Monoclonal Antibody 1A7 and Related Polypeptides

76 Pages·2016·5.08 MB·English

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Microbiology, Immunology and Molecular Microbiology, Immunology, and Molecular
Genetics Faculty Patents Genetics
11-2-1999
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Malaya Chatterjee
University of Kentucky
Kenneth A. Foon
University of Kentucky
Sunil K. Chatterjee
University of Kentucky
Follow this and additional works at: https://uknowledge.uky.edu/microbio_patents
Part of the Medical Immunology Commons, and the Medical Microbiology Commons
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Chatterjee, Malaya; Foon, Kenneth A.; and Chatterjee, Sunil K., "Monoclonal Antibody 1A7 and Related
Polypeptides" (1999). Microbiology, Immunology and Molecular Genetics Faculty Patents. 3.
https://uknowledge.uky.edu/microbio_patents/3
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US005977316A
United States Patent [19] [11] Patent Number: 5,977,316
Chatterjee et al. [45] Date of Patent: *Nov. 2, 1999
[54] MONOCLONAL ANTIBODY 1A7 AND OTHER PUBLICATIONS
RELATED POLYPEPTIDES
Angeles et al., “Isoabzymes: Structurally and mechanisti
[75] Inventors: Malaya Chatterjee; Kenneth A. F00n; cally similar catalytic antibodies from the same immuniza
tion” Biochemistry (1993) 32:12128—12135.
Sunil K. Chatterjee, all of Lexington,
Ky. Bhattacharya—Chatterjee et al., “Anti—idiotype antibodies as
potential therapeutic agents for human breast cancer” In
[73] Assignee: The Board of Trustees of the Antigen and Antibody Molecular Engineering in Breast
University of Kentucky, Lexington, Cancer Diagnosis and Treatment, Conference on Breast
Ky. Cancer Therapy Immunology, R.L. Ceriani (Ed.), Plenum
Press, N.Y., pp. 139—148, 1994.
[*] Notice: This patent is subject to a terminal dis Bhattacharya—Chatterjee et al., “Idiotype vaccines against
claimer. human T cell acute lymphoblastic leukemia. I. Generation
and characterization of biologically active monoclonal anti—
[21] Appl. No.: 08/591,196 idiotypes” J. Immunol. (1987) 139:1354—1360.
Bhattacharya—Chatterjee et al., “Idiotype vaccines against
[22] Filed: Jan. 16, 1996 human T—cell leukemia” J. Immunol. (1988)
141:1398—1403.
Related U.S. Application Data
Bhattacharya—Chatterjee et al., “Idiotypic antibody immu
notherapy of cancer” Cancer Immunol. Immunother. (1994)
[63] Continuation-in-part of application No. 08/372,676, Jan. 17,
38:75—82.
1995, Pat. NO. 5,612,030.
Bhattacharya—Chatterjee et al., “Murine monoclonal anti—
[51] Int. Cl.6 ................................................. .. A61K 39/395 idiotype antibody as a potential network antigen for human
[52] U.S. Cl. ................................... .. 530/387.2; 530/387.3; carcinoembryonic antigen” J. Immunol. (1990)
530/387.7; 424/1311; 424/1333; 424/1381 145:2758—2765.
[58] Field of Search ............................ .. 530/3872, 387.3, Bhattacharya—Chatterjee et al., “Syngeneic monoclonal
530/387.7;424/131.1, 133.3, 138.1 anti— idiotype antibodies against a monoclonal antibody to
human melanoma associated antigen” J. Immunol. (1993)
[56] References Cited 150:142A (Abstract 805).
Bird et al., “Single—chain antigen—binding proteins” Science
U.S. PATENT DOCUMENTS
(1988) 242:423—426.
4,675,287 6/1987 Reisfeld et al. . Blier et al., “A limited number of B cell lineages generates
4,693,966 9/1987 Houghton et al. . the heterogeneity of a secondary immune response” J.
4,722,840 2/1988 Valenzuela et al. . Immunol. (1987) 139:3996—4006.
4,849,509 7/1989 Thurin et al. .
4,904,596 2/1990 Hakomori . (List continued on next page.)
4,918,164 4/1990 Hellstrom et al. .
5,009,995 4/1991 Albino et al. . Primary Examiner—Sheela Huff
5,053,224 10/1991 Koprowski et al. . Assistant Examiner—Julie E. Reeves
5,057,540 10/1991 Kensil et al. . Attorney, Agent, or Firm—Morrison & Foerster LLP
5,091,177 2/1992 Hellstrom et al. .
5,102,663 4/1992 Livingston et al. . [57] ABSTRACT
5,134,075 7/1992 Hellstrom et al. .
5,141,742 8/1992 Brown et al. . The present invention relates to monoclonal antibody 1A7.
5,208,146 5/1993 Irie . This is an anti-idiotype produced by immunizing With an
5,240,833 8/1993 Nudelman et al. . antibody speci?c for ganglioside GD2, and identifying a
5,242,824 9/1993 Hellstrom et al. . hybridoma secreting antibody With immunogenic potential
5,270,202 12/1993 Raychaudhuri . in a multi-step screening process. Also disclosed are poly
5,308,614 5/1994 Hakomori .
nucleotide and polypeptide derivatives based on 1A7,
5,529,922 6/1996 Chapman et al. .
including single chain variable region molecules and fusion
5,571,900 11/1996 Wiegand et al. .
proteins, and various pharmaceutical compositions. When
5,612,030 3/1997 Chatterjee et al. .
5,653,977 8/1997 Saleh . administered to an individual, the 1A7 antibody overcomes
immune tolerance and induces an immune response against
FOREIGN PATENT DOCUMENTS
GD2, Which comprises a combination of anti-GD2 antibody
and GD2-speci?c T cells. The invention further provides
0368131 5/1990 European Pat. Off. .
0280209 9/1993 European Pat. Off. . methods for treating a disease associated With altered GD2
0661061 7/1995 European Pat. Off. . expression, particularly melanoma, neuroblastoma, glioma,
WO 86/00909 2/1986 WIPO . soft tissue sarcoma, and small cell carcinoma. Patients Who
WO 92/19266 11/1992 WIPO . are in remission as a result of traditional modes of cancer
WO 94/16731 8/1994 WIPO . therapy may be treated With a composition of this invention
WO 94/22479 10/1994 WIPO . in hopes of reducing the risk of recurrence.
WO 95/04548 2/1995 WIPO .
WO 95/34638 12/1995 WIPO .
WO 96/22373 7/1996 WIPO . 32 Claims, 22 Drawing Sheets
5,977,316
Page 2
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obtained from immuniZation With a single transition—state Miyashita et al., “A common ancestry for multiple catalytic
analog” Proc. Natl. Acad. Sci. USA (1995) 92:1694—1698. antibodies generated against a single transition—state ana
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5,977,316
U.S. Patent Nov. 2, 1999 Sheet 1 0f 22
Fi ure 1
M K L P V R L L V L M F W I P A
ATG AAG TTG CCT GTT AGG CTG TTG GTG CTG ATG TTC TGG ATT CCT GCT
S S D
r11cc AGC GAT (-1 to -19, leader)
D V L M T Q T P L S L P V
GAT GTT TTG ATG ACC CAA ACT CCA CTC TCC CTG CCT GTC AGT CTT
D Q A S I S C
GAT CAA GCC TCC ATC TCT TGC (1-23, Frame work 1)
R S S Q S I V H S N G N T
AGA TCT AG'I‘ CAG AGC ATT GTA CAT AGT AAT GGA AAC ACC
(24-39, CDR l)
W Y L Q K P G Q S P N L L
TGG TAC CTA CAG AAA CCA GGC CAG TCT CCA AAC CTC CTG ATC TAC
(40-54, Frame work 2)
F V S N R F S
TTT GTT TCC AAC CGA TTT TCT (55-61, CDR 2)
G V P D R F S G S c; s c; T
GGG GTC CCA GAC AGG TTC AGT GGC AGT GGA TCA soc ACA GAT TTC ACA
L K I S R V E A E D L G v
CTC AAG ATC AGC AGA GTG GAG GCT GAG GAT c'rc GGA GTT TAT TAC TGC
(62-93 , Frame work 3)
P Q G S H V P W T
'I'TT CAA GG'I‘ TCA CAT GTT CCG TGG ACG
(94-102, CDR 3)
F G G G T K L E I K
TTC GGT GGA GGC ACC AAG CTG GAA ATC AAA
(103-112, Frame work 4)
R A D A A P T V S I F P P
CGG GCT GAT GCT GCA CCA ACT GTA TCC ATC TTC CCA CCA
S S K L G
TCC AGT AAG CTT GGG (Constant region)
U.S. Patent Nov. 2, 1999 Sheet 2 0f 22 5,977,316
Figure 2
M A v L c L L F c L v T F P s c
ATc; ccT GTC TTG GGG CTG cTc TTc TGC CTG GTG MA MC CCA AGC TGT
v L s
GTC CTG Too (-1 to -19, Leader)
Q V Q V K E S G P F L V P P S
cAG GTG CAG GTG AAG GAG TCA GGA CCT TTC CTG/ GTG CCC CCC TCA CAG
S L S I T C T V S G F S L T
AGC CTG TCC ATC ACA TGC ACT GTC TCA GGG TTC TCA TTA ACC
(1-30, Frame work 1)
T Y c; v s
Acc TAT GGT GTA AGC (31-35, CDR 1)
W I R Q P P G K G L E W L G
TGG ATT CGC CAG CCT CCA GGA AAG GGT CTG GAG TGG CTG GGA
(36-49, Frame work 2)
A I w c D c; T T N y H s A _L I s
GCA ATT TGG GGT GAC ccc; Acc AcA AAT TAT cAT TcA GCT cTc ATA Tcc
(50-65, c012 2)
R L S I S K D N S K S Q V F L K
AGA CTG AGC ATC AGC AAG GAT AAC TCC AAG AGC CAA G'I'T TTC TTA AAA
L N S L Q T D D T A T Y Y C A K
CTG AAC AGT CTG CAA ACT GAT GAC ACG GCC ACG TAC TAC TGT GCC AAA
(66-97, Frame work 3)
L G N Y D A L D Y
CTG GGT AAc TAc GPT GCT CTG GAC TAc
(98-106, CDR 3)
W G Q G T S V T V S S
TGG GGT CAA GGA ACC TCA GTC ACC GTC TCC TCA
( 107-117 , Frame work 4)
' A K T T P P P v Y P L v P c; s L
Gcc AAA ACG AcA ccc CCA ccc GTC TAT ccA TTG GTC ccT GGA AGC TTG cc
(Constant region) '
U.S. Patent Nov. 2, 1999 Sheet 3 0f 22 5,977,316
Figure 31A!
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5 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
6 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
7 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
8 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
9 5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..S...F . . . . . . . . . . 64
1O 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
11 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6O
12 2O . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
13 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..K....K....L 60
14 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
15 5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..S...F . . . . . . . . . . 64
1A7: 61 SGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGGGTKLEIK 112
1 61 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 112
2 61 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 112
3 61 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 112
4 61 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 111
5 61 ....X . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 112
6 61 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..Y . . . . . . . . . .. 112
7 61 . . . . . . . ..C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 111
8 61 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 111
9 65 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..T . . . . . . . . . . . . . .. 116
10 61 . . . . . . . . . . . . . . . . . . ..R . . . . . . . . . . . . . . . . . ..Y . . . . . . . . . .. 112
11 61 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..R . . . . . . . . . .. 112
12 8O . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..Y...S . . . . . .. 131
13 61 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..Y . . . . . . . . . .. 112
14 61 . . . . . ..T . . . . . . . . . . . . . . . . . . . . . . . ..H . . . . ..Y . . . . . . . . . .. 112
15 65 . . . . . . . . . . . . . . . . . . . . . . . . . ..Q . . . . . . ..T . . . . . . . . . . . . . .. 116
U.S. Patent Nov. 2, 1999 Sheet 4 0f 22 5,977,316
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- - -xx.D.Y.M. . . . . . . . . . . . . 119
- -xxxxxx.Y.M. . . . . . . . . . . . 120
- -xxxx.Y.M. . . . . . . . . . . . 118
- -xxx.X.Y.M. . . . . . . . . . . . 119
..SR.WRR WM XRRRRR
- -=RDYR T 138
MKKKKMMMKKKKKH............. MMMMMMMMMMMMMH............. RRRMRRRMMMMRLH............ ......._...._S. .............T. .
111111 - -=RDYR. . . . . . . .TL 116
..VAH.HHH HH - -=RDYR. . . . . . . .T. . . . . 248
“........ I. - -=RDYR TL 135
- - - - -GYYDX.M. . . . . . . . . . . . 117
- - -xxxxx.Y.M. . . . . . . . . . . . . 139
- - - - -=RDYR. . . . . . . .T. . . . 138
- -=RDYR T 116
U.S. Patent Nov. 2, 1999 Sheet 5 0f 22 5,977,316
Fi r 3 C
WWW-It ******
v|. consensus: 1 DVLMTQTPLSLPVSLGDQASISCRSSQSIVHSNGNTYLEWYLQKKGQSPKLLIYFVSNRF 60
1A7: 1 .......................................... ..P....N ........ .. e0
* *********
VL consensus: 61 SGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPNTFGGGTKLEIK 112
1A7: 61 .................................................. .. 112
***** ***********
VH consensus: 1 QVQLKESGPGLVAPSQSLSITCTVSGFSLTSYGVHWVRQPPGKGLEWLGVIWGDGSTNYN 60
1A7: 1 ...V.....F..P ............... ..T...S.I .......... ..A.....T...H 60
***** **~k***"k****
VH consensus: 61 SALKSRLSISKDNSKSQVFLKMNSLQTDDTARYYCAREXXXXYYAMDYWGQGTSVTVSS 119
1A7: 61 ...I . . . . . . . . . . . . . . . ..L . . . . . . . ..T....KL--GN.D.L . . . . . . . . . . . .. 117
U.S. Patent Nov. 2, 1999 Sheet 6 0f 22 5,977,316
Figure 4
50000
40000l
30000-2
cprn bou nd I
20000-2
.4
10000»;
-
0.049 0.098 0.195 0.39 0.78 1.56 3.125 6.25 12.5 25
pg Ab3 added