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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.

c

s

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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 .

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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

Page 10: PFIZER EX. 1052 Page 1

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

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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

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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

Page 13: PFIZER EX. 1052 Page 1

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

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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

Page 15: PFIZER EX. 1052 Page 1

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

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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

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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

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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

Page 19: PFIZER EX. 1052 Page 1

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

Page 20: PFIZER EX. 1052 Page 1

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

Page 21: PFIZER EX. 1052 Page 1

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

Page 22: PFIZER EX. 1052 Page 1

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

Page 23: PFIZER EX. 1052 Page 1

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

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PFIZER EX. 1052 Page 23

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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

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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

+

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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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