ET AL., CANCER RES., vol. 47, 1987, pages 3169 - 3173
CUMBER ET AL., J. IMMUNOL. METHODS, vol. 135, 1990, pages 15 - 24
WAWRZYNCZAK ET AL., CANCER RES., vol. 50, 1990, pages 7519 - 7562
GHEEITE ET AL., J. IMMUNOL. METHODS, vol. 142, 1991, pages 223 - 230
THORPE ET AL., CANCER RES., vol. 47, 1987, pages 5924 - 5931
WAWRZYNCZAK ET AL., BR. J. CANCER, vol. 66, 1992, pages 361 - 366
WAWRZYNCZAK ET AL., CANCER RES, vol. 50, 1990, pages 7519 - 7562
BOLOGNESI ET AL., CLIN. EXP. IMMUNOL., vol. 89, 1992, pages 341 - 346
STIRPE ET AL., FEBS LET., vol. 195, 1986, pages 1 - 8
CASELLAS ET AL., EUR. J. BIOCHEM., vol. 176, 1988, pages 581 - 588
ANTICANCER RESEARCH, vol. 13, 1993, pages 2207 - 2212
CO ET AL., J. IMMUNOL., vol. 152, 1994, pages 2968 - 2976
BETTER ET AL., METHODS IN ENZYMOLOGY, vol. 178, 1989, pages 476 - 496
PLUECKTHUN ET AL., METHODS IN ENZYMOLOGY, vol. 178, 1989, pages 476 - 496
LAMOYI, METHODS IN ENZYMOLOGY, vol. 121, 1989, pages 652 - 663
ROUSSEAUX ET AL., METHODS IN ENZYMOLOGY, vol. 121, 1989, pages 663 - 669
BIRD ET AL., TIBTECH, vol. 9, 1991, pages 132 - 137
HOLLINGER ET AL., PROC. NATL. ACAD. SCI. USA, vol. 90, 1993, pages 6444 - 6448
HUSTON ET AL., PROC. NATL. ACAD. SCI. U.S.A., vol. 85, 1988, pages 5879 - 5883
HUDSON ET AL., J. IMMUNOL. METHODS, vol. 231, 1999, pages 177 - 189
REMINGTON'S: "Pharmaceutical Science", MARK PUBLISHING COMPANY
EWERT ET AL., METHODS, vol. 34, no. 2, October 2004 (2004-10-01), pages 184 - 199
HONEGGER ET AL., J. MOL. BIOL., vol. 309, 2001, pages 657 - 670
ANAL BIOCHEM., vol. 360, no. 1, 1 January 2007 (2007-01-01), pages 75 - 83
JEFFERIS ET AL., MABS 1, vol. 4, July 2009 (2009-07-01), pages 1 - 7
PROTEIN SCIENCE, vol. 4, 1995, pages 2411 - 2423
HETEROGENEITY OF MONOCLONAL ANTIBODIES: JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 97, no. 7, pages 2426 - 2447
J. PHARM. SCI., vol. 100, no. 4, 2010, pages 1306 - 1315
CHAPMAN ET AL., NAT. REV. DRUG DISCOV., vol. 6, 2007, pages 120 - 126
FARADY ET AL., BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 19, 2009, pages 3744 - 3747
BAKER ET AL., CURR. DRUG SAF., vol. 5, no. 4, 2010, pages 308 - 313
BRYSON ET AL., BIODRUGS, vol. 24, no. 1, 2010, pages 1 - 8
GROOT ET AL., CURR. OPIN. PHARMACOL., vol. 8, no. 5, 2008, pages 620 - 626
RODOLFO ET AL., IMMUNOLOGY LETTERS, 1999, pages 47 - 52
FERRARA ET AL., BIOTECHNOL. BIOENG., vol. 93, no. 5, 2006, pages 851 - 861
EXPERT OPIN BIOL THER., vol. 7, no. 3, March 2007 (2007-03-01), pages 405 - 418
Attorney, Agent or Firm:
HARUNA, Masao et al. (JP)
Masao Haruna (JP)
Masao Haruna (JP)
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