PFIZER EX. 1052 Page 1
Transcript of PFIZER EX. 1052 Page 1
PFIZER EX. 1052 Page 1
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SEQUENCES OF PROTEINS OF
IMMUNOLOGICAL INTEREST
FOURTH EDITION
Tabulation and Analysis of Amino Acid and Nucleic Acid Sequences of Precursors, V-Regions, C-Regions, J-Chain,
T -Cell Receptor for Antigen, T -Cell Surface Antigens,
/32-Microglobulins, Major Histocompatibility Antigens, Thy-1, Complement, C-Reactive Protein, Thymopoietin,
Post-gamma Globulin, and a 2-Macroglobulin
1987
Elvin A. Kabat*, TaiTe Wu t, Margaret Reid-Miller+, Harold M. Perry +, and Kay S. Gottesman +
* Depts. of Microbiology, Genetics and Development, and Neurology, Cancer Center/ Institute of Cancer Research, College of Physicians and Surgeons, Columbia University, New York, NY 10032 and the National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
t Depts. of Biochemistry, Molecular Biology, and Cell Biology, and Engineering Sciences and Applied Mathematics and Biomedical Engineering, Northwestern University, Evanston, IL 60201 and the Cancer Center, Northwestern University Medical School, Chicago, IL 60611
+Bolt Beranek and Newman Inc., Cambridge, MA 02238
The collection and maintenance of this data base is sponsored through Contract N01-RR-8-2158 by the following components of the National Institutes of Health, Bethesda, MD 20892:
Division of Research Resources National Cancer Institute National Institute of Allergy and Infectious Diseases National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases National Institute of General Medical Sciences
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service National institutes of Health
(1987)
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Our listing of sequences will be kept up to date. Investigators are invited to send additional sequence data when accepted for publication. Send two copies of the manuscript together with a letter of acceptance from a journal to:
Dr. E.A. Kabat National Institutes of Health Building 8, Room 126 9000 Rockville Pike Bethesda, Maryland 20892
It woufd be extremely helpful if you can send us your sequence data on magnetic tapes or floppy diskettes or a clean copy of the sequences. The file formats should be such that they can be read by a generic word processor.
When published, three reprints should be provided.
If any published sequences have been overlooked or if any errors are found, please bring them to our attention.
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TABLE OF CONTENTS
INTRODUCTION. REFERENCES TO INTRODUCTION .
SIGNAL SEQUENCES
SIGNAL PEPTIDES OF KAPPA LIGHT CHAINS . SIGNAL PEPTIDES OF LAMBDA LIGHT CHAINS. SIGNAL PEPTIDES OF HEAVY CHAINS. SIGNAL PEPTIDES OF BETA-2-MICROGLOBULINS .. SIGNAL PEPTIDES OF MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS I .. SIGNAL PEPTIDES OF I REGION ANTIGENS CLASS II. SIGNAL PEPTIDES OF COMPLEMENT . SIGNAL PEPTIDES OFT-LYMPHOCYTE RECEPTOR FOR ANTIGEN SIGNAL PEPTIDES OFT-CELL SURFACE ANTIGENS . SIGNAL PEPTIDES OF OTHER PROTEINS .
VARIABLE REGION LIGHT CHAIN SEQUENCES
HUMAN KAPPA LIGHT CHAINS SUBGROUP I . HUMAN KAPPA LIGHT CHAINS SUBGROUP II . HUMAN KAPPA LIGHT CHAINS SUBGROUP Ill .. HUMAN KAPPA LIGHT CHAINS SUBGROUP IV .
HUMAN LAMBDA LIGHT CHAINS SUBGROUP I . HUMAN LAMBDA LIGHT CHAINS SUBGROUP II. HUMAN LAMBDA LIGHT CHAINS SUBGROUP Ill . HUMAN LAMBDA LIGHT CHAINS SUBGROUP IV. HUMAN LAMBDA LIGHT CHAINS SUBGROUP V . HUMAN LAMBDA LIGHT CHAINS SUBGROUP VI .
MOUSE KAPPA LIGHT CHAINS I . MOUSE KAPPA LIGHT CHAINS II. MOUSE KAPPA LIGHT CHAINS Ill MOUSE KAPPA LIGHT CHAINS IV . MOUSE KAPPA LIGHT CHAINS V . MOUSE KAPPA LIGHT CHAINS VI . MOUSE KAPPA LIGHT CHAINS VII . MOUSE KAPPA LIGHT CHAINS MISCELLANEOUS.
MOUSE LAMBDA LIGHT CHAINS.
RAT KAPPA LIGHT CHAINS ....
RABBIT KAPPA LIGHT CHAINS . RABBIT LAMBDA LIGHT CHAINS .
OTHER KAPPA LIGHT CHAINS OTHER LAMBDA LIGHT CHAINS .. MISCELLANEOUS LIGHT CHAINS.
VARIABLE REGION HEAVY CHAIN SEQUENCES
HUMAN HEAVY CHAINS SUBGROUP I. HUMAN HEAVY CHAINS SUBGROUP II ... HUMAN HEAVY CHAINS SUBGROUP Ill ..
MOUSE HEAVY CHAINS SUBGROUP I (A) . MOUSE HEAVY CHAINS SUBGROUP I (B). MOUSE HEAVY CHAINS SUBGROUP II (A). MOUSE HEAVY CHAINS SUBGROUP II (B) ... MOUSE HEAVY CHAINS SUBGROUP II (C). MOUSE HEAVY CHAINS SUBGROUP Ill (A) .. MOUSE HEAVY CHAINS SUBGROUP Ill (B) .. MOUSE HEAVY CHAINS SUBGROUP Ill (C) .. MOUSE HEAVY CHAINS SUBGROUP Ill (D) .. MOUSE HEAVY CHAINS SUBGROUP V (A). MOUSE HEAVY CHAINS SUBGROUP V (B) .. MOUSE HEAVY CHAINS SUBGROUP MISCELLANEOUS .
RAT HEAVY CHAINS .....
RABBIT HEAVY CHAINS.
GUINEA PIG HEAVY CHAINS. CAT HEAVY CHAINS .. DOG HEAVY CHAINS .... CHICKEN HEAVY CHAINS ... SHARK HEAVY CHAINS. MISCELLANEOUS HEAVY CHAINS ..
T-LYMPHOCYTE RECEPTOR FOR ANTIGEN VARIABLE REGION (ALPHA CHAINS) ... T-LYMPHOCYTE RECEPTOR FOR ANTIGEN VARIABLE REGION (BETA CHAINS SUBGROUP I). T-LYMPHOCYTE RECEPTOR FOR ANTIGEN VARIABLE REGION (BETA CHAINS SUBGROUP II) . T-LYMPHOCYTE RECEPTOR FOR ANTIGEN VARIABLE REGION (GAMMA CHAINS)
CONSTANT REGION SEQUENCES
KAPPA LIGHT CONSTANT CHAINS. LAMBDA LIGHT CONSTANT CHAINS .
HEAVY CONSTANT CHAINS CH1 REGION. HEAVY CONSTANT CHAINS HINGE REGION. HEAVY CONSTANT CHAINS CH2 REGION. HEAVY CONSTANT CHAINS CH3 REGION HEAVY CONSTANT CHAINS EXTRA LONG CH3 REGION . HEAVY CONSTANT CHAINS CH4 REGION . HEAVY CONSTANT CHAINS EXTRA LONG CH4 AND MEMBRANE BOUND REGIONS .
SEQUENCES OF RELATED PROTEINS
J CHAIN .....
BETA-2-MICROGLOBULINS ..
MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS IN REGION MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS I C1 REGION .... MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS I C2 REGION . MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS I MEMBRANE REGION .. MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS I CYTOPLASMIC REGION .
I REGION GENE PRODUCTS CLASS II A-CHAIN A1 REGION. I REGION GENE PRODUCTS CLASS II A-CHAIN A2 REGION. I REGION GENE PRODUCTS CLASS II A-CHAIN MEMBRANE BOUND REGION.
I REGION GENE PRODUCTS CLASS II B-CHAIN B1 REGION .
...... vii . ... xxix
...... 1 . ..... 8 . .... 11
. 19 ..... 21 . .... 24
. ........... 28 . .... 30 ..... 36 . .... 38
.. 41 . .... 50
.53 . ... 60
. .... 63 .66
. .... 69 . ... 72
. .... 74 . .... 76
. ... 78 . ... 85
. .... 95 .. 102
. ... 105 . .... 117 . .... 124 ..... 126
. ... 129
. .... 134
. .... 136 . . 149
. ... 151 ..... 154
. ... 157
. ... 160 . .......... 164
. .... 167
. ... 176 . .... 181 . .... 186 . .... 192 .. ... 200 .. ... 204 . .... 214 . .... 219
. 222 .. ... 226 .. ... 232 .. ... 235
.. .... 241
. .... 243
. .... 248 . .... 250 . .... 252
. ... 254 .. ... 256 .. ... 259
.. .. 262 . .... 266 . .... 274
.. 279
. .... 282 . .... 287
.. 293 . .... 300 . .... 307
... 314 . . 321
. ... 323
.. .. 325
. 332
..334
..... 337 . .. 341
.. ......... 345 .. . 349
. 353
.. .. 359 .362
.. .. 365
. .... 370
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I REGION GENE PRODUCTS CLASS II B-CHAIN B2 REGION . I REGION GENE PRODUCTS CLASS II B-CHAIN MEMBRANE BOUND REGION .
THY-1 ANTIGENS. . ....... .
HUMAN COMPLEMENT COMPONENTS ... OTHER COMPLEMENT COMPONENTS
T -LYMPHOCYTE RECEPTOR FOR ANTIGEN CONSTANT REGION.
T-CELL SURFACE ANTIGENS.. . . . . . . . . . . ........ .
MISCELLANEOUS PROTEINS OF THE IMMUNOGLOBULIN SUPERFAMILY . MISCELLANEOUS PROTEINS ASSOCIATED WITH THE IMMUNE SYSTEM .
CO DONS OF NUCLEIC ACID SEQUENCES
CODONS OF SIGNAL PEPTIDES OF KAPPA LIGHT CHAINS. CODONS OF SIGNAL PEPTIDES OF LAMBDA LIGHT CHAINS. CODONS OF SIGNAL PEPTIDES OF HEAVY CHAINS. CO DONS OF SIGNAL PEPTIDES OF BETA-2MICROGLOBULINS . CODONS OF SIGNAL PEPTIDES OF MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS I. CO DONS OF SIGNAL PEPTIDES OF I REGION ANTIGENS CLASS II. CO DONS OF SIGNAL PEPTIDES OF COMPLEMENT . CODONS OF SIGNAL PEPTIDES OFT-LYMPHOCYTE RECEPTOR FOR ANTIGEN . CO DONS OF SIGNAL PEPTIDES OFT-CELL SURFACE ANTIGENS . CODONS OF SIGNAL PEPTIDES OF OTHER PROTEINS .
CODONS OF VARIABLE REGION KAPPA LIGHT CHAINS . CODONS OF VARIABLE REGION LAMBDA LIGHT CHAINS .. CODONS OF VARIABLE REGION HEAVY CHAINS ..
CODONS OF KAPPA LIGHT CONSTANT CHAINS .. CODONS OF LAMBDA LIGHT CONSTANT CHAINS ..
CODONS OF HEAVY CONSTANT CHAINS CH1 REGION. CODONS OF HEAVY CONSTANT CHAINS HINGE REGION. CODONS OF HEAVY CONSTANT CHAINS CH2 REGION. CO DONS OF HEAVY CONSTANT CHAINS CH3 REGION. . ......... . CODONS OF HEAVY CONSTANT EXTRA LONG CH3 REGION ........ . CODONS OF HEAVY CONSTANT CHAINS CH4 REGION. . ......... . CODONS OF HEAVY CONSTANT EXTRA LONG CH4 AND MEMBRANE BOUND REGIONS ..
CODONS OF BETA-2-MICROGLOBULINS.
CODONS OF MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS IN REGION . CODONS OF MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS I C1 REGION . CODONS OF MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS I C2 REGION . CODONS OF MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS I MEMBRANE REGION. CODONS OF MAJOR HISTOCOMPATIBILITY ANTIGENS CLASS I CYTOPLASMIC REGION .
CODONS OF I REGION GENE PRODUCTS CLASS II A-CHAIN A 1 REGION .... CODONS OF I REGION GENE PRODUCTS CLASS II A-CHAIN A2 REGION. CODONS OF I REGION GENE PRODUCTS CLASS II A-CHAIN MEMBRANE REGION .
CODONS.OF I REGION GENE PRODUCTS CLASS II B-CHAIN B1 REGION . CO DONS OF I REGION GENE PRODUCTS CLASS II B-CHAIN B2 REGION . CO DONS OF I REGION GENE PRODUCTS CLASS II B-CHAIN MEMBRANE BOUND REGION .
CODONS OF HUMAN COMPLEMENT COMPONENTS . CODONS OF OTHER COMPLEMENT COMPONENTS ...
CODONS OFT-LYMPHOCYTE RECEPTOR FOR ANTIGEN VARIABLE REGION (ALPHA CHAINS). CODONS OFT-LYMPHOCYTE RECEPTOR FOR ANTIGEN VARIABLE REGION (BETA CHAINS SUBGROUP I). CODONS OFT-LYMPHOCYTE RECEPTOR FOR ANTIGEN VARIABLE REGION (BETA CHAINS SUBGROUP II). CODONS OFT-LYMPHOCYTE RECEPTOR FOR ANTIGEN VARIABLE REGION (GAMMA CHAINS).
CODONS OFT-LYMPHOCYTE RECEPTOR FOR ANTIGEN CONSTANT REGION .
CO DONS OFT-CELL SURFACE ANTIGENS.
CODONS OF MISCELLANEOUS PROTEINS OF THE IMMUNOGLOBULIN SUPERFAMILY . CODONS OF MISCELLANEOUS PROTEINS ASSOCIATED WITH THE IMMUNE SYSTEM ..
CODONS OF HUMAN D-MINIGENES . CODONS OF MOUSE D-MINIGENES ..
CO DONS OF HUMAN T -LYMPHOCYTE RECEPTOR FOR ANTIGEN D-MINIGENES. CO DONS OF MOUSE T-L YMPHOCYTE RECEPTOR FOR ANTIGEN D-MINIGENES.
CODONS OF HUMAN KAPPA J-MINIGENES . CO DONS OF HUMAN LAMBDA J-MINIGENES .
CO DONS OF MOUSE KAPPA J-MINIGENES . CODONS OF MOUSE LAMBDA J-MINIGENES ..
CODONS OF RAT KAPPA J-MINIGENES ..
CO DONS OF RABBIT KAPPA J-MINIGENES ..
CODONS OF HUMAN HEAVY J-MINIGENES. CODONS OF MOUSE HEAVY J-MINIGENES.
CODONS OF HUMAN T-L YMPHOCYTE RECEPTOR FOR ANTIGEN ALPHA CHAIN J-MINIGENES ........... . CODONS OF HUMAN T-LYMPHOCYTE RECEPTOR FOR ANTIGEN BETA CHAIN J-MINIGENES . CO DONS OF HUMAN T-LYMPHOCYTE RECEPTOR FOR ANTIGEN GAMMA CHAIN J-MINIGENES .
CODONS OF MOUSE T-LYMPHOCYTE RECEPTOR FOR ANTIGEN ALPHA CHAIN J-MINIGENES. CODONS OF MOUSE T-LYMPHOCYTE RECEPTOR FOR ANTIGEN BETA CHAIN J-MINIGENES .
PSEUDOGENES OF IMMUNOGLOBULIN VARIABLE REGIONS. PSEUDOGENES OFT -L YMPHOCTYE RECEPTOR FOR ANTIGEN VARIABLE REGIONS . PSEUDOGENES OF IMMUNOGLOBULIN CONSTANT REGIONS .. PSEUDOGENES OF OTHER PROTEINS .
SUMMARY TABLES
AMINO ACID DISTRIBUTION IN ALL VARIABLE REGION LIGHT CHAINS . AMINO ACID DISTRIBUTION IN ALL VARIABLE REGION HEAVY CHAINS ..
CODON DISTRIBUTION IN ALL VARIABLE REGION KAPPA LIGHT CHAINS. CODON DISTRIBUTION IN ALL VARIABLE REGION LAMBDA LIGHT CHAINS . CODON DISTRIBUTION IN ALL VARIABLE REGION HEAVY CHAINS ..
. .. 375 . ... 380
. .... 387
. 389 ... 406
. .421
. ................ 429
. .. 434 . 439
. ............. 452 . .......... .458
.460 . ............... 467
. .......... 469 . ........ 471
. ... 476 . .. 478
489 . .... 491
. 494 . ..... 506
. ................ 508
. ..... 526 . ......... 528
. 530 . ......... 533
. .......... 536 . ..... 539 . .... 542
. . 545 . ... 548
. .. 553
. .... 555 . ....... 557
. . 559 . ... 561
. 563
. .......... 566 . ..... 568
. . 570
. ....... 573 . ...... 575
. ............. 577
. ......... 580 . .............. 595
. .............. 610 . ......... 616
. ...... 623 . .. 628
. 630
. ..... 637
. ..... 641 . 644
. .................. 656. . ... 659
. 663 . . 664
. . 665 . ............. 666
. . 667 . .............. 668
. ... 669
. 671
674 . ................ 675
. ...... 677 . 680
. ................... 683
. ......... 684 . ............. 685
. . 687 . 699
. .... .705 . ..... 711
. ............. 716 . . 718
. . 720 . ................. 723
. . 726
VARIABILITY PLOTS
LIGHT CHAINS . . ........................... 730 HEAVY CHAINS .......... .
KAPPA LIGHT CHAINS . LAMBDA LIGHT CHAINS.
HUMAN LIGHT CHAINS . HUMAN HEAVY CHAINS.
. .... 730
. 731 . .... 731
. .. 732 . ............ 732
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HUMAN KAPPA LIGHT CHAINS . HUMAN LAMBDA LIGHT CHAINS.
HUMAN KAPPA LIGHT CHAINS SUBGROUP I .. HUMAN KAPPA LIGHT CHAINS SUBGROUP II . HUMAN KAPPA LIGHT CHAINS SUBGROUP Ill.
HUMAN HEAVY CHAINS SUBGROUP I. HUMAN HEAVY CHAINS SUBGROUP II. HUMAN HEAVY CHAINS SUBGROUP Ill.
HUMAN LAMBDA LIGHT CHAINS SUBGROUP I . HUMAN LAMBDA LIGHT CHAINS SUBGROUP II. HUMAN LAMBDA LIGHT CHAINS SUBGROUP Ill .
MOUSE KAPPA LIGHT CHAINS .
RABBIT KAPPA LIGHT CHAINS ...
MOUSE KAPPA LIGHT CHAINS SUBGROUP II . MOUSE KAPPA LIGHT CHAINS SUBGROUP Ill .. MOUSE KAPPA LIGHT CHAINS SUBGROUP V. MOUSE KAPPA LIGHT CHAINS SUBGROUP VI .
MOUSE HEAVY CHAINS SUBGROUP lA. MOUSE HEAVY CHAINS SUBGROUP IB. MOUSE HEAVY CHAINS SUBGROUP IIA . MOUSE HEAVY CHAINS SUBGROUP liB . MOUSE HEAVY CHAINS SUBGROUP IIC . MOUSE HEAVY CHAINS SUBGROUP IIIlA . MOUSE HEAVY CHAINS SUBGROUP IIIIB .
v
T-L YMPHOCYTE RECEPTOR FOR ANTIGEN ALPHA CHAINS. T-LYMPHOCYTE RECEPTOR FOR ANTIGEN BETA CHAINS. T-LYMPHOCYTE RECEPTOR FOR ANTIGEN BETA CHAINS SUBGROUP I . T-LYMPHOCYTE RECEPTOR FOR ANTIGEN BETA CHAINS SUBGROUP II.
CYTOCHROMES C ...
HUMAN HLA DR BETA CHAIN CLASS II. HUMAN HLA DC BETA CHAIN CLASS II.
MOUSE MHC lA ALPHA CHAIN CLASS II .. MOUSE MHC IE BETA CHAIN CLASS II .
INDICES
INDEX OF PROTEINS . INDEX OF ANTIBODY SPECIFICITIES .
. . 733 . .......... 733
. .... 734 . ......... 734
. ... .734
. ......... 735 . .... 735
. 736
. .......... 737 . ................... 737
. .. 737
. ... 738
. ...... 738
. .... 739 . ...... 739
. .......... 739 . .. 739
. 740 . .......................... 740
. ....... 741 . 741
. .......... 741 . ...................... 742
. ..... 742
. .. 743 . 743
. ......... 744 . .... 744
. ......... 745
. ...... 746 . .... 746
. . 746 . ....... 746
. .................. 747 . . 795
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HUMAN KAPPA LIGHT CHAINS SUBGROUP I
F R 1
c D R 1
F R 2
c D R 2
F R 3
c D R 3
F
0 1 2 3 4
5 6 7 8 9
10 11
INVARIANT RESIDUES
THR(.98)
SER(.95) PR0(.98)
12 SER(.96) 13 14
15 VAL(-96) 16 GLY(.99) 17 18 19 VAL(-97)
20 THR(.96) 21 ILE(.95) 22 23 CYS 24
25 ALA(.95) 26 27 27A 27B
27C 270 27E 27F 28
29 30 31 32 33
34 35 36 37 38
39 40 41 42 43
44 45 46 47 48
49 50 51 52 53
54 55 56 57 58
-59 60 61 62 63
64 65 66 67 68 69 70 71 72 73
;1 ;~ 76 77 78
79 so 81 82 83
84 85 86 87 88 89 90 91 92 93
94 95 95A 958 95C
950 95E 95F 96 97 98 99
100 101 102
TRP
PR0(.95)
PRO
LEU(-98) ILE(.98)
LEU(.98)
GLY VAL(.98)
SER ARG(.95) PHE(.95)
GLY
GLY(.95)
ILE(.95) SER(.95)
ALA(.98)
TYR(.98) TYR(.98) CYS
GLY
GLY THR(.97)
R 103 4 104
105 106 106A
107 108 109 THR
1 2 3 4 5 6 7 8" 9 10 HK 134 'CL #
11 12 13 14 15 16 17 BJ 26 #
18 19 20 21 22 23 ROY AU REI HAU HK101 SCW AG WEA HK DAUDI WALKER HF3- HF2- HF2- HF2- RFZ PSM HOM ESM ESM WAT
IGG IGM 'Cl # 137 'CL #
'CL 'CL 16/6 1/138 18/2 1/17 #
# ASP ASP ASP ASP ASP ILE ILE ILE ILE ILE GLN GLN GLN GLN GLN MET MET MET MET MET
THR THR THR THR GLN GLN GLN GLN SER SER SER SER PRO PRO PRO PRO SER SER SER SER
SER SER SER SER LEU LEU LEU LEU SER SER SER SER ALA ALA ALA ALA SER SER SER SER
VAL VAL VAL VAL GLY GLY GLY GLY ASP ASP ASP ASP ARG ARG ARG ARG VAL VAL VAL VAL
THR THR THR THR ILE ILE ILE ILE THR THR THR THR CYS CYS CYS CYS GLN GLN GLN ARG
ALA ALA ALA ALA SER SER SER SER GLN GLN GLN GLN
THR GLN SER PRO SER
SER LEU SER ALA SER
VAL GLY ASP ARG VAL
THR ILE THR CYS ARG
ALA ARG GLN
# ASP ASP ASP ASP ASP ILE ILE ILE ILE ILE GLN GLN GLN GLN GLN MET MET MET MET MET
THR THR THR THR THR GLN GLN GLN GLN GLN SER SER SER SER SER PRO PRO PRO PRO PRO SER SER SER SER SER
SER SER SER SER SER LEU LEU LEU LEU LEU SER SER SER SER SER ALA ALA ALA ALA ALA SER SER SER SER SER
VAL GLY ASP ARG VAL
THR ILE THR CYS GLN
VAL GLY ASP ARG VAL
THR ILE THR CYS GLN
VAL GLY ASP ARG VAL
THR ILE THR CYS ARG
VAL VAL GLY GLY ASP ASP ARG ARG VAL VAL
THR THR ILE ILE THR THR CYS CYS ARG ARG
ALA ALA ALA ALA ALA SER SER SER SER SER GLN GLN GLN GLN GLN
ASP ASP ASP SER GLY ASP ASP GLY GLY GLY
ILE ILE SER SER ILE ASP
PHE TYR LEU LEU
ASN ASN TRP TRP TYR TYR GLN GLN GLN GLN
LYS LYS PRO PRO GLY GLY LYS LYS ALA ALA
PRO PRO LYS LYS LEU LEU LEU LEU ILE ILE
TYR TYR ASP ASP ALA ALA SER SER LYS ASN
LEU LEU GLU GLU ALA SER GLY GLY VAL VAL
PRO SER ARG PHE SER
GLY THR GLY SER GLY
THR ASP PHE THR PHE
THR ILE
SER GLY LEU
PRO SER ARG PHE SER
GLY GLY GLY SER GLY
ALA HIS PHE THR PHE
THR ILE
SER SER LEU
ILE ILE ILE SER LYS SER TYR TYR LEU LEU
ASN SER TRP TRP TYR TYR GLN GLN GLN GLN
THR LYS PRO PRO GLY GLY LYS LYS ALA ALA
PRO PRO LYS GLN LEU VAL LEU LEU ILE ILE
TYR TYR GLU ALA ALA ALA SER SER ASN SER
LEU LEU GLN PRO ALA SER GLY GLY VAL VAL
PRO SER ARG PHE SER
GLY SER GLY SER GLY
THR ASP TYR
.THR PHE
THR ILE
SER SER LEU
PRO SER ARG PHE SER
GLY SER GLY SER GLY
THR ASP PHE THR LEU
THR ILE
SER SER LEU
ILE SER SER TRP LEU
ALA TRP TYR GLN GLN
LYS PRO GLU LYS ALA
PRO LYS SER LEU ILE
TYR ALA ALA SER SER
LEU GLN SER GLY VAL
PRO SER ARG PHE SER
GLY SER GLY SER GLY
THR ASP PHE THR LEU
THR ILE SER SER LEU
ILE ILE ILE ARG ASN ARG LYS HIS ASN HIS TYR ASP LEU LEU LEU
ASN ASN THR TRP TRP TRP TYR TYR TYR ASP GLN GLN GLN GLN GLN
LYS # LYS PRO PRO PRO GLY # GLY LYS LYS THR ALA ALA ALA
PRO PRO PRO ARG LYS LYS LEU ILE ARG LEU LEU LEU ILE ILE ILE
TYR TYR TYR GLY ASP GLY ALA ALA ALA SER SER THR THR ASN SER
LEU LEU LEU GLU GLU GLN THR THR SER GLY GLY GLY VAL VAL VAL
PRO SER ARG PHE SER
GLY SER GLY SER GLY
THR ASP PHE THR LEU
THR ILE
SER THR LEU
PRO SER ARG PHE SER
GLY SER GLY PHE GLY
THR ASP PHE THR PHE
THR ILE
SER GLY LEU
PRO SER ARG PHE SER
GLY SER GLY SER GLY
THR GLU PHE THR LEU
THR ILE
ASN SER LEU
ILE SER ASN TYR LEU
ALA TRP PHE GLN GLN
LYS PRO GLY LYS ALA
PRO LYS SER LEU ILE
TYR ALA ALA SER SER
LEU GLN SER GLY VAL
PRO SER ARG PHE SER
GLY SER GLY SER GLY
THR ASP PHE THR LEU
THR ILE SER SER LEU
ILE SER SER TRP LEU
ALA TRP TYR GLN GLN
LYS PRO GLU LYS ALA
PRO LYS SER LEU ILE
TYR ALA ALA SER SER
LEU GLN SER GLY VAL
PRO SER ARG PHE SER
GLY SER GLY SER GLY
THR ASP PHE THR LEU
THR ILE
SER SER LEU
ASP ILE GLN MET
THR GLN SER PRO SER
SER LEU SER ALA SER
VAL GLY ASP ARG VAL
THR ILE THR CYS ARG
ALA GLY HIS
ASN
ILE THR ASN PHE LEU
SER TRP TYR GLN GLN
LYS PRO GLY LYS ALA
PRO THR LEULEU ILE
TYR ALA VAL SER ASN
LEU GLN VAL GLY VAL
PRO SER ARG PHE SER
GLY SER GLY SER GLY
ALA GLU PHE THR LEU
THR ILE SER SER LEU
GLN GLN GLN GLN PRO PRO PRO PRO GLU GLU GLU GLU ASP ASP ASP ASP ILE ILE ILE PHE
GLN GLN GLN GLN GLN GLN GLN PRO PRO PRO PRO PRO PRO PRO GLU GLU GLU GLU GLU GLU GLU ASP ASP ASP ASP ASP ASP ASP PHE ILE ILE PHE PHE PHE PHE
ALA ALA ALA ALA ALA THR THR THR THR THR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR CYS CYS CYS CYS CYS GLN GLN GLN GLN GLN GLN GLN GLN GLN GLN PHE TYR TYR ASN TYR ASP ASP GLN TYR ASN ASN TYR SER ILE SER
LEU LEU LEU THR TYR PRO PRO PRO PRO PRO
LEU THR PHE GLY GLY GLY THR
LYS VAL ASP PHE
TRP TYR THR THR THR SER PHE PHE PHE GLY GLY GLY GLN GLN GLN GLY GLY GLY THR THR THR
LYS LYS ARG VAL LEU VAL GLU GLN GLU ILE ILE ILE
LYS LYS THR LYS ARG ARG ARG ARG THR THR THR THR
#
GLY ALA ALA ALA ALA ASN THR THR THR THR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR CYS CYS CYS CYS CYS GLN GLN LEU GLN GLN GLN GLN GLN GLN GLN TYR TYR TYR TYR TYR ASP ASP SER ASN ASN ASN THR SER SER SER
VAL LEU PHE TYR TYR PRO PRO PRO PRO PRO
ILE ARG THR THR PHE PHE GLY GLY GLN GLN GLY GLY THR THR
ARG LYS VAL LEU GLU GLU ASN ILE
TRP THR PHE GLY GLN GLY THR
LYS VAL GLU VAL
LYS LYS LYS GLY ARG ARG THR THR THR
#
ALA THR TYR TYR CYS GLN GLN ASN TYR ASN
PHE SER
PHE THR PHE GLY GLY GLY THR
LYS VAL ASP ASN
LYS
ASP ILE GLN MET
THR GLN SER PRO SER
SER LEU SER ALA SER
VAL GLY ASP ARG VAL
THR ILE THR CYS ARG
ALA SER GLN
SER
ILE SER ASN TYR LEU
ASN TRP TYR GLN GLN
LYS PRO GLY LYS ALA
PRO LYS LEU LEU ILE
TYR ALA ALA SER SER
LEU GLN SER GLY VAL
THR SER ARG PHE SER
GLY SER GLY SER GLY
THR ASP PHE THR LEU
THR ILE SER SER LEU
GLN PRO GLU ASP SER
ALA THR TYR TYR CYS GLN GLN SER TYR SER
THR LEU
ILE THR PHE GLY GLN GLY THR
ARG LEU GLU ILE
LYS
~p ~p ~p ~p ~p ~p ~p ~p ~p ~p ~p ILE ILE ILE ILE ILE ILE ILE ILE ILE ILE ILE GLN GLN GLN GLN GLN GLN GLN GLN GLN GLN GLN MET MET MET MET MET MET MET MET MET MET MET
THR THR GLN GLN SER SER PRO PRO SER SER
SER SER LEU LEU SER SER ALA ALA SER SER
VAL VAL GLY GLY ASP ASP ARG ARG VAL VAL
THR THR ILE ILE
THR THR CYS CYS ARG ARG
ALA ALA SER SER GLN GLN
THR THR THR THR THR THR THR THR THR GLN GLN GLN GLN GLN GLN GLN GLN GLN SER SER SER SER SER SER SER SER SER PRO PRO PRO PRO PRO PRO PRO PRO PRO SER SER SER SER SER SER SER SER SER
SER SER SER SER SER SER SER SER SER LEU LEU LEU LEU LEU LEU LEU LEU LEU SER SER SER SER SER SER SER SER SER ALA ALA ALA ALA ALA ALA ALA ALA ALA SER SER SER SER SER SER SER SER SER
VAL VAL VAL VAL VAL VAL VAL VAL VAL G~ G~ G~ G~ G~ G~ G~ G~ G~ ~p ~p ~p ~p ~p ~p ~p A~ ~p
ARG ARG ARG ARG ARG ARG ARG ARG ARG VAL VAL VAL VAL VAL VAL VAL VAL VAL
THR THR THR THR THR THR THR THR THR ILE ILE ILE ILE ILE ILE ILE ILE ILE THR THR THR THR THR THR THR THR THR CYS CYS CYS CYS CYS CYS CYS CYS CYS ARG ARG GLN GLN GLN GLN ARG ARG GLX
ALA ALA ALA ALA ALA ALA ALA ALA ALA SER SER SER ASN SER ARG SER SER SER GLN GLN GLN GLN GLN H~ GLX GLX GLN
GLY GLY GLY GLY SER VAL ASP ASP SER SER ASP
ILE ARG ASN ASP LEU
GLY TRP TYR GLN GLN
LYS PRO
ILE ARG ASN ASP LEU
GLY TRP TYR GLN GLN
LYS PRO
ILE ILE ILE ARG ARG ASN ASN ASN LYS ASP ASP TYR LEU LEU ALA
GLY GLY ASN TRP TRP TRP TYR TYR TYR GLN GLN GLU GLN GLN GLN
LYS LYS # PRO PRO PRO
# LYS ALA
PRO LYS LEU
ASP SER ARG
LEU GLU THR GLY ASX
PRO SER LYS VAL SER
GLY SER GLY SER GLU
THR ASP VAL THR VAL
ASX GLX SER SER LEU
GLN PRO GLU ASP ILE
ALA PRO LYS
GLN GLN ARG ASP ASP
LEU PRO
TYR THR LEU GLY GLY GLY THR
LYS VAL GLU MET
LYS
ILE ILE SER ARG LYS SER SER TYR LEU LEU
ASN ASN TRP TRP TYR TYR GLN GLN GLN GLN
ARG LYS PRO GLN GLY GLY GLN LYS ALA ALA
PRO PRO LYS LYS LEU LEU LEU LEU ILE ILE
TYR TYR ASP ASP ALA ALA ALA SER ASX
LEU LEU GLU GLU
GLY VAL
PRO
ARG PHE THR
GLY
GLY
ILE SER ASN TYR LEU
ASN TRP PHE GLN GLN
LYS PRO GLY
ILE ILE ILE SER SER SER SER SER ASP TYR TYR TYR LEU LEU VAL
ASX ASX ASN TRP TRP TRP TYR TYR GLX GLX
PFIZER EX. 1052 Page 9
HUMAN KAPPA LIGHT CHAINS SUBGROUP I (cont'd)
F R 1
c D R 1
F R 2
c D R 2
F R 3
c D R 3
F R 4
0 1 2 3
,4
5 6 7 8 9
10 11 12 13 14
15 16 17 18 19
20 21 22 23 24
25 26 27 27A 278
27C 27D 27E 27F 28
29 30 31 32 33
34 35 36 37 38
39 40 41 42 43
44 45 46 47 48
49 50 51 52 53
54 55 56 57 58
59 60 61 62 63
64 65 66 67 68
69 70 71 72 73
74 75 76 77 78
79 80 81 82 83
84 85 86 87 88 89 90 91 92 93
94 95 95A 958 95C
95D 95E 95F 96 97 98 99
100 101 102
103 104 105 106 106A
107 108 109
24 25* 26 27 28 TEl
29 BJ 48
30 31 32 AMYLOID LOW DIE CAR CON TRA AMYLOID
LEP VIII-B A
ASP ILE
GLN MET
THR GLN SER PRO SER
SER LEU SER ALA SER
VAL GLY ASP ARG VAL
THR ILE THR CYS GLN
ALA SER GLN
ASX
ILE GLY
TYR LEU
TRP
~P A& ~P A& ~p ~p ~p ILE ILE ILE ILE ILE ILE ILE G~ G~ G~ G~ G~ G~ G~ M8 M8 M8 M8 M8 M8 M8
THR THR THR THR THR THR THR G~ G~ G~ G~ G~ G~ G~ SER SER SER SER SER SER SER PRO PRO PRO PRO PRO PRO PRO SER SER SER SER SER SER SER
SER SER SER SER SER SER SER LEU LEU LEU LEU LEU LEU LEU SER SEA SER SER SER SER SER ALA ALA ALA ALA ALA ALA ALA SER SER SER SER SER SER SER
VAL GLY ASP ARG VAL
THR ILE THR CYS ALA
ALA SER GLN
ASX
ILE SER
VAL GLY ASP ARG VAL
THR ILE THR CYS
VAL GLY ASP ARG VAL
THR ILE THR CYS
VAL GLY ASP ARG VAL
THR ILE THR CYS
VAL VAL VAL GLY GLY GLY ASP ASP ASP ARG ARG ARG VAL VAL VAL
THR THR THR ILE ILE ILE THR THR THR CYS
ALA
PRO LYS
GLY ASP ALA SER SER
LEU ASX SER GLY VAL
VAL SER ARG GLN SER
GLY SER GLY SER GLY
THR ASP PRO SER LEU
ALA VAL SER ARG
GLY GLU SER
ASP SER
ARG THR PHE GLY GLN GLY THR
LYS VAL GLU VAL
LYS
ASP ILE
GLN MET
THR GLN SER PRO SER
SER LEU SER ALA SER
VAL GLY ASP ARG VAL
THR
42
33 34 F- OU
GUI (IOC) #
ASP ILE
GLN MET
THR GLN SER PRO SER
ASP ILE
GLN MET
THR GLX SER PRO SER
35 36 37 38 39" 40 41 DEE GAL JOH KER LAY BRA WES
(I)
42 Vb 'CL
43 Vb' 'CL
ASX ASP ASP ASP ASP ASP ASP ASP ASP ILE ILE ILE ILE ILE ILE ILE ILE ILE G~ G~ G~ G~ G~ G~ G~ G~ G~ MET MET MET MET MET MET M8 MET MET
THR THR THR THR THR THR THR THR THR G~ G~ G~ G~ G~ G~ G~ G~ G~ SER SER SER SER SER SER SER SER SER PRO PRO PRO PRO PRO PRO PRO PRO PRO SER SER SER SER SER SER SER SER SER
44 HK102
'CL #
# ASP ILE GLN MET
THR GLN SER PRO SER
SER SER SER SER SER SER SER SER SER SER SER thr LEU LEU LEU LEU LEU LEU LEU LEU val val val LEU SER SER SER SER SER SER SER SER SER SER SER SER ALA ALA ALA ALA ALA ALA val val ALA ALA ALA ALA SER SER SER SER SER SER SER SER SER SER SER SER
VAL GLY ASX ARG VAL
THR ILE THR CYS
VAL GLY ASX ARG VAL
THR ILE THR CYS ARG
VAL GLY ASP ARG VAL
THR ILE THR CYS ARG
VAL GLY ASP ARG VAL
THR ILE ile
CYS ARG
ALA ALA ALA ALA SER GLY SER GLX GLN GLN
THR SER GLY
ILE VAL ILE SER ASN ARG SER LYS ASN TYR TYR ASP LEU LEU LEU
ASX ASN THR TRP TRP TRP TYR TYR TYR GLX GLN GLN GLX GLN GLN
LYS LYS LYS PRO PRO PRO GLY GLY GLY LYS LYS LYS ALA ALA ALA
PRO PRO PRO ASX LYS LYS LEU VAL GLU LEU LEU LEU ILE ILE
TYR TYR ALA ALA ALA ALA ALA ALA SER SER SER ASX SER ASN
LEU LEU LEU HIS LYS GLN SER SER SER GLY GLY GLY VAL VAL VAL
PRO PRO PRO SER SER SER ARG ARG ARG PHE PHE PHE SER SER SER
GLY GLY GLY SER SER SER GLY GLY GLY SER SER ALA GLY GLY GLY
THR THR THR ASX ASP GLU PHE PHE PHE THR THR THR PHE LEU LEU THR THR THR ILE ILE ILE SER SER SER GLY GLY SER LEU LEU LEU
GLX LEU GLN PRO PRO PRO GLX GLU GLU ASP ASP ASP PHE PHE PHE
ALA ALA ALA THR THR THR TYR TYR TYR TYR TYR TYR CYS CYS CYS GLX GLX LEU GLX GLX GLN SER SER GLN TYR TYR ASN SER THR SER
SER THR TYR PRO PRO PRO
THR TYR ARG THR THR SER PHE PHE PHE GLY GLY GLY GLX PRO GLN GLY GLY GLY THR THR THR
ARG LYS LYS LEU VAL VAL GLX GLU GLU ILE MET ILE
LYS THR LYS ARG ARG ARG THR THR THR
VAL GLY ASP ARG VAL
THR ILE ser CYS
VAL GLY ASP ARG
ile
THR ILE THR CYS GLN
ALA SER GLN
VAL VAL GLY GLY ASP glx ARG ARG VAL VAL
THR THR ILE ILE THR THR CYS CYS
GL\ ALA SER GLN"-.
ASP ASN~ ILE VAL LYS ASN
ALA TYR LEU
ASN' TRP TYR GLN GLN
LYS PRO GLY LEU ALA
PRO LYS LEU LEU ILE TYR GLY ALA SER THR
ARG GLU ALA GLY VAL
PRO SER ARG PHE SER
GLY SER GLY SER GLY
THR ASP PHE THR PHE
THR ILE
SER SER LEU
GLN PRO GLU ASP ILE
ALA THR
TYR TYR TYR TYR CYS CYS GLN GLN GLN GLN TYR TYR ASP ASN ASP ASN
LEU TRP PRO PRO
PRO PRO THR THR PHE PHE GLY GLY PRO GLN GLY GLY THR THR
LYS LYS VAL VAL ASP GLU LEU VAL
LYS LYS ARG
VAL VAL VAL GLY GLY GLY ASP ASP ASP ARG ARG ARG VAL VAL VAL
THR THR THR ILE ILE ILE THR THR THR CYS CYS CYS ARG ARG ARG
ALA ALA ALA SER SER SER GLN GLN GLN
VAL GLY ASP ARG VAL
THR ILE THR CYS ARG
ALA SER GLN
ASP GLY GLY SER
ILE ILE ILE ILE SER SER SER SER HIS SER SER SER TRP TRP TRP TRP LEU LEU LEU LEU
ALA ALA ALA TRP TRP TRP TYR TYR TYR GLN GLN GLN GLN GLN GLN
LYS LYS LYS SER PRO PRO GLY GLY GLY LYS LYS LYS ALA ALA ALA
PRO PRO PRO LYS LYS LYS LEU LEU LEU LEU LEU LEU ILE ILE ILE
TYR TYR TYR SER ALA ALA ALA ALA ALA SER SER SER SER SER SER
LEU LEU LEU GLU GLN GLN ASN SER SER GLY GLY GLY VAL VAL VAL
PRO PRO PRO SER SER SER ARG ARG ARG PHE PHE PHE SER SER SER
GLY GLY GLY SER SER SER GLY GLY GLY SER SER SER GLY GLY GLY
THR THR THR GLU ASP ASP PHE PHE PHE THR THR THR LEU LEU LEU THR THR THR ILE ILE ILE SER SER SER SER SER SER LEU LEU LEU
GLN GLN GLN PRO PRO PRO GLU GLU GLU ASP ASP ASP PHE PHE PHE
ALA ALA ALA THR THR THR TYR TYR TYR PHE TYR TYR CYS CYS CYS GLN GLN GLN GLN GLN GLN ALA ALA ALA HIS ASN ASN SER SER SER
VAL PHE PHE PRO PRO PRO
LEU THR PHE GLY GLY GLY THR
THR VAL ASP ILE
LYS ARG
ALA TRP TYR GLN GLN
LYS PRO GLY LYS ALA
PRO LYS LEU LEU ILE
TYR ASP ALA SER SER
LEU GLU SER GLY VAL
PRO SER ARG PHE SER
GLY SER GLY SER GLY
THR GLU PHE THR LEU THR ILE SER SER LEU
GLN PRO ASP ASP PHE
ALA THR TYR TYR CYS GLN GLN TYR ASN SER
TYR SER
#
45 EU
46 47 DEN PAU
ASP ASP ASP ILE ILE ILE GLN GLN GLN MET MET MET
THR THR THR GLN GLN GLN SER SER SER PRO PRO PRO SER SER SER
thr thr thr LEU LEU LEU SER SER SER ALA ALA ALA SER SER SER
VAL VAL VAL GLY GLY GLY ASP ASP ASP ARG ARG ARG VAL VAL VAL
THR THR THR ILE ILE ILE THR THR THR CYS CYS CYS ARG ARG ARG
ALA THR ALA SER SER SEA GLN GLN GLN
SER SER SER
ILE ILE ILE ASN SER SER THR ARG SER TRP TRP SER LEU LEU LEU
ALA ALA ALA TRP TRP TRP TYR TYR TYR GLN GLN GLX GLN GLN GLX
LYS LYS LYS PRO PRO PRO GLY GLY GLY LYS GLU GLX ALA ALA ALA
PRO PRO PRO LYS LYS LYS LEU VAL LEU LEU LEU LEU MET ILE ILE
TYR TYR TYR LYS GLY GLX ALA ALA SER SER SER ASN
LEU LEU GLU GLU SER SER GLY GLY VAL VAL
PRO PRO SER SER ARG ARG PHE PHE ILE SER
GLY GLY SER SER GLY GLY SER SER GLY GLY
THR THR GLU GLU PHE PHE THR THR LEU LEU THR THR ILE ILE SER SER SER SER LEU LEU
GLN GLN PRO SER ASP ASP ASP ASP PHE PHE
ALA ALA THR THR TYR TYR TYR TYR CYS CYS GLN GLN GLN GLN TYR TYR ASN ASP SER SER
ASP PHE SER PRO
LYS TYR MET THR PHE PHE GLY GLY GLN GLN GLY GLY THR THR
LYS LYS VAL LEU GLU GLU VAL ILE
LYS LYS GLY ARG THR THR
Hl
F R 1
c D R 1
F R 2
c D R 2
F R 3
7 7 7 7 7
7 8 8 8 8 8 8 g, a· __ s, 8! 9( 9" 9: 9:
PFIZER EX. 1052 Page 10
HUMAN KAPPA LIGHT CHAINS SUBGROUP I (cont'd)
F R 1
c D R 1
c D R 2
0 1 2 3 4
5 6 7 8 9
10 11 12 13 14
15 16 17 18 19
20 21 22 23 24
25 26 27 27A 27B
27C 27D 27E 27F 28
29 30 31 32 33
34 35 36 37 38
39 40 41 42 43
44 45 46 47 48
49 50 51 52 53
54 55 56 57 58
59 60 61 62 63
64 65 66 67 68
69 70 71 72 73
74 75 76 77 78
79 80 81 82 83
84 85 86 87 88 89 90 91 92 93
94 95 95A 95B 95C
95D 95E 95F 96 97 98 99
100 101
F 102 R 103 4 104
105 106 106A
107 108 109
48 49 50 51 52 53'' HBJ FRA GR' PAUL MON HEI
4
54 55 56 POT S- AMYLOID
GUI BAN # #
ASP ASP ASP ASP ASP ASP ASP ASP ILE ILE ILE ILE ILE ILE ILE ILE G~ G~ G~ G~ G~ G~ G~ G~ MU MU MU MU MU MU MU MU THR THR THR GLN GLN GLN SER SER SER PRO PRO PRO SER SER SER
thr thr thr LEU LEU LEU SER SER SER ALA ALA ALA SER SER SER
THR GLN SER PRO SER
thr u:;u SER ALA SER
VAL VAL VAL VAL GLY GLY GLY GLY ASP ASP ASP ASP ARG ARG ARG ARG VAL VAL VAL VAL
THR THR THR THR ILE ILE ILE ILE THR THR THR THR CYS CYS CYS CYS ARG ARG ARG ARG
ALA ALA ALA ALA
~E~ ~~ .;~~ ~E~
SER ASX SER SER
VAL ILE ILE ILE ASN ASX SER SER ASN ASX SER SER TAP TYR TRP SER LEU LEU LEU
ALA ALA ALA TRP TRP TRP TYR TYR TYR GLN GLX GLN GLU GLX GLY
LYS LYS ARG PRO PRO PRO GLY GLX ALA
PRO LYS LEU LEU ILE
SER LYS THR SER SER
LEU GLU ARG GLY VAL
PRO SER ARG PHE ALA
GLY SER GLY
THR THR GLN GLN SER SER PRO PRO SER SER
thr thr LEU LEU SER SER ALA ALA SER SER
THR THR GLN GLN SER ala PRO PRO ala SEA
SER SER LEU LEU SER SER ALA ALA SEA SER
VAL VAL VAL VAL GLY GLY GLY GLY ASP ASP ASP ASX ARG ARG ARG ARG VAL VAL VAL VAL
THR THR THR THR ILE ILE ILE THR THR THR
CYS CYS ARG
ALA
ASP ILE
GLN leu
THR GLN SER PRO SER
SER LEU SER ALA SER
VAL GLY ASP ARG VAL
THR ILE
THR CYS ARG
ALA SER GLN
SER
VAL TYR ASN TYR VAL
ALA TRP PHE GLN GLN
LYS PRO GLY LYS ALA
PRO LYS SER LEU ILE
TYR ASP ALA SER THR
LEU GLN SER GLY VAL
PRO SER ASN PHE THR
GLY SER GLY SER GLY THR ASP PHE ILE LEU
THR ILE SER SER LEU
GLN PRO GLU ASP PHE
ALA THR TYR TYR CYS GLN GLN TYR ASN SER
TYR PRO
TYR THR PHE GLY GLN GLY THR
LYS # #
ILE
LYS ARG
43
57 BJ 19 #
58 59 60 61 62 63 Bl BEL JBL PAP CAR MEV
#
ASP ASP ASP ILE ILE ILE
GLN GLN GLN leu leu MET
THR THR THR GLN GLN GLN SER SER SER PRO PRO PRO SER SER SER
SER SER SER LEU LEU LEU SER SER SER ALA ALA ALA SER SER tyr
VAL VAL VAL GLY GLY GLY ASP ASP ASP ARG ARG ARG VAL VAL VAL
THR THR THR ILE ILE ILE
THR THR ala CYS CYS CYS GLN GLX ARG
ALA ALA ALA SER SER SER GLN GLX GLN
ASP ASX SER
ILE ILE ILE ASN SER SER THR LYS THR PHE PHE LEU LEU
ASN # TRP TRP TYR TYR GLU GLN GLN GLN
# LYS PRO PRO
# GLY GLY LYS LYS LYS ALA PRO ALA
PRO PRO PRO LYS GLU LYS LEU LEU LEU LEU LEU LEU ILE ILE
TYR TYR TYR ASP ASP ALA ALA SER SER SER THR
LEU LEU GLU LYS THR THR GLY GLY VAL VAL
GLX PRO SER SER ARG ARG PHE PHE LEU SER
GLY GLY SER SER ASX GLY PHE SER ASX GLU
THR THR LYS HIS
PHE THR LEU
THR ILE
SER LEU
GLN PRO ALA ASP PHE
ALA THR TYR TYR CYS GLN GLN
PHE TYR ASP ASX ASP HIS
LEU PHE PRO PRO
TYR LEU THR THR PHE PHE GLY GLY PRO GLY GLY GLY THR THR
LYS GLU VAL VAL GLU GLU LEU VAL
LYS LYS
ASP ASP ASP ASP ILE ILE val ILE
GLN GLN GLN GLN MET MET MET MET
THR THR THR THR GLN GLN GLN GLN SER SER SER SER PRO PRO PRO PRO SER SER SER SER
r~n c~G r~n E£~ SER SER SER SER val ALA ALA ALA
SER SER SER SER
VAL VAL VAL VAL GLY GLY GLY GLY ASP ASP ASP ASP ARG ARG ARG ser VAL VAL VAL VAL
THR ala ile THR ILE ILE ILE ILE ala THR THR THR
CYS CYS CYS ARG ARG GLN
ALA ALA ALA SER SER SER GLN GLN GLN
ASN SER ASP
ILE SER ILE SER VAL ARG SER ASP ASN TRP TYR SER LEU LEU LEU
ALA ASN ILE TRP TRP TRP TYR TYR TYR GLN GLN GLN GLN GLN GLN
LYS LYS LYS PRO PRO PRO GLY GLY GLY LYS LYS LYS ALA ALA ALA
PRO PRO PRO LYS LYS LYS VAL LEU PHE LEU LEU LEU ILE ILE ILE
TYR PHE TYR LYS ASP ASP SER THR ALA SER SER GLU SER ASN ASN
LEU LEU LEU GLU GLN GLU SEA SER ILE GLY GLY GLY VAL VAL VAL
PRO PRO SER SER SER ARG ARG ARG PHE PHE PHE SER SER ARG
GLY GLY GLY SER GLY SER GLY ARG GLY SEA SER SER GLY GLY GLY
THR THR THR ASP ASP ASP PHE PHE PHE THR THR ALA LEU LEU LEU
THR THR SER ILE ILE ILE
SER SER SER SER SER SER LEU LEU LEU
GLX GLN GLN PRO PRO PRO ASX ASP GLU ASX ASP ASP PHE PHE PHE
ALA ALA ALA THR THR THR TYR TYR TYR TYR TYR TYR CYS CYS CYS GLN GLN GLN GLN GLN GLN TYR SER TYR ASN TYR TYR THR THR ASN
PHE ASN LEU PRO PRO GLU
PHE VAL TYR THR THR THR PHE PHE PHE GLY GLY GLY PRO GLY GLN GLY GLY GLY THR THR THR
LYS THR LYS VAL VAL LEU ASP ASP GLU ILE ILE ILE
LYS LYS LYS ARG ARG ARG THR THR
64 65 66'' 67* FIN
68 KA
69 Vd 'CL
70 LUX
71 NE
72 Va' 'CL
AMYLOID CRA DAV ES305
#
ASP ILE
GLN leu
THR GLN SER PRO SER
SER LEU SER ALA SER
VAL GLY ASP
VAL
THR #
THR CYS GLN
ALA SER GLU
ALA
#
ASN TYR LEU
TRP TYR
ASP ASP ASP ASP ASP ASP ASP ala ILE GLN leu
ILE ILE ILE ILE ILE ILE ILE G~ G~ G~ G~ G~ G~ h~ MET MET MET MET leu leu leu
THR GLN SER PRO SER
SER LEU SER ALA SER
leu arg ASP ARG VAL
THR THR THR GLN GLN GLN SER SER SER PRO PRO PRO SER SER SER
SER SER thr LEU LEU LEU SER SER SER thr thr val val val SER
VAL VAL VAL GLY GLY GLY ASP ASP ASP ARG ARG ARG VAL VAL VAL
THR GLN SER PRO SER
E~G SER ALA SER
VAL GLY ASP ARG VAL
THR GLN SER PRO SER
E~G SER ALA SER
VAL GLY ASP ARG VAL
THR GLX SER PRO SER
SER LEU SER ALA SER
VAL GLY ASX ARG VAL
THR GLN SER PRO SER
SER LEU SER ALA SER
VAL GLY ASP ARG VAL
THR THR THR THR THR THR THR ILE ILE ILE ILE ILE ILE ILE ~R ffiR ffiR ffiR ffiR ffiR ffiR
THR ILE THR CYS CYS CYS CYS CYS CYS
ASP ASP GLU ARG
ALA ALA ALA ALA SER SER SER SER GLN GLN GLN GLN
ASX ASX THR GLY
ILE ILE VAL ILE ASX ASX LEU SER SER SEA SER SER TRP TRP TYR TYR LEU LEU LEU LEU
I LE ILE ASN ALA TRP TRP TRP TRP TYR TYR TYR TYR GLN GLN GLN GLN GLN GLN GLN GLN
TYR TYR LYS LYS PRO PRO PRO PRO
GLY GLY LYS LYS ALA ALA
PRO PRO LYS LYS LEU LEU LEU LEU ILE ILE
TYR TYR ALA ALA ALA ALA SER SER SER THR
LEU LEU GLU GLN THR SEFi GLY GLY VAL VAL
PRO PRO SER SER ARG ARG PHE PHE SER SER
GLY GLY GLN SER GLY GLY SER SER GLY GLY
THR THR ASX GLU PHE PHE THR THR PHE LEU
THR THR ILE ILE SER SER SER SER VAL LEU
GLX GLN PRO PRO GLX GLU ASX ASP PHE PHE
ALA ALA THR THR TYR TYR TYR TYR CYS CYS GLN GLN GLX GLN TYR LEU LEU ASN ASP SER
LEU TYR PRO PRO
ARG THR PHE GLY GLN GLY THR
LYS VAL ASP LEU
LYS ARG THR
GLX ARG
ALA ALA SER SER GLX GLN
ASX GLY
ILE ILE SER SER ASX SER TYR ALA LEU LEU
ASX ALA TRP TAP TYR TYR GLX GLN GLX GLN
LYS LYS PRO PRO GLY GLY GLX LYS ALA ALA
PRO PRO LYS LYS VAL LEU MET LEU ILE ILE
TYR TYR ASP ALA SER SEA
LEU GLU SER GLY VAL
PRO SER ARG PHE SER
GLY SER GLY SER GLY
THR ASP PHE THR LEU
THR ILE SER SER LEU
GLN PRO GLU ASP PHE
ALA THR TYR TYR CYS GLN GLN PHE ASN SER
TYR PRO
PFIZER EX. 1052 Page 11
44
HUMAN KAPPA LIGHT CHAINS SUBGROUP I (cont'd)
73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92'' 93 . 94 95 96 Nl PW AMYLOID ALE SHE ADA KUE GO BOL Rl Ve OCO V13 V18A V19A V19B V18B HF6- SAC WAG HBJ AMYLOID WEB HOE
# X # 'CL 'CL 'CL 'CL 'CL 'CL 21/28 1 547
F R 1
c D R 1
F R 2
c D R 2
F R 3
c D R 3
F
0 1 2 .3 4
5 6 7 8 9
10 11 12 13 14
15 16 17 18 19
20 21 22 23 24
25 26 27 27A 278
ASP ASP ILE ILE
GLN his MET MET
THR THR GLN GLN SER SER PRO PRO SER SER
SER SER LEU LEU SER SER ALA ALA thr SER
VAL VAL GLY GLY ASP ASP ARG ARG VAL VAL
THR THR leu val leu arg
CYS CYS GLU ARG
ALA ALA SER SER GLN G~ SER VAL
27C LEU 27D GLU 27E 27F 28 SER SER
29 30 31 32 33
34 35 36 37 38
39 40 41 42 43
44 45 46 47 48
49 50 51 52 53
54 55 56 57 58
59 60 61 62 63
64 65 66 67 68
69 70 71 72 73
GLY ILE ASN GLY THR PHE TYR LEU SER
ALA ASX TRP TRP TYR GLN GLN GLN GLN
LYS LYS PRO LYS LYS ALA
PRO LYS LEU LEU JLE
TYR ASP ALA SER ASN
LEU GLU THR GLY VAL
PRO SER ARG PHE SER
GLY SER GLY SER GLY
THR ASP PHE THR PHE
74 THR 75 JLE 76 SER 77 GLY 78 LEU
79 GLX 80 PRO 81 GLX 82 ASX 83 PHE
84 ALA 85 VAL 86 TYR 87 TYR 88 CYS 89 GLN 90 G~ 91 TYR 92 ASP 93 THR
94 LEU 95 PRO 95A 958 95C
95D 95E 95F 96 97 98 99
100 101 102
SER THR PHE GLY VAL GLY SER
R 103 4 104
LYS VAL GLU SER
105 106 106A
107 108 109
LYS ARG THR
ASP ILE
GLN MET
THR GLN SER ala
SER
SER LEU SER ALA SER
VAL GLY ASP ARG VAL
ile ILE
CYS GLX
ALA
GLX
ASX
ILE
PRO TYR LEU
TYR
pea ASX ASP ASP ASP ASP ASP ASP ala ASX val ASP ala ILE ILE ILE ILE val ILE ILE ILE ILE ILE pro gin G~ G~ G~ G~ G~ G~ G~ a~ G~ t~ ~ ~ MET leu val MET MET ile MET MET MET MET MET leu
THR THR THR THR THR met THR THR THR THR THR THR G~ G~ G~ G~ G~ G~ G~ G~ G~ G~ G~ G~ SER SER SER SER SER SER SER SER SER SER thr thr PRO PRO PRO PRO PRO PRO PRO PRO PRO PRO PRO PRO SER thr SER SER SER SER SER SER SER SER SER ala
SER SER thr phe SER thr SER SER leu SER SER LEU LEU gin val val LEU phe LEU LEU thr val
SER SER SER pro SER SER SER SER val SER SER SER ALA ALA val ALA ALA ALA ALA ALA ser ALA ALA ALA SER SER phe SER SER SER SER SER pro SER ala ala
VAL VAL VAL VAL VAL VAL VAL thr VAL thr VAL VAL G~ G~ G~ G~ G~ G~ G~ G~ G~ G~ G~ G~ ASP ASX ASP ASP ASX ASX ASP ASP ASX ASP gly gly ARG ARG ARG ARG ARG ARG gly ARG leu ARG thr thr VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL
THR THR THR THR THR THR THR THR THR THR THR THR leu phe ILE ILE ILE ILE ILE ILE ILE ILE ILE ILE
THR THR THR THR THR THR ser THR THR ser asn asn CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS ARG GLX GLX ARG ARG ARG ARG ARG GLX ARG GLN GLN
ALA ALA ALA ALA ALA ALA ALA ALA MET SER ALA SER SER SER SER SER SER SER SER SER SER SER G~ G~ G~ G~ G~ G~ G~ G~ G~ GW
ASN VAL
ala ILE asp MET
THR GLN thr
PRO ala
SER val glu ALA ala
VAL GLY gly thr ile
THR ILE asn CYS GLN
ALA SER GLU
ala gin val leu
THR GLN thr glu SER
pro val
SER ALA pro
VAL GLY gly thr VAL
THR ILE asn CYS GLN
ALA SER GLN SER VAL
ASP val val
MET
THR GLN SER PRO leu
SER LEU pro val thr
leu GLY gly pro ala
ser ILE ser
CYS ARG
SER SER GLN SER LEU
VAL TRP SER
ASX ASX SER GLY SER GLY ASX GLY TYR SER SER TYR ASP
ILE JLE ILE SER ASN ASX ASX JLE TYR TYR TRP LEU LEU LEU
ASX ASX ALA TRP TRP TRP TYR TYR TYR HIS GLX GLN GLX TYR GLN
LYS LYS LYS PRO PRO PRO
GLU LYS ALA
PRO LYS LEU LEU JLE
TYR
ILE JLE ILE JLE SER SER SER
SER ASX TYR TYR LEU
ALA TRP TYR GLN GLN
LYS PRO GLY LYS ALA PRO LYS LEU LEU JLE
TYR
JLE SER JLE SER ASN SER SER ASN SER TYR TYR TYR LEU LEU LEU
ALA SER ASN TRP TRP TRP TYR PHE TYR GLN, GLN GLN GLN GLN GLN
JLE SER SER TRP LEU
ALA TRP TYR GLN GLN
ASP ASN ASN TRP LEU
SER TRP TYR GLN GLN
GLY ARG SER TYR LEU
GLU TRP TYR GLN GLN
L YS L YS L YS L YS L YS L YS PRO PRO LEU PRO PRO PRO GLY GLY GLY GLY GLY LYS GLN GLN GLN GLN ALA PRO PRO PRO PRO
PRO PRO PRO PRO PRO G LU L YS L YS L YS L YS LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU JLE ILE ILE ILE ILE
TYR TYR TYR TYR TYR
ASP ASP ASP ILE ILE ILE
GLN GLN leu MET MET MET
THR THR THR GLN GLN GLN SER SER SER PRO PRO PRO SER SER thr
SER SER SER LEU LEU LEU SER SER SER ALA ALA ALA SER SER SER
VAL VAL VAL GLY GLY GLY ASP ASP ASP
LYS ALA SER THR
ALA ALA SER THR
ALA GL Y TYR GLU ASP L YS
LEU GLU THR GLY VAL
PRO SER ARG PHE SER
GLY SER GLY SER GLY
THR GLN PHE THR LEU
THR ILE ASN SER LEU
GLN PRO ASP ASP PHE
ALA THR TYR TYR CYS GLN GLN TYR SER ARG
TYR PRO
TYR THR PHE GLY GLN GLY THR
LYS LEU ASP ILE
LYS ARG THR
LEU GLN SER GLY VAL
PRO SER ARG PHE SER
GLY SER GLY SER GLY
THR ASP PHE THR LEU
THR JLE SER CYS LEU
GLN SER GLU ASP PHE
ALA THR TYR TYR CYS GLN GLN TYR TYR SER
TYR PRO
ALA ALA ALA ALA ALA SER SER SER SER SER SER THR LYS THR LYS LYS
LEU LEU LEU LEU LEU GLN ALA ALA ALA ALA SER SER SER SER SER GLY GLY GLY GLY GLY VAL VAL VAL VAL VAL
PRO PRO PRO PRO PRO SER SER SER SER SER ARG ARG ARG ARG ARG PHE PHE PHE PHE PHE SER SER LYS SER SER
GLY GLY GLY GLY GLY SER SER SER SER SER GLY GLY GLY GLY GLY SER SER SER SER SER GLY GLY GLY GLY GLY
THR LYS THR THR THR ASP GLN GLU GLN GLN PHE PHE TYR PHE PHE THR THR THR THR THR LEU LEU LEU LEU LEU
THR THR THR THR THR ILE ILE ILE JLE JLE SER SER SER SER SER CYS GLY GLY GLY GLY LEU VAL VAL VAL VAL
GLN GLN GLN GLN GLN SER CYS CYS CYS CYS GLU ASP ASP ASP ASP ASP ASP ASP ASP ASP PHE ALA ALA ALA ALA
ALA ALA ALA ALA ALA THR THR THR THR THR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR CYS CYS CYS CYS CYS GLN ALA GLN GLN GLN GLN GLY HIS GLY GLY TYR TYR GLY GLY SER TYR TYR TYR TYR TYR SER TYR ILE TYR TYR
PHE SER TYR ASN SER PRO GLY SER SER SER
SER SER GLY GLY GLY GLY TRP TRP THR ASP TYR TYR
ASP
CYS GLX GLX GLX ASX ALA
ALA· THR
ILE PRO ILE GLY GLY GLY THR
LYS VAL ASX VAL
LYS ARG THR
ASP ILE
GLX MET
THR GLN SER PRO SER
SER LEU SER ALA SER
VAL
ASP ASP ILE ILE
GLN GLN MET MET
THR THR GLN GLN SER SER PRO PRO SER SER
SER thr val LEU
SER SER ALA ALA SER SER
VAL VAL
HUMA
F R 1
c D R 1
F R 2
c D R 2
F R 3
c D R 3
F R 4
__ 1
PFIZER EX. 1052 Page 12
45
HUMAN KAPPA LIGHT CHAINS SUBGROUP I (cont'd)
97 98 99 100 101 102 103 1048 105 106 107 108 109 110 111 # OF # OF OCCURRENCES
1 LOD HBJ BEN GR MAA MUK AMYLOID MAR AMYLOID BJ HBJ PEN AMYLOID CL" GM131 SEQUENCES AMINO OF MOST COMMON
10 594 6 MS 'CL ACIDS AMINO ACID # #
~ 0 1 1(PCA)
I 1 ASP ASP ASP ASP ASP ASP ASP ASP ASP ASX ASP ASP ASP 109 3: 4 1 03(ASP) 99(ASP) 2 ILE ILE ILE ILE ILE ILE ILE ILE ILE ILE ILE # 107 4 101(1LE) 3 GLN GLN GLN GLN GLN GLN GLN GLN Jlu GLN GLN GLN 108 8 97(G LNJ : 93(G LN) 4 MET MET MET leu MET MET leu ET MET MET MET MET 108 4 3(MET)
l 5 THR THR THR THR THR THR THR THR pro THR THR THR 108 3 106(THR) 6 GLN GLN GLN GLN GLN GLN GLN GLN GLN GLN GLN 107 2 107(GLN) : 100(GLN) 7 SER SER SER SER SER SER SER SER SER 105 3 100(SERl
I 8 PRO PRO PRO PRO PRO PRO PRO PRO PRO 105 3 103~PRO 9 SER SER SER SER SER SER SER SER SER 105 4 99 SER)
10 thr SER SER SER thr SER SER SER SER 104 5 81(SER) 11 LEU LEU LEU LEU LEU LEU LEU LEU 103 5 91(LEU) 12 SER SER SER SER SER SER 102 4 98(SER)
1 13 ALA ALA ALA val ALA 101 4 91(ALA)
l 14 SER 97 7 86(SER)
15 VAL 97 3 93~VA~
t 16 93 2 92 GL ) 17 93 3 4 87(ASP) : 79(ASP) 18 ARG 90 6 82(ARG)
I 19 VAL 91 3 88(VAL)
I 20 THR 91 4 87\THR)
j 21 ILE 88 4 841LE) 22 THR 88 7 75(THR) 23 CYS 83 1 83 CYS
24 GLN 75 5 43(ARG)
25 ALA 75 4 71\AL~ 26 SER 72 4 67 SE ) 27 GLN 72 4 66(GLN) 53(GLN)
l 27A 4 2 3(SER) 278 4 2 3(VAL)
i c 27C 2 2 1( +)
0 27D 2 2 1( +) 27E 1 1 1(SER)
I R 27F 1 28 ASP 72 8 25(ASP) 22(SER)
I 29 ILE 71 5 61(1LE) 30 ASN 68 10 : 11 35(SER) 31 LYS 66 10 24(SER) 32 66 7 33(TYR) 33 64 4 60(LEU)
34 60 7 8 24 ASN 22 ALA
( 35 63 1 63(TRP) 36 61 2 57(TYR)
1 37 60 4 56\GLN) : 49(GLNl 38 58 4 55 GLN) : 50(GLN
39 55 4 50(LYS) 40 57 4 54( PRO)
'l 41 44 3 40tLY) 42 46 5 35 LYS) 43 47 2 42 ALA)
~ 44 47 1 47(PRO) 45 47 6 41(LYS)
~ 46 46 7 33(LEU) 47 45 2 44(LEU) 48 43 2 42(1LE)
I 49 45 4 42 TYR 50 45 7 : 8 15( + )
I c 51 45 5 39(ALA) 52 44 4 41(SER)
D 53 43 5 18(SER) R 2 54 44 2 43(LEU)
55 44. 7 20(GLU) 56 42 7 27 SER 57 43 1 43(GLY) 58 43 2 42(VAL)
59 42 4 39(PRO) 60 42 1 42(SER) 61 43 3 41(ARG) 62 43 3 41(PHE) 63 43 7 36(SER)
i 64 43 1 43\GLY) 65 42 4 38 SER) 66 43 3 41(GLY)
' 67 41 3 38(SER) 68 41 3 38(GLY)
{ 69 41 3 38(THR)
t 70 41 5 6 25(ASP) 23(ASP)
F 71 40 4 36\PHEl 72 40 4 37 THR
l R 73 40 3 31(LEU) 3
74 40 4 37\THR)
I 75 40 3 38 ILE) 76 39 2 37(SER) 77 40 5 27(SER) 78 LEU 40 2 35(LEU)
79 GLN 40 2 : 3 39(GLN) : 35(GLN) \ 80 PRO 40 3 33(PRO)
l 81 GLU 40 3 5 29(GLU) : 26(GLU) 82 ASP 40 1 2 40(ASP) : 37(ASP) 83 PHE 40 4 28(PHE)
84 ALA 40 2 39~ALA) 85 THR 40 4 37 THR)
I 86 TyR TYR 42 2 41(TYR) 87 TYR TYR 41 2 40~TYRl 88 CYS CYS 42 1 42 CYS
l 89 GLN GLN 43 3 : 4 40(G LN) : 37(G LN) 90 GLN GLN 43 3 : 4 39(GLN) : 34(G LN)
I 91 TYR HIS 45 10 : 11 24(TYR) 92 GLU ASP ASP 46 8 15(ASN) : 13( + ) 93 ASN ILE HIS 46 9 20(SER)
c 94 LEU PHE LEU 46 10 12~LEU) D 95 PRO PRO PRO 45 5 35 PRO)
R 95A 5 3 2( + )
1 3 958 4 2 2( + )
95C 4 3 2(TYR)
I 95D 1 1(ASP) 95E 95F 96 TYR GLY LEU 32 12 9~TYR)
l 97 THR THR 31 4 27_THR)
I 98 PHE PHE 31 3 29\PHE) >1 99 GLY GLY 31 1 31 GLY)
100 GLN GLY 31 4: 5 18(GLN) : 17(GLN) 101 GLY GLY 31 1 31~GLY~
F 102 THR THR 31 2 30 THR
R 103 LYS THR 31 4 23(LYSl 4 104 VAL VAL 30 2 23(VAL
105 GLU GLU 30 3 : 4 20(GLU) : 19(GLU) 106 ILE MET 31 7 15(1LE) 106A
1 107 LYS LYS 31 2 29 LYS 108 ARG ARG 24 22(ARG) 109 THR THR 20 20(THR)
I ( l
PFIZER EX. 1052 Page 13
46
HUMAN KAPPA LIGHT CHAINS SUBGROUP I (cont'd) ANTI
VARIABILITY 8)
25)
39)
53) I
0 1 3.2 : 4.4
66) I
2 4.2 67) I
3 8.9 : 9.3 92) ' 4 4.6
5 3.1 104) ,
6 1. 2.1 7 3.2 ALLO' 8 3.1 9 4.2 79) ~
F 10 6.4
R 11 5.7
1 12 4.2 CLAS~
13 4.4 14 7.9 8) \1
15 3.1 33) f. 16 2. 55) S· 17 3.2 : 4.7 18 6.6 74) P' 19 3.1 82) Rl
20 4.2 21 4.2 22 8.2 REFER!
23 1. 24 8.7
1) R(
25 4.2 26 4.3 27 4.4 : 5.4 27A
2) AL
278 3) RE
c 27C 4) HA
0 270
R 27E 5) HK
1 27F 6) sc 28 23. : 26.
29 5.8 7) AG 30 19. : 21. 31 28.
8) WE
32 14. 9) HK· 33 4.3 10) HK· 34 18. : 22. 35 1.
11) DAI
36 2.1 12) WA
37 4.3 : 4.9 38 4.2 : 4.6 13) HF3
39 4.4 40 4.2 14) HF2
F 41 3.3 R 42 6.6 2 43 2.2 15) HF2·
44 1. 45 6.9 16) HF2·
46 9.8 47 2. 17) BJ2E 48 2. 18) RFZ: 49 4.3 50 21. : 24. 19) PSM: 51 5.8 c 52 4.3 20) HOM
0 53 12. : 14. R
21) ESM
2 54 2. 22) ESM 55 15. 56 11. 23) WAT:
57 1. 58 2. 24) AMYL
59 4.3 25) LOW: 60 1. 61 3.1 26) DIE: 62 3.1 63 8.4 27) CAR ,
64 1. 28) TEl: 65 4.4 66 3.1
29) BJ48:
67 3.2 30) CON: 68 3.2 31) TRA: 69 3.2 70 8.2 : 11.
32) AMYL<
F 71 4.4 33) F-GUI:
R 72 4.3 34) OU(IOI 3 73 3.9
74 4.3 35) DEE: 75 3.2 76 2.1 36) GAL(I): 77 7.4 78 2.3
37) JOH:
79 2.1 : 3.4 38) KER:
80 3.6 39) LAY: ' 81 4.1 : 7.7 82 1. : 2.2 40) BRA: 83 5.7
84 2.1 41) WES:
85 4.3 42) Vb'CL: 86 2. 87 2.1 43) Vb"CL: 88 1. I 89 3.2 : 4.6 90 3.3 : 5.1 44) HK102'C
91 19. : 21. 45) EU: GC 92 25. : 28. 93 21. 46) DEN:
c 94 38. 47) PAU: [
0 95 6.4 (I
R 95A 48) HBJ4: 956 3 95C
49) FRA: M T1
950 95E
50) GR': FP
95F 51) PAUL: : 96 43. 97 4.6 52) MON: ~
98 3.2 53) HEI: RIE 99 1. 54) POT:
100 6.9 : 9.1 CJ
101 1. 55) S·GUI: \
F 102 2.1 56) AMYLOID R 103 5.4 57) BJ19: 4 104 2.6
AI
105 4.5 : 6.3 58) BEL: Mlo 106 14. A~
106A 59) JBL: SEI 107 2.1 60) PAP: Nlf 108 2.2 109 1.
61) CAR: Mil 62) MEV: EU
PFIZER EX. 1052 Page 14
l \ I
I t J I ~ I
l ~
I l
I r
j
l
ANTIBODY SPECIFICITIES: HUMAN KAPPA LIGHT CHAINS SUBGROUP I
B) WEA: ANTI-3,4-PYRUVYlATED GALACTOSE MONOCLONAL
25) LOW: COLD AGGLUTININ WITH ANTI-BLOOD GROUP I ACTIVITY
39) LAY: ANTI-HUMAN GAMMA G1 AND G3 GLOBULINS; PO IDIOTYPE
47
53) HEI: COLD AGGLUTININ WITH ANTI-GO (MEMBRANE-GLYCOLIPID-DEPENDENT) ACTIVITY
66) DAV: ANTI-HUMAN GAMMA G GLOBULIN
67) FIN: ANTI-HUMAN GAMMA G GLOBULIN
92) WAG: ANTI-DINITROPHENYL
104) MAR: ANTI-LIPOPROTEIN LIPASE
ALLOTYPE: HUMAN KAPPA LIGHT CHAINS SUBGROUP I
79) KUE: INV(2)
CLASS: HUMAN KAPPA LIGHT CHAINS SUBGROUP I
B) WEA: IGM-KAPPA
33) F-GUI: IGG3-KAPPA
55) S-GUI: IGG3-KAPPA
74) PW: IGG1-KAPPA
82) Rl: IGG1-KAPPA
REFERENCE: HUMAN KAPPA LIGHT CHAINS SUBGROUP I
1) ROY: HILSCHMANN,N. & CRAIG,L.C. (1965) PROC.NAT.ACAD.SCI.USA,53, 1403-1409; HILSCH MANN,N. (1967) Z.PHYSIOL.CHEM.,348, 1077-1 080; HILSCHMANN,N.,BARNIKOL,H.U.,HESS,M.,LANGER,B.,PONSTINGL,H.,STEINMETZ-KAYNE,M.,SUTER,L. & WATANABE,S. (1969) PROC. 5TH FEBS SYMP., 15,57-74. (CHECKED BY AUTHOR WHO PROVIDED ADDITIONAL RESIDUES TO THOSE PUBLISHED AND CORRECTED RESIDUES 65 AND 67 AS GIVEN IN THE TABLE)
2) AU: SCHIECHL,H. & HILSCHMANN,N. (1971) Z.PHYSIOL.CHEM.,352,111-115; (1972) Z.PHYSIOL.CHEM.,353,345-370. (CHECKED BY AUTHOR)
3) REI: PALM,W. & HILSCHMANN,N. (1973) Z.PHYSIOL.CHEM.,354,1651-1654; (1975) Z.PHYSIOL.CHEM.,356,167-191. (CHECKED BY AUTHOR)
4) HAU: WATANABE,S. & HILSCHMANN,N. (1970) Z.PHYSIOL.CHEM.,351,1291-1295. (CHECKED BY AUTHOR)
5) HK101'CL: BENTLEY,D.L. & RABBITTS,T.H. (1980) NATURE,288,730-733. (CHECKED BY AUTHOR 11/30/82)
6) SCW: EULITZ,M.,GOTZE,D. & HILSCHMANN,N. (1972) Z.PHYSIOL.CHEM.,353,487-491; EULITZ,M. & HILSCHMANN,N. (1974) Z.PHYSIOL.CHEM.,355,842-866. (CHECKED BY AUTHOR)
7) AG: TITANI,K.,SHINODA,T. & PUTNAM,F.W. (1969) J.BIOL.CHEM.,244,3550-3560. (CHECKED BY AUTHOR 06/15/83)
8) WEA: GONI,F. & FRANGIONE,B. (1983) PROC.NAT.ACAD.SCI.USA,80,4837-4841. (CHECKED BY AUTHOR 03/23/84)
9) HK137'CL: BENTLEY,D.L. & RABBITTS,T.H. (1983) CELL,32,181-189.
10) HK134'CL: BENTLEY,D.L. & RABBITTS,T.H. (1983) CELL,32,181-189.
11) DAUDI'CL: KLOBECK,H.G.,COMBRIATO,G. & ZACHAU,H.G. (1984) NUC.ACIDS RES.,12,18,6995-7006.
12) WALKER'CL: KLOBECK,H.G.,COMBRIATO,G. & ZACHAU,H.G. (1984) NUC.ACIDS RES.,12,18,6995-7006. (CHECKED BY AUTHOR 08/22/85 WHO CORRECTED RESIDUE 34)
I 13) HF3-16/6: ATKINSON,P.M.,LAMPMAN,G.W.,FURIE,B.C.,NAPARSTEK,Y.,SCHWARTZ,R.S.,STOLlAR,B.D. & FURIE,B. (1985) J.CLIN.INVEST.,75,1138-1143.
(CHECKED BY AUTHOR 08/21/85)
14) HF2-1/13B: ATKINSON,P.M.,LAMPMAN,G.W.,FURIE,B.C.,NAPARSTEK,Y.,SCHWARTZ,R.S.,STOLlAR,B.D. & FURIE,B. (1985) J.CLIN.INVEST.,75,1138-1143. (CHECKED BY AUTHOR 08/21/85)
15) HF2-18/2: ATKINSON,P.M.,LAMPMAN,G.W.,FURIE,B.C.,NAPARSTEK,Y.,SCHWARTZ,R.S.,STOLlAR,B.D. & FURIE,B. (1985) J.CLIN.INVEST.,75,1138-1143. (CHECKED BY AUTHOR 08/21/85)
16) HF2-1/17: ATKINSON,P.M.,lAMPMAN,G.W.,FURIE,B.C.,NAPARSTEK,Y.,SCHWARTZ,R.S.,STOLlAR,B.D. & FURIE,B. (1985) J.CLIN.INVEST.,75,1138-1143. (CHECKED BY AUTHOR 08/21/85)
17) BJ26: ALESCIO-ZONTA,L. & BAGLIONI,C. (1970) EUR.J.BIOCHEM.,15,450-463. (CHECKED BY AUTHOR)
18) RFZ: SMITHIES,O.,GIBSON,D.,FANNING,E.M.,GOODFLIESH,R.M.,GILMAN,J.G. & BALlANTYNE,D.L. (1971) BIOCHEMISTRY,10,4912-4921. (CHECKED BY AUTHOR)
19) PSM: SEON,B.K. (1982) MOL.IMMUNOL.,19,83-86. (CHECKED BY AUTHOR 05/23/83)
t
1 1
I I
I t ! I
20) HOM: SAVVIDOU,G.,KLEIN,M.,HORNE,C.,HOFMANN,T. & DORRINGTON,K.J. (1981) MOL.IMMUNOL.,18,793-805.
21) ESM IGG: KUAN,T.K.,TUNG,E.,WANG,I.Y. & WANG,A.C. (1981) IMMUNOL.,44,265-271. (CHECKED BY AUTHOR 05/26/83)
22) ESM IGM: KUAN,T.K.,TUNG,E.,WANG,I.Y. & WANG,A.C. (1981) IMMUNOL.,44,265-271. (CHECKED BY AUTHOR 05/26/83)
23) WAT: STEVENS,F.J.,WESTHOLM,F.A.,PANAGIOTOPOULOS,N.,SCHIFFER,M.,POPP,R.A. & SOLOMON,A. (1981) J.MOL.BIOL.,147,185-193. AUTHOR 05/26/1983)
(CHECKED BY
24) AMYLOID Vlll-8: GLENNER,G.G.,TERRY,W.,HERADA,M.,ISERSKY,C. & PAGE,D. (1971) SCIENCE,172,1150-1151. (CHECKED BY AUTHOR 09/22/78)
25) LOW: CAPRA,J.D.,KEHOE,J.M.,WILLIAMS,R.C.,JR.,FEIZI,T. & KUNKEL,H.G. (1972) PROC.NAT.ACAD.SCI.USA,69,40-43. (CHECKED BY AUTHOR WHO CORRECTED RESIDUE 16 AS GIVEN IN TABLE)
26) DIE: CAPRA,J.D. & KUNKEL,H.G. (1970) PROC.NAT.ACAD.SCI.USA,67,87-92. (CHECKED BY AUTHOR)
27) CAR A: CAPRA,J.D. & KUNKEL,H.G. (1970) PROC.NAT.ACAD.SCI.USA,67,87-92. (CHECKED BY AUTHOR)
28) TEl: CAPRA,J.D. & KUNKEL,H.G. (1970) PROC.NAT.ACAD.SCI.USA,67,87-92. (CHECKED BY AUTHOR)
29) BJ48: ALESCIO-ZONTA,L. & BAGLIONI,C. (1970) EUR.J.BIOCHEM.,15,450-463. (CHECKED BY AUTHOR)
30) CON: NIALL,H.D. & EDMAN,P. (1967) NATURE,216,262-263. (CHECKED BY AUTHOR 07/25/79)
31) TRA: NIALL,H.D. & EDMAN,P. (1967) NATURE,216,262-263. (CHECKED BY AUTHOR 07/25/79)
32) AMYLOID LEP: LIAN,J.B.,SKINNER,M.,BENSON,M.D. & COHEN,A.S. (1977) BIOCHIM.BIOPHYS.ACTA,491,167-176.
33) F-GUI: WANG,A.C.,FUDENBERG,H.H. & CREYSSEL,R. (1982) ACTA HAEMAT.,68,187-195. (CHECKED BY AUTHOR 05/26/83)
34) OU(IOC): KOHLER,H.,SHIMIZU,A.,PAUL,C. & PUTNAM,F.W. (1970) SCIENCE,169,56-59. (KAPlAN,A.P. & METZGER,H. (1969) BIOCHEMISTRY,8,3944-3951.) (CHECKED BY AUTHOR 06/15/83)
35) DEE: MILSTEIN,C. & DEVERSON,E.V. (1971) BIOCHEM.J.,123,945-958. (CHECKED BY AUTHOR)
36) GAL(I): LAURE,C.J.,WATANABE,S. & HILSCHMANN,N. (1973) Z.PHYSIOL.CHEM.,354,1503-1504. (CHECKED BY AUTHOR)
37) JOH: CAPRA,J.D. & KUNKEL,H.G. (1970) PROC.NAT.ACAD.SCI.USA,67,87-92. (CHECKED BY AUTHOR)
38) KER: MILSTEIN,C. (1966) BIOCHEM.J.,101 ,352-368. (CHECKED BY AUTHOR WHO PROVIDED ADDITIONAL RESIDUES TO THOSE PUBLISHED)
39) LAY: KAPlAN,A.P. & METZGER,H. (1969) BIOCHEMISTRY,8,3944-3951. (CHECKED BY AUTHOR); KLAPPER,D.G. & CAPRA,J.D. (1976) ANN.IMMUNOL.(INST.PASTEUR),127C,261-271. (CHECKED BY AUTHOR 08/01/79)
40) BRA: WANG,A.C.,WELLS,J.V.,FUDENBERG,H.H. & GERGELY,J. (1974) IMMUNOCHEM.,11,341-345. (CHECKED BY AUTHOR)
41) WES: KRATZIN,H.,YANG,C.Y.,KRUSCHE,J.U. & HILSCHMANN,N. (1980) Z.PHYSIOL.CHEM.,361,1591-1598.
42) Vb'CL: PECH,M.,JAENICHEN,H.-R.,POHLENZ,H.-D.,NEUMAIER,P.S.,KLOBECK,H.-G. & ZACHAU,H.G. (1984) J.MOL.BIOL.,176,189-204. (CHECKED BY AUTHOR 12/14/84)
43) Vb"CL: PECH,M.,JAENICHEN,H.-R.,POHLENZ,H.-D.,NEUMAIER,P.S.,KLOBECK,H.-G. & ZACHAU,H.G. (1984) J.MOL.BIOL.,176,189-204. (CHECKED BY AUTHOR 12/14/84)
44) HK102'CL: BENTLEY,D.L. & RABBITTS,T.H. (1980) NATURE,288,730-733. (CHECKED BY AUTHOR 11/30/82)
.,, 45) EU: GOTTLIEB,P.D.,CUNNINGHAM,B.A.,RUTISHAUSER,U. & EDELMAN,G.M. (1970) BIOCHEMISTRY,9,3155-3161. (CHECKED BY AUTHOR)
46) DEN: YANG,C.Y.,PAULY,E.,KRATZIN,H. & HILSCHMANN,N. (1981) Z.PHYSIOL.CHEM.,362,1131-1146.
I 47) PAU: DAYHOFF,M.O. (1972) ATLAS OF PROTEIN SEQUENCE & STRUCTURE,5,D-245. SUBMITTED BY SMITHIES,O.,GIBSON,D.M. AND FANNING,E.M. (CHECKED BY AUTHOR)
I 48) HBJ4: SMITH,G.P.,HOOD,L. & FITCH,W.M. (1971) ANN.REV.BIOCHFM.,40,969-1012.
·,~ 49) FRA: MEINKE,G.C.,SIGRIST,P.H. & SPIEGELBERG,H.L. (1974) IMMUNOCHEM.,11 ,457-460. (CHECKED BY AUTHOR WHO PROVIDED ADDITIONAL RESIDUES TO THOSE PUBLISHED); MEINKE,G.C. & SPIEGELBERG,H.L. (1976) IMMUNOCHEM.,13,915-919. (CHECKED BY AUTHOR 10/17/77)
50) GR': FAIR,D.S.,SLEDGE,C.,KRUEGER,R.G.,MANN,K.G. & HOOD,L.E. (1975) BIOCHEMISTRY,14,5561-5568.
51) PAUL: SMITH,G.P.,HOOD,L. & FITCH,W.M. (1971) ANN.REV.BIOCHEM.,40,969-1012.
I' 52) MON: NIALL,H.D. & EDMAN,P. (1967) NATURE,216,262-263. (CHECKED BY AUTHOR 07/25/79)
, 53) HEI: RIESEN,W.F.,MAJANIEMI,I.,HUSER,H.,BRAUN,D.G. & ROELCKE,D. (1978) SCAND.J.IMMUNOL.,8,145-148. (CHECKED BY AUTHOR 10/10/79)
j 54) POT: CAPRA,J.D. & KUNKEL,H.G. (1970) PROC.NAT.ACAD.SCI.USA,67,87-92. (CHECKED BY AUTHOR WHO CORRECTED RESIDUE 9 AS GIVEN IN TABLE)
;j 55) S-GUI: WANG,A.C.,FUDENBERG,H.H. & CREYSSEL,R. (1982) ACTA HAEMAT.,68,187-195. (CHECKED BY AUTHOR 05/26/83)
·,J;.· 56) AMYLOID BAN: DWULET,F.E.,O'CONNOR,T.P. & BENSON,M.D. (1986) MOL.IMMUNOL.,23,73-78. 57) BJ19: ALESCIO-ZONTA,L. & BAGLIONI,C. (1970) EUR.J.BIOCHEM.,15,450-463. (CHECKED BY AUTHOR)
58) BEL: MILSTEIN,C. (1969) PROC. 5TH FEBS SYMP.,15,43-56. (CHECKED BY AUTHOR WHO PROVIDED ADDITIONAL RESIDUES TO THOSE PUBLISHED 1 AND CORRECTED RESIDUES 1 ,3,6,27,79 AND 82 AS GIVEN IN TABLE)
! 59) JBL: SEON,B.K. (1982) MOL.IMMUNOL.,19,83-86. (CHECKED BY AUTHOR 05/23/83) ! 60) PAP: NIALL,H.D. & EDMAN,P. (1967) NATURE,216,262-263. (CHECKED BY AUTHOR 07/25/79)
· 61) CAR: MILSTEIN,C.P. & DEVERSON,E.V. (1974) EUR.J.BIOCHEM.,49,377-391. (CHECKED BY AUTHOR) I '""'" '"'"'·"· ' ""'-"' ''""" """''OLC"'"·'"'·'M'·'""· ''"'".o "'"moe '"'"""
l I
PFIZER EX. 1052 Page 15
48
REFERENCE: HUMAN KAPPA LIGHT CHAINS SUBGROUP I (cont'd)
63) Bl: BRAUN,H.,LEIBOLD,W.,BARNIKOL,H.U. & HILSCHMANN,N. (1971) Z.PHYSIOL.CHEM.,352,647-651; (1972) Z.PHYSIOL.CHEM.,353,1284-1306. (CHECKED BY AUTHOR WHO PROVIDED AN ADDITIONAL RESIDUE TO THOSE PUBLISHED AND CORRECTED RESIDUE 72 AS GIVEN IN TABLE)
64) AMYLOID ES305: WESTERMARK,P.,SLETTEN,K. & NATVIG,J.B. (1981) ACTA PATH.MICROBIOL.SCAND.,C89,199-203. (CHECKED BY AUTHOR 11/09/81)
65) CRA: NIALL,H.D. & EDMAN,P. (1967) NATURE,216,262-263. (CHECKED BY AUTHOR 07/25/79)
66) DAV: CAPRA,J.D. & KUNKEL,H.G. (1970) PROC.NAT.ACAD.SCI.USA,67,87-92. (CHECKED BY AUTHOR)
67) FIN: CAPRA,J.D. & KUNKEL,H.G. (1970) PROC.NAT.ACAD.SCI.USA,67,87-92. (CHECKED BY AUTHOR)
68) KA: SHINODA,T. (1975) J.BIOCHEM.,77,1277-1296. (CHECKED BY AUTHOR)
69) Vd'CL: PECH,M.,JAENICHEN,H.-R.,POHLENZ,H.-D.,NEUMAIER,P.S.,KLOBECK,H.-G. & ZACHAU,H.G. (1984) J.MOL.BIOL.,176,189-204. (CHECKED BY AUTHOR 12/14/84)
70) LUX: NIALL,H.D. & EDMAN,P. (1967) NATURE,216,262-263. (CHECKED BY AUTHOR 07/25/79)
71) NE: MATTHEWS,J.B. & JEFFERIS,R. (1977) IMMUNOCHEM.,14,793-797. (CHECKED BY AUTHOR 08/10/79)
72) Va"CL: PECH,M.,JAENICHEN,H.-R.,POHLENZ,H.-D.,NEUMAIER,P.S.,KLOBECK,H.-G. & ZACHAU,H.G. (1984) J.MOL.BIOL.,176,189-204. (CHECKED BY AUTHOR 12/14/84)
73) Nl: SHINODA,T. (1973) J.BIOCHEM.,73,433-446. (CHECKED BY AUTHOR)
74) PW: PICK,A.I.,WANG,A.C.,FROHLICHMAN,R. & FUDENBERG,H.H. (1982) ACTA HAEMAT.,68,207-214. (CHECKED BY AUTHOR 05/26/83)
75) AMYLOID X: GLENNER,G.G.,TERRY,W.,HERADA,M.,ISERSKY,C. & PAGE,D. (1971) SCIENCE,172,1150-1151. (CHECKED BY AUTHOR 09/22/78)
76) ALE: MILSTEIN,C.,MILSTEIN,C.P.& FEINSTEIN,A. (1969) NATURE,221,151-154. (CHECKED BY AUTHOR)
77) SHE: MEINKE,G.C. & SPIEGELBERG,H.L. (1976) IMMUNOCHEM.,13,915-919. (CHECKED BY AUTHOR 10/17/77)
78) ADA: MEINKE,G.C. & SPIEGELBERG,H.L. (1976) IMMUNOCHEM.,13,915-919. (CHECKED BY AUTHOR 10/17/77)
79) KUE: EULITZ,M.,KLEY,H.P. & ZEITLER,H.J. (1979) Z.PHYSIOL.CHEM.,360,725-734. (CHECKED BY AUTHOR 07/17/79)
80) GO: WANG,A.C.,FUDENBERG,H.H. & CREYSSEL,R. (1974) EUR.J.IMMUNOL.,4,446-448. (CHECKED BY AUTHOR)
81) BOL: WANG,A.C.,WELLS,J.V.,FUDENBERG,H.H. & GERGELY,J. (1974) IMMUNOCHEM.,11,341-345. (CHECKED BY AUTHOR)
82) Rl: PICK,A.I.,WANG,A.C.,FROHLICHMAN,R. & FUDENBERG,H.H. (1982) ACTA HAEMAT.,68,207-214. (CHECKED BY AUTHOR 05/26/83)
83) Ve'CL: PECH,M.,JAENICHEN,H.-R.,POHLENZ,H.-D.,NEUMAIER,P.S.,KLOBECK,H.-G. & ZACHAU,H.G. (1984) J.MOL.BIOL.,176,189-204. (CHECKED BY AUTHOR 12/14/84)
84) OCO: WANG,A.C.,WELLS,J.V.,FUDENBERG,H.H. & GERGELY,J. (1974) IMMUNOCHEM.,11,341-345. (CHECKED BY AUTHOR)
85) V13'CL: JAENICHEN,H.-R.,PECH,M.,LINDENMAIER,W.,WILDGRUBER,N. & ZACHAU,H.G. (1984) NUC.ACIDS RES.,12,5249-5263. (CHECKED BY AUTHOR 12/14/84)
86) V18A'CL: HEIDMANN,O. & ROUGEON,F. (1984) NATURE,311,74-76.
87) V19A'CL: HEIDMANN,O. & ROUGEON,F. (1984) NATURE,311,74-76.
88) V19B'CL: HEIDMANN,O. & ROUGEON,F. (1984) NATURE,3.11,74-76.
89) V18B'CL: HEIDMANN,O. & ROUGEON,F. (1984) NATURE,311,74-76.
90) HF6-21/28: ATKINSON,P.M.,LAMPMAN,G.W.,FURIE,B.C.,NAPARSTEK,Y.,SCHWARTZ,R.S.,STOLLAR,B.D. & FURIE,B. (1985) J.CLIN.INVEST.,75,1138-1143. (CHECKED BY AUTHOR 08/21/85)
91) SAC: SMITHIES,O.,GIBSON,O.M.,FANNING,E.M.,PERCY,M.E.,PARR,D.M. & CONNELL,G.E. (1971) SCIENCE,172,574-577. (CHECKED BY AUTHOR)
92) WAG: KAPLAN,A.P. & METZGER,H. (1969) BIOCHEMISTRY,8,3944-3951. (CHECKED BY AUTHOR)
93) HBJ1: HOOD,L.,GRAY,W.R.,SANDERS,B.G. & DREYER,W.J. (1967) COLD SPRING HARBOR SYMP. QUANTITATIVE BIOL.,32,133-145.
94) AMYLOID 547: WESTERMARK,P.,SLETTEN,K. & NATVIG,J.B. (1981) ACTA PATH.MICROBIOL.SCAND.,C89,199-203. (CHECKED BY AUTHOR 11/09/81)
95) WEB: JOHNSTON,S.L.,ABRAHAM,G.N. & WELCH,E.H. (1975) BIOCHEM.BIOPHYS.RES.COMMUN.,66,842-847. (CHECKED BY AUTHOR 10/17/77)
96) HOE: JOHNSTON,S.L.,ABRAHAM,G.N. & WELCH,E.H. (1975) BIOCHEM.BIOPHYS.RES.COMMUN.,66,842-847. (CHECKED BY AUTHOR 10/17/77)
97) LOD: JOHNSTON,S.L.,ABRAHAM,G.N. & WELCH,E.H. (1975) BIOCHEM.BIOPHYS.RES.COMMUN.,66,842-847. (CHECKED BY AUTHOR 10/17/77)
98) HBJ10: HOOD,L.,GRAY,W.R.,SANDERS,B.G. & DREYER,W.J. (1967) COLD SPRING HARBOR SYMP. QUANTITATIVE BIOL.,32,133-145.
99) BEN: CAPRA,J.D.,KEHOE,J.M.,WILLIAMS,R.C.,JR.,FEIZI,T. & KUNKEL,H.G. (1972) PROC.NAT.ACAD.SCI.USA,69,40-43. (CHECKED BY AUTHOR)
100) GR: CAPRA,J.D.,KEHOE,J.M.,WILLIAMS,R.C.,JR.,FEIZI,T. & KUNKEL,H.G. (1972) PROC.NAT.ACAD.SCI.USA,69,40-43. (CHECKED BY AUTHOR)
101) MAA: CAPRA,J.D.,KEHOE,J.M.,WILLIAMS,R.C.,JR.,FEIZI,T. & KUNKEL,H.G. (1972) PROC.NAT.ACAD.SCI.USA,69,40-43. (CHECKED BY AUTHOR)
102) MUK: LITMAN,G.W.,GERBER-JENSON,B.,LITMAN,R.,MIDDAUGH,C.R. & SCHEFFEL,C. (1980) MOL.IMMUNOL.,17,337-344.
103) AMYLOID 594: WESTERMARK,P.,SLETTEN,K. & NATVIG,J.B. (1981) ACTA PATH.MICROBIOL.SCAND.,C89,199-203. (CHECKED BY AUTHOR 11/09/81) 104) MAR: KAPLAN,A.P. & METZGER,H. (1969) BIOCHEMISTRY,8,3944-3951. (CHECKED BY AUTHOR)
105) AMYLOID: COHEN,A.S.,SHIRAHAMA,T.,SKINNER,M.,BENSON,M.D. & CATHCART,E.S. (1973) PROTIDES BIOL.FLUIDS,20,73-80.
106) BJ: MILSTEIN,C. (1966) BIOCHEM.J.,101,352-368. (CHECKED BY AUTHOR)
107) HBJ6: HOOD,L~.GRAY,W.R.,SANDERS,B.G. & DREYER,W.J. (1967) COLD SPRING HARBOR SYMP. QUANTITATIVE BIOL.,32,133-145.
108) PEN: MOULIN,A. & FOUGEREAU,M. (1973) NATURE NEW BIOLOGY,246,176-178.
109) AMYLOID MS: PICK,A.I.,SCHREIBMAN,S.,LAVIE,G. & FROHLICHMAN,R. (1973) PROTIDES BIOL.FLUIDS,20,63-72.
110) CL*: SOLOMON,A.,MCLAUGHLIN,C.L. & CAPRA,J.D. (1975) J.CLINICAL INVESTIGATION,55,579-586. (CHECKED BY AUTHOR)
111) GM131'CL: MORIN,J.W.,BLACK,A.,WU,M. & BEYCHOK,S. (1985) PROC.NAT.ACAD.SCI.USA,82,7025-7029.
NOTES: HUMAN KAPPA LIGHT CHAINS SUBGROUP I
IDENTICAL SETS OF FRAMEWORK SEGMENTS:
FR1: SET 1: ROY[1],AU[2],REI[3],HAU[4],HK1 01 'CL[5],SCW[6],AG[7],WEA[8],HK137'CL[9],HK134'CL[1 O],DAUDI'CL[11],WALKER'CL[12], HF3-16/6[13] ,HF2-1/13B[14] ,H F2-18/2[15],HF2-1 /17[16] ,BJ26[17] ,RFZ[18] ,PSM[19] ,HOM[20] ,ESM IGG[21] ,ESM IG M[22], WAT[23], AMYLOID VIII-B[24],LOW[25],DIE[26],CAR A[27],TEI[28],BJ48[29],CON[30],TRA[31],F-GUI[33],0U(IOC)[34],DEE[35]. (34 IDENTICAL)
SET 2: WES[41],Vb'CL[42],Vb"CL[43]. (3 IDENTICAL) SET 3: HK102'CL[ 44],EU[45],DEN[46],PAU[ 47],HBJ4[ 48],FRA[ 49],GR'[50],PAUL[51],MON[52]. (9 IDENTICAL) SET 4: AMYLOID BAN[56],BJ19[57],BEL[58]. (3 IDENTICAL) SET 5: DAV[66],FIN[67]. (2 IDENTICAL) SET 6: Vd'CL[69],LUX[70]. (2 IDENTICAL)
FR2: SET 1: ROY[1],AU[2],WALKER'CL[12],Vb'CL[ 42],Vb"CL[ 43],HK1 02'CL[44],KA[68],Vd'CL[69],Va"CL[72],Ve'CL[83]. (1 0 IDENTICAL) SET 2: HK101'CL[5],HK134'CL[10]. (2 IDENTICAL) SET 3: HK137'CL[9],AMYLOID BAN[56]. (2 IDENtiCAL) SET 4: V18A'CL[86]. (IDENTICAL TO 7 MOUSE V-KAPPA-111: PC1229(NZB)[1],PC2880(NZB)[2],PC7132(NZB)[3],MOPC70[5],PC2413(NZB)[11],
50S10.1[27],V-21B18KB'CL[46]; AND 5 RABBIT V-KAPPA: K9-335[1],K9-338[2],K29-213[3],V20'CL[36],K16-167[64].) SET 5: V19B'CL[88],V18B'CL[89]. (2 IDENTICAL HUMAN V-KAPPA-1; ALSO 4 HUMAN V-KAPPA-IV: VJI'CL[1],VKAPPA IV GERMLINE'CL[2],
PB171V'CL[3],LEN[4]; 1 MOUSE V-KAPPA-1: MCPC603[47]; 30 MOUSE V-KAPPA-111: MPC11'CL[6],TEPC111[7],PC3741(NZB)[8], TEPC124[9],MOPC321 [12] ,PC7043(NZB)[13],PC7183(NZB)[14] ,PC6308(NZB) [15] ,PC6684(NZB)[17],PC7940(NZB)[18] ,PC7175(NZB)[19], PC2485(NZB)[20],PC4039(NZB)[21],PC721 O(NZB)[23],H36-15[26] ,2242[29],V-21 E1.5KB'CL[30] ,V-21 C9.5KB'CL[31], PC? 461 (NZB) [33], PC2960(NZB) [34], 97 .C(A. BY) [35], 1 0 .A( A. TH) [39], H36-5[ 48] ,40. C(A. TH) [52], MO PC63[ 54] ,AB PC22[ 55], PC9245(NZB)[56],PC4050(NZB)[57],V-21B16KB'CL[58],11949[62]; 1 MOUSE V-KAPPA-VI: BFPC61A'CL[64]; AND 15 RABBIT V-KAPPA: K9-335-1[19],3368[20] ,BS-5[38],BS-1 [39],K49-501 [ 45] ,3547[ 47] ,K4820[57] ,K30-267[61] ,311 [65],4422[66], 17D9'CL[68], 4192[71],4363[85], 120[103],K-25[112].)
FR3: SET 1: HAU[4],HK101'CL[5],HK137'CL[9],HK134'CL[10],Vb'CL[42],Vb"CL[43],Va"CL[72]. (7 IDENTICAL) SET 2: Ve'CL[83],V13'CL[85]. (2 IDENTICAL)
FR4:
SET 3: V19B'CL[88],V18B'CL[89]. (2 IDENTICAL)
SET
SET SET
SET SET SET
1: AU[2],GAL(I)[36],CL''[110]. (3 IDENTICAL HUMAN V-KAPPA-1; ALSO 2 HUMAN V-KAPPA-11: GM 607 'CL[5],RPM1-8410'CL[16]; 7 HUMAN V-KAPPA-111: WOL[2],PAY[7],PIE[11],GL0[15],CUR[20],REE[57],VKAPPA3'CL[82]; AND 1 HUMAN V-KAPPA-IV: PB171V'CL[3].)
2: HAU[4]. (IDENTICAL TO 1 HUMAN V-KAPPA-111: POM[48].) 3: AG[7],DE'N[46],BI[63]. (3 IDENTICAL HUMAN V-KAPPA-1; ALSO 2 HUMAN V-KAPPA-11: NIM[3],FR[14]; 6 HUMAN V-KAPPA-111: NEU[5],
GOT[6],GAR'[10],FL0[12],FR4[21],1ARC/BL41'CL[28]; AND 1 HUMAN V-KAPPA-IV: LEN[4].) 4: WEA[8],BJ48[29],LAY[39],EU[45]. (4 IDENTICAL) 5: WALKER'CL[12],0U(IOC)[34]. (2 IDENTICAL HUMAN V-KAPPA-1; ALSO 1 HUMAN V-KAPPA-11: TEW[1].) 6: WES[41],MEV[62]. (2 IDENTICAL)
IDENTICAL SETS OF COMPLEMENTARITY DETERMINING REGIONS:
CDR1: SET 1: AU[2],NE[71],SHE[77]. (3 IDENTICAL) SET 2: WEA[8],GAL(I)[36]. (2 IDENTICAL) SET 3: HK134'CL[10],Vb'CL[42],Vb"CL[43]. (3 IDENTICAL) SET 4: HF3-16/6[13],HF2-1/13B[14],HF2-18/2[15],HF2-1/17[46]. (4 IDENTICAL) SET 5: Vd'CL[69],Ve'CL[83]. (2 IDENTICAL)
CDR2: SET 1: HK101'CL[5],HK137'CL[9],HK134'CL[10],WALKER'CL[12],Vb'CL[42],Vb"CL[43]. (6 IDENTICAL) SET 2: AG[7],NI[73]. (2 IDENTICAL) SET 3: HK102'CL[44],Va"CL[72]. (2 IDENTICAL) SET 4: Vd'CL[69],Ve'CL[83],V13'CL[85]. (3 IDENTICAL) SET 5: V18A'CL[86]. (IDENTICAL TO 1 RABBIT V-KAPPA: 4153-1[24].) SET 6: V19A'CL[87]. (IDENTICAL TO 1 RABBIT V-KAPPA: AH80-5[4].)
CDR3: SET 1: HK1 01 'CL[5],HK134'CL[1 0]. (2 IDENTICAL) SET 2: LAY[39]. (IDENTICAL TO 1 HUMAN V-KAPPA-111: POM[48].) SET 3: Vb'CL[42],Vb"CL[43]. (2 IDENTICAL)
IDENTICAL SETS OF J-MINIGENES:
SET 1: AU[2]. (IDENTICAL TO 1 HUMAN V-KAPPA-11: RPM1-6410'CL[16]; 2 HUMAN V-KAPPA-111: PIE[11],VKAPPA3'CL[82]; AND 1 HUMAN V-KAPPA-IV: PB171V'CL[3].)
SET 2: AG[7]. (IDENTICAL TO 1 HUMAN V-KAPPA-111: GOT[6].) SET 3: WALKER'CL[12]. (IDENTICAL TO 1 HUMAN V-KAPPA-11: TEW[1].) SET 4: DEN[46],BI[63]. (2 IDENTICAL HUMAN V-KAPPA-1; ALSO 1 HUMAN V-KAPPA-11: FR[14]; AND 3 HUMAN V-KAPPA-111: GAR'[10],FL0[12],
IARC/BL41 'CL[28].)
+
q;
PFIZER EX. 1052 Page 16
NOTES: HUMAN KAPPA LIGHT CHAINS SUBGROUP I (cont'd)
GENERAL NOTES:
#SEE SIGNAL PEPTIDE TABLE IF # OCCURS AT POSITION 0.
SPECIFIC NOTES:
49
5) HK101'CL: THE SEQUENCE IS OBTAINED BY TRANSLATING THE NUCLEOTIDE SEQUENCE OF A CLONE OF HUMAN FOETAL LIVER DNA.
7) AG: THE AMINO ACID RESIDUES AT POSITIONS 39 AND 41 WERE REPORTED BY THE AUTHORS AS GLY AND LYS RESPECTIVELY; HOWEVER, THE PROOF WAS NOT ABSOLUTE. THUS, THEY ARE OMITTED.
9) HK137'Cl: THE AMINO ACID SEQUENCE IS OBTAINED BY TRANSLATING THE NUCLEOTIDE SEQUENCE OF A CLONE OF HUMAN FETAL DNA.
10) HK134'Cl: THE AMINO ACID SEQUENCE IS OBTAINED BY TRANSLATING THE NUCLEOTIDE SEQUENCE OF A CLONE OF HUMAN FETAL DNA.
17) BJ26: ACID RESIDUES AT POSITIONS 39 AND 41 OF BJ26 WERE REPORTED BY THE AUTHORS AS GLY AND LYS RESPECTIVELY. SINCE THIS PROTEIN WAS SEQUENCED BEFORE THE SEQUENCES OF MANY OTHER PROTEINS WERE KNOWN AT THESE TWO POSITIONS, WE HAVE OMITTED THEM.
33) F-GUI: THE SEQUENCES OF F-GUI AND 5-GUI WERE FROM THE SAME PATIENT.
44) HK102'CL: THE SEQUENCE IS OBTAINED BY TRANSLATING THE NUCLEOTIDE SEQUENCE OF A CLONE OF HUMAN FOETAL LIVER DNA.
55) S-GUI: THE SEQUENCES OF F-GUI AND 5-GUI WERE FROM THE SAME PATIENT.
56) AMYLOID BAN: AMINO ACID RESIDUES FOUND AT POSITIONS 104 AND 105 ARE VAL,LEU AND GLN,GLU RESPECTIVELY.
57) BJ19: THE AMINO ACID RESIDUES AT POSITIONS 39 AND 41 WERE REPORTED BY THE AUTHORS AS GLY AND LYS RESPECTIVELY. SINCE THIS PROTEIN WAS SEQUENCED BEFORE THE SEQUENCES OF MANY OTHER PROTEINS WERE KNOWN AT THESE TWO POSITIONS, WE HAVE OMITTED THEM.
59) JBL: THE AMINO ACID RESIDUE FOUND AT POSITION 34 WAS ALA OR SER.
64) AMYLOID ES305: THE AMINO ACID RESIDUES AT POSITIONS 21 AND 29 WERE ILE OR LEU.
74) PW: THE SEQUENCE WAS FROM A PATIENT WITH TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER.
82) Rl: THE SEQUENCE WAS FROM A PATIENT WITH TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER.
109) AMYLOID MS: THE AMINO ACID RESIDUE AT POSITION 2 MS WAS ILE OR LEU.
111) GM131'Cl: FROM AN EPSTEIN-BARR VIRUS-TRANSFORMED HUMAN LYMPHOID CELL LINE
+ THE FOLLOWING WERE EQUALLY AND MOST FREQUENTLY OCCURRING:
AT POSITION 27C 27D 50 92 95A 95B
RESIDUES (LEU,VAL) (TRP,GLU) (ALA,ASP)
(TYR,ASP,ASN) (SER,GLY) (TRP,GLY)
PFIZER EX. 1052 Page 17
167
HUMAN HEAVY CHAINS SUBGROUP Ill
F R 1
c D R 1
F . R
3
0 1 2 3 4
5 6 7 8 9
10 11 12 13 14
15 16 17 18 19
20 21 22 23 24
25 26 27 28 29
30 31 32 33 34
35 35A 35B 36 37
38 39 40 41 42
43 44 45 46 47
48 49 50 51 52
52 A 52B 52C 53 54
55 56 57 58 59
60 61 62 63 64
INVARIANT RESIDUES
LEU(.97)
SER(.97) GLY(.99) GLY(.98)
PR0(.95)
GLY
SER(.97) LEU(.97)
CYS
SER(.98) GLY(.97) PHE(.98)
TRP VAL(.95)
ARG(.97) GLN(.97)
GLY
LYS(.97)
LEU(.97)
TRP
LYS
65 GLY(.97) 66 ARG 67 PHE(.97) 68 69 ILE(.97)
70 SER(.97) 71 ARG 72 73 74
75 76 77 78 79
80 81 82 MET(.95) 82A 82B
82C 83 84 85 86
87 88 89 90 TYR(.98) 91 TYR(.95)
92 CYS 93 94 95 96
97 98 99
100 100A
; c 100B D 100C R 100D
3 188~ 100G 100H 100/ 100J 100K
101 102 103 104 GLY(.97) 105
106 GLY(.97) 107 108 109 VAL(.97) 110
111 112 SEA 113
1* TUR
2 LAMBDA
-VH26 'CL
3* 4 5 6 7 8 9 10 TEl
11 12 13 14* 15 16* FR #
17 MU
18 19 20 21 22 23 VJN HF3- BEN ZAP JON KEA POM TIL WAS HF2- HF2- HF2- H11 BRO GR' WAT LAY GRA'
GLU VAL GLN LEU
LEU GLU SER GLY GLY
GLY LEU VAL GLN PRO
GLY GLY SER LEU ARG
LEU SER CYS ALA ALA
SER GLY PHE THR PHE
SER ARG VAL LEU SER
SER
TRP VAL
ARG GLN ALA PRO GLY
LYS GLY LEU GLU TRP
VAL SER GLY ARG LEU
ASN
ALA SER
SER ASN LEU HIS PHE
ALA VAL SER ALA GLN
# #
GLU VAL GLN LEU
LEU GLU SER GLY GLY
GLY LEU VAL GLN PRO
GLY GLY SER LEU ARG
LEU SER CYS ALA ALA
SER GLY PHE THR PHE
SER SER TYR ALA MET
SER
TRP VAL
ARG GLN ALA PRO GLY
LYS GLY LEU GLU TRP
VAL SER ALA JLE
SER
GLY
SER GLY
GLY SER THR TYR TYR
GLY ASP SER VAL LYS
GLY GLY ARG ARG PHE PHE THR THR JLE JLE
SER SER ARG ARG ASN ASP ASP ASN SER SER
LYS LYS ASN ASN THR THR LEU LEU TYR TYR
LEU GLN MET LEU SER
LEU GLN MET ASN SER
GLU GLU GLU VAL VAL VAL GLN GLN GLN LEU LEU LEU
LEU LEU LEU GLU GLU GLU SER SER SER GLY GLY GLY GLY GLY GLY
GLY GLY GLY LEU LEU LEU VAL VAL VAL GLN GLN GLN PRO PRO PRO
GLY GLY GLY GLY GLY GLY SER SER SER LEU LEU LEU ARG ARG ARG
LEU LEU LEU SER SER SER CYS CYS CYS ALA ALA ALA ALA ALA ALA
SER SER SER GLY GLY GLY PHE PHE PHE THR THR ser PHE PHE PHE
SER SER SER SER THR THR SER TYR ASP ALA VAL ALA MET MET MET
SER SER TYR
TRP TRP TRP VAL VAL VAL
ARG ARG ARG GLN GLN GLN ALA ALA ALA PRO PRO PRO GLY GLY GLY
LYS LYS LYS GLY GLY GLY LEU LEU LEU GLU GLX GLU TRP TRP TRP
VAL VAL VAL ALA GLY ALA TRP ALA TRP LYS ILE LYS TYR GLX TYR
GLU GLY GLN
ASN LEU GLU GLY SER ALA
ASN VAL SER ASP SER ASN LYS GLX SER HIS SER HIS TYR TYR PHE
ALA ALA ALA ASP ASX ASP SER SER THR VAL VAL VAL ASN LYS ASN
GLY GLY GLY ARG ARG ARG PHE PHE PHE THR THR THR ILE JLE JLE
SER SER SER ARG ARG ARG ASN ASP ASN ASP ASP ASP SER SER SER
LYS LYS LYS ASN ASN ASN THR THR THR LEU LEU TYR TYR
LEU LEU LEU GLN MET MET MET ASN ASN ASN SER SER ARG
LEU GLN ALA GLU ASP
LEU LEU LEU LEU
THR ALA LEU TYR TYR
CYS ALA ARG LEU SER
VAL THR ALA VAL ALA
PHE
ASP VAL TAP GLY GLN
GLY THR LYS VAL SEA
ARG GLN ARG GLU ALA ALA ALA ALA GLU GLU GLU GLU ASP ASP ASP ASP
THR ALA VAL TYR TYR
CYS ALA LYS
#
THR THR THR ALA ALA ALA LEU VAL VAL TYR TYR TYR TYR TYR TYR
CYS CYS CYS ALA ALA ALA ARG LYS ARG ASP GLY PHE ALA LYS ARG
GLY VAL GLN PRO SEA PRO TYR ALA PHE VAL TYR VAL SEA TYR GLN
PRO PHE THR PHE
PHE PHE PHE
ALA ASX ASP HIS TYR VAL TYR TAP PHE GLY GLY GLY GLN GLX GLN
GLY GLY GLY THR THR THR LEU LEU LEU VAL VAL VAL THR THR THR
VAL SER SER
1/138 1/17 18/2 'CL 'JGM # 16/6 (Ill)
GLU VAL GLN LEU
LEU GLU SER GLY GLY
GLY LEU VAL GLN PRO
GLY GLY SER LEU ARG
LEU SER CYS ALA ALA
SER GLY PHE lys
PHE
SER SER TYR ALA MET
SER
TRP VAL
ARG GLN ALA
GW GW GW GW GW GW GW VAL VAL VAL VAL VAL VAL VAL G~ G~ G~ G~ G~ G~ G~ LEU LEU LEU LEU LEU LEU LEU
ala VAL GLN LEU
GLU GLU GLU GLU GLU GLU GLU asp GLU VAL VAL VAL VAL VAL VAL VAL VAL VAL G~ G~ G~ G~ G~ G~ G~ G~ G~ LEU LEU LEU LEU LEU LEU LEU LEU LEU
LEU LEU val val val GLU gin GLU GLU GLU SER SER SER SER SER GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY
GLY GLY GLY GLY GLY LEU .LEU LEU LEU LEU VAL VAL VAL VAL VAL GLN GLN GLN GLN GLN PRO PRO PRO PRO PRO
GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY SER SER SER SER SER LEU LEU LEU LEU LEU ARG ARG ARG ARG ARG
val val GLU GLU SER SER GLY GLY GLY GLY
GLY GLY LEU LEU VAL VAL GLN GLN PRO PRO
GLY GLY GLY GLY SER SER LEU LEU ARG ARG
LEU GLU SER GLY GLY
GLY LEU VAL GLN PRO
GLY GLY SER LEU ARG
val GLU SER GLY GLY
GLY LEU VAL GLN PRO
GLY GLY SER LEU ARG
LEU LEU LEU LEU LEU LEU SER SER SER SER SER SER CYS CYS CYS CYS CYS CYS ALA ALA ALA ALA ALA ALA ALA ALA ALA ALA ALA ALA
LEU LEU LEU SER SER SER CYS CYS CYS ALA ALA ALA ALA ALA ALA
SER SER SER SER SER SER GLY GLY GLY GLY GLY GLY PHE PHE PHE PHE PHE PHE lys THR THR THR THR THR ~E ~E ~E ~E ~E ~E
SER SER SER GLY GLY GLY PHE PHE PHE THR THR THR PHE PHE i/e
val val val asp GLU GLU SER SER SER GLY GLY GLY GLY GLY GLY
GLY GLY GLY LEU LEU LEU VAL VAL i/e GLN Jys GLN PRO PRO PRO
GLY GLY GLY GLY GLY GLY SER SER SER LEU LEU LEU ARG ARG ARG
LEU val gin GLU
SER SER GLY GLY GLY GLY
GLY GLY LEU LEU VAL ala GLN GLN PRO PRO
GLY GLY GLY GLY SER SER LEU LEU ARG ARG
LEU LEU SER SER CYS CYS ALA ALA ALA ALA
LEU LEU LEU SER gin ala CYS CYS CYS ALA ALA ALA ALA ALA ALA
SER SER GLY GLY PHE PHE THR THR PHE PHE
SER SER SER GLY GLY GLY PHE PHE PHE THR ser THR val PHE PHE
SER SER SER SER SER SER asx SER SER SER thr SER SER SER
val val val GLU GLU GLX SER SER SER GLY GLY GLY GLY GLY GLY
ala GLY GLY LEU LEU LEU VAL VAL VAL GLN lys Jys PRO PRO PRO
GLY GLY GLY GLY GLY GLY SER SER SER g/y LEU LEU
ARG ARG ARG
LEU LEU LEU SER SER SER CYS CYS CYS ALA ALA ALA ALA ALA ALA
SER SER SER GLY GLY GLY PHE PHE PHE THR THR ile PHE PHE PHE
SER SER pro SER SER SER THR TYR ALA TYR TYR TYR SER TYR ASX ALA ALA TRP ALA ASN TYR MET MET MET VAL MET MET
THR ALA L YS ASX ARG TYR SER THR PHE GL Y THR ALA VAL TYR GLY MET MET TYR MET LEU
THR PRO THR THR THR
SER SER HIS TYR ASN
TRP TRP TRP TRP TRP TRP ~L ~L ~L ~L ~L ~L
ARG ARG ARG ARG ARG PRO G~ G~ G~ G~ G~ G~ ALA ALA ALA ALA VAL ALA
PRO PRO THR PRO GLY GLY GLY GLY
LYS LYS LYS ARG GLY GLY GLY GLY LEU LEU LEU LEU VAL GLU GLU TRP TRP TRP
VAL VAL VAL SER GLY SER ARG TRP ALA JLE ARG JLE
ASN TYR GLY
SER GLU
ASP GLY THR GLY SER ALA
SER SER GLY SER LEU ASP THR THR GLN THR HIS TYR TYR TYR TYR
ALA ALA ALA ASP VAL ASP SER SER SER VAL VAL VAL LYS GLN LYS
GLY GLY GLY ARG ARG ARG PHE PHE PHE THR THR THR JLE JLE JLE
SER SER SER ARG ARG ARG ASP ASN ASN ASN ASP ASP ALA SER SER
LYS LYS LYS ASN ASN ASN THR THR THR LEU LEU LEU TYR TYR TYR
LEU LEU LEU GLN GLN ASN MET MET MET ASN LEU ASN SER SER SER
LEU LEU LEU ARG GLU ARG ALA PRO ALA GLU GLU GLU ASP ASP ASP
THR THR THR ALA ALA ALA VAL VAL VAL TYR TYR TYR TYR TYR TYR
CYS CYS CYS ALA ALA ALA ARG ARG ARG
VAL SER THR PRO
PRO VAL ALA SER ALA LEU ALA VAL SER ASP
LEU GLY THR TRP
PHE SER
LEU TYR TYR
TYR TYR GLY
ALA SER VAL TAP TAP GLY GLY GLN GLN
GLY GLY THR THR LEU LEU VAL. THR
VAL SER GLU ASP GLU
TRP TRP TRP TRP VAL VAL VAL VAL
ARG ARG ARG ARG GLN GLN GLN GLN ALA ALA ALA ALA PRO PRO PRO PRO GLY GLY GLY GLY
LYS GLY LEU GLU TRP
VAL ALA TRP LYS TYR
GLU
LYS LYS LYS GLY GLY ALA LEU LEU LEU GLU GLU GLX TRP TRP TRP
VAL VAL VAL THR ALA LEU TYR ALA VAL VAL ARG PHE GLY SER
GLN VAL
ASN VAL THR GLY SER
ASN LYS ASP PHE LYS SER LYS HIS PHE TYR TYR TYR
ALA ALA THR ASP VAL GLU SER SER SER VAL VAL LEU ASN GLN ASN
GLY GLY ARG ARG PHE PHE THR THR JLE JLE
SER SER ARG ARG ASN ASN ASP ASP SER SER
LYS LYS ASN ASN THR THR LEU LEU TYR TYR
LEU LEU GLN GLU MET MET MET ASN LYS ASN GLY THR SER
LEU GLY LEU GLN GLU ARG ALA PRO ALA GLU GLU GLX VAL ASP ASX
SER THR THR ALA ALA ALA ILE VAL VAL TYR TYR TYR TYR TYR TYR
CYS CYS CYS ALA ALA ALA ARG ARG ARG ASP HIS ALA ILE
GLY TYR PRO VAL TYR THR VAL LEU SER TYR
PRO TYR THR TYR PHE
PHE PHE MET
ALA ALA HIS VAL TAP TAP GLY GLY GLN GLN
GLY GLY THR THR LEU LEU VAL THR
ASN SER THR THR ALA TYR TYR ALA PHE SER TRP MET MET MET ARG MET
ALA GLU ASP
THR ALA VAL TYR TYR
CYS ALA ARG
SER ARG PHE L YS
TRP TRP VAL VAL
ARG ARG GLN ALA
TRP TRP VAL VAL
ARG ARG GLN GLN ALA ALA PRO PRO GLY GLY
LYS LYS GLY GLY LEU LEU GLU GLU TRP TRP
VAL VAL GLU VAL PHE TRP ARG ARG VAL VAL
GLN GLU
GLY GLN SER VAL
ALA VAL JLE GLU
SER LYS HIS ALA TYR PHE
ALA ALA ASP ASN SER SER VAL VAL GLN ASN
ALA GLY ARG ARG PHE PHE THR THR JLE JLE
SER SER ARG ARG ASN ASN ASP ASP SER SER
LYS LYS ASN ASN THR THR LEU LEU TYR TYR
LEU LEU GLN GLN MET MET MET ASN ILE ASN THR SER ASN
GLY VAL LEU GLU THR ARG ALA PRO VAL GLU GLU GLX ASP ASP ASX
THR THR THR ALA ALA ALA VAL VAL VAL TYR TYR TYR TYR TYR TYR
CYS CYS CYS ALA ALA ALA ARG ARG ARG THR VAL ASX ARG VAL ARG
PRO VAL LEU GLY SER GLY GLY THR PRO TYR SER THR PHE ALA
SER
MET
ASP ASP VAL VAL TAP TAP GLY GLY GLN GLN
GLY GLY THR THR LEU PRO VAL VAL SEA THR
CYS SER VAL
PFIZER EX. 1052 Page 18
168
HUMAN HEAVY CHAINS SUBGROUP Ill (eont'd)
F R 1
c 0 R 1
F R 2
c 0 R 2
F R 3
0 1 2 3 4
5 6 7 8 9
10 11 12 13 14
15 16 17 18 19
20 21 22 23 24
25 26 27 28 29
30 31 32 33 34
35 35A 356 36 37
38 39 40 41 42
43 44 45 46 47
48 49 50 51 52
52 A 526 52C 53 54
55 56 57 58 59
60 61 62 63 64
65 66 67 68 69
70 71 72 73 74
75 76 77 78 79
80 81 82 82A 826
82C 83 84 85 86
87 88 89 90 91
92 93 94 95 96
97 98 99
100 100A
c 1006 O 100C R 1000 3 i88~
100G 100H 1001 100J tOOK 101 102 103 104 105
106 F 107 R 108 4 109
110
111 112 113
M ~ ~ n ~ ~ ~ ~ ~ ~ ~ ~ ~ LOW BRO BUT JOR GAA CAM GO OOB ElK WEA NIE CAM' WE
37 38 39 40 41 42* AVI GAL SKI FOR EVA 333
43' 44' 45* 1H1 1611 126
46* 112 'CL
47* 48* 49* 115 2A12 2C12 'CL 'CL 'CL
GLU GLU GLU GLU GLU GLU GLU GLU GLU pea pea VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL G~ G~ G~ G~ G~ G~ G~ G~ G~ G~ G~ LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU
pea VAL glu LEU
val val GLU GLU SEA SEA GLY GLY GLY GLY
val val val GLU GLU GLU thr SEA SEA
GLY GLY GLY GLY GLY GLY
GLY ala GLY GLY ala LEU LEU LEU LEU LEU VAL VAL ile VAL VAL lys arg GLN GLX
PRO PRO PRO PRO PRO
GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY SEA SEA SEA SEA SEA LEU LEU LEU LEU LEU ARG ARG ARG ARG ARG
LEU LEU LEU val LEU SEA SEA SEA SEA SEA CYS CYS CYS CYS CYS ALA glx ALA val ALA ALA ALA ALA ALA val
SEA SEA SEA SEA val GLY GLY GLY GLY
PHE PHE PHE PHE PHE THR THR THR THR THR PHE PHE val PHE PHE
phe ala SEA SEA asx THR ALA ASX ASX ASX TYR TYR HIS TYR TYR VAL THR SEA SEA MET MET MET MET
ASX L YS SEA ASX
TAP VAL
ARG GLN ALA PRO GLY
LYS ALA LEU GLX TAP
VAL SEA ALA ILE
TYR
ARG GLY
GLY THR THR TYR TYR
ALA ASP SEA VAL LYS
GLY ARG PHE THR ILE
SEA ARG ASP ASP SEA
ARG ASX THR VAL TYR
LEU GLN MET ASX SEA
LEU ARG ALA GLU ASP
THR ALA VAL TYR TYR
CYS ALA ARG ASP LEU
ALA ALA ALA ARG LEU
PHE
GLY LYS
GLY THR THR VAL THR
VAL SEA SEA
val GLU SEA GLY GLY
val GLX SEA GLY GLY
GLY GLY LEU LEU VAL VAL GLN GLX lys PRO
GLY GLY GLY GLY SEA SEA LEU LEU lys ARG
LEU LEU SEA gly
CYS ALA ALA ALA ALA
SEA SEA GLY GLY PHE PHE THR PHE
SEA
val val GLU GLU SEA SEA GLY GLY GLY GLY
asp GLY LEU LEU VAL VAL GLN PRO PRO
GLY GLY arg GLY SEA SEA LEU LEU ARG ARG
LEU LEU SEA SEA CYS CYS ALA ALA ALA thr
SEA thr GLY GLY PHE PHE asn ala PHE PHE
his SEA GLU GLY TYR SEA ASN ALA MET VAL
HIS
TAP LEU
ARG GLN GLY PRO GLY
LYS GLY PRO GLU TAP
VAL SEA THR ILE
THR
TAP
ASN GLY
GLY SEA VAL LEU TYR
ALA ASP SEA VAL LYS
GLY ARG PHE ALA ILE
SEA ARG ASP ASN ALA
GLN LYS THR LEU TYR
LEU GLN
MET LEU ASN ASN GLY ILE
LEU LEU ARG ARG ALA PRO GLX GLU ASX ASP
GLY THR GLY ALA VAL PHE TYR TYR TYR TYR
CYS CYS VAL ALA SEA LYS ASX GLY VAL TYR
ILE TAP ASN GLY ASN
TAP PHE
ASP SEA TAP GLY GLN
GLY THR LEU VAL THR
VAL SEA SEA
val asp SEA GLY GLY
val gin
SEA GLY GLY
val GLU SEA GLY GLY
GLY GLY GLY LEU val val VAL VAL VAL glu GLN GLX
PRO PRO PRO
GLY GLY GLY GLY arg arg SEA SEA SEA LEU LEU LEU ARG ARG ARG
LEU LEU LEU SEA SEA SEA CYS CYS CYS ser ALA ALA
ALA ALA ALA
SEA SEA SEA GLY GLY GLY PHE PHE PHE THR THR THR PHE PHE PHE
SEA SEA SEA ALA ARG ASN ASN TYR TYR ASP THR ALA MET ILE MET
ASN HIS HIS
TAP TAP TAP VAL VAL VAL
ARG ARG ARG GLN GLN GLN ALA ALA PRO PRO PRO PRO GLY GLY GLY
LYS LYS LYS GLY GLY GLY LEU LEU LEU GLU GLU GLU TAP TAP TAP
LEU VAL VAL SEA ALA ALA PHE VAL VAL ILE MET ILE GLY SEA SEA
GLY TYR TYR
SEA ASX ASX GLY GLY GLY
SEA ASX THR ASX ILE LYS TYR HIS TYR TYR
ALA ALA ASP ASP SEA SEA VAL VAL LYS ASN
ASX ASX LYS TYR TYR
ALA ASX SEA VAL LYS
GLY GLY GLY ARG ARG ARG PHE PHE PHE THR THR THR ILE ILE ILE
SEA SEA SEA ARG ARG ARG ASN ASN ASP ASX ASP ASX SEA SEA SEA
LYS LYS LYS ASN ASN ASX SEA THR THR LEU LEU LEU TYR TYR TYR
LEU LEU LEU GLN ASN GLN MET MET MET SEA ASN ASN SEA SEA SEA
LEU LEU LEU ARG ARG ARG ALA PRO ALA GLU GLU GLU ASP ASP ASX
THR THR THR ALA ALA ALA VAL VAL VAL TYR TYR TYR TYR TYR TYR
CYS CYS CYS ALA ALA ALA ARG ARG ARG GLY ILE ASP TAP ARG ARG
LEU ASP PRO THR LEU ALA TYR MET GLY PHE ASX
PHE
TYR ARG ALA PHE
LEU ALA ASN ASN HIS TYR TAP TRP TAP GLY GLY GLY GLN GLN GLN
GLY GLY GLY THR THR THR LEU LEU LEU VAL VAL VAL THR THR THR
VAL VAL VAL SEA SEA SEA SEA SEA
'CL 'CL 'CL 'CL
GW GW GW GW GW GW GW GW GW GW GW GW VAL VAL VAL VAL ile VAL met met met met met met G~ G~ G~ G~ G~ G~ G~ G~ G~ G~ G~ G~ LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU
val glu val val GW GLU GLU GLU SEA SEA SEA SEA GLY GLY GLY GLY GLY GLY GLY GLY
val val GLU GLU SEA SEA GLY GLY GLY GLY
GLY GLY LEU LEU VAL VAL GLN lys PRO PRO
GLY GLY GLY GLY SEA SEA LEU LEU ARG ARG
LEU LEU SEA SEA
CYS ALA ALA ALA ALA
SEA SEA GLY GLY
asp asx GLY GLY LEU LEU LEU LEU VAL VAL VAL VAL GLN GLN lys PRO PRO gly PRO
GLY GLY GLY GLY arg GLY GLY glu SEA thr SEA LEU LEU LEU LEU ARG lys ARG ARG
LEU LEU LEU val SEA gly SEA SEA CYS CYS CYS CYS ALA ALA ALA ALA ALA ALA ALA ALA
SEA SEA SEA SEA GLY GLY GLY GLY PHE PHE PHE PHE
THR pro THR leu PHE PHE
gly gly ASX THR TYR ALA GLX GLY
MET MET MET
THR ASX SEA
TAP VAL
ARG GLN ALA PRO GLY
LYS GLY LEU GLU TAP
VAL ALA ASN ILE LYS
GLX
ASX GLY
SEA GLX GLX ASX TYR
VAL ASP SEA VAL LYS
GLY ARG PHE THR ILE
SEA ARG ASP ASN ALA
LYS ASN SEA LEU TYR
LEU GLN MET ASN SEA
LEU ARG VAL GLU ASP
THR ALA LEU TYR TYR
CYS ALA ARG GLY TAP
GLY GLY GLY
ASP TYR TAP GLY GLN
GLY THR LEU VAL THR
VAL SEA THR
MET ASX GLY
LEU LYS ILE GLX ASX
THR GLY VAL TYR TYR
CYS THR THR ASX GLX
SEA ALA THR ALA PHE
PHE
val GLU SEA GLY GLY
val GLU SEA GLY GLY
val GLU SEA GLY GLY
ala ala ala phe phe phe VAL VAL VAL GLN GLN GLN PRO PRO PRO
GLY GLY GLY GLY GLY GLY SEA SEA SEA LEU LEU LEU lys lys lys
LEU LEU LEU SEA SEA SEA CYS CYS CYS ALA ALA ALA ALA ALA ALA
SEA SEA SEA GLY GLY GLY PHE PHE PHE
val val GLU GLU SEA SEA GLY GLY GLY GLY
val gin
SEA GLY GLY
SEA GLY GLY
ala ala ala ala phe phe phe phe VAL VAL VAL VAL GLN GLN GLN GLN PRO PRO PRO PRO
GLY GLY GLY GLY GLY GLY GLY GLY SEA SEA SEA SEA LEU LEU LEU LEU lys ARG lys lys
LEU LEU LEU LEU SEA SEA SEA SEA CYS CYS CYS CYS ALA ALA ALA ALA ALA ALA ALA ALA
SEA SEA SEA SEA GLY GLY GLY GLY PHE PHE PHE PHE
GLU SEA GLY GLY
ala phe VAL GLN PRO
GLY GLY SEA LEU lys
LEU SER CYS ALA ALA
SEA GLY PHE
asn asn asn asn asn asn asn asn PHE PHE PHE PHE PHE PHE PHE PHE
SEA SEA SEA SEA SEA SEA SEA . SEA ~p ~p ~p ~p ~p ~p ~p A~
SEA SEA SEA SEA SEA SEA SEA SEA rnA rnA rnA rnA rnA rnA rnA rnA ILE ILE ILE ILE ILE ILE ILE ILE
HIS HIS HIS HIS HIS HIS HIS HIS
TAP TAP TAP TAP TAP TAP TAP TAP VAL VAL VAL VAL VAL VAL VAL VAL
ARG ARG ARG ARG ARG ARG ARG ARG G~ G~ G~ G~ G~ G~ G~ G~ ALA ALA ALA ALA ALA ALA ALA ALA SEA SEA SEA SEA SEA SEA SEA SEA G~ G~ G~ G~ G~ G~ G~ G~
LYS LYS LYS LYS LYS LYS LYS LYS SEA SEA SEA SEA SEA SEA SEA SEA LEU LEU LEU LEU LEU LEU LEU LEU GW GW GW GW GW GW GW GW TAP TAP TAP TAP TAP TAP TAP TAP
V& ~L V& ~L ~L ~L ~L V~ G~ G~ G~ G~ G~ G~ G~ G~
HIS HIS HIS HIS HIS HIS HIS HIS ILE ILE ILE ILE ILE ILE ILE ILE GW GW GW GW GW GW GW GW
ASN ASN LYS LYS THR THR LYS LYS ASN ASN
L YS ASN GLU L YS ASP LYS LYS LYS LYS LYS SEA THR SEA SEA THR LYS ASN LYS LYS LYS LYS ASN LYS LYS ASN
TYR TYR TYR ALA ALA ALA THR THR THR ILE MET ILE TYR TYR TYR
ARG ARG ARG ALA ALA ALA SEA SEA SEA VAL VAL VAL LYS LYS LYS
TYR TYR TYR TYR ALA ALA ALA ALA THR THR THR THR VAL ILE ILE ILE TYR PHE TYR TYR
ARG ARG ARG ARG ALA ALA ALA ALA SEA SEA SEA SEA VAL VAL VAL VAL LYS LYS LYS LYS
G~ G~ G~ G~ G~ G~ G~
ARG ARG ARG PHE PHE PHE THR THR THR ILE ILE ILE
SEA SEA SEA ARG ARG ARG ASP ASP ASP ASP ASP ASP SEA SEA SEA
LYS LYS LYS ASN ASN ASN MET MET THR ALA ALA ALA PHE PHE PHE
LEU LEU LEU GLN GLN GLN MET MET MET ASP ASP ASP SEA SEA SEA
LEU LEU LEU ARG ARG ARG PRO PRO PRO ASP ASP ASP ASP ASP ASP
ARG ARG ARG ARG PHE PHE PHE PHE ASN ILE THR THR ILE ILE ILE ILE
SEA SEA SEA SEA ARG ARG ARG ARG ASP ASP ASP ASP ASP ASP ASP ASP SEA SEA SEA SEA
LYS LYS ASN LYS ASN ASN ASN ASN MET THR THR THR THR ALA ALA ALA PHE PHE PHE PHE
LEU LEU LEU LEU GLN GLN GLN GLN MET MET MET MET ASP ASP ASP ASP SEA SEA SEA SEA
LEU LEU LEU LEU ARG ARG ARG ARG PRO PRO PRO PRO ASP ASP ASP ASP ASP ASP ASP ASP
LYS LYS SER LYS ASN
TYR ALA THR ILE TYR
ARG ALA SER VAL LYS
GLY ARG PHE THR ILE
SER ARG ASP ASP SER
LYS ASN THR ALA PHE
LEU GLN MET ASP SER
LEU ARG PRO ASP ASP
THR THR THR THR THR THR THR THR ALA ALA ALA ALA ALA ALA ALA ALA LEU LEU LEU LEU LEU LEU LEU LEU TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR
CYS CYS CYS CYS CYS CYS CYS CYS rnA rnA rnA rnA rnA rnA rnR mR PRO PRO PRO PRO PRO PRO PRO PRO p~ p~ p~ p~ ~0 p~ p~ p~ p~ p~ ~0 p~ p~ p~ p~ ~0
GLU GLU GLU VAL VAL VAL GLU GLU GLU SEA SEA SEA LEU LEU LEU
GLU GLU GLU GLU VAL VAL VAL VAL GLU GLU GLU GLU SEA SEA SEA SEA LEU LEU LEU LEU
GLU VAL GLU SEA LEU
ARG ARG ARG ARG ARG ARG ARG ARG SEA SEA SEA SEA SEA SEA SER SER TAP GLY ARG
GLY THR LEU VAL THR
TAP TAP TAP TAP GLY GLY GLY GLY ARG ARG ARG ARG
GLY GLY THR THR LEU LEU VAL VAL THR THR
VAL VAL SEA SEA SEA SEA
GLY GLY THR THR LEU LEU VAL VAL THR THR
TAP GLY ARG
GLY THR LEU VAL THR
TAP TRP GLY GLY ARG ARG
GLY GLY THR THR LEU LEU VAL VAL THR THR
VAL SER SER
c 0 R 1
F R 2
F R 1
Hl
~ __ 4
c D R 2
5 5
5 5 5 5 5·
5' 51 5: 51 5! 6( 61 6~ 63 64
__ 6_5
F R 3
66 67 68 69
70 71 72 73 74
75 76 77 78 79
80 81 82 82A 82E
82C 83 84 85 86
87 88 89 90 91
97 98 99
100 100A
c 1006 D 100C R 1000 3 i88~
100G 100H 1001 100J tOOK 101 ~
103 104 105
'F i8~ 'R 108 'j 109
110
111 112 113
PFIZER EX. 1052 Page 19
HUMAN HEAVY CHAINS SUBGROUP Ill (eont'd)
50 51 52 53 54 TRO KOL WEI ESM V.N.
55 56 57 HIL BUR ERI
58 wo
59* HEI
169
60* 61 62 KN PS GA
(SHA) #
63* 64* . L. WAG TH.
65 LR
66 HI
67* 68* 69 70 R.K. GOE POD PAL
II
71 GIT
72 HA
73 SEI
74 75 PAC KOO
0 1 2 3 4
pea pea asp GLU GLU pea pea GLU GLU GLU GLU GLU ~L ~L ~L ~L V~ V~ ~L ~ ~L ~L V~ ~L GLN GLN GLN GLN GLN lys GLN GLN GLN GLN GLN GLN LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU
pea GLU GLU GLU gly GLU GLU GLU GLU GLU GLU GLU GLU GLU VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL leu VAL GLX GLN lys leu GLN GLN GLN GLN GLN GLN GLN GLN GLN LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU
F R 1
c D R 1
F R 2
c D R 2
F R 3
5 6 7 8 9
10 11 12 13 14 15 16 17 18 19
20 21 22 23 24
25 26 27 28 29
30 31 32 33 34
35 35A 356 36 37
38 39 40 41 42
43 44 45 46 47
48 49
val val met val gin GLU GLU GLU
SER SER SER SER GLY GLY GLY GLY GLY GLY GLY GLY
GLY GLY ala GLY LEU val LEU LEU VAL VAL VAL VAL lys G LN lys lys
PRO PRO PRO PRO
GLY GLY GLY GLY GLY arg glu GLY SER SER SER SER LEU LEU LEU LEU ARG ARG ARG ARG
LEU LEU LEU LEU SER SER SER SER CYS CYS CYS CYS val ser val ALA
ALA ser ALA ALA
SER SER SER GLY GLY GLY PHE PHE PHE ser ile leu
PHE PHE PHE
arg SER SER ASP SER THR PHE TYR TYR TYR ALA GLY MET MET MET
SER TYR ASX
TRP TRP ILE VAL
ARG ARG GLN GLN THR ALA PRO PRO GLY GLY
LYS LYS GLY GLY LEU LEU GLU GLU TRP TRP
VAL VAL SER ALA
50 TYR ILE 51 ILE ILE 52 GLY TRP
52A GLY ASP 526 52C 53 SER ASP 54 GLY GLY
55 SER SER 56 THR ASP 57 LEU GLN 58 TYR HIS 59 TYR TYR
60 ALA ALA 61 ASP ASP 62 SER SER 63 VAL VAL 64 LYS LYS
65 66 67 68 69
70 71 72 73 74
75 76 77 78 79
GLY GLY ARG ARG PHE PHE THR THR ILE ILE
SER SER ARG ARG ASP ASP ASN ASN ALA SER
GLN LYS LYS ASN SER THR LEU LEU TYR PHE
80 LEU LEU 81 GLN GLN 82 MET MET 82A ASN ASP 826 SER SER
82C LEU LEU 83 ARG ARG 84 THR PRO 85 GLU GLU 86 ASP ASP
87 THR THR 88 ALA GLY 89 VAL VAL 90 TYR TYR 91 TYR PHE
92 CYS CYS 93 ALA ALA 94 ALA ARG 95 96
97 98 99
100 100A
THR ASP ASN GLY
ASN GLY PHE HIS ASN GLY TRP PHE SER CYS
c 1006 D 100C R 1000
3 jgg~
THR SER PHE SER SER ALA LEU SER
CYS
100G PHE 100H GLY 1001 PRO 100J 100K
101 ASN ASP 102 TYR TYR 103 104 105
106 F 107 R 108 4 109
110
111 112 113
TRP TRP GLY GLY GLN GLN
GLY GLY ASN THR LEU PRO VAL VAL THR THR
VAL VAL SER SER SER SER
val val GLU gin SER ala GLY GLY GLY GLY
GLY GLY ser val
VAL VAL GLX GLN PRO PRO
GLY GLY GLY arg ala SER
LEU LEU ARG ARG
LEU LEU SER CYS
ALA ile ALA ALA
SER SER GLY GLY ile PHE
THR PHE PHE
SER ASN
ALA TYR GLY
MET MET
HIS
val val GLU GLU SER SER GLY GLY GLY GLY
GLY GLY val LEU
VAL ile GLN GLN ala PRO
GLY GLY thr arg
SER SER LEU LEU ARG ARG
LEU ile SER SER CYS CYS thr thr
ALA ALA
SER ala GLY
PHE PHE asn leu
SER ASP TYR ALA MET
HIS
TRP TRP ·VAL VAL VAL
ARG ARG GLN GLN
ALA ALA ALA PRO PRO GLY GLY
LYS LYS GLY GLY LEU LEU GLU GLX TRP TRP
VAL VAL ALA ALA VAL LEU ILE ILE TRP SER
TYR TYR
ASN GLY GLY GLY
SER SER ARG ASX THR THR TYR TYR TYR TYR
GLY ALA ASP ASP SER SER VAL VAL LYS ARG
GLY GLY ARG ARG PHE PHE THR THR ILE ILE
SER SER ARG ARG ASP ASX ASN ILE SER SER
LYS LYS ARG ASX THR THR LEU LEU TYR TYR
MET LEU GLX GLX MET MET ASN LYS SER THR
LEU LEU ARG ARG THR THR GLU GLU ASP ASP
THR THR ALA ALA VAL VAL TYR TYR TYR TYR
CYS CYS ALA ALA ARG LYS ASP LEU PRO ILE
ASP ALA ILE VAL LEU ALA THR GLY ALA THR
PHE ARG SER PHE
ASP ASX TYR PHE TRP TRP GLY GLY GLN GLN
GLY GLY VAL THR LEU LEU
·VAL VAL THR THR
VAL VAL SER SER
LEU
val val val GLU GLU GLU SER SER SER GLY GLY GLY GLY GLY GLY
GLY GLY GLY LEU LEU LEU VAL VAL VAL GLN GLN GLN PRO PRO PRO
GLY GLY GLY GLY GLY GLY SER SER SER LEU LEU LEU ARG ARG ARG
LEU LEU LEU
met GLU SER GLY GLY
val val GLX GLU SER SER GLY GLY GLY GLY
GLY val
VAL lys
PRO
GLY LEU VAL GLX PRO
GLY GLY GLY SER LEU ARG
arg GLY SER SER LEU LEU ARG ARG
LEU SER CYS
LEU LEU SER CYS ALA ALA
SER GLY PHE ser
PHE
MET
HIS
TRP VAL
ARG GLN ALA PRO GLY
LYS GLY LEU GLX TRP
LEU SER VAL ILE SER
TYR
ASX GLY
ASX ASX GLX TYR TYR
ALA ALA SER VAL LYS
GLY ARG PHE THR ILE
SER ARG ASX
LYS ASX THR MET TYR
LEU GLU
MET MET ASX ASN SER SER
LEU LEU ARG ARG LEU ALA GLX GLU ASX ASN
THR THR GLY ALA VAL VAL TYR TYR PHE TYR
CYS CYS ALA ALA THR ARG LEU SER ASX GLY
ILE ALA LEU GLY SER
VAL ALA GLY THR
ASP TYR TRP GLY GLX
GLY THR LEU VAL THR
ILE SER SER
val GLU SER GLY GLY
GLY LEU VAL GLN PRO
GLY GLY SER LEU
val val val GLU GLU GLU SER SER SER GLY GLY GLY GLY GLY GLY
GLY val GLY LEU ser val VAL ile VAL glu arg
PRO PRO PRO
GLY GLY GLY glu GLY GLY
SER SER SER LEU LEU LEU ARG ARG
LEU LEU val
CYS CYS
ALA
SER GLY PHE
ile
gly
PHE
MET
val val LEU val GLU SER GLY GLY GLY GLY GLY
GLY GLY GLY ala LEU LEU LEU LEU VAL VAL VAL VAL leu GLN GLN lys
PRO PRO PRO PRO
GLY GLY GLY GLY GLY SER
LEU LEU LEU ARG ARG ARG
.LEU LEU LEU
ALA ALA ALA ALA ALA
val GLU SER GLY GLY
GLY LEU VAL gly
PRO
GLY
LEU GLU SER GLY GLY
GLY LEU VAL
glx
GLY
GLY LEU VAL lys lys
GLY
LEU lhr
LEU
ALA ALA
val GLU SER GLY GLY
GLY LEU VAL
PFIZER EX. 1052 Page 20
170
HUMAN HEAVY CHAINS SUBGROUP Ill (eont'd)
76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 BER HIN KNI SHE LIV PUT HER MOY PIT TOL CRI GLU THA KAR PAR PAV NA SLA LES ANT ARP GRA HOW GUI DAU BUS
;,.
0 1 GLU GLU GLU GLU GLU GLU GLU GLU GLU GLU GLU GLU GLU GLU GLU GLU GLU GLU asp GLU leu GLU gly pea pea 2 VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL ile VAL VAL VAL VAL VAL ser ser 3 GLN GLN GLN GLN GLN GLN GLN GLN GLN GLN GLN GLN GLN lys GLN GLN GLN glu GLN his arg GLN GLN val val '4 LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU 5 val val val val val val val val val val val val val val val ala val val val val val val asx asx 6 GLU GLU GLU GLU GLU GLU GLU GLU GLU GLU GLU GLU ~In GLU GLU GLU ~In GLU gly gly 7 SEA SEA SEA SEA SEA SEA SEA SEA SEA SEA SEA SEA ER SEA SEA SEA ER SEA 8 GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY 9 GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY ala GLY
10 GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY ala GLY GLY asp glx GLY 11 LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU val LEU LEU LEU LEU val 12 VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL ala VAL VAL VAL 13 arg GLN GLN
F 14 PRO PRO PRO PRO F R 15 R 1 16 GLY ser GLY 1
17 18 LEU val 19 ARG 20 LEU val 21 22 23 val ALA 24 gly ALA 25 26 27 28 29 30 31
c 32 c 33 D 34 D R R 1 35 MET 1
35A 358 36 TAP 37 VAL 38 39 GLN 40 ALA
F 41 PRO F
R 42 GLY R 2 43 LYS 2
44 GLY 45 LEU 46 GLU 47 48 VAL 49 SEA ' 50 VAL 51 ILE 52 THR 52A 5 52B 5 52C 5 53 ASX 5 54 GLY s.
c 55 c 5i D D R 56 R Sf
2 57 THR 2 s; 58 TYR 5E 59 TYR 5S 60 ILE 60 61 ASX 61 62 SEA 62 63 VAL 63 64 64 65 GLY ~ 66 66 67 PHE 67 68 THR 68 69 ILE 69 70 SEA 70 71 ARG 71 72 72 73 73 74 74 75 75 76 76 77 77 78 78 79 79
F 80 80 R 81 81 3 82 MET 82
82A SEA 82A 828 SEA 828 82C LEU 82C 83 ARG 83 84 THR 84 85 GLU 85 86 ASP 86 87 THR 87 88 ALA 88 89 VAL 89 90 TYR 90 91 TYR 91 92 CYS 92 93 ALA 93 94 LEU 94 -95 95 96 LEU 96 97 GLU 97 98 SEA ALA 98 99 ASF 99
100 TYR TYR 100 100A HIS SEA 100A
c 1008 TYR LEU ~ c 1008 D 100C TYR D 100C R 100D ALA :·a 100D 3 100E l 100E
100F 100F 100G 100G 100H 100H 1001 1001 100J 100J 100K MET 100K 101 VAL ASP 101 102 THR VAL 102 --103 VAL TAP 103 104 SEA 104 105 SEA 105 106 ALA GLY 106
F 107 SER 107 R 108 THR i 108 4 109 LYS VAL 109
110 GLY THR 110 111 VAL 111 112 112 113 113 -
PFIZER EX. 1052 Page 21
171
HUMAN HEAVY CHAINS SUBGROUP Ill (eont'd)
102 103 104 105 106 107 108 # OF # OF OCCURRENCES VARIABILITY RE DOS BAL CRA U266 LAMBDA LAMBDA SEQUENCES AMINO OF MOST COMMON
# 'CL -VH52 -VH32 ACIDS AMINO ACID 'CL 'CL
0 1 pea pea pea gly 102 6 81(GLU) 7.6 2 ser ser ser phe 103 7 87(VAL) 8.3 3 ala val val # 100 8 87(GLN) : 86(GLN) 9.2 9.3 4 LEU ala ala asp 95 3 92(LEU) 3.1
5 asx glx asn 100 6 8 78(VAL) 7.7 : 10. 6 arg 91 5 78(GLU) · 75(GLU) 5.8 : 6.1 7 thr 90 3 87(SER) 3.1 8 thr 90 2 89(!3LY) 2. 9 glu 98 3 96(GLY) 3.1
10 96 6 76(GLY) 6.3 : 7.6 11 94 4 75(LEU) 5. 12 92 3 86(VA~ 3.2 13 71 6 52(GLN) : 4 (GLN) 8.2 : 9.1
F 14 76 4 72(PRO) 4.2
R 15 68 1 68~GLY) 1. 1 16 75 5 62 GLY) 6.
17 67 3 65(SER) 3.1 18 73 3 71(LEU) 3.1 19 70 3 60(ARG) 3.5
20 72 3 67(LEU) 3.2 21 58 4 54(SER) 4.3 22 58 1 58~CYS) 1. 23 63 6 53 ALA) 7.1 24 65 5 61(ALA) 5.3
25 56 2 55(SER) 2. 26 58 3 56(GLY) 3.1 27 56 2 55(PHE) 2. 28 51 8 30~THRl 14. 29 53 4 47 PHE 4.5
30 50 9 . 10 39(SER) 12. 13.
31 47 11 15(ASP) 11(THR) 34. : 47.
c 32 50 10 21(TYR) 24. 33 46 12 13~A~ 42.
D 34 50 7 35 ME) 10. R 1 35 46 12 15(HIS) 37.
35A 35B 36 40 1 40(TRP) 1. 37 41 3 39(VAL) 3.2
38 39 2 38(ARG) 2.1 39 39 2 38(GLN) 2.1 40 40 5 36(ALA) 5.6
F 41 35 3 26(PRO) 4.
R 42 35 1 35(GLY) 1.
2 43 35 2 34(LY~ 2.1 44 35 3 25(GL ) 4.2 45 35 2 34(LEU) 2.1 46 34 3 33(GLU) : 28(GLU) 2.1 3.6 47 33 33(TRP) 1.
48 34 2 32(VAL) 2.1 49 34 7 10( + 24. 50 34 12 8(HIS) 51. 51 34 6 23(1LE) 8.9 52 33 10 :11 9(GLU) 8(GLU) 37. : 45.
52A 30 10 6(GLU) : 5( + ) 52B 8 1 8(LYS) 52C 8 2 4( + ) 53 33 12 1 O(ASNJ : 7(L YS) 40. : 57. 54 32 6 1 (GLY) 12.
c 55 31 7 8 10(SER) 22. : 25. D R 56 31 10 11 8( + ) : 8(ALA) 39. : 43.
2 57 33 7 8 15(THR) 15. 18. 58 32 11 10(TYR) 35. 59 33 2 29(TYR) 2.3
60 33 6 20(ALA) 9.9 61 33 5 19(ASP) 16(ASP) 8.7 : 10. 62 ARG 34 3 32(SER) 3.2 63 PHE 34 4 31(VAL) 4.4 64 GLN 33 4 21(LYS) 6.3
65 GLY 33 2 32 GLY 2.1 66 ARG 32 1 32(ARG) 1. 67 VAL 33 2 32(PHE) 2.1 68 THR 33 4 30(THR) 4.4 69 MET 33 2 32(1LE) 2.1
70 THR 33 2 32~SER) 2.1 71 ARG 33 1 33 ARG) 1. 72 ASP 32 2 21 (ASP) 19(ASP) 3. 3.4 73 ALA 31 4 22(ASP) : 20(ASP) 5.6 : 6.2 74 SER 31 2 27(SER) 2.3
75 PHE 32 5 27(LYS) 5.9 76 SER 32 4 28(ASN) : 24(ASN) 4.6 6.7 77 THR 32 3 26(THR) 3.7 78 ALA 31 5 20(LEU) 7.8 79 TYR TYR 32 2 23(TYR) 2.8
F 80 MET LEU 32 2 30(LEU) 2.1
R 81 ASP GLN 32 5 26(GLN) : 24(GLN) 6.2 : 6.7
3 82 LEU MET 39 2 37(MET) 2.1 82A ARG ASN ASN 40 7 23(ASN) : 20(ASN) 82B SER SER SER 40 6 31(SER)
82C LEU LEU LEU 40 3 37(LEU) 83 ARG ARG ARG 40 .5 31(ARG) 6.5 84 SER ALA ALA 41 7 18(ALA) 16. 85 ASP GLU GLU 41 2 3 32(GLU) : 27(GLU) 2.6 4.6 86 ASP ASP ASP 41 3 39(ASP) : 33(ASP) 3.2 : 3.7
87 SER MET THR 41 4 37(THR) 4.4 88 ALA ALA ALA 41 2 37(ALA) 2.2 89 VAL VAL VAL 41 4 28~VAL~ 5.9 90 PHE TYR TYR 41 2 40 TYR 2.1 91 TYR TYR TYR 41 2 39(TYR) 2.1
92 CYS CYS CYS 41 1 41(CYS) 1. 93 ALA ALA VAL 41 3 30(ALA) 4.1 94 LYS ARG LYS 41 7 22(ARG) 13. 95 SER 34 10 : 11 9(ASP) . 8(PRO) 38. : 47. 96 ASP 35 15 10(PR0) 53.
97 PRO 33 12 9(GLU) 44. 98 PHE 33 11 10(VAL) 36. 99 TRP 32 11 8(GLU) 44.
100 SER 32 11 10(SER) 35. 100A ASP 31 11 9(LEU)
c 100B TYR 20 11 4( + )
D 100C TYR 14 7 3( + ) R 100D ASN 11 7 3( + )
3 100E PHE 6· 5 2(PHE) 100F ASP 3 3 1( +) 100G TYR 3 2 2(TYR) 100H SER 3 3 1( +) 1001 TYR 4 4 1( +) 100J THR 5 3 3(PHE) 100K LEU 7 4 3(PHE)
101 ASP 32 8 13(ASP) : 11(ASP) 20. : 23. 102 VAL 30 7 9(SER) 23. 103 TRP 31 4 28(TRP) 4.4 104 GLY 31 2 30(GLY) 2.1 105 GLN 31 4 5 21 (GLN) : 19(GLN) 5.9 8.2
106 GLY 32 2 31(GLY) 2.1 F 107 THR 31 4 28(THR) 4.4 R 108 THR 31 4 25(LEU) 5. 4 109 VAL 30 2 29(VAL) 2.1
110 THR 30 3 27(THR) 3.3 111 VAL 17 2 16(VAL) 2.1 112 SER 16 1 16(SER) 1. 113 SER 14 3 12(SER) 3.5
PFIZER EX. 1052 Page 22
ANTIBODY SPECIFICITIES: HUMAN HEAVY CHAINS SUBGROUP Ill
1) TUR: COLD AGGLUTININ WITH ANTI-PR ACTIVITY
3) POM: ANTI-HUMAN GAMMA G1 GLOBULIN; PO IDIOTYPE
14) LAY: ANTI-HUMAN GAMMA G1 AND G3 GLOBULINS; PO IDIOTYPE
16) FR: ANTI-PHOSPHOCHOLINE(BINDING CONSTANT ~6.4X1 OEXP4)
33) WEA: ANTI-3.4-PYRUVYLATED GALACTOSE MONOCLONAL
172
42) 333'CL: HETEROHYBRIDOMA ANTIBODY TO LYMPHOMA CELLS POSSESSING IDIOTOPE REACTING WITH ANTI-IDIOTYPE 7011 BEFORE TREATMENT WITH 7011.
43) 1H1'CL: HETEROHYBRIDOMA ANTIBODY TO LYMPHOMA CELLS POSSESSING IDIOTOPE REACTING WITH ANTI-IDIOTYPE 7011 BEFORE TREATMENT WITH 7011.
44) 1B11'CL: HETEROHYBRIDOMA ANTIBODY TO LYMPHOMA CELLS POSSESSING IDIOTOPE REACTING WITH ANTI-IDIOTYPE 7011 AFTER TREATMENT WITH 7011.
45) 126'CL: HETEROHYBRIDOMA ANTIBODY TO LYMPHOMA CELLS POSSESSING IDIOTOPE REACTING WITH ANTI-IDIOTYPE 7011 AFTER TREATMENT WITH 7011.
46) 112'CL: HETEROHYBRIDOMA ANTIBODY TO LYMPHOMA CELLS POSSESSING IDIOTOPE REACTING WITH ANTI-IDIOTYPE 7011 AFTER TREATMENT WITH 7011.
47) 115'CL: HETEROHYBRIDOMA ANTIBODY TO LYMPHOMA CELLS POSSESSING IDIOTOPE REACTING WITH ANTI-IDIOTYPE 7011 AFTER TREATMENT WITH 7011.
48) 2A12'CL: HETEROHYBRIDOMA ANTIBODY TO LYMPHOMA CELLS POSSESSING IDIOTOPE REACTING WITH ANTI-IDIOTYPE 7011 BEFORE TREATMENT WITH 7011.
49) 2C12'CL: HETEROHYBRIDOMA ANTIBODY TO LYMPHOMA CELLS POSSESSING IDIOTOPE REACTING WITH ANTI-IDIOTYPE 7011 BEFORE TREATMENT WITH 7011.
59) HEI: COLD AGGLUTININ WITH ANTI-GO (MEMBRANE-GLYCOLIPID-DEPENDENT) ACTIVITY
60) KN: COLD AGGLUTININ WITH ANTI-GO (MEMBRANE-GLYCOLIPID-DEPENDENT) ACTIVITY
63) L.TH.: COLD AGGLUTININ WITH ANTI-PR2 ACTIVITY (RBC MEMBRANE ANTIGEN ON HUMAN, RAT AND GUINEA PIG ERYTHROCYTES INACTIVATED BY PROTEOLYTIC ENZYMES AND NEURAMINIDASE)
64) WAG: ANTI-DINITROPHENYL
67) R.K.: COLD AGGLUTININ WITH ANTI-PR1H ACTIVITY (RBC MEMBRANE ANTIGEN ON HUMAN ERYTHROCYTES INACTIVATED BY PROTEOLYTIC ENZYMES AND NEURAMINIDASE)
68) GOEII: ANTI-MEASLES VIRUS (WOODFOLK STRAIN); ANTI-SUBACUTE SCLEROSING PANENCEPHALITIS VIRUS (LEG STRAIN)
CLASS: HUMAN HEAVY CHAINS SUBGROUP Ill
1) TUR: IGA1-KAPPA
3) POM: IGM-KAPPA
4) TIL: IGG2 & IGM-KAPPA
5) WAS: IGG1-
10) TEl: IGG1-KAPPA
11) BRO'IGM: IGM-LAMBDA
12) GR': IGG & IGA-KAPPA
13) WAT: IGG2-LAMBDA
14) LAY: IGM-KAPPA
16) FR: IGM-KAPPA
17) MU: IGA-
18) VIN: IGG4-LAMBDA
20) BEN(III): IGM-
21) ZAP: IGA1-KAPPA
22) JON: IGG3-
24) LOW: IGA2-KAPPA
25) BRO: IGA1-LAMBDA
26) BUT: IGA2 A2M(2)-
27) JOR: IGA1-LAMBDA
28) GAA: IGG1-LAMBDA
30) GO: IGG1-
31) DOB: IGG1 GM(1,-17)-KAPPA KM(3)
33) WEA: IGM-KAPPA
34) NIE: IGG1-
35) CAM': IGM-KAPPA
36) WE: IGG-KAPPA
37) AVI: IGA2-KAPPA
38) GAL: IGM-KAPPA
39) SKI: IGA1-LAMBDA
40) FOR: IGA2-LAMBDA
41) EVA: IGM-LAMBDA
50) TRO: IGA1-LAMBDA
51) KOL: IGG1-LAMBDA
52) WEI: IGG1-LAMBDA
53) ESM: IGM-
54) V.N.: IGG1-KAPPA
55) HIL: IGG1-LAMBDA
56) BUR: IGA1-LAMBDA
58) WO: IGM-
61) PS (SHA): IGE-LAMBDA
62) GA: IGM-
63) L.TH.: IGM-KAPPA
64) WAG: IGM-
65) LR: IGM-LAMBDA PYROGLOBULIN
66) HI: IGG-
67) R.K.: IGA-KAPPA
69) POD: IGA1-
70) PAL: IGG1-
71) GIT: IGM-
72) HA: IGA1-
73) SEI: IGA1-KAPPA
74) PAC: IGG1-
75) KOO: IGA1-KAPPA
76) BER: IGA1-KAPPA
77) HIN: IGA1-KAPPA
78) KNI: IGA1-KAPPA
79) SHE: IGA1-KAPPA
80) LIV: IGA1-KAPPA
81) PUT: IGA1-LAMBDA
82) HER: IGA2-LAMBDA
83) MOY: IGA1-LAMBDA
84) PIT: IGA1-LAMBDA
85) TOL: IGA1-LAMBDA
86) CRI: IGA1-LAMBDA
87) GLU: IGA1-LAMBDA
88) THA: IGA1-KAPPA
89) KAR: IGA1-KAPPA
90) PAR: IGA2-
91) PAV: IGG3-KAPPA
c
1• 11
11
11
11
11
R
2
2
2
3!
3~
4(
41
4~
~
44
45
4E
47
4E
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65:
PFIZER EX. 1052 Page 23
173 1 l CU"' """'" """ '"""' '""M"' m (Wei'O) 92) NA: IGM-
93) SLA: IGA1-LAMBDA
94) LES: IGA1-KAPPA
95) ANT: IGM-
96) ARP: IGA1-
97) GRA: IGG3-
98) HOW: IGM-
99) GUI: IGG1-LAMBDA
100) DAU: IGM-
101) BUS: IGM-
102) RE: IGM-
103) DOS: IGM-
104) BAL: IGM-
105) CRA: IGG1-
REFERENCE: HUMAN HEAVY CHAINS SUBGROUP Ill
1) TUR: CAPRA,J.D. & KEHOE,J.M. (1974) PROC.NAT.ACAD.SCI.USA,71,845-848. (CHECKED BY AUTHOR WHO CORRECTED RESIDUES 85,86 AS GIVEN IN TABLE)
2) LAMBDA-VH26'CL: RABBITTS,T.H.,BENTLEY,D.L.,DUNNICK,W.,FORSTER,A.,MATTHYSSENS,G. & MILSTEIN,C. (1980) COLD SPRING HARB.SYMP.OUANTI.BIOL.,45,867-878; MATTHYSSENS,G. & RABBITTS,T.H. (1980) PROC.NAT.ACAD.SCI.USA,77,6561-6565. (CHECKED BY AUTHOR 12/09/80)
3) POM: CAPRA,J.D. & KEHOE,J.M. (1974) PROC.NAT.ACAD.SCI.USA,71,4032-4036. (CHECKED BY AUTHOR WHO CORRECTED RESIDUES 85,86 AS GIVEN IN TABLE)
4) TIL: WANG,A.C.,GERGELY,J. & FUDENBERG,H.H. (1973) BIOCHEMISTRY,12,528-534. (CHECKED BY AUTHOR); WANG,A.C. & FUDENBERG,H.H. (1975) ARCH.BIOCHEM.BIOPHYS.,168,657-664; WANG,A.C.,WANG,I.T. & FUDENBERG,H.H. (1977) J.BIOL.CHEM.,252,7192-7199. (CHECKED BY AUTHOR 09/23/77)
5) WAS: CAPRA,J.D. & KEHOE,J.M. (1974) PROC.NAT.ACAD.SCI.USA,71,845-848. (CHECKED BY AUTHOR WHO CORRECTED RESIDUES 85,86 AS GIVEN IN TABLE)
6) HF2-1/13B: ATKINSON,P.M.,LAM PMAN,G.W., FURIE,B.C.,NAPARSTEK, Y.,SCHWARTZ,R.S.,STO LLAR,B.D. & FURIE,B. (1985) J.CLIN.INVEST., 75,1138-1143. (CHECKED BY AUTHOR 08/21/85)
7) HF2-1/17: ATKINSON,P.M.,LAMPMAN,G.W.,FURIE,B.C.,NAPARSTEK,Y.,SCHWARTZ,R.S.,STOLLAR,B.D. & FURIE,B. (1985) J.CLIN.INVEST., 75,1138-1143. (CHECKED BY AUTHOR 08/21/85)
8) HF2-18/2: ATKINSON, P.M.,LAMPMAN,G.W.,FURIE, B.C.,NAPARSTEK, Y.,SCHWARTZ,R.S.,STOLLAR,B.D. & FURIE,B. (1985) J.CLIN.INVEST.,75,1138-1143. (CHECKED BY AUTHOR 08/21/85)
9) H11'CL: RECHAVI,G.,BIENZ,B.,RAM,D.,BEN-NERIAH,Y.,COHEN,J.B.,ZAKUT,R. & GIVOL,D. (1982) PROC.NAT.ACAD.SCI.USA,79,4405-4409.
10) TEl: CAPRA,J.D. & KEHOE,J.M. (1974) PROC.NAT.ACAD.SCI.USA,71,845-848. (CHECKED BY AUTHOR WHO CORRECTED RESIDUES 85,86 AS GIVEN IN TABLE)
11) BRO'IGM: CAPRA,J.D. & HOPPER,J.E. (1976) IMMUNOCHEMISTRY,13,995-999; HOPPER,J.E.,NOYES,C.,HEINRIKSON,R. & KESSEL,J.W. (1976) J.IMMUNOL., 116,743-746. (CHECKED BY AUTHOR 08/01/79)
12) GR': FAIR,D.S.,SLEDGE,C.,KRUEGER,R.G.,MANN,K.G. & HOOD,L.E. (1975) BIOCHEMISTRY,14,5561-5568.
13) WAT: WANG,A.C.,FUDENBERG,H.H. & PINK,J.R.L. (1971) PROC.NAT.ACAD.SCI.USA,68,1143-1147. (CHECKED BY AUTHOR)
14) LAY: CAPRA,J.D. & KEHOE,J.M. (1974) PROC.NAT.ACAD.SCI.USA,71,4032-4036. (CHECKED BY AUTHOR WHO CORRECTED RESIDUE 85 AS GIVEN IN TABLE)
15) GRA': CAPRA,J.D. (1977) IN ANTIBODIES IN HUMAN DIAGNOSIS AND THERAPY,RAVEN PRESS,NEW YORK,87-102. (CHECKED BY AUTHOR 03/18/81)
16) FR: RIESEN,W.,RUDIKOFF,S.,ORIOL,R. & POTTER,M. (1975) BIOCHEMISTRY,14,1052-1057; RIESEN,W.F.,BRAUN,D.G. & JATON,J.C. (1976) PROC.NAT.ACAD.SCI.USA,73,2096-2100. (CHECKED BY AUTHOR WHO PROVIDED ADDITIONAL RESIDUES FOR POSITIONS 39 TO 51 AND 82 TO 94. 12/05/77)
17) MU: SHINODA,T. (1973) BIOCHEM.BIOPHYS.RES.COMMUN.,52,1246-1251. (CHECKED BY AUTHOR WHO CORRECTED RESIDUE 46 AS GIVEN IN TABLE)
18) VIN: PINK,J.R.L. & MILSTEIN,C. (1969) PROC. 5TH FEBS SYMP.,15,177-182. (CHECKED BY AUTHOR)
19) HF3-16/6: ATKINSON, P.M., LAMPMAN,G.W., FURIE,B.C.,NAPARSTEK, Y.,SCHWARTZ,R.S.,STOLLAR,B.D. & FURIE,B. (1985) J.CLIN.INVEST., 75,1138-1143. (CHECKED BY AUTHOR 08/21/85)
20) BEN(Ill): CAPRA,J.D. (1971) NATURE NEW BIOLOGY,230,61-63. (CHECKED BY AUTHOR)
21) ZAP: CAPRA,J.D. & KEHOE,J.M. (1974) PROC.NAT.ACAD.SCI.USA,71,845-848. (CHECKED BY AUTHOR WHO CORRECTED RESIDUES 85,86 AS GIVEN IN TABLE)
22) JON: CAPRA,J.D. & KEHOE,J.M. (1974) PROC.NAT.ACAD.SCI.USA,71,845-848. (CHECKED BY AUTHOR WHO CORRECTED RESIDUES 85,86 AS GIVEN IN TABLE)
23) KEA: WANG,A.C. & FUDENBERG,H.H. (1975) IMMUNOL.COMMUN.,4,483-497. (CHECKED BY AUTHOR 09/23/77)
24) LOW: WANG,A.C., FUDENBERG,H.H. & PINK,J.R. L. (1971) PROC.NAT.ACAD.SCI.USA,68, 1143-1147. (CHECKED BY AUTHOR)
25) BRO: WANG,A.C.,FUDENBERG,H.H. & PINK,J.R.L. (1971) PROC.NAT.ACAD.SCI.USA,68,1143-1147. (CHECKED BY AUTHOR)
26) BUT: TORANO,A. & PUTNAM,F.W. (1978) PROC.NAT.ACAD.SCI.USA,75,966-969. (CHECKED BY AUTHOR 06/15/83)
27) JOR: WANG,A.C.,FUDENBERG,H.H. & PINK,J.R.L. (1971) PROC.NAT.ACAD.SCI.USA,68,1143-1147. (CHECKED BY AUTHOR)
28) GAA: WANG,A.C.,FUDENBERG,H.H. & PINK,J.R.L. (1971) PROC.NAT.ACAD.SCI.USA,68,1143-1147. (CHECKED BY AUTHOR)
29) CAM: HOPPER,J.E.,NOYES,C.,HSU,R.,HEINRIKSON,R. & GALLAGHER,W. (1979) J.IMMUNOL.,122,2007-2010. (CHECKED BY AUTHOR 01/26/83)
30) GO: WANG,A.C.,FUDENBERG,H.H. & CREYSSEL,R. (1974) EUR.J.IMMUNOL.,4,446-448. (CHECKED BY AUTHOR)
31) DOB: STEINER,L.A.,GARCIA-PARDO,A. & MARGOLIES,M.N. (1979) BIOCHEMISTRY,18,4068-4080. (CHECKED BY AUTHOR 07/20/79)
32) ElK: SMITH,G.P.,HOOD,L. & FITCH,W.M. (1971) ANN.REV.BIOCHEM.,40,969-1012.
33) WEA: GONI,F. & FRANGIONE,B. (1983) PROC.NAT.ACAD.SCI.USA,80,4837-4841. (CHECKED BY AUTHOR 03/23/84)
34) NIE: PONSTINGL,H.,SCHWARZ,J.,REICHEL,W. & HILSCHMANN,N. (1970) Z.PHYSIOL.CHEM.,351,1591-1594. (CHECKED BY AUTHOR WHO CORRECTED RESIDUES 85,86 AS GIVEN IN TABLE)
35) CAM': LEHMAN,D.W. & PUTNAM,F.W. (1980) PROC.NAT.ACAD.SCI.USA,77,3239-3243. (CHECKED BY AUTHOR 05/01/80)
36) WE: DWORSKY,E.,SLETTEN,K.,HARBOE,M. & WETTELAND,P. (1980) SCAND.J.IMMUNOL., 12,281-287. (CHECKED BY AUTHOR 02/28/1984)
37) AVI: PINK,J.R.L.,MCNALLY,M.P.,WANG,A.C. & FUDENBERG,H.H. (1972) IMMUNOCHEMISTRY,9,84-88; WOLFENSTEIN-TODEL,C.,FRANGIONE,B. & FRANKLIN, E.G. (1975) BIOCHIM.BIOPHYS.ACTA,379,627-637. (CHECKED BY AUTHOR WHO PROVIDED ADDITIONAL RESIDUES TO THOSE PUBLISHED)
38) GAL: WATANABE,S.,BARNIKOL,H.U.,HORN,J.,BERTRAM,J. & HILSCHMANN,N. (1973) Z.PHYSIOL.CHEM.,354,1505-1509. (CHECKED BY AUTHOR)
39) SKI'> WANG,A.C.,FUDENBERG,H.H. & PINK,J.R.L. (1971) PROC.NAT.ACAD.SCI.USA,68,1143-1147. (CHECKED BY AUTHOR)
40) FOR: WANG,A.C.,FUDENBERG,H.H. & PINK,J.R.L. (1971) PROC.NAT.ACAD.SCI.USA,68,1143-1147. (CHECKED BY AUTHOR); WANG,A.C. & FUDENBERG,H.H. (1975) ARCH.BIOCHEM.BIOPHYS.,168,657-664. (CHECKED BY AUTHOR 09/23/77)
41) EVA: WANG,A.C.,FUDENBERG,H.H. & PINK,J.R.L. (1971) PROC.NAT.ACAD.SCI.USA,68,1143-1147. (CHECKED BY AUTHOR)
42) 333'Cl: CLEARY,M.L.,MEEKER,T.C.,LEVY,S.,LEE,E.,TRELA,M.,SKLAR,J. & LEVY,R. (1986) CELL,44,97-106.
43) 1H1'Cl: CLEARY,M.L.,MEEKER,T.C.,LEVY,S.,LEE,E.,TRELA,M.,SKLAR,J. & LEVY,R. (1986) CELL,44,97-106.
44) 1B11'CL: CLEARY,M.L.,MEEKER,T.C.,LEVY,S.,LEE,E.,TRELA,M.,SKLAR,J. & LEVY,R. (1986) CELL,44,97-106.
45) 126'CL: CLEARY,M.L.,MEEKER,T.C.,LEVY,S.,LEE,E.,TRELA,M.,SKLAR,J. & LEVY,R. (1986) CELL,44,97-106.
46) 112'Cl: CLEARY,M.L.,MEEKER,T.C.,LEVY,S.,LEE,E.,TRELA,M.,SKLAR,J. & LEVY,R. (1986) CELL,44,97-106.
47) 115'CL: CLEARY,M.L.,MEEKER,T.C.,LEVY,S.,LEE,E.,TRELA,M.,SKLAR,J. & LEVY,R. (1986) CELL,44,97-106.
48) 2A12'CL: CLEARY,M.L.,MEEKER,T.C.,LEVY,S.,LEE,E.,TRELA,M.,SKLAR,J. & LEVY,R. (1986) CELL,44,97-106.
49) 2C12'CL: CLEARY,M.L.,MEEKER,T.C.,LEVY,S.,LEE,E.,TRELA,M.,SKLAR,J. & LEVY,R. (1986) CELL,44,97-106.
50) TRO: KRATZIN,H.,ALTEVOGT,P.,RUBAN,E.,KORTT,A.,STAROSCIK,K. & HILSCHMANN,N. (1975) Z.PHYSIOL.CHEM.,356,1337-1342; KRATZIN,H.,ALTEVOGT,P., KORTT,A., RUBAN,E. & HILSCHMANN,N. (1978) Z.PHYSIOL.CHEM.,359,1717-1745.
51) KOL: SCHMIDT,W.E.,JUNG,H-.D.,PALM,W. & HILSCHMANN,N. (1983) Z.PHYSIOL.CHEM.,364,713-747.
52) WEI: WANG,A.C.,FUDENBERG,H.H. & PINK,J.R.L. (1971) PROC.NAT.ACAD.SCI.USA,68,1143-1147. (CHECKED BY AUTHOR)
53) ESM: WANG,A.C.,MATHER,S.,TUNG,E.,SARVAS,H.,RIVAT,C. & RIVAT,L. (1980) MOL.IMMUNOL.,17,313-318. (CHECKED BY AUTHOR 11/15/82.)
54) V.N.: WANG,A.C.,FUDENBERG,H.H.,GOLDROSEN,M.H. & FREEDMAN,M.H. (1972) IMMUNOCHEMISTRY,9,473-479. (CHECKED BY AUTHOR 09/23/77)
55) Hll: CHIU,Y.Y.H.,LOPEZ DE CASTRO,J.A. & POLJAK,R.J. (1979) BIOCHEMISTRY,18,553-560. (CHECKED BY AUTHOR 07/16/79)
56) BUR: LIU,V.Y.S.,LOW,T.L.K.,INFANTE,A. & PUTNAM,F.W. (1976) SCIENCE,193,1017-1020. (CHECKED BY AUTHOR 06/15/83)
57) ERI: MILSTEIN,C.P. & NORTHROP,F. (1976) EUR.J.IMMUNOL.,6,222-224. (CHECKED BY AUTHOR 09/08/78)
58) WO: KOHLER,H.,SHIMIZU,A.,PAUL,C.,MOORE,V. & PUTNAM,F.W. (1970) NATURE,227,1318-1320. (CHECKED BY AUTHOR 06/15/83)
59) HEI: RIESEN,W.F.,MAJANIEMI,I.,HUSER,H.,BRAUN,D.G. & ROELCKE,D. (1978) SCAND.J.IMMUNOL.,8,145-148. (CHECKED BY AUTHOR 10/10/79)
60) KN: RIESEN,W.F.,MAJANIEMI,I.,HUSER,H.,BRAUN,D.G. & ROELCKE,D. (1978) SCAND.J.IMMUNOL.,8,145-148. (CHECKED BY AUTHOR 10/10/79)
61) PS (SHA): TERRY,W.D.,OGAWA,M. & KOCHWA,S. (1970) J.IMMUNOL.,105,783-785; KOCHWA,S.,TERRY,W.D.,CAPRA,J.D. & YANG,N.Y. (1971) ANN.N.Y.ACAD.SCI.,190,49-70. (CHECKED BY AUTHOR WHO PROVIDED ADDITIONAL RESIDUES TO THOSE PUBLISHED)
62) GA: FLORENT,G.,LEHMAN,D. & PUTNAM,F.W. (1974) BIOCHEMISTRY,13,2482-2498. (CHECKED BY AUTHOR 06/15/83)
63) LTH.: WANG,A.C.,FUDENBERG,H.H.,WELLS,J.V. & ROELCKE,D. (1973) NATURE NEW BIOLOGY,243,126-128. (CHECKED BY AUTHOR)
64) WAG: KAPLAN,A.P.,HOOD,L.,TERRY,W.D. & METZGER,H. (1971) IMMUNOCHEMISTRY,8,801-811.
65) LR: CAULIN-GLASER,T.,PRELLI,F. & FRANKLIN,E.C. (1982) J.LAB.CLIN.MED.,99,845-851. (CHECKED BY AUTHOR 12/10/82)
PFIZER EX. 1052 Page 24
174
REFERENCE: HUMAN HEAVY CHAINS SUBGROUP Ill (cont'd)
66) HI: TERRY,W.D. & OHMS,J. (1970) PROC.NAT.ACAD.SCI.USA,66,558-563.
67) R.K.: WANG,A.C.,FUDENBERG,H.H.,WELLS,J.V. & ROELCKE,D. (1973) NATURE NEW BIOLOGY,243,126-128. (CHECKED BY AUTHOR)
68) GOEII: STROSBERG,A.D.,KARCHER,D. & LOWENTHAL,A. (1975) J.IMMUNOL.,115,157-160. (CHECKED BY AUTHOR)
69) POD: WANG,A.C.,MATHER,S.,TUNG,E.,SARVAS,H.,RIVAT,C. & RIVAT,L. (1980) MOL.IMMUNOL.,17,313-318. (CHECKED BY AUTHOR 11/15/82.)
70) PAL: WANG,A.C.,MATHER,S.,TUNG,E.,SARVAS,H.,RIVAT,C. & RIVAT,L. (1980) MOL.IMMUNOL.,17,313-318. (CHECKED BY AUTHOR 11/15/82.)
71) GIT: WANG,A.C.,MATHER,S.,TUNG,E.,SARVAS,H.,RIVAT,C. & RIVAT,L. (1980) MOL.IMMUNOL.,17,313-318. (CHECKED BY AUTHOR 11/15/82.)
72).HA: KOHLER,H.,SHIMIZU,A.,PAUL,C.,MOORE,V. & PUTNAM,F.W. (1970) NATURE,227,1318-1320. (CHECKED BY AUTHOR 06/15/83)
73) SEI: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
74) PAC: WANG,A.C.,MATHER,S.,TUNG,E.,SARVAS,H.,RIVAT,C. & RIVAT,L. (1980) MOL.IMMUNOL.,17,313-318. (CHECKED BY AUTHOR 11/15/82.)
75) KOO: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
76) BER: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
77) HIN: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
78) KNI: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
79) SHE: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
80) LIV: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
81) PUT: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
82) HER: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
83) MOY: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
84) PIT: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
85) TOL: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
86) CRI: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
87) GLU: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
88) THA: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
89) KAR: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
90) PAR: WANG,A.C.,MATHER,S.,TUNG,E.,SARVAS,H.,RIVAT,C. & RIVAT,L. (1980) MOL.IMMUNOL.,17,313-318. (CHECKED BY AUTHOR 11/15/82.)
91) PAY: PARR,D.M. (1977) BIOCHEM.J.,165,303-308; PARR,D.M. & HOFMANN,T. (1980) MOL.IMMUNOL.,17,1-7. (CHECKED BY AUTHOR 05/29/80 WHO PROVIDED ADDITIONAL RESIDUES FOR POSITIONS 98 TO 100H) .
92) NA: KOHLER,H.,SHIMIZU,A.,PAUL,C.,MOORE,V. & PUTNAM,F.W. (1970) NATURE,227,1318-1320. (CHECKED BY AUTHOR 06/15/83)
93) SLA: CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
94) LES:
95) ANT:
96) ARP:
97) GRA:
CAPRA,J.D. & KEHOE,J.M. (1975) J.IMMUNOLOGY,114,678-681. (CHECKED BY AUTHOR)
WANG,A.C.,MATHER,S.,TUNG,E.,SARVAS,H.,RIVAT,C. & RIVAT,L. (1980) MOL.IMMUNOL.,17,313-318.
WANG,A.C.,MATHER,S.,TUNG,E.,SARVAS,H.,RIVAT,C. & RIVAT,L. (1980) MOL.IMMUNOL.,17,313-318.
WANG,A.C.,MATHER,S.,TUNG,E.,SARVAS,H.,RIVAT,C. & RIVAT,L. (1980) MOL.IMMUNOL.,17,313-318.
98) HOW: KAPLAN,A.P.,HOOD,L.,TERRY,W.D. & METZGER,H. (1971) IMMUNOCHEMISTRY,8,801-811.
(CHECKED BY AUTHOR 11/15/82.)
(CHECKED BY AUTHOR 11/15/82.)
(CHECKED BY AUTHOR 11/15/82.)
99) GUI: PINK,J.R.L.,MCNALLY,M.P.,WANG,A.C. & FUDENBERG,H.H. (1972) IMMUNOCHEMISTRY,9,84-88. (CHECKED BY AUTHOR)
100) DAU: BENNETT,J.C. (1968) BIOCHEMISTRY,7,3340-3344. (CHECKED BY AUTHOR 11/01/77); FLORENT,G.,LEHMAN,D. & PUTNAM,F.W. (1974) BIOCHEMISTRY,13,2482-2498. (CHECKED BY AUTHOR 02/15/82)
101) BUS: BENNETT,J.C. (1968) BIOCHEMISTRY,7,3340-3344. (CHECKED BY AUTHOR 11/01/77)
102) RE: KOHLER,H.,SHIMIZU,A.,PAUL,C.,MOORE,V. & PUTNAM,F.W. (1970) NATURE,227,1318-1320. (CHECKED BY AUTHOR 06/15/83)
103) DOS: BENNETT,J.C. (1968) BIOCHEMISTRY,7,3340-3344. (CHECKED BY AUTHOR 11/01/77)
104) BAL: BENNETT,J.C. (1968) BIOCHEMISTRY,7,3340-3344. (CHECKED BY AUTHOR 11/01/77)
105) CRA: FRANGIONE,B. & FRANKLIN,E.C. (1977) PROG.IMMUNOL.,3,278-288. (CHECKED BY AUTHOR 07/18/79)
1 06) U266'C~~ 9-~~~0,M.,KUROKAWA,T.,ONO,Y.,ONDA,H.,SASADA,R.,IGARASHI,K.,KIKUCHI,M.,SUGINO, Y.,NISHIDA,Y. & HONJO,T. (1 983) NUC.ACIDS RES., 11,
107) LAMBDA-VH52'CL: RABBITTS,T.H.,BENTLEY,D.L.,DUNNICK,W.,FORSTER,A.,MATTHYSSENS,G. & MILSTEIN,C. (1980) COLD SPRING HARB.SYMP.QUANTI.BIOL.,45,867-878.
108) LAMBDA-VH32'CL: RABBITTS,T.H.,BENTLEY,D.L.,DUNNICK,W.,FORSTER,A.,MATTHYSSENS,G. & MILSTEIN,C. (1980) COLD SPRING HARB.SYMP.QUANTI.BIOL.,45,867-878.
NOTES: HUMAN HEAVY CHAINS SUBGROUP Ill
IDENTICAL SETS OF FRAMEWORK SEGMENTS:
FR1: SET SET SET SET
FR2: SET SET SET SET SET
FR3: SET SET SET
FR4: SET
SET SET
1: TUR[1],LAMBDA-VH26'CL[2],POM[3],TIL[4]. (4 IDENTICAL) 2: HF2-1/13B[6],HF2-1/17[7]. (2 IDENTICAL) 3: H11 'CL(9],TE1[1 O],BRO'IGM[11],GR'[12]. (4 IDENTICAL) 4: 333'CL[ 42], 1 H1 'CL[ 43], 1 B11'CL[ 44], 126'CL[45]. (4 IDENTICAL)
1: TIL[4],TE1[10]. (2 IDENTICAL HUMAN V-H-111; ALSO 1 HUMAN V-H-1: WOL[4].) 2: TUR[1],LAMBDA-VH26'CL[2]. (2 IDENTICAL) 3: POM[3],WAS[5],LAY[14],FR[16],NIE[34],GAL[38],KOL[51], HIL[55],BUR[56]. (9 IDENTICAL) 4: WEA[33],GA[62]. (2 IDENTICAL) 5: 333'CL[42],1 H1 'CL[43],1 B11'CL[44], 126'CL[45],112'CL[46],115'CL(47],2A12'CL[48],2C12'CL[49]. (8 IDENTICAL)
1: U266'CL[106]. (IDENTICAL TO 1 HUMAN V-H-1: ND'CL[6].) 2: 333'CL[42],1H1'CL(43]. (2 IDENTICAL) 3: 1B11'CL(44],2A12'CL[48],2C12'CL[49]. (3 IDENTICAL)
1: TIL[4],DOB[31],WEA[33],NIE[34]. (4 IDENTICAL HUMAN V-H-111; ALSO 1 HUMAN V-H-1: WOL[4]; 2 HUMAN V-H-11: MCE'[4],NZU[15]; AND 1 MOUSE V-H-IIIA: MOPC47A[48].)
2: U266'CL[106]. (IDENTICAL TO 1 HUMAN V-H-1: ND'CL[6]; 1 HUMAN V-H-11: HIG1'CL(10]; AND 1 MOUSE V-H-IIA: HDEX12[15].) 3: 1H1'CL[43],1B11'CL[44],2C12'CL[49]. (3 IDENTICAL)
IDENTICAL SETS OF COMPLEMENTARITY DETERMINING REGIONS:
CDR1: SET 1: LAMBDA-VH26'CL[2],HF2-1/13B[6],HF2-1/17[7],HF2-18/2[8]. (4 IDENTICAL HUMAN V-H-111; ALSO 4 MOUSE V-H-IIID: 40-20[1], 40-100[2],40-90[4],SP1/HL'CL[7]; AND 1 RABBIT V-H: 3374[11].)
SET 2: H11'CL[9]. (IDENTICAL TO 31 MOUSE V-H-IIB: B1-8'CL[1],B1-8.DELTA1V3[2],186-2'CL[3],B1-48'CL[4],186-1'CL[5],S1F12'CL[6], S2D8'CL[7],S2E9'CL[8] ,N-HYB'CL[9] ,124'CL[11], VNP'CL(12] ,B1-8.V1/V2[13],B1-8. V1 'CL(14], 1 02'CL[15],33'CL[17],23'CL(18], F17. 170.2[20],S2H5'CL[22], 132.16'CL[25],AC38 15.3[32], 1 04B'CL[33],MVAR1 'CL[37],N1 C12'CL( 40],119.13'CL[ 47], 167.1 'CL[ 48], 21 9.7'CL[ 49],S1 F2'CL[51],N1 G9'CL[53], 167.2'CL[56],AC38 260.2[58],AC38 251 .5[59].)
SET 3: 333'CL[42],1 H1'CL[43], 1 B11 'CL[44],126'CL(45],112'CL[46],115'CL[47],2A12'CL[48],2C12'CL[49]. (8 IDENTICAL) SET 4: BUR[56]. (IDENTICAL TO 1 MOUSE V-H-IIA: BCL1'CL[49].)
CDR2: SET 1: POM[3],LAY[14]. (2 IDENTICAL) SET 2: 1B11'CL[44],115'CL[47]. (2 IDENTICAL)
CDR3: SET 1: LAMBDA-VH26'CL[2]. (IDENTICAL TO 1 HUMAN V-H-1: HG3'CL[3]; 1 MOUSE V-H-IB: PJ14'CL[22]; AND 5 MOUSE V-H-IIB: 186-2'CL[3], 186-1 'CL[5], 1 02'CL[15],23'CL[18],3'CL[26].)
SET 2: U266'CL[106]. (IDENTICAL TO 1 HUMAN V-H-1: ND'CL[6].) SET 3: POM[3],LAY[14]. (2 IDENTICAL) SET 4: 333'CL[42],1 H1 'CL[43],1 B11 'CL[44],126'CL[45],112'CL[46],115'CL[47],2A12'CL[48],2C12'CL[49]. (8 IDENTICAL)
IDENTICAL SETS OF J-MINIGENES:
SET 1: U266'CL[106]. (IDENTICAL TO 1 HUMAN V-H-1: ND'CL(6]; AND 1 HUMAN V-H-11: HIG1'CL[10].) SET 2: 1H1'CL[43],1B11'CL[44],2C12'CL[49]. (3 IDENTICAL)
GENERAL NOTES:
# SEE SIGNAL PEPTIDE TABLE IF # OCCURS AT POSITION 0.
SPECIFIC NOTES:
2) LAMBDA-VH26'CL: THE SEQUENCE IS OBTAINED BY TRANSLATING THE NUCLEOTIDE SEQUENCE OF A CLONE OF HUMAN FOETAL LIVER DNA. TWO OTHER CLONES HAVE SLIGHT DIFFERENT SEQUENCES: LAMBDA-VH52'CL HAS MET AT POSITION 87 AND ARG AT POSITION 94, AND LAMBDA-VH32'CL HAS VAL AT POSITION 93.
15) GRA': PERSONAL COMMUNICATION FROM THE AUTHOR INDICATES THAT IT IS A CRYOGLOBULIN.
16) FR: AN IDIOTYPIC ANTIBODY TO FA NOT INHIBITABLE BY PHOSPHORYLCHOLINE REACTED BETTER WITH THE FA HEAVY CHAIN THAN WITH THE LIGHT CHAIN. THE CROSS-REACTION WITH MOPC167 WAS 10,000 TIMES WEAKER. (RIESEN,W.F. (1979) EUR.J.IMMUNOL.,9,421-425.)
61) PS (SHA): PS AND SHA ARE THE SAME PROTEIN AS POINTED OUT BY HASSNER,A. & SAXON,A. (1984) J.IMMUNOL.,132,2844-2846.
105) CRA: IT WAS FROM A CASE OF HEAVY CHAIN DISEASE. AT POSITION 3, LEU AND ILE WERE FOUND. AFTER POSITION 9, THE CHAIN CONTINUES IN THE C-REGION AS RESIDUE 216 (EU NUMBERING) GLU.
N
+
PFIZER EX. 1052 Page 25
NOTES: HUMAN HEAVY CHAINS SUBGROUP Ill (cont'd)
+ THE FOLLOWING WERE EQUALLY AND MOST FREQUENTLY OCCURRING:
AT POSITION
49 52A 57 72
1008 100C 100D 100F 100H 1001
RESIDUES (ALA,SER)
(TYR,SER,GLU) (TYR,SER) (TYR,THR) (ASP,ASN) (TYR,PHE)
(TYR,THR,SER) (PHE,ALA)
(TYR,CYS,ASP) (TYR,SER,GLY)
(TYR, PHE, PRO,GL Y)
175
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