throbber

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`PFIZER EX. 1052
`
`Page 1
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`PFIZER EX. 1052
`Page 1
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`PFIZER EX. 1052
`Page 2
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`

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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)
`
`PFIZER EX. 1052
`Page 3
`
`

`

`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.
`
`c
`
`s
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`PFIZER EX. 1052
`Page 4
`
`

`

`iii
`
`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
`
`. h a
`
`>py
`ead
`
`n to
`
`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
`
`PFIZER EX. 1052
`Page 5
`
`

`

`iv
`
`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.
`
`. .. 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
`
`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 .
`
`. ...... 677
`. 680
`. ................... 683
`
`CODONS OF MOUSE T-LYMPHOCYTE RECEPTOR FOR ANTIGEN ALPHA CHAIN J-MINIGENES.
`CODONS OF MOUSE T-LYMPHOCYTE RECEPTOR FOR ANTIGEN BETA CHAIN J-MINIGENES .
`
`. ......... 684
`. ............. 685
`
`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 ..
`
`VARIABILITY PLOTS
`
`LIGHT CHAINS .
`HEAVY CHAINS .......... .
`
`KAPPA LIGHT CHAINS .
`LAMBDA LIGHT CHAINS.
`
`HUMAN LIGHT CHAINS .
`HUMAN HEAVY CHAINS.
`
`. . 687
`. 699
`. .... .705
`. ..... 711
`
`. ............. 716
`. . 718
`
`. . 720
`. ................. 723
`. . 726
`
`. ........................... 730
`. .... 730
`
`. 731
`. .... 731
`
`. .. 732
`. ............ 732
`
`PFIZER EX. 1052
`Page 6
`
`

`

`v
`
`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 .
`
`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
`
`PFIZER EX. 1052
`Page 7
`
`

`

`
`
`
`
`
`
`vi
`
`T
`
`PFIZER EX. 1052
`Page 8
`
`

`

`HUMAN KAPPA LIGHT CHAINS SUBGROUP I
`
`41
`
`INVARIANT
`RESIDUES
`
`2
`1
`ROY AU
`
`9
`8"
`7
`6
`5
`4
`3
`REI HAU HK101 SCW AG WEA HK
`#
`137
`'Cl
`'CL
`#
`#
`
`16
`15
`14
`13
`12
`11
`DAUDI WALKER HF3- HF2- HF2- HF2-
`'CL
`'CL
`16/6 1/138 18/2 1/17
`
`23
`22
`21
`20
`19
`18
`RFZ PSM HOM ESM ESM WAT
`IGG
`IGM
`
`17
`BJ
`26
`#
`
`#
`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
`VAL VAL VAL VAL
`GLY
`GLY GLY GLY GLY
`ASP
`ASP ASP ASP ASP
`ARG
`ARG ARG ARG ARG
`VAL
`VAL VAL VAL VAL
`THR
`THR THR THR THR
`ILE
`ILE
`ILE
`ILE
`ILE
`THR THR THR THR
`THR
`CYS CYS CYS CYS
`CYS
`GLN GLN GLN ARG
`ARG
`ALA ALA ALA ALA
`ALA
`SER SER SER SER
`ARG
`GLN
`GLN GLN GLN GLN
`
`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
`
`10
`HK
`134
`'CL
`#
`#
`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 VAL
`VAL
`VAL
`VAL
`GLY GLY
`GLY
`GLY
`GLY
`ASP ASP
`ASP
`ASP
`ASP
`ARG
`ARG ARG
`ARG
`ARG
`VAL
`VAL VAL
`VAL
`VAL
`THR
`THR THR
`THR
`THR
`ILE
`ILE
`ILE
`ILE
`ILE
`THR
`THR THR
`THR
`THR
`CYS
`CYS CYS
`CYS
`CYS
`ARG
`ARG ARG
`GLN
`GLN
`ALA ALA ALA ALA ALA
`SER SER SER SER SER
`GLN GLN GLN GLN GLN
`
`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
`
`~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
`THR THR THR THR THR THR THR THR THR
`GLN GLN
`GLN GLN GLN GLN GLN GLN GLN GLN GLN
`SER SER SER SER SER SER SER SER SER
`SER SER
`PRO PRO
`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 SER SER
`SER SER
`LEU
`LEU LEU LEU
`LEU LEU LEU LEU LEU
`LEU
`LEU
`SER SER SER SER SER SER SER SER SER
`SER SER
`ALA ALA ALA ALA ALA ALA ALA ALA ALA
`ALA ALA
`SER SER SER SER SER SER SER SER SER
`SER SER
`VAL VAL VAL VAL VAL VAL VAL VAL VAL
`VAL
`VAL
`GLY GLY
`G~ G~ G~ G~ G~ G~ G~ G~ G~
`ASP ASP
`~p ~p ~p ~p ~p ~p ~p A~ ~p
`ARG ARG
`ARG ARG ARG ARG ARG ARG ARG ARG ARG
`VAL
`VAL
`VAL VAL VAL VAL VAL VAL VAL VAL VAL
`THR
`THR
`THR THR THR THR THR THR THR THR THR
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`THR
`THR
`THR THR THR THR THR THR THR THR THR
`CYS CYS CYS CYS CYS CYS CYS CYS CYS
`CYS CYS
`ARG ARG
`ARG ARG GLN GLN GLN GLN ARG ARG GLX
`ALA ALA
`ALA ALA ALA ALA ALA ALA ALA ALA ALA
`SER SER
`SER SER SER ASN SER ARG SER SER SER
`GLN GLN
`GLN GLN GLN GLN GLN H~ GLX GLX GLN
`
`GLY GLY GLY GLY SER VAL ASP ASP SER SER ASP
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`SER
`ARG
`SER SER SER
`SER ARG
`ARG
`ARG ARG ASN
`SER SER ASP
`ASN
`LYS SER
`ASN
`ASN ASN
`LYS
`ASN
`TYR TYR TYR
`TYR
`ASP
`SER TYR
`ASP ASP TYR
`ASP
`LEU LEU VAL
`LEU
`LEU
`LEU LEU
`LEU LEU ALA
`LEU
`ASX ASX ASN
`GLY
`ASN
`ASN ASN
`GLY GLY ASN
`GLY
`TRP TRP TRP
`TRP
`TRP TRP
`TRP TRP TRP
`TRP
`TRP
`TYR
`TYR TYR
`TYR TYR TYR
`PHE
`TYR
`TYR TYR
`GLN
`GLX GLX
`GLN
`GLN GLN
`GLN GLN GLU
`GLN
`GLN GLN GLN
`GLN
`GLN GLN
`GLN
`GLN
`LYS
`ARG LYS
`LYS
`LYS
`#
`LYS
`LYS
`PRO
`PRO
`PRO PRO PRO
`PRO
`PRO GLN
`GLY
`GLY GLY
`#
`LYS
`GLN LYS
`ALA ALA
`ALA
`PRO
`PRO PRO
`LYS
`LYS
`LYS
`LEU 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
`
`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
`
`THR(.98)
`
`SER(.95)
`PR0(.98)
`
`SER(.96)
`
`VAL(-97)
`THR(.96)
`ILE(.95)
`
`CYS
`
`ALA(.95)
`
`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
`
`F
`R
`1
`
`c
`D
`R
`1
`
`F
`R
`2
`
`c
`D
`R
`2
`
`F
`R
`3
`
`c
`D
`R
`3
`
`0
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`VAL(-96)
`15
`16 GLY(.99)
`17
`18
`19
`20
`21
`22
`23
`24
`25
`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
`F
`R 103
`4 104
`105
`106
`106A
`107
`108
`109
`
`ASN
`ASP ASP GLY GLY GLY
`ASP ASP ASP SER GLY
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`THR
`SER
`SER
`SER SER
`ARG ASN ARG
`ILE SER
`SER
`ASN
`ILE ASP
`LYS HIS ASN
`ASN
`SER
`LYS SER
`SER
`PHE
`PHE TYR
`HIS TYR ASP
`TYR
`TYR TYR
`TRP
`TRP
`LEU
`LEU LEU
`LEU
`LEU LEU LEU
`LEU
`LEU LEU
`LEU
`SER
`ASN ASN THR
`ASN ASN
`ASN SER
`ALA
`ALA
`ALA
`TRP
`TRP
`TRP
`TRP TRP TRP
`TRP TRP
`TRP TRP
`TRP
`TYR
`PHE
`TYR TYR
`TYR
`TYR TYR TYR
`TYR TYR
`TYR
`GLN
`GLN GLN
`GLN
`GLN GLN
`GLN
`ASP GLN GLN
`GLN
`GLN
`GLN GLN
`GLN
`GLN GLN
`GLN
`GLN GLN GLN
`GLN
`LYS
`LYS
`THR LYS
`LYS
`LYS LYS
`LYS
`LYS
`LYS
`#
`PRO
`PRO
`PRO PRO PRO
`PRO PRO
`PRO PRO
`PRO
`PRO
`GLY
`#
`GLY
`GLY GLY
`GLY
`GLU
`GLY
`GLY GLY
`GLU
`LYS LYS THR
`LYS
`LYS
`LYS
`LYS
`LYS
`LYS LYS
`LYS
`ALA ALA ALA
`ALA
`ALA ALA
`ALA
`ALA
`ALA ALA
`ALA
`PRO
`PRO PRO PRO
`PRO
`PRO PRO
`PRO PRO
`PRO
`PRO
`LYS GLN
`LYS
`LYS
`THR
`ARG LYS
`LYS
`LYS
`LYS
`LYS
`LEU(cid:173)
`SER
`LEU VAL
`LEU LEU
`LEU
`ILE ARG
`SER
`SER
`LEU
`LEU LEU LEU
`LEU
`LEU LEU
`LEU LEU
`LEU
`LEU
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`TYR TYR
`TYR
`TYR
`TYR TYR TYR
`TYR
`TYR
`TYR TYR
`GLY ASP GLY
`GLU ALA
`ASP ASP
`ALA
`ALA
`ALA
`ALA
`ALA ALA
`ALA
`ALA ALA
`VAL
`ALA
`ALA ALA ALA
`ALA
`SER SER
`SER
`SER SER
`SER
`SER
`SER SER THR
`SER
`LYS ASN
`SER
`ASN SER
`ASN
`SER
`THR ASN SER
`SER
`LEU LEU
`LEU LEU LEU
`LEU LEU
`LEU
`LEU
`LEU
`LEU
`GLU GLU
`GLN
`GLN
`GLN PRO
`GLU GLU GLN
`GLN
`GLN
`ALA SER
`VAL
`SER
`ALA SER
`THR THR SER
`SER
`SER
`GLY GLY
`GLY
`GLY GLY
`GLY GLY GLY
`GLY
`GLY
`GLY
`VAL VAL
`VAL
`VAL
`VAL
`VAL VAL
`VAL VAL VAL
`VAL
`PRO
`PRO
`PRO
`PRO
`PRO
`PRO
`PRO
`PRO
`PRO
`PRO
`PRO
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`ARG
`ARG
`ARG
`ARG
`ARG
`ARG
`ARG
`ARG
`ARG
`ARG
`ARG
`PHE
`PHE
`PHE
`PHE
`PHE
`PHE
`PHE
`PHE
`PHE
`PHE
`PHE
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`SER
`SER
`SER
`THR
`SER
`SER
`SER
`SER
`SER
`SER
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`PHE
`SER
`SER
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`GLY
`THR
`ALA
`THR
`THR
`THR
`ALA
`THR
`THR
`THR
`THR
`THR
`ASP
`HIS
`ASP
`ASP
`ASP
`ASP
`GLU
`GLU
`ASP
`ASP
`ASP
`PHE
`PHE
`PHE
`TYR
`PHE
`PHE
`PHE
`PHE
`PHE
`PHE
`PHE
`.THR
`THR
`THR
`THR
`THR
`THR
`THR
`THR
`THR
`THR
`THR
`PHE
`LEU
`PHE
`PHE
`LEU
`PHE
`LEU
`LEU
`LEU
`LEU
`LEU
`THR
`THR
`THR
`THR
`THR
`THR
`THR
`THR
`THR
`THR
`THR
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`SER
`SER
`SER
`SER
`SER
`ASN
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`SER
`GLY
`GLY
`SER
`SER
`SER
`SER
`THR
`LEU
`LEU
`LEU
`LEU
`LEU
`LEU
`LEU
`LEU
`LEU
`LEU
`LEU
`GLN GLN GLN GLN GLN GLN GLN
`GLN GLN GLN GLN
`PRO
`PRO PRO PRO PRO PRO
`PRO PRO PRO PRO
`PRO
`GLU GLU GLU GLU
`GLU GLU GLU GLU GLU GLU GLU
`ASP
`ASP ASP ASP ASP ASP
`ASP
`ASP ASP ASP ASP
`ILE PHE PHE PHE
`PHE
`PHE
`ILE
`ILE
`ILE
`ILE PHE
`ALA ALA ALA ALA
`ALA
`GLY ALA ALA ALA ALA
`ALA
`THR
`THR THR THR THR
`THR
`ASN THR THR THR THR
`TYR
`TYR TYR TYR TYR
`TYR
`TYR TYR TYR TYR TYR
`TYR
`TYR TYR TYR TYR
`TYR
`TYR TYR TYR TYR TYR
`CYS CYS CYS CYS CYS
`CYS CYS CYS CYS
`CYS
`CYS
`GLN GLN LEU GLN GLN
`GLN GLN GLN GLN GLN
`GLN
`GLN
`GLN GLN GLN GLN GLN
`GLN GLN GLN GLN GLN
`PHE TYR TYR ASN
`TYR
`TYR TYR TYR TYR TYR
`ASN
`ASP ASP GLN TYR
`ASN
`ASP ASP SER ASN ASN
`TYR
`ASN TYR SER
`ILE
`SER
`ASN THR SER SER SER
`ASN
`LEU LEU LEU THR
`TYR
`VAL LEU PHE TYR TYR
`PHE
`PRO PRO PRO PRO
`PRO
`PRO PRO PRO PRO PRO
`SER
`#
`#
`
`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 THR LYS
`LYS
`ARG ARG ARG ARG
`THR THR THR THR
`
`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
`
`PHE
`THR
`PHE
`GLY
`GLY
`GLY
`THR
`LYS
`VAL
`ASP
`ASN
`
`ILE
`THR
`PHE
`GLY
`GLN
`GLY
`THR
`ARG
`LEU
`GLU
`ILE
`
`LYS
`
`LYS
`
`GLY
`
`GLY
`THR(.97)
`
`THR
`
`PFIZER EX. 1052
`Page 9
`
`

`

`HUMAN KAPPA LIGHT CHAINS SUBGROUP I (cont'd)
`
`42
`
`27
`26
`25*
`24
`AMYLOID LOW DIE CAR
`VIII-B
`A
`
`28
`TEl
`
`29
`BJ
`48
`
`32
`31
`30
`CON TRA AMYLOID
`LEP
`
`33
`F-
`GUI
`#
`
`34
`OU
`(IOC)
`
`41
`40
`39"
`38
`37
`36
`35
`DEE GAL JOH KER LAY BRA WES
`(I)
`
`42
`Vb
`'CL
`
`43
`Vb'
`'CL
`
`45
`EU
`
`47
`46
`DEN PAU
`
`44
`HK102
`'CL
`#
`
`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
`
`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
`
`F
`R
`1
`
`c
`D
`R
`1
`
`F
`R
`2
`
`c
`D
`R
`2
`
`F
`R
`3
`
`c
`D
`R
`3
`
`F
`R
`4
`
`~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 VAL VAL
`VAL
`VAL
`VAL
`VAL
`GLY
`GLY GLY GLY
`GLY
`GLY
`GLY
`ASP ASP ASP
`ASP
`ASP
`ASP
`ASP
`ARG ARG ARG
`ARG
`ARG
`ARG
`ARG
`VAL
`VAL
`VAL
`VAL VAL VAL
`VAL
`THR
`THR
`THR
`THR THR THR
`THR
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`THR THR THR
`THR
`THR
`THR
`THR
`CYS
`CYS
`CYS
`CYS
`CYS
`ALA
`ALA
`SER
`GLN
`
`ASP
`ILE
`GLN
`MET
`THR
`GLN
`SER
`PRO
`SER
`SER
`LEU
`SER
`ALA
`SER
`VAL
`GLY
`ASP
`ARG
`VAL
`THR
`
`ASX ASP ASP ASP ASP ASP ASP ASP ASP
`ASP
`ASP
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`ILE
`GLN
`GLN
`G~ G~ G~ G~ G~ G~ G~ G~ G~
`MET
`MET
`MET MET MET MET MET MET M8 MET MET
`THR
`THR THR THR THR THR THR THR THR THR
`THR
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`
`PFIZER EX. 1052
`Page 10
`
`

`

`HUMAN KAPPA LIGHT CHAINS SUBGROUP I (cont'd)
`
`43
`
`53''
`52
`51
`50
`49
`48
`HBJ FRA GR' PAUL MON HEI
`4
`
`54
`POT
`
`55
`S-
`GUI
`#
`
`56
`AMYLOID
`BAN
`#
`
`57
`BJ
`19
`#
`
`62
`61
`60
`59
`58
`BEL JBL PAP CAR MEV
`#
`
`63
`Bl
`
`66''
`65
`64
`AMYLOID CRA DAV
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`#
`
`67*
`FIN
`
`68
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`
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`
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`
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`
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`
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`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

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