NZ320978A - Hematopoietic proteins and nucleic acid sequences encoding them - Google Patents

Hematopoietic proteins and nucleic acid sequences encoding them

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NZ320978A
NZ320978A NZ320978A NZ32097896A NZ320978A NZ 320978 A NZ320978 A NZ 320978A NZ 320978 A NZ320978 A NZ 320978A NZ 32097896 A NZ32097896 A NZ 32097896A NZ 320978 A NZ320978 A NZ 320978A
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leu
ala
ser
xaa
pro
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NZ320978A
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Marie H Caparon
Stephen C Lee
Charles A Mcwherter
Judith G Giri
Barbara Kure Klein
Yiging Feng
S C Baur
Linda L Zurfluh
John P Mckearn
Nicholas R Staten
Charles M Baum
Neena L Summers
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    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62DNA sequences coding for fusion proteins
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    • C07K14/52Cytokines; Lymphokines; Interferons
    • C07K14/524Thrombopoietin, i.e. C-MPL ligand
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    • C07K2319/00Fusion polypeptide
    • C07K2319/70Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
    • C07K2319/75Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones

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Abstract

A substantially pure hematopoietic protein comprising an amino acid sequence of R1-L1-R2, R2-L1-R1, R1-R2 or R2-R1 wherein: R1 and R2 are independently a polypeptide comprising a modified G-CSF amino acid sequence as defined in the specification, a polypeptide comprising a modified IL-3 amino acid sequence as defined in the specification, a polypeptide comprising a modified c-mpl ligand amino acid sequence as defined in the specification or a colony stimulating factor and L1 is a linker capable of linking R1 to R2. The hematopoietic protein can be optionally be immediately preceded by (methione-1), (alanine-1) or (methione-2 alanine-1). A nucleic acid molecule encoding the above hematopoietic protein is disclosed. A pharmaceutical composition thereof is useful for stimulating the production of hematopoietic cells in a patient.

Description

<div class="application article clearfix" id="description"> <p class="printTableText" lang="en">WO 97/12985 <br><br> 1 <br><br> PCT/US96/15774 <br><br> MULTI-FUNCTIONAL HEMATOPOIETIC RECEPTOR AGONISTS <br><br> The present application claims priority under 3 5 USC §119(e) of United States provisional application Serial No. <br><br> 5 60/004,834 filed October 05, 1995. <br><br> Fielfl of che inversion <br><br> The present invention relates to multi-functional hematopoietic receptor agonists. <br><br> 10 <br><br> Background of the Invention <br><br> Colony stimulating factors (CSFs) which stimulate the differentiation and/or proliferation of bone marrow cells have generated much interest because of their therapeutic 15 potential for restoring depressed levels of hematopoietic stem cell-derived cells. CSFs in both human and murine systems have been identified and distinguished according to their activities. For example, granulocyte-CSF (G-CSF) and macrophage-CSF (M-CSF) stimulate the in vitro formation of 20 neutrophilic granulocyte and macrophage colonies, <br><br> respectively, while GM-CSF and interleukin-3 (IL-3) have broader activities and stimulate the formation of both macrophage, neutrophilic and eosinophilic granulocyte colonies. IL-3 also stimulates the formation of mast, 25 megakaryocyte and pure and mixed erythroid colonies. <br><br> U.S. 4,877,729 and U.S. 4,959,455 disclose human IL-3 and gibbon IL-3 cDNAs and the protein sequences for which they code. The hIL-3 disclosed has serine rather than 30 proline at position 8 in the protein sequence. <br><br> International Patent Application (PCT) WO 88/00598 discloses gibbon- and human-like IL-3. The hIL-3 contains a Ser8 -&gt; ProS replacement. Suggestions are made to replace Cys by Ser, thereby breaking the disulfide bridge, and to 3 5 replace one or more amino acids at the glycosylation sites. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 2 <br><br> PCT/US96/15774 <br><br> U.S. 4,810,643 discloses the DNA sequence encoding human G-CSF. <br><br> WO 91/02754 discloses a fusion protein comprised of GM-CSF and IL-3 which has increased biological activity 5 compared to GM-CSF or IL-3 alone. Also disclosed are nonglycosylated IL-3 and GM-CSF analog proteins as components of the multi-functional hematopoietic receptor agonist. <br><br> WO 92/04455 discloses fusion proteins composed of IL-3 10 fused to a lymphokine selected from the group consisting of IL-3, IL-6, IL-7, IL-9, IL-11, EPO and G-CSF. <br><br> WO 95/21197 and WO 95/21254 disclose fusion proteins capable of broad multi-functional hematopoietic properties. <br><br> GB 2,285,446 relates to the c-mpl ligand 15 (thrombopoietin) and various forms of thrombopoietin which are shown to influence the replication, differentiation and maturation of megakaryocytes and megakaryocytes progenitors which may be used for the treatment of thrombocytopenia. <br><br> EP 675,201 Al relates to the c-mpl ligand 20 (Megakaryocyte growth and development factor (MGDF), allelic variations of c-mpl ligand and c-mpl ligand attached to water soluble polymers such as polyethylene glycol. <br><br> WO 95/21920 provides the murine and human c-mpl ligand and polypeptide fragments thereof. The proteins are useful 25 for in vivo and ex vivo therapy for stimulating platelet production. <br><br> Rearrangement of Protein Sequences <br><br> 3 0 In evolution, rearrangements of DNA sequences serve an important role in generating a diversity of protein structure and function. Gene duplication and exon shuffling provide an important mechanism to rapidly generate diversity and thereby provide organisms with a competitive advantage, 35 especially since the basal mutation rate is low (Doolittle, <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 3 PCT/US96/15774 <br><br> Protein Science 1:191-200, 1992). <br><br> The development of recombinant DNA methods has made it possible to study the effects of sequence transposition on protein folding, structure and function. The approach used 5 in creating new sequences resembles that of naturally occurring pairs of proteins that are related by linear reorganization of their amino acid sequences (Cunningham, et al., Proc. Natl. Acad. Sci. U.S.A. 76:3218-3222, 1979; Teather &amp; Erfle, J. Bacteriol. 172: 3837-3841, 1990; 10 Schimming et al., Eur. J. Biochem. 204: 13-19, 1992; <br><br> Yamiuchi and Minamikawa, FEBS Lett. 260:127-130, 1991; MacGregor et al., FEBS Lett. 378:2 63-266). The first in vitro application of this type of rearrangement to proteins was described by Goldenberg and Creighton (J. Mol. Biol. 15 165:407-413, 1983). A new N-terminus is selected at an internal site (breakpoint) of the original sequence, the new sequence having the same order of amino acids as the original from the breakpoint until it reaches an amino acid that is at or near the original C-terminus. At this point 20 the new sequence is joined, either directly or through an additional portion of sequence (linker), to an amino acid that is at or near the original N-terminus, and the new sequence continues with the same sequence as the original until it reaches a point that is at or near the amino acid 25 that was N-terminal to the breakpoint site of the original sequence, this residue forming the new C-terminus of the chain. <br><br> This approach has been applied to proteins which range in size from 58 to 462 amino acids (Goldenberg &amp; Creighton, 30 J. Mol. Biol. 165:407-413, 1983; Li &amp; Coffino, Mol. Cell. Biol. 13:2377-2383, 1993). The proteins examined have represented a broad range of structural classes, including proteins that contain predominantly a-helix (interleukin-4; Kreitman et al., Cytokine 7:311-318, 1995), ^-sheet 3 5 (interleukin-1; Horlick et al. , Protein Eng. 5:427-431, <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 4 <br><br> PCT/US96/15774 <br><br> 1992), or mixtures of the two (yeast phosphoribosyl anthranilate isomerase; Luger et al., Science 243:206-210, 1989). Broad categories of protein function are represented in these sequence reorganization studies: <br><br> Enzymes <br><br> 10 <br><br> T4 lysozyme <br><br> Zhang et al., Biochemistry 32:12311-12318, 1993; Zhang et al.. Nature Struct. Biol. 1:434-438 (1995) <br><br> 15 <br><br> dihydrofolate reductase <br><br> Buchwalder et al., Biochemistry 31:1621-1630, 1994; Protasova et al., Prot. Eng. 7:1373-1377, 1995) <br><br> 20 <br><br> ribonuclease T1 <br><br> Mullins et al., J. Am. Chem. Soc. 116:5529-5533, 1994; Garrett et al. Protein Science 5:204-211, 1996) <br><br> Bacillus |}-glucanse Hahn et al., Proc. Natl. Acad. Sci. <br><br> U.S.A. 91:10417-10421, 1994) <br><br> aspartate Yang &amp; Schachman, Proc. Natl. Acad. <br><br> 25 transcarbamoylase Sci. U.S.A. 90:11980-11984, 1993) <br><br> 30 <br><br> pho sphor ibo sy1 <br><br> anthranilate isomerase pepsin/pepsinogen <br><br> Luger et al., Science 243:206-210 (1989; Luger et al., Prot. Eng. 3:249-258, 1990) <br><br> Lin et al., Protein Science 4:159-166, 1995) <br><br> glyceraldehyde-3- Vignais et al., Protein Science 35 phosphate dehydro- 4:994-1000, 1995) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 5 <br><br> PCT/US96/15774 <br><br> genase ornithine decarboxylase <br><br> Li &amp; Coffino, Mol. Cell. Biol. 13:2377-2383, 1993) <br><br> yeast phosphoglycerate dehydrogenase <br><br> Ritco-Vonsovici et al., Biochemistry 34:16543-16551, 1995) <br><br> 10 Enzyme Inhibitor basic pancreatic Goldenberg &amp; Creighton, j. Mol. trypsin inhibitor Biol. 165:407-413, 1983) <br><br> 15 Cytokines interleukin- IP <br><br> Horlick et al., Protein Eng. 5:427-431, 1992) <br><br> 20 interleukin-4 <br><br> Kreitman et al., Cytokine 7:311-318, 1995) <br><br> 25 <br><br> Tyrosine Kinase Recognition Domain a-spectrin SH3 domain <br><br> Viguera, et al. , J. <br><br> Mol. Biol. 247:670-681, 1995) <br><br> Transmembrane 30 Protein ortip A <br><br> Koebnik &amp; Kramer, J. Mol. Biol. 250:617-626, 1995) <br><br> 35 Chimeric Protein. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 6 <br><br> PCT/US96/15774 <br><br> interleukin-4— Kreitman et al., Proc. Natl. Acad. <br><br> Pseudomonas Sci. U.S.A. 91:6889-6893, 1994). <br><br> exotoxin <br><br> 5 <br><br> The results of these studies have been highly variable. In many cases substantially lower activity, solubility or thermodynamic stability were observed (E. coli dihydrofolate reductase, aspartate transcarbamoylase, phosphoribosyl 10 anthranilate isomerase, glyceraldehyde-3-phosphate dehydrogenase, ornithine decarboxylase, omp A, yeast phosphoglycerate dehydrogenase). In other cases, the sequence rearranged protein appeared to have many nearly identical properties as its natural counterpart (basic 15 pancreatic trypsin inhibitor, T4 lysozyme, ribonuclease Tl, Bacillus |i-glucanase, interleukin-lfi, a-spectrin SH3 domain, <br><br> pepsinogen, interleukin-4). In exceptional cases, an unexpected improvement over some properties of the natural sequence Wc.s observed, e.g., the solubility and refolding 20 rate for rearranged a-spectrin SH3 domain sequences, and the receptor affinity and anti-tumor activity of transposed interleukin-4—Pseudomonas exotoxin fusion molecule (Kreitman et al., Proc. Natl. Acad. Sci. U.S.A. 91:6889-6893, 1994; Kreitman et al., Cancer Res. 55:3357-3363, 1995). <br><br> 2 5 The primary motivation for these types of studies has been to study the role of short-range and long-range interactions in protein folding and stability. Sequence rearrangements of this type convert a subset of interactions that are long-range in the original sequence into short- <br><br> 3 0 range interactions in the new sequence, and vice versa. The fact that many of these sequence rearrangements are able to attain a conformation with at least some activity is persuasive evidence that protein folding occurs by multiple folding pathways (Viguera, et al., J. Mol. Biol. 247:67 0-35 681, 1995). In the case of the SH3 domain of a-spectrin, choosing new termini at locations that corresponded to |J- <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 7 <br><br> PCT/US96/15774 <br><br> hairpin turns resulted in proteins with slightly less stability, but which were nevertheless able to fold. <br><br> The positions of the internal breakpoints used in the studies cited here are found exclusively on the surface of 5 proteins, and are distributed throughout the linear sequence without any obvious bias towards the ends or the middle (the variation in the relative distance from the original N-terminus to the breakpoint is ca. 10 to 80% of the total sequence length). The linkers connecting the 10 original N- and C-termini in these studies have ranged from 0 to 9 residues. In one case (Yang &amp; Schachman, Proc. Natl. Acad. Sci. U.S.A. 90:11980-11984, 1993), a portion of sequence has been deleted from the original C-terminal segment, and the connection made from the truncated C-15 terminus to the original N-terminus. Flexible hydrophilic residues such as Gly and Ser are frequently used in the linkers. Viguera, et al.(J. Mol. Biol. 247:670-681, 1995) compared joining the original N- and C- termini with 3- or 4-residue linkers; the 3-residue linker was less 20 thermodynamically stable. Protasova et al. (Protein Eng. 7:1373-1377, 1994) used 3- or 5-residue linkers in connecting the original N-termini of E. coli dihydrofolate reductase; only the 3-residue linker produced protein in good yield. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 8 <br><br> PCT/US96/15774 <br><br> Summary of the Invention <br><br> Novel hematopoietic proteins of this invention are 5 represented by the formulas: <br><br> RI-L1-R2, R2-L1-R1, R1-R2, or R2-R1 <br><br> wherein Ri and R2 are independently selected from the 10 group consisting of; <br><br> (I) A polypeptide comprising; a modified human G-CSF amino acid sequence of the formula: <br><br> 15 1 10 <br><br> Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gin Ser Xaa <br><br> 20 <br><br> 20 <br><br> Leu Leu Xaa Xaa Xaa Glu Gin Val Xaa Lys Xaa Gin Gly Xaa Gly <br><br> 30 40 <br><br> Ala Xaa Leu Gin Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa <br><br> 50 <br><br> 25 Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly lie Pro Trp <br><br> 60 70 <br><br> Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly <br><br> 30 80 <br><br> Xaa Leu Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu <br><br> 90 100 <br><br> Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu <br><br> 35 <br><br> 110 <br><br> Xaa Thr Leu Gin Xaa Asp Val Ala Asp Phe Ala Xaa Thr lie Trp <br><br> 120 130 <br><br> 40 Gin Gin Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gin Pro Thr <br><br> 140 <br><br> Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gin Xaa Xaa Ala <br><br> 45 150 160 <br><br> Gly Gly Val Leu Val Ala Ser Xaa Leu Gin Xaa Phe Leu Xaa Xaa <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 9 <br><br> PCT/US96/15774 <br><br> 170 <br><br> Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gin Pro (SEQ ID NO:l&gt; wherein <br><br> 5 <br><br> Xaa at position 1 is Thr, Ser, Arg, Tyr or Gly; <br><br> Xaa at position 2 is Pro or Leu; <br><br> Xaa at position 3 is Leu, Arg, Tyr or Ser; <br><br> Xaa at position 13 is Phe, Ser, His, Thr or Pro; 10 Xaa at position 16 is Lys, Pro, Ser, Thr or His; <br><br> Xaa at position 17 is Cys, Ser, Gly, Ala, lie, Tyr or Arg; Xaa at position 18 is Leu, Thr, Pro, His, lie or Cys; Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala; <br><br> Xaa at position 24 is lie, Pro, Tyr or Leu; <br><br> 15 Xaa at position 27 is Asp, or Gly; <br><br> Xaa at position 30 is Ala, lie, Leu or Gly; <br><br> Xaa at position 34 is Lys or Ser; <br><br> Xaa at position 36 is Cys or Ser; <br><br> Xaa at position 42 is Cys or Ser; <br><br> 20 Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu; <br><br> Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, <br><br> Trp, Gin, or Thr; <br><br> Xaa at position 46 is Glu, Arg, Phe, Arg, lie or Ala; 25 Xaa at position 47 is Leu or Thr; <br><br> Xaa at position 49 is Leu, Phe, Arg or Ser; <br><br> Xaa at position 50 is Leu, lie, His, Pro or Tyr; <br><br> Xaa at position 54 is Leu or His; <br><br> Xaa at position 64 is Cys or Ser; <br><br> 30 Xaa at position 67 is Gin, Lys, Leu or Cys; <br><br> Xaa at position 70 is Gin, Pro, Leu, Arg or Ser; <br><br> Xaa at position 74 is Cys or Ser; <br><br> Xaa at position <br><br> 104 <br><br> is <br><br> Asp, <br><br> Gly or Val; <br><br> Xaa at position <br><br> 108 <br><br> is <br><br> Leu, <br><br> Ala, Val, Arg, Trp, Gin or Gly; <br><br> 35 <br><br> Xaa at position <br><br> 115 <br><br> is <br><br> Thr, <br><br> His, Leu or Ala; <br><br> Xaa at position <br><br> 120 <br><br> is <br><br> Gin, <br><br> Gly, Arg, Lys or His <br><br> Xaa at position <br><br> 123 <br><br> is <br><br> Glu, <br><br> Arg, Phe or Thr <br><br> Xaa at position <br><br> 144 <br><br> is <br><br> Phe, <br><br> His, Arg, Pro, Leu, Gin or Glu; <br><br> Xaa at position <br><br> 146 <br><br> is <br><br> Arg or Gin; <br><br> 40 <br><br> Xaa at position <br><br> 147 <br><br> is <br><br> Arg or Gin; <br><br> Xaa at position <br><br> 156 <br><br> is <br><br> His, <br><br> Gly or Ser; <br><br> Xaa at position <br><br> 159 <br><br> is <br><br> Ser, <br><br> Arg, Thr, Tyr, Val or Gly; <br><br> Xaa at position <br><br> 162 <br><br> is <br><br> Glu, <br><br> Leu, Gly or Trp; <br><br> Xaa at position <br><br> 163 <br><br> is <br><br> Val, <br><br> Gly, Arg or Ala; <br><br> 45 <br><br> Xaa at position <br><br> 169 <br><br> is <br><br> Arg, <br><br> Ser, Leu, Arg or Cys; <br><br> Xaa at position <br><br> 170 <br><br> is <br><br> His, <br><br> Arg or Ser; <br><br> wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted; and <br><br> 50 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 10 <br><br> PCT/US96/15774 <br><br> wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids; <br><br> 5 <br><br> 38-39 <br><br> 62-63 <br><br> 123-124 <br><br> 39-40 <br><br> 63-64 <br><br> 124-125 <br><br> 40-41 <br><br> 64-65 <br><br> 125-126 <br><br> 41-42 <br><br> 65-66 <br><br> 126-127 <br><br> 10 <br><br> 42-43 <br><br> 66-67 <br><br> 128-129 <br><br> 43-44 <br><br> 67-68 <br><br> 128-129 <br><br> 45-46 <br><br> 68-69 <br><br> 129-130 <br><br> 48-49 <br><br> 69-70 <br><br> 130-131 <br><br> 49-50 <br><br> 70-71 <br><br> 131-132 <br><br> 15 <br><br> 52-53 <br><br> 71-72 <br><br> 132-133 <br><br> 53-54 <br><br> 91-92 <br><br> 133-134 <br><br> 54-55 <br><br> 92-93 <br><br> 134-135 <br><br> 55-56 <br><br> 93-94 <br><br> 135-136 <br><br> 56-57 <br><br> 94-95 <br><br> 136-137 <br><br> 20 <br><br> 57-58 <br><br> 95-96 <br><br> 137-138 <br><br> 58-59 <br><br> 96-97 <br><br> 138-139 <br><br> 59-60 <br><br> 97-98 <br><br> 139-140 <br><br> 60-61 <br><br> 98-99 <br><br> 140-141 <br><br> 61-62 <br><br> 99-100 <br><br> 141-142 <br><br> 25 <br><br> or 142-143; <br><br> (II) A polypeptide comprising; a modified hIL-3 amino acid sequence of the formula: <br><br> 30 <br><br> Ala Pro Met Thr Gin Thr Thr Ser Leu Lys Thr Ser Trp Val Asn 15 10 15 <br><br> 3 5 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa <br><br> 20 25 30 <br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 <br><br> 40 <br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 50 55 60 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65 70 75 <br><br> 5 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa <br><br> 80 85 90 <br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 <br><br> 10 <br><br> Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 <br><br> Xaa Xaa Xaa Gin Gin Thr Thr Leu Ser Leu Ala lie Phe 15 125 130 (SEQ ID NO:2); <br><br> wherein Xaa at position 17 <br><br> is Ser, Lys, Gly, Asp, Met, Gin, or Arg; <br><br> Xaa at position <br><br> 18 <br><br> is <br><br> Asn, <br><br> His, <br><br> Leu, <br><br> He, <br><br> Phe, <br><br> Arg, <br><br> or Gin; <br><br> Xaa at position <br><br> 19 <br><br> is <br><br> Met, <br><br> Phe, <br><br> lie, <br><br> Arg, <br><br> Gly, <br><br> Ala, <br><br> or Cys; <br><br> Xaa at position <br><br> 20 <br><br> is <br><br> He, <br><br> Cys, <br><br> Gin, <br><br> Glu, <br><br> Arg, <br><br> Pro, <br><br> or Ala; <br><br> Xaa at position <br><br> 21 <br><br> is <br><br> Asp, <br><br> Phe, <br><br> Lys, <br><br> Arg, <br><br> Ala, <br><br> Gly, <br><br> Glu, Gin, Asn, <br><br> Thr, Ser or Val <br><br> Xaa at position <br><br> 22 <br><br> is <br><br> Glu, <br><br> Trp, <br><br> Pro, <br><br> Ser, <br><br> Ala, <br><br> His, <br><br> Asp, Asn, Gin, <br><br> Leu, Val or Gly <br><br> Xaa at position <br><br> 23 <br><br> is lie, <br><br> Val, <br><br> Ala, <br><br> Gly, <br><br> Trp, <br><br> Lys, <br><br> Phe, <br><br> Leu, Ser, <br><br> or <br><br> Arg; <br><br> Xaa at position <br><br> 24 <br><br> is lie, <br><br> Gly, <br><br> Val, <br><br> Arg, <br><br> Ser, <br><br> Phe, <br><br> or Leu; <br><br> Xaa at position <br><br> 25 <br><br> is <br><br> Thr, <br><br> His, <br><br> Gly, <br><br> Gin, <br><br> Arg, <br><br> Pro, <br><br> or Ala; <br><br> Xaa at position <br><br> 26 <br><br> is <br><br> His, <br><br> Thr, <br><br> Phe, <br><br> Gly, <br><br> Arg, <br><br> Ala, <br><br> or Trp; <br><br> Xaa at position <br><br> 27 <br><br> is <br><br> Leu, <br><br> Gly, <br><br> Arg, <br><br> Thr, <br><br> Ser, <br><br> or Ala; <br><br> Xaa at position <br><br> 28 <br><br> is <br><br> Lys, <br><br> Arg, <br><br> Leu, <br><br> Gin, <br><br> Gly, <br><br> Pro, <br><br> Val or Trp; <br><br> Xaa at position <br><br> 29 <br><br> is <br><br> Gin, <br><br> Asn, <br><br> Leu, <br><br> Pro, <br><br> Arg, <br><br> or Val; <br><br> Xaa at position <br><br> 30 <br><br> is <br><br> Pro, <br><br> His, <br><br> Thr, <br><br> Gly, <br><br> Asp, <br><br> Gin, <br><br> Ser, Leu, or Lys <br><br> Xaa at position <br><br> 31 <br><br> is <br><br> Pro, <br><br> Asp, <br><br> Gly, <br><br> Ala, <br><br> Arg, <br><br> Leu, <br><br> or Gin; <br><br> Xaa at position <br><br> 32 <br><br> is <br><br> Leu, <br><br> Val, <br><br> Arg, <br><br> Gin, <br><br> Asn, <br><br> Gly, <br><br> Ala, or Glu; <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 12 <br><br> PCT/US96/15774 <br><br> Xaa at position 33 is Pro, Leu, Gin, Ala, Thr, or Glu; <br><br> Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gin, Thr, <br><br> Arg, Ala, Phe, lie or Met; <br><br> Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gin, or Val; <br><br> 5 Xaa at position 36 is Asp, Leu, or Val; <br><br> Xaa at position 37 is Phe, Ser, Pro, Trp, or lie; <br><br> Xaa at position 38 is Asn, or Ala; <br><br> Xaa at position 40 is Leu, Trp, or Arg; <br><br> Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; 10 Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, lie. Met or Ala; <br><br> Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, <br><br> Gin, Arg, Thr, Gly or Ser; <br><br> Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, 15 Glu, Asn, Gin, Ala or Pro; <br><br> Xaa at position 45 is Gin, Pro, Phe, Val, Met, Leu, Thr, Lys, <br><br> Trp, Asp, Asn, Arg, Ser, Ala, lie, Glu or His; <br><br> Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gin, Lys, His, Ala, Tyr, lie, Val or Gly; <br><br> 20 Xaa at position 47 is lie, Gly, Val, Ser, Arg, Pro, or His; <br><br> Xaa at position 48 is Leu, Ser, Cys, Arg, lie. His, Phe, Glu, <br><br> Lys, Thr, Ala, Met, Val or Asn; <br><br> Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, 25 Ala, lie, Val, His, Phe, Met or Gin; <br><br> Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; <br><br> Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; <br><br> Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg, Asp, lie, Ser, Val, Thr, Gin, Asn, 30 Lys, His, Ala or Leu; <br><br> Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; <br><br> Xaa at position 56 is Pro, Gly, Cys, Ser, Gin, Glu, Arg, His, <br><br> Thr, Ala, Tyr, Phe, Leu, Val or Lys; <br><br> Xaa at position 57 is Asn or Gly; <br><br> 35 Xaa at position 58 is Leu, Ser, Asp, Arg, Gin, Val, or Cys; <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 13 <br><br> PCT/US96/15774 <br><br> Xaa at position <br><br> 59 <br><br> is <br><br> Glu Tyr, His, Leu, ] <br><br> Pro, or Arg; <br><br> Xaa at position <br><br> 60 <br><br> is <br><br> Ala, <br><br> Ser, <br><br> Pro, <br><br> Tyr, <br><br> Asn, <br><br> or Thr; <br><br> Xaa at position <br><br> 61 <br><br> is <br><br> Phe, <br><br> Asn, <br><br> Glu, <br><br> Pro, <br><br> Lys, <br><br> Arg, <br><br> or Ser; <br><br> Xaa at position <br><br> 62 <br><br> is <br><br> Asn, <br><br> His, <br><br> Val, <br><br> Arg, <br><br> Pro, <br><br> Thr, <br><br> Asp, <br><br> or lie; <br><br> 5 <br><br> Xaa at position <br><br> 63 <br><br> is <br><br> Arg, <br><br> Tyr, <br><br> Trp, <br><br> Lys, <br><br> Ser, <br><br> His, <br><br> Pro, <br><br> or Val; <br><br> Xaa at positi on <br><br> 64 <br><br> is <br><br> Ala, <br><br> Asn, <br><br> Pro, <br><br> Ser, <br><br> or Lys; <br><br> Xaa at position <br><br> 65 <br><br> is <br><br> Val, <br><br> Thr, <br><br> Pro, <br><br> His, <br><br> Leu, <br><br> Phe, <br><br> or Ser; <br><br> Xaa at position <br><br> 66 <br><br> is <br><br> Lys, <br><br> lie, <br><br> Arg, <br><br> Val, <br><br> Asn, <br><br> Glu, <br><br> or Ser; <br><br> Xaa at position <br><br> 67 <br><br> is <br><br> Ser, <br><br> Ala, <br><br> Phe, <br><br> Val, <br><br> Gly, <br><br> Asn, <br><br> lie, <br><br> Pro, or <br><br> 10 <br><br> Xaa at position <br><br> 68 <br><br> is <br><br> Leu, <br><br> Val, <br><br> Trp, <br><br> Ser, <br><br> He, <br><br> Phe, <br><br> Thr, <br><br> or His; <br><br> Xaa at position <br><br> 69 <br><br> is <br><br> Gin, <br><br> Ala, <br><br> Pro, <br><br> Thr, <br><br> Glu, <br><br> Arg, <br><br> Trp, <br><br> Gly, or <br><br> Xaa at position <br><br> 70 <br><br> is <br><br> Asn, <br><br> Leu, <br><br> Val, <br><br> Trp, <br><br> Pro, <br><br> or Ala; <br><br> Xaa at position <br><br> 71 <br><br> is <br><br> Ala, <br><br> Met, <br><br> Leu, <br><br> Pro, <br><br> Arg, <br><br> Glu, <br><br> Thr, <br><br> Gin, <br><br> Trp, or Asn; <br><br> 15 <br><br> Xaa at position <br><br> 72 <br><br> is <br><br> Ser, <br><br> Glu, <br><br> Met, <br><br> Ala, <br><br> His, <br><br> Asn, <br><br> Arg, <br><br> or Asp; <br><br> Xaa at position <br><br> 73 <br><br> is <br><br> Ala, <br><br> Glu, <br><br> Asp, <br><br> Leu, <br><br> Ser, <br><br> Gly, <br><br> Thr, <br><br> or Arg; <br><br> Xaa at position <br><br> 74 <br><br> is lie <br><br> , Met, Thr <br><br> , Pro, Arg, <br><br> Gly, <br><br> Ala; <br><br> Xaa at position <br><br> 75 <br><br> is <br><br> Glu, <br><br> Lys, <br><br> Gly, <br><br> Asp, <br><br> Pro, <br><br> Trp, <br><br> Arg, <br><br> Ser, <br><br> Gin, or Leu; <br><br> 20 <br><br> Xaa at position <br><br> 76 <br><br> is <br><br> Ser, <br><br> Val, <br><br> Ala, <br><br> Asn, <br><br> Trp, <br><br> Glu, <br><br> Pro, <br><br> Gly, or <br><br> Xaa at position <br><br> 77 <br><br> is lie, <br><br> Ser, <br><br> Arg, <br><br> Thr, <br><br> or Leu; <br><br> Xaa at position <br><br> 78 <br><br> is <br><br> Leu, <br><br> Ala, <br><br> Ser, <br><br> Glu, <br><br> Phe, <br><br> Gly, <br><br> or Arg; <br><br> Xaa at position <br><br> 79 <br><br> is <br><br> Lys, <br><br> Thr, <br><br> Asn, <br><br> Met, <br><br> Arg, <br><br> lie, <br><br> Gly, <br><br> or Asp; <br><br> Xaa at position <br><br> 80 <br><br> is <br><br> Asn, <br><br> Trp, <br><br> Val, <br><br> Gly, <br><br> Thr, <br><br> Leu, <br><br> Glu, <br><br> or Arg; <br><br> 25 <br><br> Xaa at position <br><br> 81 <br><br> is <br><br> Leu, <br><br> Gin, <br><br> Gly, <br><br> Ala, <br><br> Trp, <br><br> Arg, <br><br> Val, <br><br> or Lys ,- <br><br> Xaa at position <br><br> 82 <br><br> is <br><br> Leu, <br><br> Gin, <br><br> Lys, <br><br> Trp, <br><br> Arg, <br><br> Asp, <br><br> Glu, <br><br> Asn, <br><br> His, Thr, <br><br> Ser, Ala, <br><br> Tyr, <br><br> Phe, <br><br> He, <br><br> Met or Val; <br><br> Xaa at position <br><br> 83 <br><br> is <br><br> Pro, <br><br> Ala, <br><br> Thr, <br><br> Trp, <br><br> Arg, <br><br> or Met; <br><br> Xaa at position <br><br> 84 <br><br> is <br><br> Cys, <br><br> Glu, <br><br> Gly, <br><br> Arg, <br><br> Met, <br><br> or Val; <br><br> 30 <br><br> Xaa at position <br><br> 85 <br><br> is <br><br> Leu, <br><br> Asn, <br><br> Val, <br><br> or Gin; <br><br> Xaa at position <br><br> 86 <br><br> is <br><br> Pro, <br><br> Cys, <br><br> Arg, <br><br> Ala, <br><br> or Lys; <br><br> Xaa at position <br><br> 87 <br><br> is <br><br> Leu, <br><br> Ser, <br><br> Trp, <br><br> or Gly; <br><br> Xaa at position <br><br> 88 <br><br> is <br><br> Ala, <br><br> Lys, <br><br> Arg, <br><br> Val, <br><br> or Trp; <br><br> Xaa at position <br><br> 89 <br><br> is <br><br> Thr, <br><br> Asp, <br><br> Cys, <br><br> Leu, <br><br> Val, <br><br> Glu, <br><br> His, <br><br> Asn, or <br><br> 35 <br><br> Xaa at position <br><br> 90 <br><br> is <br><br> Ala, <br><br> Pro, <br><br> Ser, <br><br> Thr, <br><br> Gly, <br><br> Asp, <br><br> lie. <br><br> or Met; <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 14 <br><br> PCT/US96/15774 <br><br> Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, lie or Leu ; <br><br> Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; 5 Xaa at position 94 is Arg, lie, Ser, Glu, Leu, Val, Gin, Lys, His, Ala, or Pro; <br><br> Xaa at position 95 is His, Gin, Pro, Arg, Val, Leu, Gly, Thr, Asn, <br><br> Lys, Ser, Ala, Trp, Phe, lie, or Tyr; <br><br> Xaa at position 96 is Pro, Lys, Tyr, Gly, lie, or Thr; <br><br> 10 Xaa at position 91 is lie, Val, Lys, Ala, or Asn; <br><br> Xaa at position 98 is His, lie, Asn, Leu, Asp, Ala, Thr, <br><br> Glu, Gin, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro; <br><br> Xaa at position <br><br> 9 9 is lie, Leu, Arg, Asp, Val, Pro, Gin, <br><br> Gly, Ser, <br><br> Phe, <br><br> or His; <br><br> 15 <br><br> Xaa at position <br><br> 100 <br><br> is Lys, <br><br> Tyr, <br><br> Leu, <br><br> His, <br><br> Arg, <br><br> He, <br><br> Ser, <br><br> Gin, or <br><br> Xaa at position <br><br> 101 <br><br> is Asp, <br><br> Pro, <br><br> Met, <br><br> Lys, <br><br> His, <br><br> Thr, <br><br> Val, <br><br> Tyr, Glu, <br><br> Asn, <br><br> Ser, Ala, Gly, lie, Leu, or Gin, <br><br> Xaa at position <br><br> 102 <br><br> is Gly, <br><br> Leu, <br><br> Glu, <br><br> Lys, <br><br> Ser, <br><br> Tyr, <br><br> or Pro; <br><br> Xaa at position <br><br> 103 <br><br> is Asp, <br><br> or Ser; <br><br> 20 <br><br> Xaa at position <br><br> 104 <br><br> is Trp, <br><br> Val, <br><br> Cys, <br><br> Tyr, <br><br> Thr, <br><br> Met, <br><br> Pro, <br><br> Leu, <br><br> Gin, Lys, <br><br> Ala, <br><br> Phe, or Gly; <br><br> Xaa at position <br><br> 105 <br><br> is Asn, <br><br> Pro, <br><br> Ala, <br><br> Phe, <br><br> Ser, <br><br> Trp, <br><br> Gin, <br><br> Tyr, <br><br> Leu, Lys, <br><br> lie, <br><br> Asp, or His; <br><br> Xaa at position <br><br> 106 <br><br> is Glu, <br><br> Ser, <br><br> Ala, <br><br> Lys, <br><br> Thr, <br><br> He, <br><br> Gly, <br><br> or Pro; <br><br> 25 <br><br> Xaa at position <br><br> 108 <br><br> is Arg, <br><br> Lys, <br><br> Asp, <br><br> Leu, <br><br> Thr, <br><br> He, <br><br> Gin, <br><br> His, Se: <br><br> Ala or Pro; <br><br> Xaa at position <br><br> 109 <br><br> is Arg, <br><br> Thr, <br><br> Pro, <br><br> Glu, <br><br> Tyr, <br><br> Leu, <br><br> Ser, <br><br> or Gly; <br><br> Xaa at position <br><br> 110 <br><br> is Lys, <br><br> Ala, <br><br> Asn, <br><br> Thr, <br><br> Leu, <br><br> Arg, <br><br> Gin, <br><br> His, Gl' <br><br> Ser, or Trp; <br><br> 30 <br><br> Xaa at position <br><br> 111 <br><br> is Leu, <br><br> lie, <br><br> Arg, <br><br> Asp, <br><br> or Met; <br><br> Xaa at position <br><br> 112 <br><br> is Thr, <br><br> Val, <br><br> Gin, <br><br> Tyr, <br><br> Glu, <br><br> His, <br><br> Ser, <br><br> or Phe; <br><br> Xaa at position <br><br> 113 <br><br> is Phe, <br><br> Ser, <br><br> Cys, <br><br> His, <br><br> Gly , <br><br> Trp, <br><br> Tyr, <br><br> Asp, <br><br> Lys, Leu, <br><br> He <br><br> , Val or <br><br> Asn; <br><br> Xaa at position <br><br> 114 <br><br> is Tyr, <br><br> Cys, <br><br> His, <br><br> Ser, <br><br> Trp, <br><br> Arg, <br><br> or Leu; <br><br> 35 <br><br> Xaa at position <br><br> 115 <br><br> is Leu, <br><br> Asn, <br><br> Val, <br><br> Pro, <br><br> Arg, <br><br> Ala, <br><br> His, <br><br> Thr, <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 15 <br><br> PCT/US96/15774 <br><br> Trp, or Met; <br><br> Xaa at position <br><br> 116 <br><br> is <br><br> Lys, <br><br> Leu, <br><br> Pro, <br><br> Thr, <br><br> Met, <br><br> Asp, <br><br> Val, Glu, <br><br> Arg, T^p, <br><br> Ser, <br><br> Asn, His, Ala, Tyr, Phe, Gin, or lie; <br><br> Xaa at position <br><br> 117 <br><br> is <br><br> Thr, <br><br> Ser, <br><br> Asn, <br><br> He, <br><br> Trp, <br><br> Lys, <br><br> or Pro; <br><br> Xaa at position <br><br> 118 <br><br> is <br><br> Leu, <br><br> Ser, <br><br> Pro, <br><br> Ala, <br><br> Glu, <br><br> Cys, <br><br> Asp, or Tyr; <br><br> Xaa at position <br><br> 119 <br><br> is <br><br> Glu, <br><br> Ser, <br><br> Lys, <br><br> Pro, <br><br> Leu, <br><br> Thr, <br><br> Tyr, or Arg; <br><br> Xaa at position <br><br> 120 <br><br> is <br><br> Asn, <br><br> Ala, <br><br> Pro, <br><br> Leu, <br><br> His, <br><br> Val, <br><br> or Gin; <br><br> Xaa at position <br><br> 121 <br><br> is <br><br> Ala, <br><br> Ser, <br><br> lie. <br><br> Asn, <br><br> Pro, <br><br> Lys, <br><br> Asp, or Gly; <br><br> Xaa at position <br><br> 122 <br><br> is <br><br> Gin, <br><br> Ser, <br><br> Met, <br><br> Trp, <br><br> Arg, <br><br> Phe, <br><br> Pro, His, <br><br> lie, Tyr, <br><br> or Cys; <br><br> Xaa at position <br><br> 123 <br><br> is <br><br> Ala, <br><br> Met, <br><br> Glu, <br><br> His, <br><br> Ser. <br><br> Pro, <br><br> Tyr, or Leu; <br><br> ■wherein optionally from 1 to 14 amino acids can be deleted from the N-terminus and/or from 1 to 15 amino acids can be <br><br> 15 deleted from the C-terminus; and wherein from 0 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; and <br><br> 20 wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids; <br><br> 26-27 <br><br> 49-50 <br><br> 83-84 <br><br> 27-28 <br><br> 50-51 <br><br> 84-85 <br><br> 28-29 <br><br> 51-52 <br><br> 85-86 <br><br> 29-30 <br><br> 52-53 <br><br> 86-87 <br><br> 30-31 <br><br> 53-54 <br><br> 87-88 <br><br> 31-32 <br><br> 54-55 <br><br> 88-89 <br><br> 32-33 <br><br> 64-65 <br><br> 89-90 <br><br> 33-34 <br><br> 65-66 <br><br> 90-91 <br><br> 34-35 <br><br> 66-67 <br><br> 91-92 <br><br> 35-36 <br><br> 67-68 <br><br> 92-93 <br><br> 36-37 <br><br> 68-69 <br><br> 97-98 <br><br> 37-38 <br><br> 69-70 <br><br> 98-99 <br><br> 38-39 <br><br> 70-71 <br><br> 99-100 <br><br> 39-40 <br><br> 71-72 <br><br> 100-101 <br><br> 40-41 <br><br> 72-73 <br><br> 101-102 <br><br> 41-42 <br><br> 82-83 <br><br> 102-103 <br><br> or 103-104 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 16 <br><br> PCT/US96/15774 <br><br> or <br><br> (III) A polypeptide comprising; a modified human c-mpl 5 ligand amino acid sequence of the formula: <br><br> SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer 15 10 15 <br><br> 10 HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 25 30 35 <br><br> ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55 <br><br> 15 <br><br> ThrLysAlaGlnAsplleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 60 65 70 75 <br><br> AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 20 80 85 90 95 <br><br> GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110 <br><br> 25 XaaGlyArgThrThrAlaHisLysAspProAsnAlallePheLeuSerPheGlnHis 115 120 125 130 <br><br> LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150 <br><br> 30 <br><br> ArgArgAlaProProThrThrAlaValProSerArgThrSerLeuValLeuThrLeu 155 160 165 170 <br><br> AsnGluLeuProAsnArgThrSerGlyLeuLeuGluThrAsnPheThrAlaSerAla 35 175 180 185 190 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 17 <br><br> PCT/US96/15774 <br><br> ArgThrThrGlySerGlyLeuLeuLysTrpGlnGlnGlyPheArgAlaLysIlePro 195 200 205 <br><br> GlyLeuLeuAsnGlnThrSerArgSerLeuAspGlnlleProGlyTyrLeuAsnArg 5 210 215 220 225 <br><br> IleHisGluLeuLeuAsnGlyThrArgGlyLeuPheProGlyProSerArgArgThr 230 235 240 245 <br><br> 10 LeuGlyAlaProAspIleSerSerGlyThrSerAspThrGlySerLeuProProAsn 250 255 260 265 <br><br> LeuGlnProGlyTyrSerProSerProThrHisProProThrGlyGlnTyrThrLeu 270 275 280 285 <br><br> 15 <br><br> PheProLeuProProThrLeuProThrProValValGlnLeuHisProLeuLeuPro 290 295 300 <br><br> AspProSerAlaProThrProThrProThrSerProLeuLeuAsnThrSerTyrThr 20 305 310 315 320 <br><br> HisSerGlnAsnLeuSerGlnGluGly (SEQ ID NO:3) 325 330 332 <br><br> 153 <br><br> 25 <br><br> wherein; <br><br> Xaa at position 112 is deleted or Leu, Ala, Val, lie, Pro, Phe, Trp, or Met; <br><br> 30 Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, lie, Trp, or Met; <br><br> Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, <br><br> lie, Trp, or Met; <br><br> Xaa at position 115 is deleted or Gin, Gly, Ser, Thr, Tyr, 3 5 or Asn; and <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 18 <br><br> PCT/US96/15774 <br><br> wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino 5 acids; <br><br> 26-27 <br><br> 51-52 <br><br> 108-109 <br><br> 27-28 <br><br> 52-53 <br><br> 109-110 <br><br> 28-29 <br><br> 53-54 <br><br> 110-111 <br><br> 29-30 <br><br> 54-55 <br><br> 111-112 <br><br> 30-31 <br><br> 55-56 <br><br> 112-113 <br><br> 32-33 <br><br> 56-57 <br><br> 113-114 <br><br> 33-34 <br><br> 57-58 <br><br> 114-115 <br><br> 34-35 <br><br> 58-59 <br><br> 115-116 <br><br> 36-37 <br><br> 59-60 <br><br> 116-117 <br><br> 37-38 <br><br> 78-79 <br><br> 117-118 <br><br> 38-39 <br><br> 79-80 <br><br> 118-119 <br><br> 40-41 <br><br> 80-81 <br><br> 119-120 <br><br> 41-42 <br><br> 81-82 <br><br> 120-121 <br><br> 42-43 <br><br> 82-83 <br><br> 121-122 <br><br> 43-44 <br><br> 83-84 <br><br> 122-123 <br><br> 44-45 <br><br> 84-85 <br><br> 123-124 <br><br> 46-47 <br><br> 85-86 <br><br> 124-125 <br><br> 47-48 <br><br> 86-87 <br><br> 125-126 <br><br> 48-49 <br><br> 87-88 <br><br> 126-127 <br><br> 50-51 <br><br> 88-89 <br><br> or 127-128; <br><br> or <br><br> 10 (IV) A polypeptide comprising; a modified hIL-3 amino acid sequence of the formula: <br><br> Ala Pro Met Thr Gin Thr Thr Ser Leu Lys Thr Ser Trp Val Asn 15 1 5 10 15 <br><br> Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 <br><br> 20 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa <br><br> 35 40 45 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 19 <br><br> PCT/US96/15774 <br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa <br><br> 50 55 60 <br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa <br><br> 5 65 70 75 <br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa <br><br> 80 85 90 <br><br> 10 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa <br><br> 95 100 105 <br><br> Xaa Phe Xac&lt; Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa <br><br> 110 115 120 <br><br> 15 <br><br> Xaa Xaa Xaa Gin Gin Thr Thr Leu Ser Leu Ala lie Phe <br><br> 125 130 (SEQ ID NO:2) <br><br> wherein Xaa at position 17 20 Xaa at position 18 is Asn, Xaa at position 19 is Met, Xaa at position 20 is lie, Xaa at position 21 is Asp, Thr, Ser or Val; 25 Xaa at position 22 is Glu, Leu, Val or Gly; Xaa at position 23 is lie. <br><br> Leu, Ser, or Arg; Xaa at position 24 is lie, 30 Xaa at position 25 is Thr, Xaa at position 26 is His, Xaa at position 27 is Leu, Xaa at position 28 is Lys, Xaa at position 29 is Gin, 3 5 Xaa at position 30 is Pro, <br><br> is Ser, Lys, Gly, Asp, Met, Gin, or Arg; <br><br> His, Leu, lie, Phe, Arg, or Gin; <br><br> Phe, lie, Arg, Gly, Ala, or Cys; <br><br> Cys, Gin, Glu, Arg, Pro, or Ala; <br><br> Phe, Lys, Arg, Ala, Gly, Glu, Gin, Asn, <br><br> Trp, Pro, Ser, Ala, His, Asp, Asn, Gin, <br><br> Val, Ala, Gly, Trp, Lys, Phe, <br><br> Gly, Val, Arg, Ser, Phe, or Leu; <br><br> His, Gly, Gin, Arg, Pro, or Ala; <br><br> Thr, Phe, Gly, Arg, Ala, or Trp; <br><br> Gly, Arg, Thr, Ser, or Ala; <br><br> Arg, Leu, Gin, Gly, Pro, Val or Trp; <br><br> Asn, Leu, Pro, Arg, or Val; <br><br> His, Thr, Gly, Asp, Gin, Ser, Leu, or Lys; <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 25 <br><br> 20 <br><br> PCT/US96/15774 <br><br> 'Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gin; <br><br> I <br><br> jXaa at position 32 is Leu, Val, Arg, Gin, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro, Leu, Gin, Ala, Thr, or Glu; <br><br> i <br><br> Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gin, Thr, 5 J Arg, Ala, Phe, lie or Met; <br><br> Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gin, or Val; <br><br> Xaa at position 36 is Asp, Leu, or Val; <br><br> Xaa at position 37 is Phe, Ser, Pro, Trp, or lie; <br><br> I <br><br> Xaa at position 38 is Asn, or Ala; <br><br> | <br><br> 10 Xaa at position 40 is Leu, Trp, or Arg; <br><br> Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; <br><br> Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, I Val, Glu, Phe, Tyr, lie, Met or Ala; <br><br> Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, 15 Gin, Arg, Thr, Gly or Ser; <br><br> Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, j Glu, Asn, Gin, Ala or Pro; <br><br> Xaa at position 45 is Gin, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Arp, Asn, Arg, Ser, Ala, He, Glu or His; <br><br> 20 Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gin, Lys, His, Ala, Tyr, lie, Val or Gly; <br><br> Xaa at position 47 is lie, Gly, Val, Ser, Arg, Pro, or His; <br><br> Xaa at position 48 is Leu, Ser, Cys, Arg, lie, His, Phe, Glu, | Lys, Thr, Ala, Met, Val or Asn; <br><br> Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; <br><br> i <br><br> Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, I Ala, lie, Val, His, Phe, Met or Gin; <br><br> Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; <br><br> Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; 30 Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro. Lys, Ser, or Met Xaa at position 54 is Arg, Asp, lie, Ser, Val, Thr, Gin, Asn, j Lys, His, Ala or Leu; <br><br> Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; <br><br> Xaa at position 56 is Pro, Gly, Cys, Ser, Gin, Glu, Arg, His, 3 5 Thr, Ala, Tyr, Phe, Leu, Val or Lys; <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 21 <br><br> PCT/US96/15774 <br><br> Xaa at position <br><br> 57 <br><br> is <br><br> Asn or Gly; <br><br> Xaa at position <br><br> 58 <br><br> is <br><br> Leu, <br><br> Ser, <br><br> Asp, <br><br> Arg, <br><br> Gin, <br><br> Val, <br><br> or Cys; <br><br> Xaa at position <br><br> 59 <br><br> is <br><br> Glu <br><br> Tyr, His, Leu, <br><br> Pro, <br><br> or Arg; <br><br> Xaa at position <br><br> 60 <br><br> is <br><br> Ala, <br><br> Ser, <br><br> Pro, <br><br> Tyr, <br><br> Asn, <br><br> or Thr; <br><br> 5 <br><br> Xaa at position <br><br> 61 <br><br> is <br><br> Phe, <br><br> Asn, <br><br> Glu, <br><br> Pro, <br><br> Lys, <br><br> Arg, <br><br> or Ser; <br><br> Xaa at position <br><br> 62 <br><br> is <br><br> Asn, <br><br> His, <br><br> Val, <br><br> Arg, <br><br> Pro, <br><br> Thr, <br><br> Asp, <br><br> or lie; <br><br> Xaa at position <br><br> 63 <br><br> is <br><br> Arg, <br><br> Tyr, <br><br> Trp, <br><br> Lys, <br><br> Ser, <br><br> His, <br><br> Pro, <br><br> or Val; <br><br> Xaa at position <br><br> 64 <br><br> is <br><br> Ala, <br><br> Asn, <br><br> Pro, <br><br> Ser, <br><br> or Lys; <br><br> Xaa at position <br><br> 65 <br><br> is <br><br> Val, <br><br> Thr, <br><br> Pro, <br><br> His, <br><br> Leu, <br><br> Phe, <br><br> or Ser; <br><br> 10 <br><br> Xaa at position <br><br> 66 <br><br> is <br><br> Lys, <br><br> lie, <br><br> Arg, <br><br> Val, <br><br> Asn, <br><br> Glu, <br><br> or Ser; <br><br> Xaa at position <br><br> 67 <br><br> is <br><br> Ser, <br><br> Ala, <br><br> Phe, <br><br> Val, <br><br> Gly, <br><br> Asn, <br><br> He, <br><br> Pro, or <br><br> Xaa at position <br><br> 68 <br><br> is <br><br> Leu, <br><br> Val, <br><br> Trp, <br><br> Ser, <br><br> lie. <br><br> Phe, <br><br> Thr, <br><br> or His; <br><br> Xaa at position <br><br> 69 <br><br> is <br><br> Gin, <br><br> Ala, <br><br> Pro, <br><br> Thr, <br><br> Glu, <br><br> Arg, <br><br> Trp, <br><br> Gly, or <br><br> Xaa at position <br><br> 70 <br><br> is <br><br> Asn, <br><br> Leu, <br><br> Val, <br><br> Trp, <br><br> Pro, <br><br> or Ala; <br><br> 15 <br><br> Xaa at position <br><br> 71 <br><br> is <br><br> Ala, <br><br> Met, <br><br> Leu, <br><br> Pro, <br><br> Arg, <br><br> Glu, <br><br> Thr, <br><br> Gin, <br><br> Trp, or Asn; <br><br> Xaa at position <br><br> 72 <br><br> is <br><br> Ser, <br><br> Glu, <br><br> Met, <br><br> Ala, <br><br> His, <br><br> Asn, <br><br> Arg, <br><br> or Asp; <br><br> Xaa at position <br><br> 73 <br><br> is <br><br> Ala, <br><br> Glu, <br><br> Asp, <br><br> Leu, <br><br> Ser, <br><br> Gly, <br><br> Thr, <br><br> or Arg; <br><br> Xaa at position <br><br> 74 <br><br> is lie, <br><br> Met, <br><br> Thr, <br><br> Pro, <br><br> Arg, <br><br> Gly, <br><br> Ala ; <br><br> 20 <br><br> Xaa at position <br><br> 75 <br><br> is <br><br> Glu, <br><br> Lys, <br><br> Gly, <br><br> Asp, <br><br> Pro, <br><br> Trp, <br><br> Arg, <br><br> Ser, <br><br> Gin, or Leu; <br><br> Xaa at position <br><br> 76 <br><br> is <br><br> Ser, <br><br> Val, <br><br> Ala, <br><br> Asn, <br><br> Trp, <br><br> Glu, <br><br> Pro, <br><br> Gly, or <br><br> Xaa at position <br><br> 77 <br><br> is lie, <br><br> Ser, <br><br> Arg, <br><br> Thr, <br><br> or Leu ,- <br><br> Xaa at position <br><br> 78 <br><br> is <br><br> Leu, <br><br> Ala, <br><br> Ser, <br><br> Glu, <br><br> Phe, <br><br> Gly, <br><br> or Arg; <br><br> 25 <br><br> Xaa at position <br><br> 79 <br><br> is <br><br> Lys, <br><br> Thr, <br><br> Asn, <br><br> Met, <br><br> Arg, <br><br> lie. <br><br> Gly, <br><br> or Asp; <br><br> Xaa at position <br><br> 80 <br><br> is <br><br> Asn, <br><br> Trp, <br><br> Val, <br><br> Gly, <br><br> Thr, <br><br> Leu, <br><br> Glu, <br><br> or Arg; <br><br> Xaa at position <br><br> 81 <br><br> is <br><br> Leu, <br><br> Gin, <br><br> Gly, <br><br> Ala, <br><br> Trp, <br><br> Arg, <br><br> Val, <br><br> or Lys; <br><br> Xaa at position <br><br> 82 <br><br> is <br><br> Leu, <br><br> Gin, <br><br> Lys, <br><br> Trp, <br><br> Arg, <br><br> Asp, <br><br> Glu, <br><br> Asn, <br><br> His, Thr, <br><br> Ser, <br><br> Ma, <br><br> Tyr, <br><br> Phe, <br><br> lie, <br><br> Met or Val; <br><br> 30 <br><br> Xaa at position <br><br> 83 <br><br> is <br><br> Pro, <br><br> Ala, <br><br> Thr, <br><br> Trp, <br><br> Arg, <br><br> or Met; <br><br> Xaa at position <br><br> 84 <br><br> is <br><br> Cys, <br><br> Glu, <br><br> Gly, <br><br> Arg, <br><br> Met, <br><br> or Val; <br><br> Xaa at position <br><br> 85 <br><br> is <br><br> Leu, <br><br> Asn, <br><br> Val, <br><br> or Gin; <br><br> Xaa at position <br><br> 86 <br><br> is <br><br> Pro, <br><br> Cys, <br><br> Arg, <br><br> Ala, <br><br> or Lys; <br><br> Xaa at position <br><br> 87 <br><br> is <br><br> Leu, <br><br> Ser, <br><br> Trp, <br><br> or Gly; <br><br> 35 <br><br> Xaa at position <br><br> 88 <br><br> is <br><br> Ala, <br><br> Lys, <br><br> Arg, <br><br> Val, <br><br> or Trp; <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 22 <br><br> PCT/US96/15774 <br><br> Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; <br><br> Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, lie, or Met; <br><br> Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His; <br><br> Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, lie or 5 Leu; <br><br> Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg; <br><br> Xaa at position 94 is Arg, lie, Ser, Glu, Leu, Val, Gin, Lys, His, Ala, or Pro; <br><br> Xaa at position 9 5 is His, Gin, Pro, Arg, Val, Leu, Gly, Thr, Asn, 10 Lys, Ser, Ala, Trp, Phe, lie, or Tyr; <br><br> Xaa at position 96 is Pro, Lys, Tyr, Gly, lie, or Thr; <br><br> Xaa at position 97 is lie, Val, Lys, Ala, or Asn; <br><br> Xaa at position 98 is His, lie, Asn, Leu, Asp, Ala, Thr, <br><br> Glu, Gin, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro; <br><br> 15 <br><br> Xaa at position <br><br> 99 is lie, Leu, Arg, Asp, Val, Pre, Gin, <br><br> Gly, Ser, <br><br> Phe, <br><br> or <br><br> His; <br><br> Xaa at position <br><br> 100 <br><br> is <br><br> Lys, <br><br> Tyr, <br><br> Leu, <br><br> His, <br><br> Arg, <br><br> He, <br><br> Ser, <br><br> Gin, or Pi <br><br> Xaa at posit;.tn <br><br> 101 <br><br> is <br><br> Asp, <br><br> Pro. <br><br> Met, <br><br> Lys, <br><br> His, <br><br> Thr, <br><br> Val, <br><br> Tyr, Glu, <br><br> Asn, <br><br> Ser, Ala, Gly, lie, Leu, or Gin; <br><br> 20 <br><br> Xaa at position <br><br> 102 <br><br> is <br><br> Gly, <br><br> Leu, <br><br> Glu, <br><br> Lys, <br><br> Ser, <br><br> Tyr, <br><br> or Pro; <br><br> Xaa at position <br><br> 103 <br><br> is <br><br> Asp, <br><br> or Ser; <br><br> Xaa at position <br><br> 104 <br><br> is <br><br> Trp, <br><br> Val, <br><br> Cys, <br><br> Tyr, <br><br> Thr, <br><br> Met, <br><br> Pro, <br><br> Leu, <br><br> Gin, Lys, <br><br> Ala, <br><br> Phe, or Gly; <br><br> Xaa at position <br><br> 105 <br><br> is <br><br> Asn, <br><br> Pro, <br><br> Ala, <br><br> Phe, <br><br> Ser, <br><br> Trp, <br><br> Gin, <br><br> Tyr, <br><br> 25 <br><br> Leu, Lys, <br><br> lie, <br><br> Asp, or His; <br><br> Xaa at position <br><br> 106 <br><br> is <br><br> Glu, <br><br> Ser, <br><br> Ala, <br><br> Lys, <br><br> Thr, <br><br> He, <br><br> Gly, <br><br> or Pro; <br><br> Xaa at position <br><br> 108 <br><br> is <br><br> Arg, <br><br> Lys, <br><br> Asp, <br><br> Leu, <br><br> Thr, <br><br> lie, <br><br> Gin, <br><br> His, Ser, <br><br> Ala or Pro; <br><br> Xaa at position <br><br> 109 <br><br> is <br><br> Arg, <br><br> Thr, <br><br> Pro, <br><br> Glu, <br><br> Tyr, <br><br> Leu, <br><br> Ser, <br><br> or Gly; <br><br> 30 <br><br> Xaa at position <br><br> 110 <br><br> is <br><br> Lys, <br><br> Ala, <br><br> Asn, <br><br> Thr, <br><br> Leu, <br><br> Arg, <br><br> Gin, <br><br> His, Glu, <br><br> Ser, or Trp; <br><br> Xaa at position <br><br> 111 <br><br> is <br><br> Leu, <br><br> lie, <br><br> Arg, <br><br> Asp, <br><br> or Met; <br><br> Xaa at position <br><br> 112 <br><br> is <br><br> Thr, <br><br> Val, <br><br> Gin, <br><br> Tyr, <br><br> Glu, <br><br> His, <br><br> Ser, <br><br> or Phe; <br><br> Xaa at position <br><br> 113 <br><br> is <br><br> Phe, <br><br> Ser, <br><br> Cys, <br><br> His, <br><br> Gly, <br><br> Trp, <br><br> Tyr, <br><br> Asp, <br><br> 35 <br><br> Lys, Leu, <br><br> lie, Val or <br><br> Asn; <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 23 <br><br> PCT/US96/15774 <br><br> Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; <br><br> Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, <br><br> Trp, or Met; <br><br> Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, <br><br> 5 Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gin, or lie; <br><br> Xaa at position 117 is Thr, Ser, Asn, lie, Trp, Lys, or Pro; <br><br> Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; <br><br> Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; <br><br> Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gin; <br><br> 10 Xaa at position 121 is Ala, Ser, lie, Asn, Pro, Lys, Asp, or Gly; <br><br> Xaa at position 122 is Gin, Ser, Met, Trp, Arg, Phe, Pro, His, <br><br> lie, Tyr, or Cys; <br><br> Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu; <br><br> 15 wherein optionally from 1 to 14 amino acids can be deleted from the N-terminus and/or from 1 to 15 amino acids can be deleted from the C-terminus; and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human 20 interleukin-3; <br><br> or <br><br> (V) a colony stimulating factor; <br><br> 25 <br><br> and wherein Li is a linker capable of linking Ri to R2; <br><br> with the proviso that at least Ri or R2 is selected from the polypeptide of formula (I) , (II), or (III); and <br><br> 30 <br><br> said hematopoietic protein can optionally be immediately preceded by (methionine-!), (alanine--'-! or (methionine-^, alanine-^). <br><br> 35 The more preferred breakpoints at which new c- <br><br> terminus and N-terminus can be made in the polypeptide (I) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 24 <br><br> PCT/US96/15774 <br><br> above are; 38-39, 39-40, 40-41, 41-42, 48-49, 53-54, 54-55, 55-56, 56-57, 57-58, 58-59, 59-60, 60-61, 61-62, 62-63, 64-65, 65-66, 66-67, 67-68, 68-69, 69-70, 96-97, 125-126, 126-127, 127-128, 128-129, 129-130, 130-131, 131-132, 132-133, 5 133-134, 134-135, 135-136, 136-137, 137-138, 138-139, 139-140, 140-141 and 141-142. <br><br> The most preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (I) above are; 10 38-39, 48-49, 96-97, 125-126, 132-133 and 141-142. <br><br> The more preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (II) above are; 28-29, 29-30, 30-31, 31-32, 32-33, 33-34, 34-35, 35-36, 15 36-37, 37-38, 38-39, 39-40, 66-67, 67-68, 68-69, 69-70, 70-71, 84-85, 85-86, 86-87, 87-88, 88-89, 89-90, 90-91, 98-99, 99-100, 100-101 and 101-102. <br><br> The most preferred breakpoints at which new C-terminus 20 and N-terminus can be made in the polypeptide (II) above are; 34-35, 69-70 and 90-91. <br><br> The more preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (III) above 25 or the amino acid sequence of (SEQ ID NO:256) are; 80-81, <br><br> 81-82, 82-83, 83-84, 84-85, 85-86, 86-87, 108-109, 109-110, 110-111, 111-112, 112-113, 113-114, 114-115, 115-116, 116-117, 117-118, 118-119, 119-120, 120-121, 121-122, 122-123, 123-124, 124-125, 125-126 and 126-127. <br><br> 30 <br><br> The most preferred breakpoints at which new C-terminus and N-terminus can be made in the polypeptide (III) above or the amino acid sequence of (SEQ ID NO:256) are; 81-82, 108-109, 115-116, 119-120, 122-123 and 125-126. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 25 <br><br> PCT/US96/15774 <br><br> The multifunctional receptor agonist of the present invention can also be represented by the following formula: <br><br> (T1)a- (L^b-X^fDc-X2- (L2)d- (T2 ) e <br><br> 5 <br><br> X1-(L)c-X2-(L)-Y1-(L)c-Y2 <br><br> in which: <br><br> X^- is a peptide comprising an amino acid sequence 10 corresponding to the sequence of residues n+1 through J of the original protein having amino acids residues numbered sequentially 1 through J with an amino terminus at residue 1; <br><br> L is an optional linker; <br><br> 15 X2 is a peptide comprising an amino acid sequence of residues 1 through n of the original protein; <br><br> Y1 is a peptide comprising an amino acid sequence corresponding to the sequence of residues n=l through K of the original protein having amino acids residues numbered 20 sequentially 1 through K with an amino terminus at residue 1; <br><br> Y2 is a peptide comprising an amino acid sequence of residues 1 through n of the original protein; <br><br> iA and L2 are optional peptide spacers: 25 n is an integer ranging from 1 to J-l; <br><br> b, c, and d are each independently 0 or 1; <br><br> a and e are either 0 or 1, provided that both a and e cannot both be 0; and <br><br> T^ and T2 are proteins. <br><br> 30 <br><br> Additionally, the present invention relates to recombinant expression vectors comprising nucleotide sequences encoding the multi-functional hematopoietic receptor agonists, related microbial expression systems, and 3 5 processes for making the multi-functional hematopoietic <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 26 <br><br> PCT/US96/15774 <br><br> receptor agonists. The invention also relates to pharmaceutical compositions containing the multi-functional hematopoietic receptor agonists, and methods for using the multi-functional hematopoietic receptor agonists. <br><br> 5 In addition to the use of the multi-functional hematopoietic receptor agonists of the present invention in vivo, it is envisioned that in vitro uses would include the ability to stimulate bone marrow and blood cell activation and growth before infusion into patients. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 27 <br><br> PCT/US96/15774 <br><br> Brief Description of the Figures <br><br> Figure 1 schematically illustrates the sequence 5 rearrangement of a protein. The N-terminus (N) and the C-terminus (C) of the native protein are joined through a linker, or joined directly. The protein is opened at a breakpoint creating a new N-terminus (new N) and a new c-terminus (new-C) resulting in a protein with a new linear 10 amino acid sequence. A rearranged molecule may be synthesized de novo as linear molecule and not go through the steps of joining the original N-terminus and the C-terminus and opening of the protein at the breakpoint. <br><br> 15 Figure 2 shows a schematic of Method I, for creating new proteins in which the original N-terminus and C-terminus of the native protein are joined with a linker and different N-terminus and C-terminus of the protein are created. In the example shown the sequence rearrangement results in a new 20 gene encoding a protein with a new N-terminus created at amino acid 97 of the original protein, the original C-terminus (a.a. 174) joined to the amino acid 11 (a.a. 1- 10 are deleted) through a linker region and a new C-terminus created at amino acid 96 of the original sequence. <br><br> 25 <br><br> Figure 3 shows a schematic of Method II, for creating new proteins in which the original N-terminus and C-terminus of the native protein are joined without a linker and different N-terminus and C-terminus of the protein are 30 created. In the example shown the sequence rearrangement results in a new gene encoding a protein with a new N~ terminus created at amino acid 97 of the original protein, the original C-terminus (a.a. 174) joined to the original N-terminus and a new c-terminus created at amino acid 9 6 of 35 the original sequence. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 28 <br><br> PCT/US96/15774 <br><br> Figure 4 shows a schematic of Method III, for creating new proteins in which the original N-terminus and C-terminus of the native protein are joined with a linker and different 5 N-terminus and C-terminus of the protein are created. In the example shown the sequence rearrangement results in a new gene encoding a protein with a new N-terminus created at amino acid 97 of the original protein, the original C-terminus (a.a. 174) joined to amino acid 1 through a linker 10 region and a new C-terminus created at amino acid 96 of the original sequence. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 29 <br><br> PCT/US96/15774 <br><br> Detailed Description of the Invention <br><br> The present invention encompasses multi-functional 5 hematopoietic receptor agonists formed from covalently linked polypeptides, each of which may act through a different and specific cell receptor to initiate complementary biological activities. Hematopoiesis requires a complex series of cellular events in which stem cells 10 generate continuously into large populations of maturing cells in all major lineages. There are currently at least 20 known regulators with hematopoietic proliferative activity. Most of these proliferative regulators can jnly stimulate one or another type of colony formation in vitro, the 15 precise pattern of colony formation stimulated by each regulator is quite distinctive. No two regulators stimulate exactly the same pattern of colony formation, as evaluated by colony numbers or, more importantly, by the lineage and maturation pattern of the cells making up the developing 20 colonies. Proliferative responses can most readily be analyzed in simplified in vitro culture systems. Three quite different parameters can be distinguished: alteration in colony size, alteration in colony numbers and cell lineage. Two or more factors may act on the progenitor cell, inducing 25 the formation of larger number of progeny thereby increasing the colony size. Two or more factors may allow increased number of progenitor cells to proliferate either because distinct subsets of progenitors cells exist that respond exclusively to one factor or because some progenitors 30 require stimulation by two or more factors before being able to respond. Activation of additional receptors on a cell by the use of two or more factors is likely to enhance the mitotic signal because of coalescence of initially differing signal pathways into a common final pathway reaching the 35 nucleus (Metcalf, Nature 339:27, 19891. Other mechanisms <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 30 <br><br> PCT/US96/15774 <br><br> could explain synergy. For example, if one signaling pathway is limited by an intermediate activation of an additional signaling pathway which is caused by a second factor, then this may result in a super additive response. In some cases, 5 activation of one receptor type can induce an enhanced expression of other receptors (Metcalf, Blood 82:3515-3523, 1993). Two or more factors may result in a different pattern of cell lineages than from a single factor. The use of multi-functional hematopoietic receptor agonists may have a 10 potential clinical advantage resulting from a proliferative response that is not possible by any single factor. <br><br> The receptors of hematopoietic and other growth factors can be grouped into two distinct families of related proteins: (1) tyrosine kinase receptors, including those for 15 epidermal growth factor, M-CSF (Sherr, Blood 75:1, 1990) and SCF (Yarden et al., EMBO J. 6:3341, 1987): and (2) hematopoietic receptors, not containing a tyrosine kinase domain, but exhibiting obvious homology in their extracellular domain (Bazan, PNAS USA 87:6934-6938, 1990). 20 Included in this latter group are erythropoietin (EPO) <br><br> (D'Andrea et al.. Cell 57:277, 1989), GM-CSF (Gearing et al., EMBO J. 0:3667, 1989), IL-3 (Kitamura et al.. Cell 66:1165, 1991), G-CSF (Fukunaga et al., J. Bio. Chem. 265:14008-15, 1990), IL-4 (Harada et al., PNAS USA 87:857, 25 1990), IL-5 (Takaki et al., EMBO J. 9:4367, 1990), IL-6 <br><br> (Yamasaki et al., Science 241:825, 1988), IL-7 (Goodwin et al., Cell 60:941-51, 1990), LIF (Gearing et al., EMBO J. 10:283 9, 1991) and IL-2 (Cosman et al., Mol-Immunol. 23: 935-94, 1986) . Most of the latter group of receptors exists 30 in a high-affinity form as heterodimers. After ligand binding, the specific a-chains become associated with at least one other receptor chain (P-chain, y-chain). Many of these factors share a common receptor subunit. The a-chains for GM-CSF, IL-3 and IL-5 share the same (3-chain (Kitamura 35 et al., Cell 66:1165, 1991), Takaki et al., EMBO J. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 31 <br><br> PCMJS96/15774 <br><br> 10:2833-8, 1991) and receptor complexes for IL-6, LIF and IL-11 share a common p-chain (gpl30) (Taga et al., Cell <br><br> 58:573-81, 1989; Gearing et al.. Science 255:1434-7, 1992). The receptor complexes of IL-2, IL-4, IL-7, IL-9 and IL-15 5 share a common y-chain (Kondo et al., Science 262:1874, <br><br> 1993; Russell et al.. Science 266: 1042-1045, 1993; <br><br> Noguchi et al., Science 262:1877, 1993; Giri et al., EMBO J. 13:2822-2830, 1994) . <br><br> The use of a multiply acting hematopoietic factor may 10 also have a potential advantage by reducing the demands placed on factor-producing cells and their induction systems. If there are limitations in the ability of a cell to produce a factor, then by lowering the required concentrations of each of the factors, and using them in 15 combination may usefully reduce demands on the factor- <br><br> producing cells. The use of a multiply acting hematopoietic factor may lower the amount of the factors that would be needed, probably reducing the likelihood of adverse side-effects . <br><br> 20 Novel compounds of this invention are represented by a formula selected from the group consisting of: <br><br> RI-L1-R2, R2-L1-R1, R1-R2, and R2-R1 <br><br> 25 Where Ri and R2 are as defined above. <br><br> R2 is preferably a colony stimulating factor with a different but complementary activity than Ri. By complementary activity is meant activity which enhances or changes the response to another cell modulator. The Ri 30 polypeptide is joined either directly or through a linker segment to the R2 polypeptide. The term "directly" defines multi-functional hematopoietic receptor agonists in which the polypeptides are joined without a peptide linker. Thus Li represents a chemical bond or polypeptide segment to 35 which both Ri and R2 are joined in frame, most commonly Li <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 32 <br><br> is a linear peptide to which Rl and R2 are joined by amide bonds linking the carboxy terminus of Ri to the amino terminus or Li and carboxy terminus of Li to the amino terminus of R2. By "joined in frame" is meant that there is 5 no translation termination or disruption between the reading frames of the DNA encoding Ri and R2. <br><br> A non-exclusive list of other growth factors, i.e. colony stimulating factors (CSFs), are cytokines, 10 lymphokines, interleukins, hematopoietic growth factors which can be joined to (I), (II) or (III) include GM-CSF, G-CSF, c-mpl ligand (also known as TPO or MGDF), M-CSF, erythropoietin (EPO), IL-1, IL-4, IL-2, IL-3, IL-5, IL 6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-15, LIF, 15 flt3/flk2 ligand, human growth hormone, B-cell growth factor, B-cell differentiation factor, eosinophil differentiation factor and stem cell factor (SCF) also known as steel factor or c-kit ligand. Additionally, this invention encompasses the use of modified Ri or R2 molecules 20 or mutated or modified DNA sequences encoding these Ri or R2 molecules. The present invention also includes multifunctional hematopoietic receptor agonists in which Ri or R2 is an hIL-3 variant, c-mpl ligand variant, or G-CSF variant. A "hIL-3 variant" is defined as a hIL-3 molecule which has 25 amino acid substitutions and/or portions of hIL-3 deleted as disclosed in WO 94/12638, WO 94/12639 and WO 95/00646, as well as other variants known in the art. A "c-mpl ligand variant" is defined an c-mpl ligand molecule which has amino acid substitutions and/or portions of c-mpl ligand deleted, 3 0 disclosed in United States Application Serial Number <br><br> 08/383,035 as well as other variants known in the art. A "G-CSF variant" is defined an G-CSF molecule which has amino acid substitutions and/or portions of G-CSF deleted, as disclosed herein, as well as other variants known in the 3 5 art. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 33 <br><br> PCT/US96/15774 <br><br> The linking group (Li) is generally a polypeptide of between 1 and 500 amino acids in length. The linkers joining the two molecules are preferably designed to (1) allow the 5 two molecules to fold and act independently of each other, (2) not have a propensity for developing an ordered secondary structure which could interfere with the functional domains of the two proteins, (3) have minimal hydrophobic characteristics which could interact with the 10 functional protein domains and (4) provide steric separation of Ri and R2 such that Ri and R2 could interact simultaneously with their corresponding receptors on a single cell. Typically surface amino acids in flexible protein regions include Gly, Asn and Ser. Virtually any 15 permutation of amino acid sequences containing Gly, Asn and Ser would be expected to satisfy the above criteria for a linker sequence. Other neutral amino acids, such as Thr and Ala, may also be used in the linker sequence. Additional amino acids may also be included in the linkers due to the 20 addition of unique restriction sites in the linker sequence to facilitate construction of the multi-functional hematopoietic receptor agonists. <br><br> Preferred Li linkers of the present invention include sequences selected from the group of formulas: <br><br> 25 (Gly3Ser)n (SEQ ID NO:4), (Gly4Ser)n (SEQ ID NO:5), <br><br> (Gly5Ser)n (SEQ ID NO.-6), (GlynSer)n (SEQ ID NO:7) or (AlaGlySer)n (SEQ ID NO:8). <br><br> One example of a highly-flexible linker is the glycine and serine-rich spacer region present within the pill 30 protein of the filamentous bacteriophages, e.g. <br><br> bacteriophages M13 or fd (Schaller et al., PNAS USA 72: 737-741, 1975). This region provides a long, flexible spacer region between two domains of the pill surface protein. The spacer region consists of the amino acid sequence: 35 GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGluGlyGlyGlySerGlu <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 34 <br><br> PCT/US96/15774 <br><br> GlyGlyGlySerGluGlyGlyGlySerGluGlyGlyGlySerGlyGlyGlySer (SEQ ID NO:9) . <br><br> The present invention also includes linkers in which an endopeptidase recognition sequence is included. Such a 5 cleavage site may be valuable to separate the individual components of the multi-functional hematopoietic receptor agonist to determine if they are properly folded and active in vitro. Examples of various endopeptidases include, but are not limited to, plasmin, enterokinase, kallikrein, 10 urokinase, tissue plasminogen activator, clostripain, chymosin, collagenase, Russell's viper venom protease, postproline cleavage enzyme, V8 protease. Thrombin and factor Xa. <br><br> Peptide linker segments from the hinge region of heavy 15 chain immunoglobulins IgG, IgA, IgM, IgD or IgE provide an angular relationship between the attached polypeptides. Especially useful are those hinge regions where the cysteines are replaced with serines. Preferred linkers of the present invention include sequences derived from murine 20 IgG gamma 2b hinge region in which the cysteines have been changed to serines. These linkers may also include an endopeptidase cleavage site. Examples of such linkers include the following sequences: <br><br> 25 IleSerGluProSerGlyProIleSerThrlleAsnProSerProProSerLys GluSerHisLysSerPro (SEQ ID NO:10) and <br><br> IleGluGlyArglleSerGluProSerGlyProIleSerThrlleAsnProSer ProProSerLysGluSerHisLysSerPro (SEQ ID NO:ll). <br><br> 30 <br><br> The present invention is, however, not limited by the form, size or number of linker sequences employed and the only requirement of the linker is that functionally it does not interfere with the folding and function of the 3 5 individual molecules of the multi-functional hematopoietic <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 35 <br><br> PCT/US96/15774 <br><br> receptor agonist. <br><br> Determination of the Linker L9- <br><br> 5 The length of the amino acid sequence of the linker L2 <br><br> to be used in Ri and/or R2 can be selected empirically or with guidance from structural information, or by using a combination of the two approaches. <br><br> When no structural information is available, a small 10 series of linkers can be prepared for testing using a design whose length is varied in order to span a range from 0 to 50 A and whose sequence is chosen in order to be consistent with surface exposure (hydrophilicity, Hopp &amp; Woods, Mol. Immunol. 20: 483-489, 1983), Kyte &amp; Doolittle, J. Mol. Biol. 15 157:105-132; solvent exposed surface area, Lee &amp; Richards, J. Mol. Biol. 55:379-400, 1971) and the ability to adopt the necessary conformation with out deranging the conformation of R1 or R2 (conformationally flexible; Karplus Sc Schulz, Naturwissenschaften 72:212-213, 1985). Assuming 20 an average of translation of 2.0 to 3.8 k per residue, this would mean the length to test would be between 0 to 30 residues, with 0 to 15 residues being the preferred range. Exemplary of such an empirical series would be to construct linkers using a cassette sequence such as Gly-Gly-Gly-Ser 25 (SEQ ID NO:12) repeated n times, where n is 1, 2, 3 or 4. <br><br> Those skilled in the art will recognize that there are many such sequences that vary in length or composition that can serve as linkers with the primary consideration being that they be neither excessively long nor short (cf., Sandhu, 30 Critical Rev. Biotech. 12: 437-462, 1992); if they are too long, entropy effects will likely destabilize the three-dimensional fold, and may also make folding kinetically impractical, and if they are too short, they will likely destabilize the molecule because of torsional or steric 35 strain. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 36 <br><br> PCT/US96/15774 <br><br> Those skilled in the analysis of protein structural information will recognize that using the distance between the chain ends, defined as the distance between the c-alpha 5 carbons, can be used to define the length of the sequence to be used, or at least to limit the number of possibilities that must be tested in an empirical selection of linkers. They will also recognize that it is sometimes the case that the positions of the ends of the polypeptide chain are ill-10 defined in structural models derived from x-ray diffraction or nuclear magnetic resonance spectroscopy data, and that when true, this situation will therefore need to be taken into account in order to properly estimate the length of the linker required. From those residues whose positions are 15 well defined are selected two residues that are close in sequence to the chain ends, and the distance between their c-alpha carbons is used to calculate an approximate length for a linker between them. Using the calculated length as a guide, linkers with a range of number of residues 20 (calculated using 2 to 3.8A per residue) are then selected. These linkers may be composed of the original sequence, shortened or lengthened as necessary, and when lengthened the additional residues may be chosen to be flexible and hydrophilic as described above; or optionally the original 25 sequence may be substituted for using a series of linkers, one example being the Gly-Gly-Gly-Ser (SEQ ID NO:12) <br><br> cassette approach mentioned above; or optionally a combination of the original sequence and new sequence having the appropriate total length may be used. <br><br> 30 <br><br> Determination of the Amino and Carboxvl Termini of and R? <br><br> Sequences of Ri and R2 capable of folding to 3 5 biologically active states can be prepared by appropriate <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 37 <br><br> PCT/US96/15774 <br><br> selection cf the beginning (amino terminus) and ending (carboxyl terminus) positions from within the original polypeptide chain while using the linker sequence L2 as described above. Amino and carboxyl termini are selected 5 from within a common stretch of sequence, referred to as a breakpoint region, using the guidelines described below. A novel amino acid sequence is thus generated by selecting amino and carboxyl termini from within the same breakpoint region. In many cases the selection of the new termini will 10 be such that the original position of the carboxyl terminus immediately preceded that of the amino terminus. However, those skilled in the art will recognize that selections of termini anywhere within the region may function, and that these will effectively lead to either deletions or additions 15 to the amino or carboxyl portions of the new sequence. <br><br> It is a central tenet of molecular biology that the primary amino acid sequence of a protein dictates folding to the three-dimensional structure necessary for expression of its biological function. Methods are known to those skilled 20 in the art to obtain and interpret three-dimensional structural information using x-ray diffraction of single protein crystals or nuclear magnetic resonance spectroscopy of protein solutions. Examples of structural information that are relevant to the identification of breakpoint 25 regions include the location and type of protein secondary structure (alpha and 3-10 helices, parallel and anti-parallel beta sheets, chain reversals and turns, and loops; Kabsch &amp; Sander, Biopolymers 22: 2577-2637, 1983), the degree of solvent exposure of amino acid residues, the 3 0 extent and type of interactions of residues with one another (Chothia, Ann. Rev. Biochem. 53:537-572, 1984) and the static and dynamic distribution of conformations along the polypeptide chain (Alber &amp; Mathews, Methods Enzymol. 154: 511-533, 1987). In some cases additional information is 3 5 known about solvent exposure of residues; one example is a <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 38 <br><br> PCT/US96/15774 <br><br> site of post-translational attachment of carbohydrate which is necessarily on the surface of the protein. When experimental structural information is not available, or is not feasible to obtain, methods are also available to 5 analyze the primary amino acid sequence in order to make predictions of protein tertiary and secondary structure, solvent accessibility and the occurrence of turns and loops. Biochemical methods are also sometimes applicable for empirically determining surface exposure when direct 10 structural methods are not feasible; for example, using the identification of sites of chain scission following limited proteolysis in order to infer surface exposure (Gentile &amp; Salvatore, Eur. J. Biochem. 218:603-621, 1993) <br><br> Thus using either the experimentally derived structural 15 information or predictive methods (e.g., Srinivisan &amp; Rose Proteins: Struct., Funct. &amp; Genetics, 22: 81-99, 1995) the parental amino acid sequence is inspected to classify regions according to whether or not they are integral to the maintenance of secondary and tertiary structure. The 20 occurrence of sequences within regions that are known to be involved in periodic secondary structure (alpha and 3-10 helices, parallel and anti-parallel beta sheets) are regions that should be avoided. Similarly, regions of amino acid sequence that are observed or predicted to have a low degree 25 of solvent exposure are more likely to be part of the so-called hydrophobic core of the protein and should also be avoided for selection of amino and carboxyl termini. In contrast, those regions that are known or predicted to be in surface turns or loops, and especially those regions that 30 are known not to be required for biological activity, are the preferred sites for location of the extremes of the polypeptide chain. Continuous stretches of amino acid sequence that are preferred based on the above criteria are referred to as a breakpoint region. <br><br> 35 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 39 <br><br> PCT/U S96/15774 <br><br> Non-covalent Multifunctional hematopoietic growth factors <br><br> An alternative method for connecting two hematopoietic growth factors is by means of a non-covalent interaction. <br><br> 5 Such complexed proteins can be described by one of the formulae: <br><br> Rl-Ci + R2-C2; or Cl-Rl + C2-R2; C1-R1 + R2-C2; or C1-R1 + R2-C2- <br><br> 10 <br><br> Rl and R2 are as is defined above. Domains Ci and C2 are either identical or non-identical chemical structures, typically proteinaceous, which can form a non-covalent, specific association. Complexes between Ci and C2 result in 15 a one-to-one stoichiometric relationship between Ri and R2 for each complex. Examples of domains which associate are "leucine zipper" domains of transcription factors, dimerization domains of bacterial transcription repressors and immunoglobulin constant domains. Covalent bonds link Ri 20 and Ci, and R2 and C2, respectively. As indicated in the formulae, the domains Ci and C2 can be present either at the N-terminus or C-terminus of their corresponding hematopoietic growth factor (R). These multimerization domains (C± and C2) include those derived from the bZIP 25 family of proteins (Abel et al., Nature 341:24-25, 1989; Landshulz et al., Science 240:1759-1764, 1988; Pu et al., Nuc. Acid Res. 21:4348-4355, 1993; Kozarides et al., Nature 336:646-65i, 1988), as well as multimerization domains of the helix-loop-helix family of proteins (Abel et al., Nature 30 341:24-25, 1989; Murre et al., Cell 56:777-783, 1989; <br><br> Tapscott et al., Science 242:405-411, 1988; Fisher et al. , Genes &amp; Dev. 5:2342-2352, 1991). Preferred multi-functional hematopoietic receptor agonists of the present invention include colony stimulating factors dimerized by virtue of 35 their incorporation as translational multi-functional <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 40 <br><br> PCT/US96/15774 <br><br> hematopoietic receptor agonists with the leucine zipper dimerization domains of the bziP family proteins Fos and Jun. The leucine zipper domain of Jun is capable of interacting with identical domains. On the other hand, the 5 leucine zipper domain of Fos interacts with the Jun leucine zipper domain, but does not interact with other Fos leucine zipper domains. Mixtures of Fos and Jun predominantly result in formation of Fos-Jun heterodimers. Consequently, when joined to colony stimulating factors, the Jun domain 10 can be used to direct the formation of either homo- or heterodimers. Preferential formation of heterodimers can be achieved if one of the colony stimulating factor partners is engineered to possess the Jun leucine zipper domain while the other is engineered to possess the Fos zipper. 15 Additional peptide sequences may also be added to facilitate purification or identification of multifunctional hematopoietic receptor agonist proteins (e.g., poly-His). A highly antigenic peptide may also be added that would enabiv rapid assay and facile purification of the 20 multi-functional hematopoietic receptor agonist protein by a specific monoclonal antibody. <br><br> "Mutant amino acid sequence," "mutant protein", 25 "variant protein", "mutein", or "mutant polypeptide" refers to a polypeptide having an amino acid sequence which varies from a native sequence due to amino acid deletions, substitutions, or both, or is encoded by a nucleotide sequence intentionally made variant from a native sequence.. 3 0 "Native sequence" refers to an amino acid or nucleic acid sequence which is identical to a wild-type or native form of a gene or protein. <br><br> Hematopoietic growth factors can be characterized by 3 5 their ability to stimulate colony formation by human <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 41 <br><br> PCT/US96/15774 <br><br> hematopoietic progenitor cells. The colonies formed include erythroid, granulocyte, megakaryocyte, granulocytic macrophages and mixtures thereof. Many of the hematopoietic growth factors have demonstrated the ability to restore 5 bone marrow function and peripheral blood cell populations to therapeutically beneficial levels in studies performed initially in primates and subsequently in humans. Many or all of these biological activities of hematopoietic growth factors involve signal transduction and high affinity 10 receptor binding. Multi-functional hematopoietic receptor agonists of the present invention may exhibit useful properties such as having similar or greater biological activity when compared to a single factor or by having improved half-life or decreased adverse side effects, or a 15 combination of these properties. <br><br> Multi-functional hematopoietic receptor agonists which have little or no agonist activity maybe useful as antagonists, as antigens for the production of antibodies 20 for use in immunology or immunotherapy, as genetic probes or as intermediates used to construct other useful hIL-3 muteins. <br><br> Biological activity of the multi-functional 25 hematopoietic receptor agonist proteins of the present invention can be determined by DNA synthesis in factor-dependent cell lines or by counting the colony forming units in an in vitro bone marrow assay. <br><br> 30 The multi-functional hematopoietic receptor agonists of the present invention may have an improved therapeutic profile as compared to single acting hematopoietic agonists. For example, some multi-functional hematopoietic receptor agonists of the present invention may have a similar or more 3 5 potent growth factor activity relative to other <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 42 <br><br> hematopoietic agonists without having a similar or corresponding increase in side-effects. <br><br> The present invention also includes the DNA sequences which code for the multi-functional hematopoietic 5 receptor agonist proteins, DNA sequences which are substantially similar and perform substantially the same function, and DNA sequences which differ from the DNAs encoding the multi-functional hematopoietic receptor agonists of the invention only due to the degeneracy of the 10 genetic code. Also included in the present invention are the oligonucleotide intermediates used to construct the mutant DNAs and the polypeptides coded for by these oligonucleotides. <br><br> 15 Genetic engineering techniques now standard in the art <br><br> (United States Patent 4,935,233 and Sambrook et al., "Molecular Cloning A Laboratory Manual", Cold Spring Harbor Laboratory, 1989) may be used in the construction of the DNA sequences of the present invention. One such method is 20 cassette mutagenesis (Wells et al., Gene 34:315-323, 1985) in which a portion of the coding sequence in a plasmid is replaced with synthetic oligonucleotides that encode the desired amino acid substitutions in a portion of the gene between two restriction sites. <br><br> 25 Pairs of complementary synthetic oligonucleotides encoding the desired gene can be made and annealed to each other. The DNA sequence of the oligonucleotide would encode sequence for amino acids of desired gene with the exception of those substituted and/or deleted from the sequence. 30 Plasmid DNA can be treated with the chosen restriction endonucleases then ligated to the annealed oligonucleotides. The ligated mixtures can be used to transform competent JM101 cells to resistance to an appropriate antibiotic. Single colonies can be picked and the plasmid DNA examined 3 5 by restriction analysis and/or DNA sequencing to identify <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 43 <br><br> PCT/US96/15774 <br><br> plasmids with the desired genes. <br><br> Cloning of the DNA sequences of the novel multifunctional hematopoietic agonists wherein at least one of the with the DNA sequence of the other colony 5 stimulating factor may be accomplished by the use of intermediate vectors. Alternatively one gene can be cloned directly into a vector containing the other gene. Linkers and adapters can be used for joining the DNA sequences, as well as replacing lost sequences, where a restriction site 10 was internal to the region of interest. Thus genetic material (DNA) encoding one polypeptide, peptide linker, and the other polypeptide is inserted into a suitable expression vector which is used to transform bacteria, yeast, insect cells or mammalian cells. The transformed organism is grown 15 and the protein isolated by standard techniques. The resulting product is therefore a new protein which has a colony stimulating factor joined by a linker region to a second colony stimulating factor. <br><br> Another aspect of the present invention provides 20 plasmid DNA vectors for use in the expression of these novel multi-functional hematopoietic receptor agonists. These vectors contain the novel DNA sequences described above which code tor the novel polypeptides of the invention. Appropriate vectors which can transform microorganisms 25 capable of expressing the multi-functional hematopoietic receptor agonists include expression vectors comprising nucleotide sequences coding for the multi-functional hematopoietic receptor agonists joined to transcriptional and translational regulatory sequences which are selected 30 according to the host cells used. <br><br> Vectors incorporating modified sequences as described above are included in the present invention and are useful in the production of the multi-functional hematopoietic receptor agonist polypeptides. The vector employed in the 35 method also contains selected regulatory sequences in <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 44 <br><br> PCT/US96/15774 <br><br> operative association with the DNA coding sequences of the invention and which are capable of directing the replication and expression thereof in selected host cells. <br><br> As another aspect of the present invention, there is 5 provided a method for producing the novel multi-functional hematopoietic receptor agonists. The method of the present invention involves culturing suitable cells or cell line, which has been transformed with a vector containing a DNA sequence coding for expression of a novel multi-functional 10 hematopoietic receptor agonist. Suitable cells or cell lines may be bacterial cells. For example, the various strains of E. coli are well-known as host cells in the field of biotechnology. Examples of such strains include E. coli strains JM^.01 (Yanish-Perron et al. Gene 33: 103-119, 1985) 15 and MON105 (Obukowicz et al. , Applied Environmental <br><br> Microbiology 58: 1511-1523, 1992). Also included in the present invention is the expression of the multi-functional hematopoietic receptor agonist protein utilizing a chromosomal expression vector for E. coli based on the 20 bacteriophage Mu (Weinberg et al.. Gene 126: 25-33, 1993). Various strains of B. subtilis may also be employed in this method. Many strains of yeast cells known to those skilled in the art are also available as host cells for expression of the polypeptides of the present invention. When 25 expressed in the E. coli cytoplasm, the gene encoding the multi-functional hematopoietic receptor agonists of the present invention may also be constructed such that at the 5' end of the gene codons are added to encode Met 2-Ala x- or Met 1 at the N-terminus of the protein. The N termini of 30 proteins made in the cytoplasm of E. coli are affected by post-translational processing by methionine aminopeptidase (Ben Bassat et al., J. Bac. 169:751-757, 1987) and possibly by other peptidases so that upon expression the methionine is cleaved off the N-terminus. The multi-functional 3 5 hematopoietic receptor agonists of the present invention may <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 45 <br><br> PCT/US96/15774 <br><br> include multi-functional hematopoietic receptor agonist polypeptides having Met 1, Ala 1 or Met ^-Ala 1 at the N-terminus. These mutant multi-functional hematopoietic receptor agonists may also be expressed in E. coli by fusing 5 a secretion signal peptide to the N-terminus. This signal peptide is cleaved from the polypeptide as part of the secretion process. <br><br> Also suitable for use in the present invention are mammalian cells, such as Chinese hamster ovary cells (CHO). 10 General methods for expression of foreign genes in mammalian cells are reviewed in Kaufman, R. J., 1987) Genetic Engineering, Principles and Methods, Vol. 9, J. K. Setlow, editor, Plenum Press, New York. An expression vector is constructed in which a strong promoter capable of 15 functioning in mammalian cells drives transcription of a eukaryotic secretion signal peptide coding region, which is translationally joined to the coding region for the multifunctional hematopoietic receptor agonist. For example, plasmids such as pcDNA I/Neo, pRc/RSV, and pRc/CMV (obtained 20 from Invitrogen Corp., San Diego, California) can be used. <br><br> The eukaryotic secretion signal peptide coding region can be from the gene itself or it can be from another secreted mammalian protein (Bayne, M. L. et al., Proc. Natl. Acad. Sci. USA 84: 2638-2642, 1987). After construction of the 25 vector containing the gene, the vector DNA is transfected into mammalian cells. Such cells can be, for example, the COS7, HeLa, BHK, CHO, or mouse L lines. The cells can be cultured, for example, in DMEM media (JRH Scientific). The polypeptide secreted into the media can be recovered by 3 0 standard biochemical approaches following transient expression for 24 - 72 hours after transfection of the cells or after establishment of stable cell lines following selection for antibiotic resistance. The selection of suitable mammalian host cells and methods for 35 transformation, culture, amplification, screening and <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 46 <br><br> PCT/US96/15774 <br><br> product production and purification are known in the art. See, e.g., Gething and Sambrook, Nature, 293:620-625, 1981), or alternatively, Kaufman et al, Mol. Cell. Biol., 5(7):1750-1759 , 1985) or Howley et al., U.S. Pat. No. 5 4,419,446. Another suitable mammalian cell line is the monkey COS-1 cell line. A similarly useful mammalian cell line is the CV-1 cell line. <br><br> Where desired, insect cells may be utilized as host cells in the method of the present invention. See, e.g., 10 Miller et al.. Genetic Engineering, 8:277-298 (Plenum Press 1986) and references cited therein. In addition, general methods for expression of foreign genes in insect cells using Baculovirus vectors are described in: Summers, M. D. and Smith, G. E., 1987) - A manual of methods for 15 Baculovirus vectors and insect cell culture procedures, <br><br> Texas Agricultural Experiment Station Bulletin No. 1555. An expression vector is constructed comprising a Baculovirus transfer vector, in which a strong Baculovirus promoter (such as the polyhedron promoter) drives transcription of a' 20 eukaryotic secretion signal peptide coding region, which is translationally joined to the coding region for the multifunctional hematopoietic receptor agonist polypeptide. For example, the plasmid pVLl392 (obtained from Invitrogen Corp., San Diego, California) can be used. After 25 construction of the vector carrying the gene encoding the multi-functional hematopoietic receptor agonist polypeptide, two micrograms of this DNA is co-transfected with one microgram of Baculovirus DNA (see Summers &amp; Smith, 1987) <br><br> into insect cells, strain SF9. Pure recombinant Baculovirus 30 carrying the multi-functional hematopoietic receptor agonist is used to infect cells cultured, for example, in Excell 401 serum-free medium (JRH Biosciences, Lenexa, Kansas). The multi-functional hematopoietic receptor agonist secreted into the medium can be recovered by standard biochemical 35 approaches. Supernatants from mammalian or insect cells <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 47 <br><br> PCT/US96/15774 <br><br> expressing the multi-functional hematopoietic receptor agonist protein can be first concentrated using any of a number of commercial concentration units. <br><br> 5 The multi-functional hematopoietic receptor agonists of the present invention may be useful in the treatment of diseases characterized by decreased levels of either myeloid, erythroid, lymphoid, or megakaryocyte cells of the hematopoietic system or combinations thereof. In addition, 10 they may be used to activate mature myeloid and/or lymphoid cells. Among conditions susceptible to treatment with the polypeptides of the present invention is leukopenia, a reduction in the number of circulating leukocytes (white cells) in the peripheral blood. Leukopenia may be induced 15 by exposure to certain viruses or to radiation. It is often a side effect of various forms of cancer therapy, e.g., exposure to chemotherapeutic drugs, radiation and of infection or hemorrhage. Therapeutic treatment of leukopenia with these multi-functional hematopoietic 20 receptor agonists of the present invention may avoid undesirable side effects caused by treatment with presently available drugs. <br><br> The multi-functional hematopoietic receptor agonists of the present invention may be useful in the treatment of 25 neutropenia and, for example, in the treatment of such conditions as aplastic anemia, cyclic neutropenia, <br><br> idiopathic neutropenia, Chediak-Higashi syndrome, systemic lupus erythematosus (SLE), leukemia, myelodysplastic syndrome and myelofibrosis. <br><br> 30 The multi-functional hematopoietic receptor agonist of the present invention may be useful in the treatment or prevention of thrombocytopenia. Currently the only therapy for thrombocytopenia is platelet transfusion which are costly and carry the significant risks of infection (HIV, 35 HBV) and alloimunization. The multi-functional hematopoietic <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 48 <br><br> PCT/US96/15774 <br><br> receptor agonist may alleviate or diminish the need for platelet transfusion. Severe thrombocytopenia may result from genetic defects such as Fanconi's Anemia, Wiscott-Aldrich, or May Hegglin syndromes. Acquired thrombocytopenia 5 may result from auto- or allo-antibodies as in Immune Thrombocytopenia Purpura, Systemic Lupus Erythromatosis, hemolytic anemia, or fetal maternal incompatibility. In addition, splenomegaly, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, infection 10 or prosthetic heart valves may result in thrombocytopenia. Severe thrombocytopenia may also result from chemotherapy and/or radiation therapy or cancer. Thrombocytopenia may also result from marrow invasion by carcinoma, lymphoma, leukemia or fibrosis. <br><br> 15 <br><br> The multi-functional hematopoietic receptor agonists of the present invention may be useful in the mobilization of hematopoietic progenitors and stem cells in peripheral blood. Peripheral blood derived progenitors have been shown 20 to be effective in reconstituting patients in the setting of autologous marrow transplantation. Hematopoietic growth factors including G-CSF and GM-CSF have been shown to enhance the number of circulating progenitors and stem cells in the peripheral blood. This has simplified the procedure 25 for peripheral stem cell collection and dramatically decreased the cost of the procedure by decreasing the number of pheresis required. The multi-functional hematopoietic receptor agonist may be useful in mobilization of stem cells and further enhance the efficacy of peripheral stem cell 30 transplantation. <br><br> The multi-functional hematopoietic receptor agonists of the present invention may also be useful in the ex vivo expansion of hematopoietic progenitors and stem cells. 35 Colony stimulating factors (CSFs), such as hIL-3, have been <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 49 <br><br> PCT/US96/15774 <br><br> administered alone, co-administered with other CSFs, or in combination with bone marrow transplants subsequent to high dose chemotherapy to treat the neutropenia and thrombocytopenia which are often the result of such 5 treatment. However the period of severe neutropenia and thrombocytopenia may not be totally eliminated. The myeloid lineage, which is comprised of monocytes (macrophages), granulocytes (including neutrophils) and megakaryocytes, is critical in preventing infections and bleeding which can be 10 life-threatening. Neutropenia and thrombocytopenia may also be the result of disease, genetic disorders, drugs, toxins, radiation and many therapeutic treatments such as conventional oncology therapy. <br><br> Bone marrow transplants have been used to treat this 15 patient population. However, several problems are associated with the use of bone marrow to reconstitute a compromised hematopoietic system including: 1) the number of stem cells in bone marrow, spleen, or peripheral blood is limited, 2) Graft Versus Host Disease, 3) graft rejection and 4) 20 possible contamination with tumor cells. Stem cells make up a very small percentage of the nucleated cells in the bone marrow, spleen and peripheral blood. It is clear that a dose response exists such that a greater number of stem cells will enhance hematopoietic recovery. Therefore, the in vitro 25 expansion of stem cells should enhance hematopoietic recovery and patient survival. Bone marrow from an allogeneic donor has been used to provide bone marrow for transplant. However, Graft Versus Host Disease and graft rejection limit bone marrow transplantation even in 30 recipients with HLA-matched sibling donors. An alternative to allogeneic bone marrow transplants is autologous bone marrow transplants. In autologous bone marrow transplants, some of the patient's own marrow is harvested prior to myeloablative therapy, e.g. high dose chemotherapy, and is 3 5 transplanted back into the patient afterwards. Autologous <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 50 <br><br> PCT/US96/15774 <br><br> transplants eliminate the risk of Graft Versus Host Disease and graft rejection. However, autologous bone marrow transplants still present problems in terms of the limited number of stems cells in the marrow and possible 5 contamination with tumor cells. The limited number of stem cells may be overcome by ex-vivo expansion of the stem cells. In addition, stem cells can be specifically isolated, based on the presence of specific surface antigens such as CD34+ in order to decrease tumor cell contamination of the 10 marrow graft. <br><br> The following patents contain further details on separating stem cells, CD34+ cells, culturing the cells with hematopoietic factors, the use of the cells for the 15 treatment of patients with hematopoietic disorders and the use of hematopoietic factors for cell expansion and gene therapy. <br><br> 5,061,620 relates to compositions comprising human 20 hematopoietic stem cells provided by separating the stem cells from dedicated cells. <br><br> 5,199,942 describes a method for autologous hematopoietic cell transplantation comprising: (1) obtaining hematopoietic 25 progenitor cells from a patient; (2) ex-vivo expansion of cells with a growth factor selected from the group consisting of IL-3, flt3 ligand, c-kit ligand, GM-CSF, IL-1, GM-CSF/IL-3 fusion protein and combinations thereof; (3) administering cellular preparation to a patient. <br><br> 30 <br><br> 5,240,856 relates to a cell separator that includes an apparatus for automatically controlling the cell separation process. <br><br> 35 WO 91/16116 describes devices and methods for selectively <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 51 <br><br> PCT/US96/15774 <br><br> isolating and separating target cells from a mixture of cells. <br><br> WO 91/18972 describes methods for in vitro culturing of bone 5 marrow, by incubating suspension of bone marrow cells, using a hollow fiber bioreactor. <br><br> WO 92/18615 relates to a process for maintaining and expanding bone marrow cells, in a culture medium containing 10 specific mixtures of cytokines, for use in transplants. <br><br> WO 93/0826c- describes a method for selectively expanding stem cells, comprising the steps of (a) separating CD34+ <br><br> stem cells from other cells and (b) incubating the separated 15 cells in a selective medium, such that the stem cells are selectively expanded. <br><br> WO 93/1813 6 describes a process for in vitro support of mammalian cells derived from peripheral blood. <br><br> 20 <br><br> WO 93/18648 relates to a composition comprising human neutrophil precursor cells with a high content of myeloblasts and promyelocytes for treating genetic or acquired neutropenia. <br><br> 25 <br><br> WO 94/08039 describes a method of enrichment for human hematopoietic stem cells by selection for cells which express c-kit protein. <br><br> 30 WO 94/11493 describes a stem cell population that are CD34+ and small in size, which are isolated using a counterflow elutriation method. <br><br> WO 94/27698 relates to a method combining immunoaffinity 35 separation and continuous flow centrifugal separation for <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 52 <br><br> PCT7US96/15774 <br><br> the selective separation of a nucleated heterogeneous cell population from a heterogeneous cell mixture. <br><br> WO 94/25848 describes a cell separation apparatus for 5 collection and manipulation of target cells. <br><br> The long term culturing of highly enriched CD34+ precursors of hematopoietic progenitor cells from human bone marrow in cultures containing IL-la, IL-3, IL-6 or GM-CSF is discussed 10 in Brandt et al J. Clin. Invest. 86:932-941, 1990). <br><br> One aspect of the present invention provides a method for selective ex-vivo expansion of stem cells. The term "stem cell" refers to the totipotent hematopoietic stem cells as 15 well as early precursors and progenitor cells which can be isolated from bone marrow, spleen or peripheral blood. The term "expansion" refers to the differentiation and proliferatjon of the cells. The present invention provides a method for selective ex-vivo expansion of stem cells, 20 comprising the steps of: (a) separating stem cells from other cells, (b) culturing said separated stem cells with a selective media which contains multi-functional hematopoietic receptor agonist protein(s) and (c) harvesting said stems cells. Stem cells, as well as committed 25 progenitor cells destined to become neutrophils, <br><br> erythrocytes, platelets, etc. may be distinguished from most other cells by the presence or absence of particular progenitor marker antigens, such as CD34, that are present on the surface of these cells and/or by morphological 30 characteristics. The phenotype for a highly enriched human stem cell fraction is reported as CD34+, Thy-1+ and lin-, but it is to be understood that the present invention is not limited to the expansion of this stem cell population. The CD34+ enriched human stem cell fraction can be separated by 35 a number of reported methods, including affinity columns or <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 53 <br><br> PCT/US96/15774 <br><br> beads, magnetic beads or flow cytometry using antibodies directed to surface antigens such as the CD34+. Further, physical separation methods such as counterflow elutriation may be used to enrich hematopoietic progenitors. The CD34+ 5 progenitors are heterogeneous, and may be divided into several sub-populations characterized by the presence or absence of co-expression of different lineage associated cell surface associated molecules. The most immature progenitor cells do not express any known lineage associated 10 markers, such as HLA-DR or CD3 8, but they may express CD90(thy-l). Other surface antigens such as CD33, CD38, CD41, CD71, HLA-DR or c-kit can also be used to selectively isolate hematopoietic progenitors. The separated cells can be incubated in selected medium in a culture flask, sterile 15 bag or in hollow fibers. Various colony stimulating factors may be utilized in order to selectively expand cells. Representative factors that have been utilized for ex-vivo expansion of bone marrow include, c-kit ligand, IL-3, G-CSF, GM-CSF, IL-1, IL-6, IL-11, flt-3 ligand or combinations 20 thereof. The proliferation of the stem cells can be monitored by enumerating the number of stem cells and other cells, by standard techniques (e.g. hemacytometer, CFU, LTCIC) or by flow cytometry prior and subsequent to incubation. <br><br> 25 <br><br> Several methods for ex-vivo expansion of stem cells have been reported utilizing a number of selection methods and expansion using various colony stimulating factors including c-kit ligand (Brandt et al., Blood 83:1507-1514 30 [1994], McKenna et al., Blood 86:3413-3420 [1995]), IL-3 (Brandt et al., Blood 83:1507-1514 [1994], Sato et al., Blood 82:3600-3609 [1993]), G-CSF (Sato et al., Blood 82:3600-3609 [1993]), GM-CSF (Sato et al., Blood 82:3600-3609 [1993]), IL-1 (Muench et al., Blood 81:3463-3473 35 [1993]), IL-6 (Sato et al., Blood 82:3600-3609 [1993]), IL- <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 54 <br><br> PCT/US96/15774 <br><br> 11 (Lemoli et al., Exp. Hem. 21:1668-1672 [1993], Sato et al., Blood 82:3600-3609 [1993]), flt-3 ligand (McKenna et al.. Blood 86:3413 3420 [1995]) and/or combinations thereof (Brandt et al. , Blood 83:1507 1514 [1994], Haylock et al., 5 Blood 80:1405-1412 [1992], Roller et al., Biotechnology 11:358-363 [1993], (Lemoli et al. , Exp. Hem. 21:1668-1672 [1993]), McKenna et al., Blood 86:3413-3420 [1995], Muench et al., Blood 81:3463-3473 [1993], Patchen et al., <br><br> Biotherapy 7:13-26 [1994], Sato et al., Blood 82:3600-3609 10 [1993], Smith et al., Exp. Hem. 21:870-877 [1993], Steen et al., Stem Cells 12:214-224 [1994], Tsujino et al., Exp. Hem. 21:1379-1386 [1993]). Among the individual colony stimulating factors, hIL-3 has been shown to be one of the most potent in expanding peripheral blood CD34+ cells (Sato 15 et al., Blood 82:3600-3609 [1993], Kobayashi et al., Blood 73:1836-1841 [1989]). However, no single factor has been shown to be as effective as the combination of multiple factors. The present invention provides methods for ex vivo expansion that utilize multi-functional hematopoietic 20 receptor agonists that are more effective than a single factor alone. <br><br> Another aspect of the invention provides methods of sustaining and/or expanding hematopoietic precursor cells 25 which includes inoculating the cells into a culture vessel which contains a culture medium that has been conditioned by exposure to a stromal cell line such as HS-5 (WO 96/02662, Roecklein and Torok-Strob, Blood 85:997-1105, 1995) that has been supplemented with a multi-functional hematopoietic 30 receptor agonist of the present invention. <br><br> Another projected clinical use of growth factors has been in the in vitro activation of hematopoietic progenitors and stem cells for gene therapy. Due to the long life-span 35 of hematopoietic progenitor cells and the distribution of <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 55 <br><br> PCT/US96/15774 <br><br> their daughter cells throughout the entire body, hematopoietic progenitor cells are good candidates for ex vivo gene transfection. In order to have the gene of interest incorporated into the genome of the hematopoietic 5 progenitor or stem cell one needs to stimulate cell division and DNA replication. Hematopoietic stem cells cycle at a very low frequency which means that growth factors may be useful to promote gene transduction and thereby enhance the clinical prospects for gene therapy. Potential applications 10 of gene therapy (review Crystal, Science 270:404-410 [1995]) include; 1) the treatment of many congenital metabolic disorders and immunodeficiencies (Kay and Woo, Trends Genet. 10:253-257 [1994]), 2) neurological disorders (Friedmann, Trends Genet. 10:210-214 [1994]), 3) cancer IS (Culver and Blaese, Trends Genet. 10:174-178 [1994]) and 4) infectious diseases (Gilboa and Smith, Trends Genet. 10:139-144 [1994]). <br><br> There are a variety of methods, known to those with skill in the art, for introducing genetic material into a 20 host cell. A number of vectors, both viral and non-viral have been developed for transferring therapeutic genes into primary cells. Viral based vectors include; 1) replication deficient recombinant retrovirus (Boris-Lawrie and Temin, Curr. Opin. Genet. Dev. 3:102-109 [1993], Boris-Lawrie and 25 Temin, Annal. New York Acad. Sci. 716:59-71 [1994], Miller, Current Top. Microbiol. Immunol. 158:1-24 [1992]) and replication-deficient recombinant adenovirus (Berkner, BioTechniques 6:616-629 [1988], Berkner, Current Top. Microbiol. Immunol. 158:39-66 [1992], Brody and Crystal, 30 Annal. New York Acad. Sci. 716:90-103 [1994]). Non-viral based vectors include protein/DNA complexes (Cristiano et al., PNAS USA. 90:2122-2126 [1993], Curiel et al., PNAS USA 88:8850-8854 [1991], Curiel, Annal. New York Acad. Sci. 716:36-58 [1994]), electroporation and liposome mediated 35 delivery such as cationic liposomes (Farhood et al., Annal. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 56 <br><br> PCT/US96/15774 <br><br> New York Acad. Sci. 716:23-35 [1994]). <br><br> The present invention provides an improvement to the existing methods of expanding hematopoietic cells, which new genetic material has been introduced, in that it provides 5 methods utilizing multi-functional hematopoietic receptor agonist proteins that have improved biological activity, including an activity not seen by any single colony stimulation factor. <br><br> Many drugs may cause bone marrow suppression or 10 hematopoietic deficiencies. Examples of such drugs are AZT, DDI, alkylating agents and anti-metabolites used in chemotherapy, antibiotics such as chloramphenicol, <br><br> penicillin, gancyclovir, daunomycin and sulfa drugs, phenothiazones, tranquilizers such as meprobamate, 15 analgesics such as aminopyrine and dipyrone, anticonvulsants such as phenytoin or carbamazepine, antithyroids such as propylthiouracil and methimazole and diuretics. The multi-functional hematopoietic receptor agonists of the present invention may be useful in preventing or treating 20 the bone marrow suppression or hematopoietic deficiencies which often occur in patients treated with these drugs. <br><br> Hematopoietic deficiencies may also occur as a result of viral, microbial or parasitic infections and as a result of treatment for renal disease or renal failure, e.g., 25 dialysis. The multi-functional hematopoietic receptor agonists of the present invention may be useful in treating such hematopoietic deficiencies. <br><br> The treatment of hematopoietic deficiency may include administration of a pharmaceutical composition containing 30 the multi-functional hematopoietic receptor agonists to a patient. The multi-functional hematopoietic receptor agonists of the present invention may also be useful for the activation and amplification of hematopoietic precursor cells by treating these cells in vitro with the multi-3 5 functional hematopoietic receptor agonist proteins of the <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 57 <br><br> PCT/US96/15774 <br><br> present invention prior to injecting the cells into a patient. <br><br> Various immunodeficiencies, e.g., in T and/or B lymphocytes, or immune disorders, e.g., rheumatoid 5 arthritis, may also be beneficially affected by treatment with the multi-functional hematopoietic receptor agonists of the present invention. Immunodeficiencies may be the result of viral infections, e.g., HTLVI, HTLVII, HTLVIII, severe exposure to radiation, cancer therapy or the result of other 10 medical treatment. The multi-functional hematopoietic receptor agonists of the present invention may also be employed, alone or in combination with other colony stimulating factors, in the treatment of other blood cell deficiencies, including thrombocytopenia (platelet 15 deficiency), or anemia. Other uses for these novel polypeptides are the in vivo and ex vivo treatment of patients recovering from bone marrow transplants, and in the development of monoclonal and polyclonal antibodies generated by standard methods for diagnostic or therapeutic 20 use. <br><br> Other aspects of the present invention are methods and therapeutic compositions for treating the conditions referred to above. Such compositions comprise a therapeutically effective amount of one or more of the 25 multi-functional hematopoietic receptor agonists of the present invention in a mixture with a pharmaceutically acceptable carrier. This composition can be administered either parenterally, intravenously or subcutaneously. When administered, the therapeutic composition for use in this 30 invention is preferably in the form of a pyrogen-free, <br><br> parenterally acceptable aqueous solution. The preparation of such a parenterally acceptable protein solution, having due regard to pH, isotonicity, stability and the like, is within the skill of the art. <br><br> 35 The dosage regimen involved in a method for treating <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 58 <br><br> the above-described conditions will be determined by the attending physician considering various factors which modify the action of drugs, e.g., the condition, body weight, sex and diet of the patient, the severity of any infection, time 5 of administration and other clinical factors. Generally, a daily regimen may be in the range of 0.2 - 150 ng/kg of multi-functional hematopoietic receptor agonist protein per kilogram of body weight. Dosages would be adjusted relative to the activity of a given multi-functional hematopoietic 10 receptor agonist protein and it would not be unreasonable to note that dosage regimens may include doses as low as 0.1 microgram and as high as 1. milligram per kilogram of body weight per day. In addition, there may exist specific circumstances where dosages of multi-functional 15 hematopoietic receptor agonist would be adjusted higher or lower than the range of 0.2 - 150 micrograms per kilogram of body weight. These include co-administration with other colony stimulating factors or IL-3 variants or growth factors; co-administration with chemotherapeutic drugs 20 and/or radiation; the use of glycosylated multi-functional hematopoietic receptor agonist protein; and various patient-related issues mentioned earlier in this section. As indicated above, the therapeutic method and compositions may also include co-administration with other human factors. A 25 non-exclusive list of other appropriate colony stimulating factors (CSFs), cytokines, lymphokines, hematopoietic growth factors and interleukins for simultaneous or serial coadministration with the polypeptides of the present invention includes GM-CSF, G-CSF, c-mpl ligand (also known 30 as TPO or MGDF), M-CSF, erythropoietin (EPO), IL-1, IL-4, <br><br> IL-2, IL-3, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-15, IL-16, LIF, flt3/flk2 ligand, B-cell growth factor, B-cell differentiation factor and eosinophil differentiation factor, stem cell factor (SCF) also known as 35 steel factor or c-kit ligand, or combinations thereof. The <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 59 <br><br> PCT/US96/15774 <br><br> dosage recited above would be adjusted to compensate for such additional components in the therapeutic composition. Progress of the treated patient can be monitored by periodic assessment of the hematological profile, e.g., differential 5 cell count and the like. <br><br> MATERIALS AND METHODS <br><br> 10 unless noted otherwise, all specialty chemicals were obtained from Sigma, Co. (St. Louis, MO). Restriction endonucleases and T4 DNA ligase were obtained from New England Biolabs (Beverly, MA) or Boehringer Mannheim (Indianapolis, IN). <br><br> 15 <br><br> Transformation of E. coli strains <br><br> E. coli strains, such as DH5a™ (Life Technologies, Gaithersburg, MD) and TGI (Amersham Corp., Arlington 20 Heights, IL) are used for transformation of ligation reactions and are the source of plasmid DNA for transfecting mammalian cells. E. coli strains, such as JM101 (Yanisch-Perron, et al., Gene, 33: 103-119, 1985) and MONIOS (Obukowicz, et al., Appl. and Envir. Micr., 58: 1511-1523, 25 1992) can be used for expressing the multi-functional hematopoietic receptor agonist of the present invention in the cytoplasm or periplasmic space. <br><br> MON105 ATCC# 55204: F-, lambda-,IN(rrnD, rrE)l, rpoD+, 3 0 rpoH3 58 <br><br> DH5a™ : F-, phi80dlacZdeltaMl5, delta(lacZYA-argF)U169, <br><br> deoR, recAl, endAl, hsdRl7(rk-,mk+), phoA, supE441amda-, thi-1, gyrA96, relAl <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 60 <br><br> PCT/US96/15774 <br><br> TGI: delta(lac-pro), supE, thi-1, hsdD5/F'(traD36, proA+B+, laclq, lacZdeltaMl5) <br><br> 5 JM101 ATCC#33876: delta (pro lac), supE, thi, F'(traD36, proA+B+, laclq, lacZdeltaM15) <br><br> DH5a™ Subcloning efficiency cells are purchased as competent cells and are ready for transformation using the 10 manufacturer's protocol, while both £. coli strains TGI and MON105 are rendered competent to take up DNA using a CaCl2 method. Typically, 20 to 50 mL of cells are grown in LB medium (1% bacto-tryptone, 0.5% bacto-yeast extract, 150 mM NaCl) to a density of approximately 1.0 optical density unit 15 at 600 nanometers (OD6OO) as measured by a Baush &amp; Lomb <br><br> Spectronic spectrophotometer (Rochester, NY). The cells are collected by centrifugation and resuspended in one-fifth culture volume of CaCl2 solution (50 mM CaCl2, 10 mM Tris-Cl, pH7.4) and are held at 4'C for 30 minutes. The cells 20 are again collected by centrifugation and resuspended in one-tenth culture volume of CaCl2 solution. Ligated DNA is added to 0.2 mL of these cells, and the samples are held at 4'C for 30-60 minutes. The samples are shifted to 42'C for two minutes and 1.0 mL of LB is added prior to shaking the 25 samples at 37'C for one hour. Cells from these samples are spread on plates (LB medium plus 1.5% bacto-agar) containing either ampicillin (100 micrograms/mL, ug/mL) when selecting for ampicillin-resistant transformants, or spectinomycin (75 ug/mL) when selecting for spectinomycin-resistant 30 transformants. The plates are incubated overnight at 37"C. <br><br> Colonies are picked and inoculated into LB plus appropriate antibiotic (100 ug/mL ampicillin or 75 ug/mL spectinomycin) and are grown at 37°C while shaking. <br><br> 35 Methods for creation of aenes with new N-terminus/C-terminus <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 61 <br><br> PCT /US96/15774 <br><br> Method I. Creation of genes with new N-terminus/C-terminus which contain a linker region (L2). <br><br> Genes with new N-terminus/C-terminus which contain a 5 linker region (L2) separating the original C-terminus and N-terminus can be made essentially following the method described in L. s. Mullins, et al J. Am. Chem. Soc. 116, 5529-5533, 1994). Multiple steps of polymerase chain reaction (PCR) amplifications are used to rearrange the DNA 10 sequence encoding the primary amino acid sequence of the protein. The steps are illustrated in Figure 2. <br><br> In the first step, the first primer set ("new start" and "linker start") is used to create and amplify, from the original gene sequence, the DNA fragment ("Fragment Start") 15 that contains the sequence encoding the new N-terminal portion of the new protein followed by the linker (L2) that connects the C-terminal and N-terminal ends of the original protein. In the second step, the second primer set ("new stop" and "linker stop") is used to create and amplify, from 20 the original gene sequence, the DNA fragment ("Fragment <br><br> Stop") that encodes the same linker as used above, followed by the new C-terminal portion of the new protein. The "new start" and "new stop" primers are designed to include the appropriate restriction sites which allow cloning of the new 25 gene into expression plasmids. Typical PCR conditions are one cycle 95°C melting for two minutes; 25 cycles 94°C denaturaticr for one minute, 5 0°C annealing for one minute and 72°C extension for one minute; plus one cycle 72°C extension for seven minutes. A Perkin Elmer GeneAmp PCR 30 Core Reagents kit is used. A 100 ul reaction contains 100 pmole of each primer and one ug of template DNA; and lx PCR buffer, 200 uM dGTP, 200 uM dATP, 200 uM dTTP, 200 uM dCTP, 2.5 units AmpliTaq DNA polymerase and 2 mM MgCl2. PCR reactions are performed in a Model 480 DNA thermal cycler 35 (Perkin Elmer Corporation, Norwalk, CT). <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 62 <br><br> PCT/US96/15774 <br><br> "Fragment Start" and "Fragment Stop", which have complementary sequence in the linker region and the coding sequence for the two amino acids on both sides of the 5 linker, are joined together in a third PCR step to make the full-length gene encoding the new protein. The DNA fragments "Fragment Start" and "Fragment Stop" are resolved on a 1% TAE gel, stained with ethidium bromide and isolated using a Qiaex Gel Extraction kit (Qiagen). These fragments 0 are combined in equimolar quantities, heated at 70°C for ten minutes and slow cooled to allow annealing through their shared sequence in "linker start" and "linker stop". In the third PCR step, primers "new start" and "new stop" are added to the annealed fragments to create and amplify the full-5 length new N-terminus/C-terminus gene. Typical PCR <br><br> conditions are one cycle 95°C melting for two minutes; 25 cycles 94°C denaturation for one minute, 60°C annealing for one minute and 72°C extension for one minute; plus one cycle 72°C extension for seven minutes. A Perkin Elmer GeneAmp 0 PCR Core Reagents kit is used. A 100 ul reaction contains 100 pmole of each primer and approximately 0.5 ug of DNA; and lx PCR buffer, 200 uM dGTP, 200 uM dATP, 200 uM dTTP, 200 uM dCTP, 2.5 units AmpliTaq DNA polymerase and 2 mM MgCl2. PCR reactions are purified using a Wizard PCR Preps .5 kit (Promega). <br><br> Method II. Creation of genes with new N-terminus/C-terminus without a linker region. <br><br> 10 New N-terminus/C-terminus genes without a linker joining the original N-terminus and C-terminus can be made using two steps of PCR amplification and a blunt end ligation, ^he steps are illustrated in Figure 3. In the first step, the primer set ("new start" and "P-bl start") is 35 used to create and amplify, from the original gene sequence, <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 53 <br><br> the DNA fragment ("Fragment Start") that contains the sequence encoding the new N-terminal portion of the new protein. In the second step, the primer set ("new stop" and "P-bl stop") is used to create and amplify, from gene 5 sequence, the DNA fragment ("Fragment Stop") that contains the sequence encoding the new C-terminal portion of the new protein. The "new start" and "new stop" primers are designed to include appropriate restriction sites which allow cloning of the new gene into expression vectors. Typical PCR 10 conditions are one cycle 95°C melting for two minutes; 25 cycles 94°C denaturation for one minute, 50°C annealing for 45 seconds and 72°C extension for 45 seconds. Deep Vent polymerase (New England Biolabs) is used to reduce the occurrence of overhangs in conditions recommended by the 15 manufacturer. The "P-bl start" and "P-bl stop" primers are phosphorylated at the 5' end to aid in the subsequent blunt end ligation of "Fragment Start" and "Fragment Stop" to each other. A 100 ul reaction contained 150 pmole of each primer and one ug of template DNA; and lx Vent buffer (New England 20 Biolabs), 300 uM dGTP, 300 uM dATP, 300 uM dTTP, 300 uM <br><br> dCTP, and 1 unit Deep Vent polymerase. PCR reactions are performed in a Model 480 DNA thermal cycler (Perkin Elmer Corporation, Norwalk, CT). PCR reaction products are purified using a Wizard PCR Preps kit (Promega). <br><br> 25 <br><br> The primers are designed to include appropriate restriction sites which allow for the cloning of the new gene into expression vectors. Typically "Fragment Start" is designed to create Ncol restriction site , and "Fragment 30 Stop" is designed to create a Hindlll restriction site. <br><br> Restriction digest reactions are purified using a Magic DNA Clean-up System kit (Promega). Fragments Start and Stop are resolved on a 1% TAE gel, stained with ethidium bromide and isolated using a Qiaex Gel Extraction kit (Qiagen). These 3 5 fragments are combined with and annealed to the ends of the <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 64 <br><br> PCT/US96/15774 <br><br> ~ 3800 base pair Ncol/Hindlll vector fragment of pMON3934 by-heating at 50°C for ten minutes and allowed to slow cool. The three fragments are ligated together using T4 DNA ligase (Boehringer Mannheim). The result is a plasmid containing 5 the full-length new N-terminus/C-terminus gene. A portion of the ligation reaction is used to transform E. coli strain DH5a cells (Life Technologies, Gaithersburg, MD). Plasmid <br><br> DNA is purified and sequence confirmed as below. <br><br> 10 Method III. Creation of new N-terminus/C-terminus genes by tandem-duplication method <br><br> New N-terminus/C-terminus genes can be made based on the method described in R. A. Horlick, et al Protein Eng. 15 5:427-431, 1992). Polymerase chain reaction (PCR) <br><br> amplification of the new N-terminus/C-terminus genes is performed using a tandemly duplicated template DNA. The steps are illustrated in Figure 3. <br><br> 20 The tandemly-duplicated template DNA is created by cloning and contains two copies of the gene separated by DNA sequence encoding a linker connecting the original C- and N-terminal ends of the two copies of the gene. Specific primer sets are used to create and amplify a full-length hew 25 N terminus/C-terminus gene from the tandemly-duplicated template DNA. These primers are designed to include appropriate restriction sites which allow for the cloning of the new gene into expression vectors. Typical PCR conditions are one cycle 95°C melting for two minutes; 25 cycles 94°C 3 0 denaturation for one minute, 50°C annealing for one minute and 72°C extension for one minute; plus one cycle 72°C extension for seven minutes. A Perkin Elmer GeneAmp PCR Core Reagents kit (Perkin Elmer Corporation, Norwalk, CT) is used. A 100 ul reaction contains 100 pmole of each primer 35 and one ug of template DNA; and Ix PCR buffer, 200 uM dGTP, <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 65 <br><br> PCT/US96/15774 <br><br> 200 uM dATP, 200 uM dTTP, 200 uM dCTP, 2.5 units AmpliTaq DNA polymerase and 2 mM MgCl2- PCR reactions are performed in a Model 480 DNA thermal cycler (Perkin Elmer Corporation, Norwalk, CT). PCR reactions are purified using a Wizard PCR 5 Preps kit (Promega). <br><br> Cloning of new N-terminus/C-terminus aenes into multifunctional receptor agonist expression vectors. <br><br> 10 The new N-terminus/C-terminus gene is digested with restriction endonucleases to create ends that are compatible to insertion into an expression vector containing another colony stimulating factor gene. This expression vector is likewise digested with restriction endonucleases to form 15 compatible ends. After purification, the gene and the vector DNAs are combined and ligated using T4 DNA ligase. A portion of the ligation reaction is used to transform E. coli. Plasmid DNA is purified and sequenced to confirm the correct insert. The correct clones are grown for protein 20 expression. <br><br> DNA isolation and characterization <br><br> 25 Plasmid DNA can be isolated by a number of different methods and using commercially available kits known to those skilled in the art. A few such methods are shown herein. Plasmid DNA is isolated using the Promega Wizard™ Miniprep kit (Madison, WI), the Qiagen QIAwell Plasmid isolation kits 30 (Chatsworth, CA) or Qiagen Plasmid Midi kit. These kits follow the same general procedure for plasmid DNA isolation. Briefly, cells are pelleted by centrifugation (5000 x g), plasmid DNA released with sequential NaOH/acid treatment, and cellular debris is removed by centrifugation (10000 x 3 5 g). The supernatant (containing the plasmid DNA) is loaded <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 66 <br><br> PCT/US96/15774 <br><br> onto a column containing a DNA-binding resin, the column is washed, and plasmid DNA eluted with TE. After screening for the colonies with the plasmid of interest, the E. coli cells are inoculated into 50-100 mis of LB plus appropriate 5 antibiotic for overnight growth at 37°C in an air incubator while shaking. The purified plasmid DNA is used for DNA sequencing, further restriction enzyme digestion, additional subcloning of DNA fragments and transfection into mammalian, E. coli or other cells. <br><br> 10 <br><br> Sequence confirmation. <br><br> Purified plasmid DNA is resuspended in d^O and quantitated by measuring the absorbance at 260/280 nm in a 15 Bausch and Lomb Spectronic 601 UV spectrometer. DNA samples are sequenced using ABI PRISM™ DyeDeoxy™ terminator sequencing chemistry (Applied Biosystems Division of Perkin Elmer Corporation, Lincoln City, CA) kits (Part Number 401388 or 402078) according to the manufacturers suggested 20 protocol usually modified by the addition of 5% DMSO to the sequencing mixture. Sequencing reactions are performed in a Model 480 DNA thermal cycler (Perkin Elmer Corporation, Norwalk, CT) following the recommended amplification conditions. Samples are purified to remove excess dye 25 terminators with Centri-Sep™ spin columns (Princeton <br><br> Separations, Adelphia, NJ) and lyophilized. Fluorescent dye labeled sequencing reactions are resuspended in deionized formamide, and sequenced on denaturing 4.75% polyacrylamide-8M urea gels using an ABI Model 373A automated DNA 3 0 sequencer. Overlapping DNA sequence fragments are analyzed and assembled into master DNA contigs using Sequencher v2.1 DNA analysis software (Gene Codes Corporation, Ann Arbor, MI) . <br><br> 3 5 Expression of multi-functional receptor agonists in mammalian cells <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 67 <br><br> PCT/US96/15774 <br><br> Mammalian Cell Transfection/Production of Conditioned Media <br><br> The BHK-21 cell line can be obtained from the ATCC 5 (Rockville, MD) . The cells are cultured in Dulbecco's modified Eagle media (DMEM/high-glucose), supplemented to 2 mM (mM) L-glutamine and 10% fetal bovine serum (FBS). This formulation is designated BHK growth media. Selective media is BHK growth media supplemented with 453 units/mL 10 hygromycin B (Calbiochem, San Diego, CA). The BHK-21 cell line was previously stably transfected with the HSV transactivating protein VP16, which transactivates the IE110 promoter found on the plasmid pMON3359 (See Hippenmeyer et al. , Bio/Technology, pp.1037-1041, 1993). The VP16 protein 15 drives expression of genes inserted behind the IE110 promoter. BHK-21 cells expressing the transactivating protein VP16 are designated BHK-VP16. The plasmid pMON1118 (See Highkin et al., Poultry Sci., 70: 970-981, 1991) expresses the hygromycin resistance gene from the SV40 20 promoter. A similar plasmid is available from ATCC, pSV2-hph. <br><br> BHK-VP16 cells are seeded into a 60 millimeter (mm) tissue culture dish at 3 X 10^ cells per dish 24 hours prior to transfection. Cells are transfected for 16 hours in 3 mL 25 of "OPTIMEM"™ (Gibco-BRL, Gaithersburg, MD) containing 10 ug of plasmid DNA containing the gene of interest, 3 ug hygromycin resistance plasmid, pMONlll8, and 80 ug of Gibco-BRL "LIPOFECTAMINE"™ per dish. The media is subsequently aspirated and replaced with 3 mL of growth media. At 48 3 0 hours post-transfection, media from each dish is collected and assayed for activity (transient conditioned media). The cells are removed from the dish by trypsin-EDTA, diluted 1:10 and transferred to 100 mm tissue culture dishes containing•10 mL of selective media. After approximately 7 35 days in selective media, resistant cells grow into colonies <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 68 <br><br> PCT/US96/15774 <br><br> several millimeters in diameter. The colonies are removed from the dish with filter paper (cut to approximately the same size as the colonies and soaked in trypsin/EDTA) and transferred to individual wells of a 24 well plate 5 containing 1 mL of selective media. After the clones are grown to confluence, the conditioned media is re-assayed, and positive clones are expanded into growth media. <br><br> 10 Expression of multi-functional receptor agonists in E. coli <br><br> E. coli strain MON105 or JM101 harboring the plasmid of interest are grown at 37°C in M9 plus casamino acids medium with shaking in a air incubator Model G25 from New Brunswick 15 Scientific (Edison, New Jersey). Growth is monitored at OD600 until it reaches a value of 1.0 at which time Nalidixic acid (10 milligrams/mL) in 0.1 N NaOH is added to a final concentration of 50 ug/mL. The cultures are then shaken at 37°C for three to four additional hours. A high 20 degree of aeration is maintained throughout culture period in order to achieve maximal production of the desired gene product. The cells are examined under a light microscope for the presence of inclusion bodies (IB). One mL aliguots of the culture are removed for analysis of protein content 25 by boiling the pelleted cells, treating them with reducing buffer and electrophoresis via SDS-PAGE (see Maniatis et al. Molecular Cloning: A Laboratory Manual, 1982). The culture is centrifuged (5000 x g) to pellet the cells. <br><br> 30 inclusion Body preparation. Extraction. Refolding. Dialysis. DEAE Chromatography, and Characterization of the multifunctional hematopoietic receptor agonists which accumulate as inclusion bodies in E. coli. <br><br> 35 Isolation of Inclusion Bodies: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 69 <br><br> PCT/US96/15774 <br><br> The cell pellet from a 330 mL E. coli culture is resuspended in 15 mL of sonication buffer (10 mM 2-amino-2-(hydroxymethyl) 1,3-propanediol hydrochloride (Tris-HCl), pH 5 8 . 0 + 1 mM ethylenediaminetetraacetic acid (EDTA). These resuspended cells are sonicated using the microtip probe of a Sonicator Cell Disruptor (Model W-375, Heat Systems-ultrasonics, Inc., Farmingdale, New York). Three rounds of sonication in sonication buffer followed by centrifugation 10 are employed to disrupt the cells and wash the inclusion bodies (IB). The first round of sonication is a 3 minute burst followed by a 1 minute burst, and the final two rounds of sonication are for 1 minute each. <br><br> 15 Extraction and refolding of proteins from inclusion body pellets: <br><br> Following the final centrifugation step, the IB pellet is resuspended in 10 mL of 50 mM Tris-HCl, pH 9.5, 8 M urea 20 and 5 mM dithiothreitol (DTT) and stirred at room temperature for approximately 45 minutes to allow for denaturation of the expressed protein. <br><br> The extraction solution is transferred to a beaker containing 70 mL of 5 mM Tris-HCl, pH 9.5 and 2.3 M urea and 25 gently stirred while exposed to air at 4DC for 18 to 48 hours to allow the proteins to refold. Refolding is monitored by analysis on a Vydac (Hesperia, Ca.) C18 reversed phase high pressure liquid chromatography (RP-HPLC) column (0.46x25 cm). A linear gradient of 40% to 65% 30 acetonitrile, containing 0.1% trifluoroacetic acid (TFA), is employed to monitor the refold. This gradient is developed over 30 minutes at a flow rate of 1.5 mL per minute. Denatured proteins generally elute later in the gradient than the refolded proteins. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 70 <br><br> PCT/US96/15774 <br><br> Purification: <br><br> Following the refold, contaminating E. coli proteins are removed by acid precipitation. The pH of the refold 5 solution is titrated to between pH 5.0 and pH 5.2 using 15% (v/v) acetic acid (HOAc). This solution is stirred at 4°C for 2 hours and then centrifuged for 20 minutes at 12,000 x g to pellet any insoluble protein. <br><br> The supernatant from the acid precipitation step is 10 dialyzed using a Spectra/Por 3 membrane with a molecular weight cut off (MWCO) of 3,500 daltons. The dialysis is against 2 changes of 4 liters (a 50-fold excess) of 10 mM Tris-HCl, pH 8.0 for a total of 18 hours. Dialysis lowers the sample conductivity and removes urea prior to DEAE 15 chromatography. The sample is then centrifuged (20 minutes at 12,000 x g) to pellet any insoluble protein following dialysis. <br><br> A Bio-Rad Bio-Scale DEAE2 column (7 x 52 mm) is used for ion exchange chromatography. The column is equilibrated 20 in a buffer containing 10 mM Tris-HCl, pH 8.0, and a 0-to-500 mM sodium chloride (NaCl) gradient, in equilibration buffer, over 45 column volumes is used to elute the protein. A flow rate of 1.0 mL per minute is used throughout the run. Column fractions (2.0 mL per fraction) are collected across 25 the gradient and analyzed by RP HPLC on a Vydac (Hesperia, <br><br> Ca.) C18 column (0.46 x 25 cm). A linear gradient of 40% to 65% acetonitrile, containing 0.1% trifluoroacetic acid (TFA), is employed. This gradient is developed over 30 minutes at a flow rate of 1.5 mL per minute. Pooled 30 fractions are then dialyzed against 2 changes of 4 liters (50-to-500-fold excess) of 10 mM ammonium acetate (NH4Ac), pH 4.0 for a total of 18 hours. Dialysis is performed using a Spectra/Por 3 membrane with a MWCO of 3,500 daltons. Finally, the sample is sterile filtered using a 0.22jam 35 syringe filter (^iStar LB syringe filter, Costar, Cambridge, <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 71 <br><br> PCT/US96/15774 <br><br> Ma.), and stored at 4°C. <br><br> In some cases the folded proteins can be affinity purified using affinity reagents such as mAbs or receptor subunits attached to a suitable matrix. Alternatively, (or 5 in addition) purification can be accomplished using any of a variety of chromatographic methods such as: ion exchange, gel filtration or hydrophobic chromatography or reversed phase HPLC. <br><br> 10 These and other protein purification methods are described in detail in Methods in Enzymology, Volume 182 'Guide to Protein Purification' edited by Murray Deutscher, Academic Press, San Diego, CA (1990). <br><br> 15 Protein Characterization: <br><br> The purified protein is analyzed by RP-HPLC, electrospray mass spectrometry, and SDS-PAGE. The protein quantitation is done by amino acid composition, RP-HPLC, and <br><br> 20 Bradford protein determination. In some cases tryptic peptide mapping is performed in conjunction with electrospray mass spectrometry to confirm the identity of the protein. <br><br> 25 AML Proliferation Assay for Bioactive Human Interleukin-3 <br><br> The factor-dependent cell line AML 193 was obtained from the American Type Culture Collection (ATCC, Rockville, MD). This cell line, established from a patient with acute myelogenous leukemia, is a growth factor dependent cell line <br><br> 3 0 which displayed enhanced growth in GM-CSF supplemented medium (Lange, B., et al.. Blood 70: 192, 1987; Valtieri, M. , et al., J. Immunol. 138:4042, 1987). The ability of AML 193 cells to proliferate in the presence of human IL-3 has also been documented. (Santoli, D., et al., J. Immunol. <br><br> 35 139: 348, 1987). A cell line variant was used, AML 193 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 72 <br><br> PCT/US96/15774 <br><br> 1.3, which was adapted for long terra growth in IL-3 by washing out the growth factors and starving the cytokine dependent AML 193 cells for growth factors for 24 hours. The cells are then replated at 1x10^ cells/well in a 24 well 5 plate in media containing 100 U/mL IL-3 . It took approximately 2 months for the cells to grow rapidly in IL-3. These cells are maintained as AML 193 1.3 thereafter by supplementing tissue culture medium (see below) with human IL-3 . <br><br> 10 AML 193 1.3 cells are washed 6 times in cold Hanks balanced salt solution (HBSS, Gibco, Grand Island, NY) by centrifuging cell suspensions at 250 x g for 10 minutes followed by decantation of the supernatant. Pelleted cells are resuspended in HBSS and the procedure is repeated until 15 six wash cycles are completed. Cells washed six times by this procedure are resuspended in tissue culture medium at a density ranging from 2 x 105 to 5 x 10^ viable cells/mL. <br><br> This medium is prepared by supplementing Iscove's modified Dulbecco's Medium (IMDM, Hazelton, Lenexa, KS) with albumin, 20 transferrir, lipids and 2-mercaptoethanol. Bovine albumin (Boehringer-Mannheim, Indianapolis, IN) is added at 500 Ug/mL; human transferrin (Boehringer-Mannheim, Indianapolis, IN) is added at 100 ug/mL; soybean lipid (Boehringer-Mannheim, Indianapolis, IN) is added at 50 ^.g/mL; and 2-25 mercaptoethanol (Sigma, St. Louis, MO) is added at 5 x 10~5 M. <br><br> Serial dilutions of human interleukin-3 or multifunctional hematopoietic receptor agonist proteins are made in triplicate series in tissue culture medium supplemented 30 as stated above in 96 well Costar 3596 tissue culture plates. Each well contained 50 (il of medium containing interleukin-3 or multi-functional hematopoietic receptor agonist proteins once serial dilutions are completed. <br><br> Control wells contained tissue culture medium alone 35 (negative control). AML 193 1.3 cell suspensions prepared <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 73 <br><br> PCT/US96/15774 <br><br> as above are added to each well by pipetting 50 |xl (2.5 x 104 cells) into each well. Tissue culture plates are incubated at 37°C with 5% C02 in humidified air for 3 days. On day 3, 0.5 |lCi ^H-thymidine (2 Ci/mM, New England 5 Nuclear, Boston, MA) is added in 50 Jil of tissue culture medium. Cultures are incubated at 37°C with 5% C02 in humidified air for 18-24 hours. Cellular DNA is harvested onto glass filter mats (Pharmacia LKB, Gaitnersburg, MD) using a TOMTEC cell harvester (TOMTEC, Orange, CT) which 10 utilized a water wash cycle followed by a 70% ethanol wash cycle. Filter mats are allowed to air dry and then placed into sample bags to which scintillation fluid (Scintiverse II, Fisher Scientific, St. Louis, MO or BetaPlate Scintillation Fluid, Pharmacia LKB, Gaithersburg, MD) is 15 added. Beta emissions of samples from individual tissue culture wells are counted in a LKB BetaPlate model 1205 scintillation counter (Pharmacia LKB, Gaithersburg, MD) and data is expressed as counts per minute of 3n-thymidine incorporated into cells from each tissue culture well. 20 Activity of each human interleukin-3 preparation or multifunctional hematopoietic receptor agonist protein preparation is quantitated by measuring cell proliferation (3H-thymidine incorporation) induced by graded concentrations of interleukin-3 or multi-functional 25 hematopoietic receptor agonist. Typically, concentration ranges from 0.05 pM - 10^ pM are quantitated in these assays. Activity is determined by measuring the dose of interleukin-3 or multi-functional hematopoietic receptor agonist protein which provides 50% of maximal proliferation 30 (ec50 = 0.5 x (maximum average counts per minute of 3h- <br><br> thymidine incorporated per well among triplicate cultures of all concentrations of interleukin-3 tested - background proliferation measured by ^H-thymidine incorporation observed in triplicate cultures lacking interleukin-3). 35 This ec50 value is also equivalent to 1 unit of bioactivity. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 74 <br><br> PCT/US96/15774 <br><br> Every assay is performed with native interleukin-3 as a reference standard so that relative activity levels could be assigned. <br><br> Typically, the multi-functional hematopoietic receptor 5 agonist proteins were tested in a concentration range of 2000 pM to 0.06 pM titrated in serial 2 fold dilutions. <br><br> Activity for each sample was determined by the concentration which gave 50% of the maximal response by fitting a four-parameter logistic model to the data. It was 10 observed that the upper plateau (maximal response) for the sample and the standard with which it was compared did not differ. Therefore relative potency calculation for each sample was determined from EC50 estimations for the sample and the standard as indicated above. AML 19 3.1.3 cells 15 proliferate in response to hIL-3, hGM-CSF and hG-CSF. <br><br> Therefore the following additional assays were performed for some samples to demonstrate that the G-CSF receptor agonist portion of the multi-functional hematopoietic receptor agonist proteins was active. The proliferation assay was 20 performed with the multi-functional hematopoietic receptor agonist plus and minus neutralizing monoclonal antibodies to the hIL-3 receptor agonist portion. In addition, a fusion molecule with the factor Xa cleavage site was cleaved then purified and the halves of the molecule were assayed for 25 proliferative activity. These experiments showed that both components of the multi-functional hematopoietic receptor agonist proteins were active. <br><br> TF1 c-mpl licrand dependent proliferation assay <br><br> 30 <br><br> The c-mpl ligand proliferative activity can be assayed using a subclone of the pluripotential human cell line TF1 (Kitamura et al., J. Cell Physiol 140:323-334. [1989]). TF1 cells are maintained in h-IL3 (100 U/mL). To establish a 35 sub-clone responsive to c-mpl ligand, cells are maintained <br><br> Printed from Mimosa 08:37.19 <br><br> WO 97/12985 <br><br> 75 <br><br> PCT/US96/15774 <br><br> in passage media containing 10% supernatant from BHK cells transfected with the gene expressing the 1-153 form of c-mpl ligand (pMON26448). Most of the cells die, but a subset of cells survive. After dilution cloning, a c-mpl ligand 5 responsive clone is selected, and these cells are split into passage media to a density of 0.3 x 10^ cells/mL the day prior to at-say set-up. Passage media for these cells is the following: RPMI 1640 (Gibco), 10% FBS (Harlan, Lot #91206), 10% c-mpl ligand supernatant from transfected BHK cells, 1 10 mM sodium pyruvate (Gibco), 2 mM glutamine (Gibco), and 100 ug/mL penicillin-streptomycin (Gibco). The next day, cells are harvested and washed twice in RPMI or IMDM media with a final wash in the ATL, or assay media. ATL medium consists of the following:IMDM (Gibco), 500 ug/mL of bovine serum 15 albumin, 100 ug/mL of human transferrin, 50 ug/mL soybean lipids, 4 x 10-8M beta-mercaptoethanol and 2 mL of A9909 (Sigma, antibiotic solution) per 1000 mL of ATL. Cells are diluted in assay media to a final density of 0.25 x 10® cells/mL in a 96-well low evaporation plate (Costar) to a 20 final volume of 50 ul. Transient supernatants (conditioned media) from transfected clones are added at a volume of 50 ul as duplicate samples at a final concentration of 50% and diluted three-fold to a final dilution of 1.8%. Triplicate samples of a dose curve of IL-3 variant pMONl3288 starting 25 at 1 ng/mL and diluted using three-fold dilutions to <br><br> 0.0014ng/mL is included as a positive control. Plates are incubated at 5% CO2 and 37° C. At day six of culture, the plate is pulsed with 0.5 Ci of 3H/well (NEN) in a volume of 20 ul/well and allowed to incubate at 5% CO2 and 37° C for 30 four hours. The plate is harvested and counted on a Betaplate counter. <br><br> Other in vitro cell based proliferation assays 3 5 Other in vitro cell based assays, known to those <br><br> Printed from Mimosa 08.37.19 <br><br> WO 97/12985 <br><br> 76 <br><br> PCT/US96/15774 <br><br> skilled in the art, may also be useful to determine the activity of the multi-functional hematopoietic receptor agonists depending on the factors that comprise the molecule in a similar manner as described in the AML 193.1.3 cell 5 proliferation assay. The following are examples of other useful assays. <br><br> TFl proliferation assay: TF1 is a pluripotential human cell line (Kitamura et al., J. Cell Physiol 140:323-334. [1989]) 10 that responds to hIL-3. <br><br> 32D proliferation assay: 32D is a murine IL-3 dependent cell line which does not respond to human IL-3 but does respond to human G-CSF which is not species restricted. <br><br> 15 <br><br> Baf/3 proliferation assay: Baf/3 is a murine IL-3 dependent cell line which does not respond to human IL-3 or human c-mpl ligand but does respond to human G-CSF which is not species restricted. <br><br> 20 <br><br> T1165 proliferation assay: T1165 cells are a IL-6 dependent murine cell line (Nordan et al., 1986) which respond to IL-6 and IL-11. <br><br> 25 Human Plasma Clot meg-CSF Assay: Used to assay megakaryocyte colony formation activity (Mazur et al., 1981). <br><br> Transfected cell lines: <br><br> Cell lines such as the murine Baf/3 cell line can be 30 transfected with a colony stimulating factor receptor, such as the human G-CSF receptor or human c-mpl receptor, which the cell line does not have. These transfected cell lines can be used to determine the activity of the ligand for which the receptor has been transfected into the cell line. 3 5 One such transfected Baf/3 cell line was made by <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 77 <br><br> PCT/US96/15774 <br><br> cloning the cDNA encoding c-mpl from a library made from a c-mpl responsive cell line and cloned into the multiple cloning site of the plasmid pcDNA3 (Invitrogen, San Diego Ca.). Baf/3 cells were transfected with the plasmid via 5 electroporat.ion. The cells were grown under G418 selection in the presence of mouse IL-3 in Wehi conditioned media. Clones were established through limited dilution. <br><br> In a similar manner the human G-CSF receptor can be transfected into the Baf/3 cell line and used to determine 10 the bioactivity of the multi-functional hematopoietic receptor agoinsts. <br><br> Analysis of c-mpl ligand proliferative activity <br><br> 15 Methods <br><br> 1. Bone marrow proliferation assay a. CD34+ Cell Purification: <br><br> 20 Bone narrow aspirates (15-20 mL) were obtained from normal allogeneic marrow donors after informed consent. <br><br> Cells were diluted 1:3 in phosphate buffered saline (PBS, Gibco-BRL), 30 mL were layered over 15 mL Histopaque-1077 (Sigma) and centrifuged for 30 minutes at 300 RCF. The 2 5 mononuclear interface layer was collected and washed in PBS. CD3 4+ cells were enriched from the mononuclear cell preparation using an affinity column per manufacturers instructions (CellPro, Inc, Bothell WA). After enrichment, the purity of CD34+ cells was 70% on average as determined 30 by using flow cytometric analysis using anti-CD34 monoclonal antibody conjugated to fluorescein and anti-CD38 conjugated to phycoerythrin (Becton Dickinson, San Jose CA). <br><br> Cells were resuspended at 40,000 cells/mL in x-Vivo 10 media (Bio-Whittaker, Walkersville, MD) and 1 mL was plated 35 in 12-well tissue culture plates (Costar). The growth <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 78 <br><br> PCT/US96/15774 <br><br> factor rhIL-3 was added at 100 ng/mL (pMON5873) was added to some wells. hIL3 variants were used at 10 ng/mL to 100 ng/mL. Conditioned media from BHK cells transfected with plasmid encoding c-mpl ligand or multi-functional 5 hematopoietic receptor agonists were tested by addition of 100 (Xl of supernatant added to 1 mL cultures (approximately a 10% dilution). Cells were incubated at 37°C for 8-14 days at 5% C02 in a 37°C humidified incubator. <br><br> 10 b. Cell Harvest and Analysis: <br><br> At the end of the culture period a total cell count was obtained for each condition. For fluorescence analysis and ploidy determination cells were washed in megakaryocyte buffer (MK buffer, 13.6 mM sodium citrate, 1 mM 15 theophylline, 2.2 |J.m PGE1, 11 mM glucose, 3% w/v BSA, in PBS, pH 7.4,) (Tomer et al., Blood 70: 1735-1742, 1987) resuspended in 500 |i.l of MK buffer containing anti-CD41a FITC antibody (1:200, AMAC, Westbrook, ME) and washed in MK buffer. For DNA analysis cells were permeablized in MK 20 buffer containing 0.5% Tween 20 (Fisher, Fair Lawn NJ)for 20 min. on ice followed by fixation in 0.5% Tween-20 and 1% paraformaldehyde (Fisher Chemical) for 3 0 minutes followed by incubation in propidium iodide (Calbiochem , La Jolla Ca) (50 fig/mL) with RNA-ase (400 U/mL) in 55% v/v MK buffer 25 (200m0sm) for 1-2 hours on ice. Cells were analyzed on a FACScan or Vantage flow cytometer (Becton Dickinson, San Jose, CA). Green fluorescence (CD41a-FITC) was collected along with linear and log signals for red fluorescence (PI) to determine DNA ploidy. All cells were collected to 30 determine the percent of cells that were CD41+. Data analysis was performed using software by LYSIS (Becton Dickinson, San Jose, CA). Percent of cells expressing the CD41 antigen was obtained from flow cytometry analysis(Percent). Absolute (Abs) number of CD41+ cells/mL 35 was calculated by: (Abs)=(Cell Count)*(Percent)/100. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 79 <br><br> PCT/US96/15774 <br><br> 2. Megakaryocyte fibrin clot assay. <br><br> CD34+ enriched population were isolated as described above. 5 Cells were suspended at 25,000 cells/mL with or without cytokine(s) in a media consisting of a base Iscoves IMDM media supplemented with 0.3% BSA, 0.4mg/mL apo-transferrin, 6.67fiM FeCl2, 25|ig/mL CaCl2, 25fig/mL L-asparagine, 500ng/mL e-amino-n-caproic acid and penicillin/streptomycin. Prior <br><br> 10 to plating into 3 5mm plates, thrombin was added (0.25 <br><br> Units/mL) to initiate clot formation. Cells were incubated at 37°C for 13 days at 5% C02 in a 37°C humidified incubator. <br><br> 15 At the end of the culture period plates were fixed with methanol:acetone (1:3), air dried and stored at -200C until staining. A peroxidase immunocytochemistry staining procedure was used (Zymed, Histostain-SP. San Francisco, CA) using a cocktail of primary monoclonal antibodies consisting 20 of anti-CD41a, CD42 and CD61. Colonies were counted after staining and classified as negative, CFU-MK (small colonies, 1-2 foci and less that approx. 25 cells), BFU-MK (large, multi-foci colonies with &gt; 25 cells) or mixed colonies (mixture of both positive and negative cells. <br><br> 25 <br><br> MethylcellulQse Assay <br><br> This assay reflects the ability of colony stimulating factors to stimulate normal bone marrow cells to produce 30 different types of hematopoietic colonies in vitro (Bradley et al., Aust. Exp Biol. Sci. 44:287-300, 1966), Pluznik et al., J. Cell Comp. Physio 66:319-324, 1965). <br><br> Methods <br><br> 3 5 Approximately 30 mL of fresh, normal, healthy bone marrow <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 80 <br><br> PCT/US96/15774 <br><br> aspirate are obtained from individuals following informed consent. Under sterile conditions samples are diluted 1:5 with a IX PBS {#14040.059 Life Technologies, Gaithersburg, MD.) solution in a 50 mL conical tube (#25339-50 Corning, 5 Corning MD). .Ficoll (Histopaque 1077 Sigma H-8889) is layered under the diluted sample and centrifuged, 300 x g for 30 min. The mononuclear cell band is removed and washed two times in IX PBS and once with 1% BSA PBS (CellPro Co., Bothel, WA). Mononuclear cells are counted and CD34+ cells 10 are selected using the Ceprate LC (CD34) Kit (CellPro Co., Bothel, VJA) column. This fractionation is performed since all stem and progenitor cells within the bone marrow display CD34 surface antigen. <br><br> 15 Cultures are set up in triplicate with a final volume of 1.0 mL in a 35 X 10 mm petri dish (Nunc#174926). Culture medium is purchased from Terry Fox Labs. (HCC-423 0 medium (Terry Fox Labs, Vancouver, B.C., Canada) and erythropoietin (Amgen, Thousand Oaks, CA.) is added to the culture media. 20 3,000-10,000 CD34+ cells are added per dish. Recombinant IL-3, purified from mammalian cells or E. coli, and multifunctional hematopoietic receptor agonist proteins, in conditioned media from transfected mammalian cells or purified from conditioned media from transfected mammalian 25 cells or E. coli, are added to give final concentrations ranging from .001 nM to 10 nM. Recombinant hIL-3, GM-CSF, c-mpl ligand and multi-functional hematopoietic receptor agonist are supplied in house. G-CSF (Neupogen) is from Amgen (Thousand Oaks Calf.). Cultures are resuspended using 30 a 3cc syringe and 1.0 mL is dispensed per dish. Control <br><br> (baseline response) cultures received no colony stimulating factors. Positive control cultures received conditioned media (PHA stimulated human cells: Terry Fox Lab. H2400). Cultures are incubated at 37°C, 5% C02 in humidified air. 35 Hematopoietic colonies which are defined as greater than 50 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 81 <br><br> PCT/US96/15774 <br><br> cells are counted on the day of peak response (days 10-11) using a Nikon inverted phase microscope with a 40x objective combination. Groups of cells containing fewer than 50 cells are referred to as clusters. Alternatively colonies can be 5 identified by spreading the colonies on a slide and stained or they can be picked, resuspended and spun onto cytospin slides for staining. <br><br> Human Cord Blood Hemopoietic Growth Factor Assays <br><br> 10 <br><br> Bone marrow cells are traditionally used for in vitro assays of hematopoietic colony stimulating factor (CSF) activity. However, human bone marrow is not always available, and there is considerable variability between donors. Umbilical 15 cord blood is comparable to bone marrow as a source of hematopoietic stem cells and progenitors (Broxmeyer et al., PNAS USA 89:4109-113, 1992: Mayani et al., Blood 81:3252-3258, 1993). In contrast to bone marrow, cord blood is more readily available on a regular basis. There is also a 20 potential to reduce assay variability by pooling cells obtained fresh from several donors, or to create a bank of cryopreserved cells for this purpose. By modifying the culture conditions, and/or analyzing for lineage specific markers, it is be possible to assay specifically for 25 granulocyte / macrophage colonies (CFU-GM), for megakaryocyte CSF activity, or for high proliferative potential colony forming cell (HPP-CFC) activity. <br><br> Methods <br><br> 30 Mononuclear cells (MNC) are isolated from cord blood within 24 hr. of collection, using a standard density gradient (1.077 g/mL Histopaque). Cord blood MNC have been further enriched for stem cells and progenitors by several procedures, including immunomagnetic selection for CD14-, 35 CD34 + cells; panning for SBA-, CD34+ fraction using coated <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 g2 PCT/US96/15774 <br><br> flasks from Applied Immune Science (Santa Clara, CA) ,- and CD34+ selection using a CellPro (Bothell, WA) avidin column. Either freshly isolated or cryopreserved CD34 + cell enriched fractions are used for the assay. Duplicate cultures for 5 each serial dilution of sample (concentration range from 1 pM to 1204 pM) are prepared with 1x104 cells in 1ml of 0.9% methycellulose containing medium without additional growth factors (Methocult H4230 from Stem Cell Technologies, Vancouver, BC.). In some experiments, Methocult H4330 10 containing erythropoietin (EPO) was used instead of Methocult H4230, or Stem Cell Factor (SCF), 50 ng/mL (Biosource International, Camarillo, CA) was added. After culturing for 7-9 days, colonies containing &gt;30 cells are counted. In order to rule out subjective bias in scoring, 15 assays are scored blind. <br><br> Additional details about recombinant DNA methods which may be used to create the variants, express them in bacteria, mammalian cells or insect cells, purification and 20 refold of the desired proteins and assays for determining the bioactvity of the proteins may be found in co-filed Applications WO 95/00646, WO 94/12639, WO 94/12638, WO 95/20976, WO 95/21197, WO 95/20977, WO 95/21254 and US 08/383,035 which are hereby incorporated by reference in 25 their entirety. <br><br> Further details known to those skilled in the art may be found in T. Maniatis, et al., Molecular Cloning. A Laboratory Manual. Cold Spring Harbor Laboratory, 1982) and 30 references cited therein, incorporated herein by reference; and in J. Sambrook, et al., Molecular Cloning. A Laboratory Manual. 2nd edition, Cold Spring Harbor Laboratory, 1989) and references cited therein, incorporated herein by reference. <br><br> 35 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 83 <br><br> PCT/US96/15774 <br><br> TABLE I <br><br> OI.TGONTjrT.EOTIDF.S <br><br> c-mplNcol <br><br> ACGTCCATGGCNTCNCCNGCNCCNCCTGCTTGTGCACTCCGAGTC (SEQ ID NO:13) <br><br> N=A,C,G or T <br><br> 10 <br><br> 15 <br><br> 20 <br><br> 25 <br><br> 30 <br><br> 35 <br><br> 40 <br><br> 45 <br><br> 50 <br><br> Ecorapl c-raplHindlll <br><br> 4L-5' <br><br> 4L-3 ' <br><br> 5L-5' <br><br> 5L-3' <br><br> 8L-5' <br><br> 8L-3 ' <br><br> 31-5' <br><br> 31-3' <br><br> 35-5' <br><br> 35-3' <br><br> 39-5' <br><br> 39-3 ' <br><br> 43-5' <br><br> 43-3 ' <br><br> 45-5' <br><br> 45-3' <br><br> 49-5' <br><br> 49-3' <br><br> ATGCACGAATTCCCTGACGCAGAGGGTGGA (SEQ ID NO: 14) ^ <br><br> TGACAAGCTTACCTGACGCAGAGGGTGGACCCT (SEQ ID NO:15) <br><br> AATTCGGCAA (SEQ ID NO:16) <br><br> CATGTTGCCG (SEQ ID NO:17) <br><br> AATTCGGCGGCAA (SEQ ID NO:18) <br><br> CATGTTGCCGCCG (SEQ ID NO:19) <br><br> AATTCGGCGGCAACGGCGGCAA (SEQ ID NO:20) <br><br> CATGTTGCCGCCGTTGCCGCCG (SEQ ID NO:21) <br><br> CGATCCATGGAGGTTCACCCTTTGCCT (SEQ ID NO:22) <br><br> GATCAAGCTTATGGGCACTGGCTCAGTCT (SEQ ID NO:23) <br><br> CGATACATGTTGCCTACACCTGTCCTG (SEQ ID NO:24) <br><br> GATCAAGCTTAAGGGTGAACCTCTGGGCA (SEQ ID NO:25) <br><br> CGATCCATGGTCCTGCTGCCTGCTGTG (SEQ ID NO:26) <br><br> GATCAAGCTTAAGGTGTAGGCAAAGGGTG (SEQ ID NO:27) <br><br> CGATCCATGGCTGTGGACTTTAGCTTGGGA (SEQ ID NO:28) <br><br> GATCAAGCTTAAGGCAGCAGGACAGGTGT (SEQ ID NO:29) CGATCCATGGACTTTAGCTTGGGAGAA (SEQ ID NO:30) GATCAAGCTTACACAGCAGGCAGCAGGAC (SEQ ID NO:31) CGATCCATGGGAGAATGGAAAACCCAG (SEQ ID NO:32) GATCAAGCTTACAAGCTAAAGTCCACAGC (SEQ ID NO:33) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 84 <br><br> PCT/US96/15774 <br><br> 82-5' 82-3' <br><br> 5 <br><br> 109-5' 109-3' 10 116-5' 116-3 ' <br><br> 15 120-5' <br><br> 120-3 ' 20 123-5' <br><br> 123-3 ' 25 126-5' <br><br> 30 <br><br> 126-3■ <br><br> SYNNOXA1.REQ <br><br> CGATCCATGGGACCCACTTGCCTCTCA (SEQ ID NO:34) <br><br> GATCAAGCTTACAGTTGTCCCCGTGCTGC (SEQ ID NO:35) <br><br> CAGTCCATGGGAACCCAGCTTCCTCCA (SEQ ID NO:36) <br><br> GATCAAGCTTAAAGGAGGCTCTGCAGGGC (SEQ ID NO:37) <br><br> CGATCCATGGGCAGGACCACAGCTCAC (SEQ ID NO:38) <br><br> GATCAAGCTTACTGTGGAGGAAGCTGGGTT (SEQ ID NO:39) <br><br> CGATCCATGGCTCACAAGGATCCCAATGCC (SEQ ID NO:40) <br><br> GATCAAGCTTATGTGGTCCTGCCCTGTGG (SEQ ID NO:41) <br><br> CGATCCATGGATCCCAATGCCATCTTCCTG (SEQ ID NO:42) <br><br> GATCAAGCTTACTTGTGAGCTGTGGTCCT (SEQ ID NO:43) <br><br> CGATCCATGGCCATCTTCCTGAGCTTCCAA (SEQ ID NO:44) <br><br> GATCAAGCTTAATTGGGATCCTTGTGAGCTGT (SEQ ID NO:45) <br><br> AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC TCC (SEQ ID NO:46) <br><br> 3 5 SYNNOXA2.REQ CCGGGGAGCC TCCACCGCCC TCTACGTACT GTTGAGCCTG <br><br> CGCGTTCTCC AAGGTTTTCA GATAGAAGGT CAGTTTACGA CGG (SEQ ID NO:47) <br><br> Llsyn.for GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT^ <br><br> 40 CTAACTGCTC TATAATGAT (SEQ ID NO:48) <br><br> Llsyn.rev CGATCATTAT AGAGCAGTTA GAGCCACCAC CCTGTTGTTC <br><br> CTGCGCTTGC TCAAGG (SEQ ID NO:49) <br><br> 45 L3syn.for GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT <br><br> CTGGCGGTGG CAGCGGCGGC GGTTCTAACT GCTCTATAAT GAT (SEQ ID NO:50) <br><br> L3 syn.rev CGATCATTAT AGAGCAGTTA GAACCGCCGC CGCTGCCACC <br><br> 50 GCCAGAGCCA CCACCCTGTT GTTCCTGCGC TTGCTCAAGG <br><br> (SEQ ID NO:51) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 85 <br><br> PCT/US96/15774 <br><br> 15 <br><br> 20 <br><br> 30 <br><br> 40 <br><br> 45 <br><br> 35start.seq <br><br> 3 4rev.seq <br><br> 70start.seq <br><br> 10 69rev.seq <br><br> 91start.seq <br><br> 90rev.seq lOlstart.seq lOOrev.seq <br><br> 25 L-llstart.seq <br><br> L-llstop.seq <br><br> P-blstart.seq P-blstop.seq 35 39start.seq <br><br> 38stop.Seq <br><br> 97 start.seq <br><br> 96stop.Seq <br><br> 126start.seq <br><br> 50 125stop.Seq <br><br> GATCGACCAT GGCTCTGGAC CCGAACAACC TC (SEQ ID NO:52) <br><br> CTCGATTACG TACAAAGGTG CAGGTGGT (SEQ ID NO:53) <br><br> GATCGACCAT GGCTAATGCA TCAGGTATTG AG (SEQ ID NO:54) <br><br> CTCGATTACG TATTCTAAGT TCTTGACA (SEQ ID NO:55) <br><br> GATCGACCAT GGCTGCACCC TCTCGACATC CA (SEQ ID NO:56) <br><br> CTCGATTACG TAGGCCGTGG CAGAGGGC (SEQ ID NO:57) <br><br> GATCGACCAT GGCTGCAGGT GACTGGCAAG AA (SEQ ID NO:58) <br><br> CTCGATTACG TACTTGATGA TGATTGGA (SEQ ID NO:59) <br><br> GCTCTGAGAG CCGCCAGAGC CGCCAGAGGG CTGCGCAAGG TGGCGTAGAA CGCG (SEQ ID NO:60) <br><br> CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAG (SEQ ID NO:61) <br><br> GGGCTGCGCA AGGTGGCG (SEQ ID NO:62) <br><br> ACACCATTGG GCCCTGCCAG C (SEQ ID NO:63) <br><br> GATCGACCAT GGCTTACAAG CTGTGCCACC CC (SEQ ID NO:64) <br><br> CGATCGAAGC TTATTAGGTG GCACACAGCT TCTCCT (SEQ ID NO:65) <br><br> GATCGACCAT GGCTCCCGAG TTGGGTCCCA CC (SEQ ID NO:66) <br><br> CGATCGAAGC TTATTAGGAT ATCCCTTCCA GGGCCT (SEQ ID NO:67) <br><br> GATCGACCAT GGCTATGGCC CCTGCCCTGC AG (SEQ ID NO:68) <br><br> CGATCGAAGC TTATTATCCC AGTTCTTCCA TCTGCT (SEQ ID NO:69) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 86 <br><br> PCT/US96/15774 <br><br> 133start.seq 132stop.seq <br><br> 5 <br><br> 142start.seq <br><br> 10 141stop.Seq <br><br> GLYXAl 15 GLYXA2 <br><br> lGGGSfor <br><br> 20 lGGGSrev <br><br> Synnoxal.req <br><br> 25 <br><br> Synnoxa2.req <br><br> GATCGACCAT GGCTACCCAG GGTGCCATGC CG (SEQ ID NO:70) <br><br> CGATCGAAGC TTATTAGGGC TGCAGGGCAG GGGCCA (SEQ ID NO:71) <br><br> GATCGACCAT GGCTTCTGCT TTCCAGCGCC GG (SEQ ID NO:72) <br><br> CGATCGAAGC TTATTAGGCG AAGGCCGGCA TGGCAC (SEQ ID NO:73) <br><br> GTAGAGGGCG GTGGAGGCTC C (SEQ ID NO:74) <br><br> CCGGGGAGCC TCCACCGCCC TCTAC (SEQ ID NO:75) <br><br> TTCTACGCCA CCTTGCGCAG CCCGGCGGCG GCTCTGACAT GTCTACACCA TTG (SEQ ID NO:76) <br><br> CAATGGTGTA GACATGTCAG AGCCGCCGCC GGGCTGCGCA AGGTGGCGTA GAA (SEQ ID NO:77) <br><br> AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC TCC (SEQ ID NO:240) <br><br> CCGGGGAGCC TCCACCGCCC TCTACGTACT GTTGAGCCTG CGCGTTCTCC AAGGTTTTCA GATAGAAGGT CAGTTTACGA CGG (SEQ ID NO:241) <br><br> 30 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 87 <br><br> PCT/US96/15774 <br><br> TASLE 2 <br><br> GENE SEQUENCES <br><br> 5 pMC&gt;N3 0304 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT 10 ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGT (SEQ ID NO:78) <br><br> 15 <br><br> pMON2 6458 <br><br> TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT 20 GTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTG CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCA CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAA CTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCT <br><br> 2 5 CACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGT <br><br> TTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTC (SEQ ID NO:79) <br><br> pMON2 854 8 <br><br> 3 0 TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT <br><br> gtccttcacagcagactgagccagtgcccagaggttcaccctttgcctacacctgtcctg ctgcctgctgtggactttagcttgggagaatggaaaacccagatggaggagaccaaggca caggacattctgggagcagtgacccttctgctggagggagtgatggcagcacggggacaa ctgggacccacttgcctctcatccctcctggggcagctttctggacaggtccgtctcctc <br><br> 3 5 CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCT <br><br> cacaaggatcccaatgccatcttcctgagcttccaacacctgctccgaggaaaggtgcgt ttcctgatgcttgtaggagggtccaccctctgcgtcagggaattcggcggcaacatggcg tctcccgctccgcctgcttgtgacctccgagtcctcagtaaactgcttcgtgactcccat gtccttcacagcagactgagccagtgcccagaggttcaccctttgcctacacctgtcctg <br><br> 4 0 CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCA <br><br> CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAA CTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGGGCAGGACCACAGCTCACAAGGATCCC AATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTT 45 GTAGGAGGGTCCACCCTCTGCGTCAGG (SEQ ID NO:80) <br><br> pMON2 8500 <br><br> TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT 50 GTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTG CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCA <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 88 <br><br> PCT/US96/15774 <br><br> CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAA CTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCT CACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGT 5 TTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCT CCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTC CTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTG CCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAG GACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG 10 GGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTT GGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCAC AAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTC CTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG (SEQ ID NO:81) <br><br> 15 pMON28501 <br><br> TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT GTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACGTGTCCTG CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCA 2 0 CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAA CTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCT CACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGT TTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCG <br><br> 2 5 TCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT <br><br> GTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTG CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCA CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAA CTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC <br><br> 3 0 CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCT <br><br> CACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGT TTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG (SEQ ID NO:82) <br><br> PMON2 8502 <br><br> 35 <br><br> TCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT GTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTG CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCA CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAA 40 CTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCT CACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGT TTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGC AACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGT 45 GACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACA CCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAG ACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCA CGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTC CGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGG 5 0 ACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGA AAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG (SEQ ID NO:83) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 89 <br><br> PCT/US96/15774 <br><br> Syntanl <br><br> 5 <br><br> 1 <br><br> CATGGCTAAC <br><br> 51 <br><br> GACCACCTGC <br><br> 101 <br><br> TCTATCCTGA <br><br> 151 <br><br> AAGGGCTGTC <br><br> 201 <br><br> GTAATCTCCA <br><br> 10 <br><br> 251 <br><br> CCAATCATCA <br><br> 301 <br><br> GTTCTATCTG <br><br> 351 <br><br> CTAACTGCTC <br><br> 401 <br><br> CCTGCACCTT <br><br> 451 <br><br> CCTGATGGAC <br><br> 15 <br><br> 501 <br><br> CTGTCAAGAA <br><br> 551 <br><br> CTCCAACCAT <br><br> 601 <br><br> CATCATCAAG <br><br> 651 <br><br> ATCTGGTTAC (SEQ ID NO: <br><br> 20 <br><br> Syntan3 <br><br> 1 <br><br> CATGGCTAAC <br><br> 25 <br><br> 51 <br><br> GACCACCTGC <br><br> 101 <br><br> TCTATCCTGA <br><br> 151 <br><br> AAGGGCTGTC <br><br> 201 <br><br> GTAATCTCCA <br><br> 251 <br><br> CCAATCATCA <br><br> 30 <br><br> 301 <br><br> GTTCTATCTG <br><br> 351 <br><br> CTGGCGGTGG <br><br> 401 <br><br> attatacatc <br><br> 451 <br><br> CCTCAATGAC <br><br> 501 <br><br> CAAACCTGGA <br><br> 35 <br><br> 551 <br><br> GGTATTGAGG <br><br> 601 <br><br> GGCCGCACCC <br><br> 651 <br><br> AATTCCGGGA <br><br> 701 <br><br> GAACAACAGT <br><br> 40 <br><br> pMON31104 <br><br> 1 <br><br> ATGGCTCTGG <br><br> 51 <br><br> GGACCGAAAC <br><br> 101 <br><br> AGAACTTAGA <br><br> 151 <br><br> CCATGTCTGC <br><br> 201 <br><br> CAAGGCAGGT <br><br> 251 <br><br> TTACCCTTGA <br><br> 301 <br><br> ATAATGATCG <br><br> 351 <br><br> GTACGTAGAG <br><br> 401 <br><br> CTACTATCAA <br><br> 451 <br><br> ATGGCTACCC <br><br> TGCTCTATAA TGATCGATGA ACCTTTGCTG GACCCGAACA TGGACCGAAA CCTTCGACTT AAGAACTTAG AAAATGCATC ACCATGTCTG CCCTCTGCCA TCAAGGCAGG TGACTGGCAA GTTACCCTTG AGCAAGCGCA TATAATGATC GATGAAATTA TGCTGGACCC GAACAACCTC CGAAACCTTC GACTTCCAAA CTTAGAAAAT GCATCAGGTA GTCTGCCCTC TGCCACGGCC GCAGGTGACT GGCAAGAATT CCTTGAGCAA GCGCAGGAAC 84) <br><br> TGCTCTATAA TGATCGATGA ACCTTTGCTG GACCCGAACA TGGACCGAAA CCTTCGACTT AAGAACTTAG AAAATGCATC ACCATGTCTG CCCTCTGCCA TCAAGGCAGG TGACTGGCAA GTTACCCTTG AGCAAGCGCA CAGCGGCGGC GGTTCTAACT ACTTAAAGAG ACCACCTGCA GAAGACGTCT CTATCCTGAT GAGCTTCGTA AGGGCTGTCA CAATTCTTCG TAATCTCCAA TCTCGACATC CAATCATCAT AAAACTGACG TTCTATCTGG AC (SEQ ID NO:85) <br><br> ACCCGAACAA CCTCAATGAC CTTCGACTTC CAAACCTGGA AAATGCATCA GGTATTGAGG CCTCTGCCAC GGCCGCACCC GACTGGCAAG AATTCCGGGA GCAAGCGCAG GAACAACAGG ATGAAATTAT ACATCACTTA GGCGGTGGAG GCTCCCCGGG CCCGTCTCCT CCGTCTAAAG AGGGTGCCAT GCCGGCCTTC <br><br> AATTATACAT CACTTAAAGA ACCTCAATGA CGAAGACGTC CCAAACCTGG AGAGCTTCGT AGGTATTGAG GCAATTCTTC CGGCCGCACC CTCTCGACAT GAATTCCGGG AAAAACTGAC GGAACAACAG GGTGGTGGCT TACATCACTT AAAGAGACCA AATGACGAAG ACGTCTCTAT CCTGGAGAGC TTCGTAAGGG TTGAGGCAAT TCTTCGTAAT GCACCCTCTC GACATCCAAT CCGGGAAAAA CTGACGTTCT AACAGTAC <br><br> AATTATACAT CACTTAAAGA ACCTCAATGA CGAAGACGTC CCAAACCTGG AGAGCTTCGT AGGTATTGAG GCAATTCTTC CGGCCGCACC CTCTCGACAT GAATTCCGGG AAAAACTGAC GGAACAACAG GGTGGTGGCT GCTCTATAAT GATCGATGAA CCTTTGCTGG ACCCGAACAA GGACCGAAAC CTTCGACTTC AGAACTTAGA AAATGCATCA CCATGTCTGC CCTCTGCCAC CAAGGCAGGT GACTGGCAAG TTACCCTTGA GCAAGCGCAG <br><br> GAAGACGTCT CTATCCTGAT GAGCTTCGTA AGGGCTGTCA CAATTCTTCG TAATCTCCAA TCTCGACATC CAATCATCAT AAAACTGACG TTCTATCTGG GTGGTGGCTC TAACTGCTCT AAGAGACCAC CTGCACCTTT TGAACCGTCT GGTCCAATCT AATCTCATAA ATCTCCAAAC GCCTCTGCTT TCCAGCGCCG <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 90 <br><br> PCT/US96/15774 <br><br> 10 <br><br> 501 551 601 651 701 751 801 851 901 951 <br><br> GGCAGGAGGG CGTACCGCGT TCTCAGAGCT CGATGGCGCA ACCCCGAGGA CCCCTGAGCT CCAACTCCAT AAGGGATATC GTCGCCGACT GGCCCCTGCC <br><br> GTCCTGGTTG TCTACGCCAC TCCTGCTCAA GCGCTCCAGG GCTGGTGCTG CCTGCCCCAG AGCGGCCTTT CCCCGAGTTG TTGCCACCAC CTGCAGCCCT <br><br> CTAGCCATCT CTTGCGCAGC GTCTTTAGAG AGAAGCTGTG CTCGGACACT CCAGGCCCTG TCCTCTACCA GGTCCCACCT CATCTGGCAG AATAA (SEQ <br><br> GCAGAGCTTC CCTCTGGCGG CAAGTGAGAA TGCCACCTAC CTCTGGGCAT CAGCTGGCAG GGGGCTCCTG TGGACACACT CAGATGGAAG ID NO:86) <br><br> CTGGAGGTGT CTCTGGCGGC AGATCCAGGG AAGCTGTGCC CCCCTGGGCT GCTGCTTGAG CAGGCCCTGG GCAGCTGGAC AACTGGGAAT <br><br> pMON31105 <br><br> 15 <br><br> 1 <br><br> ATGGCTAATG <br><br> 51 <br><br> TCTGCCCTCT <br><br> 101 <br><br> CAGGTGACTG <br><br> 151 <br><br> CTTGAGCAAG <br><br> 201 <br><br> GATCGATGAA <br><br> 20 <br><br> 251 <br><br> ACCCGAACAA <br><br> 301 <br><br> CTTCGACTTC <br><br> 351 <br><br> ATACGTAGAG <br><br> 401 <br><br> CTACTATCAA <br><br> 451 <br><br> ATGGCTACCC <br><br> 25 <br><br> 501 <br><br> GGCAGGAGGG <br><br> 551 <br><br> CGTACCGCGT <br><br> 601 <br><br> TCTCAGAGCT <br><br> 651 <br><br> CGATGGCGCA <br><br> 701 <br><br> ACCCCGAGGA <br><br> 30 <br><br> 751 <br><br> CCCCTGAGCT <br><br> 801 <br><br> CCAACTCCAT <br><br> 851 <br><br> AAGGGATATC <br><br> 901 <br><br> GTCGCCGACT <br><br> 951 <br><br> GGCCCCTGCC <br><br> 35 <br><br> CATCAGGTAT TGAGGCAATT GCCACGGCCG CACCCTCTCG GCAAGAATTC CGGGAAAAAC CGCAGGAACA ACAGGGTGGT ATTATACATC ACTTAAAGAG CCTCAATGAC GAAGACGTCT CAAACCTGGA GAGCTTCGTA GGCGGTGGAG GCTCCCCGGG CCCGTCTCCT CCGTCTAAAG AGGGTGCCAT GCCGGCCTTC GTCCTGGTTG CTAGCCATCT TCTACGCCAC CTTGCGCAGC TCCTGCTCAA GTCTTTAGAG GCGCTCCAGG AGAAGCTGTG GCTGGTGCTG CTCGGACACT CCTGCCCCAG CCAGGCCCTG AGCGGCCTTT TCCTCTACCA CCCCGAGTTG GGTCCCACCT TTGCCACCAC CATCTGGCAG CTGCAGCCCT AATAA (SEQ <br><br> CTTCGTAATC TCCAACCATG ACATCCAATC ATCATCAAGG TGACGTTCTA TCTGGTTACC GGCTCTAACT GCTCTATAAT ACCACCTGCA CCTTTGCTGG CTATCCTGAT GGACCGAAAC AGGGCTGTCA AGAACTTAGA TGAACCGTCT GGTCCAATCT AATCTCATAA ATCTCCAAAC GCCTCTGCTT TCCAGCGCCG GCAGAGCTTC CTGGAGGTGT CCTCTGGCGG CTCTGGCGGC CAAGTGAGAA AGATCCAGGG TGCCACCTAC AAGCTGTGCC CTCTGGGCAT CCCCTGGGCT CAGCTGGCAG GCTGCTTGAG GGGGCTCCTG CAGGCCCTGG TGGACACACT GCAGCTGGAC CAGATGGAAG AACTGGGAAT ID NO:87) <br><br> pMON31106 <br><br> 1 <br><br> ATGGCTGCAC <br><br> 40 <br><br> 51 <br><br> AGAATTCCGG <br><br> 101 <br><br> AGGAACAACA <br><br> 151 <br><br> ATACATCACT <br><br> 201 <br><br> CAATGACGAA <br><br> 251 <br><br> ACCTGGAGAG <br><br> 45 <br><br> 301 <br><br> ATTGAGGCAA <br><br> 351 <br><br> CTACGTAGAG <br><br> 401 <br><br> CTACTATCAA <br><br> 451 <br><br> ATGGCTACCC <br><br> 501 <br><br> GGCAGGAGGG <br><br> 50 <br><br> 551 <br><br> CGTACCGCGT <br><br> 601 <br><br> TCTCAGAGCT <br><br> 651 <br><br> CGATGGCGCA <br><br> CCTCTCGACA TCCAATCATC GAAAAACTGA CGTTCTATCT GGGTGGTGGC TCTAACTGCT TAAAGAGACC ACCTGCACCT GACGTCTCTA TCCTGATGGA CTTCGTAAGG GCTGTCAAGA TTCTTCGTAA TCTCCAACCA GGCGGTGGAG GCTCCCCGGG CCCGTCTCCT CCGTCTAAAG AGGGTGCCAT GCCGGCCTTC GTCCTGGTTG CTAGCCATCT TCTACGCCAC CTTGCGCAGC TCCTGCTCAA GTCTTTAGAG GCGCTCCAGG AGAAGCTGTG <br><br> ATCAAGGCAG GTGACTGGCA GGTTACCCTT GAGCAAGCGC CTATAATGAT CGATGAAATT TTGCTGGACC CGAACAACCT CCGAAACCTT CGACTTCCAA ACTTAGAAAA TGCATCAGGT TGTCTGCCCT CTGCCACGGC TGAACCGTCT GGTCCAATCT AATCTCATAA ATCTCCAAAC GCCTCTGCTT TCCAGCGCCG GCAGAGCTTC CTGGAGGTGT CCTCTGGCGG CTCTGGCGGC CAAGTGAGAA AGATCCAGGG TGCCACCTAC AAGCTGTGCC <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 91 <br><br> PCT/US96/15774 <br><br> 701 ACCCCGAGGA 751 CCCCTGAGCT 801 CCAACTCCAT <br><br> 851 AAGGGATATC 901 GTCGCCGACT <br><br> 951 GGCCCCTGCC <br><br> gctggtgctg cctgccccag agcggccttt ccccgagttg ttgccaccac ctgcagccct ctcggacact ccaggccctg tcctctacca ggtcccacct catctggcag aataa (seq ctctgggcat cagctggcag ggggctcctg tggacacact cagatggaag id no:88) <br><br> cccctgggct gctgcttgag caggccctgg gcagctggac aactgggaat pMON31107 <br><br> 10 <br><br> 1 <br><br> atggctgcag <br><br> 51 <br><br> ggttaccctt <br><br> 101 <br><br> ctataatgat <br><br> 151 <br><br> ttgctggacc <br><br> 15 <br><br> 201 <br><br> ccgaaacctt <br><br> 251 <br><br> acttagaaaa <br><br> 301 <br><br> tgtctgccct <br><br> 351 <br><br> gtacgtagag <br><br> 401 <br><br> ctactatcaa <br><br> 20 <br><br> 451 <br><br> atggctaccc <br><br> 501 <br><br> ggcaggaggg <br><br> 551 <br><br> cgtaccgcgt <br><br> 601 <br><br> tctcagagct <br><br> 651 <br><br> cgatggcgca <br><br> 25 <br><br> 701 <br><br> accccgagga <br><br> 751 <br><br> cccctgagct <br><br> 801 <br><br> ccaactccat <br><br> 851 <br><br> aagggatatc <br><br> 901 <br><br> gtcgccgact <br><br> 30 <br><br> 951 <br><br> ggcccctgcc gtgactggca agaattccgg gagcaagcgc aggaacaaca cgatgaaatt atacatcact cgaacaacct caatgacgaa cgacttccaa acctggagag tgcatcaggt attgaggcaa ctgccacggc cgcaccctct ggcggtggag gctccccggg cccgtctcct ccgtctaaag agggtgccat gccggccttc gtcctggttg ctagccatct tctacgccac cttgcgcagc tcctgctcaa gtctttagag gcgctccagg agaagctgtg gctggtgctg ctcggacact cctgccccag ccaggccctg agcggccttt tcctctacca ccccgagttg ggtcccacct ttgccaccac catctggcag ctgcagccct aataa (seq gaaaaactga cgttctatct gggtggtggc tctaactgct taaagagacc acctgcacct gacgtctcta tcctgatgga cttcgtaagg gctgtcaaga ttcttcgtaa tctccaacca cgacatccaa tcatcatcaa tgaaccgtct ggtccaatct aatctcataa atctccaaac gcctctgctt tccagcgccg gcagagcttc ctggaggtgt cctctggcgg ctctggcggc caagtgagaa agatccaggg tgccacctac aagctgtgcc ctctgggcat cccctgggct cagctggcag gctgcttgag ggggctcctg caggccctgg tggacacact gcagctggac cagatggaag aactgggaat ID NO:89) <br><br> PMON31108 <br><br> 35 <br><br> 1 <br><br> atggctctgg <br><br> 51 <br><br> ggaccgaaac <br><br> 101 <br><br> agaacttaga <br><br> 151 <br><br> ccatgtctgc <br><br> 201 <br><br> caaggcaggt <br><br> 40 <br><br> 251 <br><br> ttacccttga <br><br> 301 <br><br> agcggcggcg <br><br> 351 <br><br> cttaaagaga <br><br> 401 <br><br> cgggtgaacc <br><br> 451 <br><br> aaagaatctc <br><br> 45 <br><br> 501 <br><br> cttcgcctct <br><br> 551 <br><br> atctgcagag <br><br> 601 <br><br> cagccctctg <br><br> 651 <br><br> agagcaagtg <br><br> 701 <br><br> tgtgtgccac <br><br> 50 <br><br> 751 <br><br> cactctctgg <br><br> 801 <br><br> cctgcagctg <br><br> 851 <br><br> accaggggct acccgaacaa cctcaatgac cttcgacttc caaacctgga aaatgcatca ggtattgagg cctctgccac ggccgcaccc gactggcaag aattccggga gcaagcgcag gaacaacagg gttctaactg ctctataatg ccacctgcac ctttgtacgt gtctggtcca atctctacta ataaatctcc aaacatggct gctttccagc gccgggcagg cttcctggag gtgtcgtacc gcggctctgg cggctctcag agaaagatcc agggcgatgg ctacaagctg tgccaccccg gcatcccctg ggctcccctg gcaggctgct tgagccaact cctgcaggcc ctggaaggga gaagacgtct ctatcctgat gagcttcgta agggctgtca caattcttcg taatctccaa tctcgacatc caatcatcat aaaactgacg ttctatctgg gtggtggctc tggcggtggc atcgatgaaa ttatacatca agagggcggt ggaggctccc tcaacccgtc tcctccgtct acccagggtg ccatgccggc aggggtcctg gttgctagcc gcgttctacg ccaccttgcg agcttcctgc tcaagtcttt cgcagcgctc caggagaagc aggagctggt gctgctcgga agctcctgcc ccagccaggc ccatagcggc cttttcctct tatcccccga gttgggtccc <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 92 <br><br> PCT/US96/15774 <br><br> 901 ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG 951 GCAGCAGATG GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA (SEQ ID NO:90) <br><br> pMON31109 <br><br> 10 <br><br> 15 <br><br> 20 <br><br> 25 <br><br> 30 <br><br> 35 <br><br> 40 <br><br> 45 <br><br> 50 <br><br> 1 51 101 151 201 251 301 351 401 451 501 551 601 651 701 751 801 851 901 951 <br><br> atggctaatg tctgccctct caggtgactg cttgagcaag cggcggttct agagaccacc gtctctatcc cgtaagggct cgggtgaacc aaagaatctc cttcgcctct atctgcagag cagccctctg agagcaagtg tgtgtgccac cactctctgg cctgcagctg accaggggct accttggaca gcagcagatg (SEQ ID NO <br><br> catcaggtat gccacggccg gcaagaattc cgcaggaaca aactgctcta tgcacctttg tgatggaccg gtcaagaact gtctggtcca ataaatctcc gctttccagc cttcctggag gcggctctgg agaaagatcc ctacaagctg gcatcccctg gcaggctgct cctgcaggcc cactgcagct gaagaactgg : 91) <br><br> TGAGGCAATT CACCCTCTCG CGGGAAAAAC ACAGGGTGGT TAATGATCGA CTGGACCCGA AAACCTTCGA TAGAATACGT ATCTCTACTA AAACATGGCT GCCGGGCAGG GTGTCGTACC CGGCTCTCAG AGGGCGATGG TGCCACCCCG GGCTCCCCTG TGAGCCAACT CTGGAAGGGA GGACGTCGCC GAATGGCCCC <br><br> cttcgtaatc acatccaatc tgacgttcta ggctctggcg tgaaattata acaacctcaa cttccaaacc agagggcggt tcaacccgtc acccagggtg aggggtcctg gcgttctacg agcttcctgc cgcagcgctc aggagctggt agctcctgcc ccatagcggc tatcccccga gactttgcca tgccctgcag tccaaccatg atcatcaagg tctggttacc gtggcagcgg catcacttaa tgacgaagac tggagagctt ggaggctccc tcctccgtct ccatgccggc gttgctagcc ccaccttgcg tcaagtcttt caggagaagc gctgctcgga ccagccaggc cttttcctct gttgggtccc ccaccatctg ccctaataa pMON31110 <br><br> 1 51 101 151 201 251 301 351 401 451 501 551 601 651 701 751 801 851 901 951 <br><br> atggctgcac agaattccgg aggaacaaca tgctctataa acctttgctg tggaccgaaa aagaacttag accatgtctg cgggtgaacc aaagaatctc cttcgcctct atctgcagag cagccctctg agagcaagtg tgtgtgccac cactctctgg cctgcagctg accaggggct accttggaca gcagcagatg (SEQ ID NO <br><br> cctctcgaca gaaaaactga gggtggtggc tgatcgatga gacccgaaca ccttcgactt aaaatgcatc ccctctgcca gtctggtcca ataaatctcc gctttccagc cttcctggag gcggctctgg agaaagatcc ctacaagctg gcatcccctg gcaggctgct cctgcaggcc cactgcagct gaagaactgg : 92) <br><br> TCCAATCATC <br><br> CGTTCTATCT <br><br> TCTGGCGGTG <br><br> AATTATACAT <br><br> ACCTCAATGA <br><br> CCAAACCTGG <br><br> AGGTATTGAG <br><br> CGGCCTACGT <br><br> ATCTCTACTA <br><br> AAACATGGCT <br><br> GCCGGGCAGG <br><br> GTGTCGTACC <br><br> CGGCTCTCAG <br><br> AGGGCGATGG <br><br> TGCCACCCCG <br><br> GGCTCCCCTG <br><br> TGAGCCAACT <br><br> CTGGAAGGGA <br><br> GGACGTCGCC <br><br> GAATGGCCCC <br><br> atcaaggcag ggttaccctt gcagcggcgg cacttaaaga cgaagacgtc agagcttcgt gcaattcttc agagggcggt tcaacccgtc acccagggtg aggggtcctg gcgttctacg agcttcctgc cgcagcgctc aggagctggt agctcctgcc ccatagcggc tatcccccga gactttgcca tgccctgcag <br><br> GTGACTGGCA GAGCAAGCGC CGGTTCTAAC GACCACCTGC TCTATCCTGA AAGGGCTGTC GTAATCTCCA GGAGGCTCCC TCCTCCGTCT CCATGCCGGC GTTGCTAGCC CCACCTTGCG TCAAGTCTTT CAGGAGAAGC GCTGCTCGGA CCAGCCAGGC CTTTTCCTCT GTTGGGTCCC CCACCATCTG CCCTAATAA <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 93 <br><br> PCT/US96/15774 <br><br> PM0N31111 <br><br> 10 <br><br> 15 <br><br> 20 <br><br> 1 51 101 151 201 251 301 351 401 451 501 551 601 651 701 751 801 851 901 951 <br><br> ATGGCTGCAG GGTTACCCTT GCAGCGGCGG CACTTAAAGA CGAAGACGTC AGAGCTTCGT GCAATTCTTC CTCTCGACAT CGGGTGAACC AAAGAATCTC CTTCGCCTCT ATCTGCAGAG CAGCCCTCTG AGAGCAAGTG TGTGTGCCAC CACTCTCTGG CCTGC /.GCTG ACCAGGGGCT ACCTTGGACA GCAGCAGATG (SEQ ID NO <br><br> GTGACTGGCA GAGCAAGCGC CGGTTCTAAC GACCACCTGC TCTATCCTGA AAGGGCTGTC GTAATCTCCA CCAATCATCA GTCTGGTCCA ATAAATCTCC GCTTTCCAGC CTTCCTGGAG GCGGCTCTGG AGAAAGATCC CTACAAGCTG GCATCCCCTG GCAGGCTGCT CCTGCAGGCC CACTGCAGCT GAAGAACTGG : 93) <br><br> AGAATTCCGG AGGAACAACA TGCTCTATAA ACCTTTGCTG TGGACCGAAA AAGAACTTAG ACCATGTCTG TCAAGTACGT ATCTCTACTA AAACATGGCT GCCGGGCAGG GTGTCGTACC CGGCTCTCAG AGGGCGATGG TGCCACCCCG GGCTCCCCTG TGAGCCAACT CTGGAAGGGA GGACGTCGCC GAATGGCCCC <br><br> GAAAAACTGA GGGTGGTGGC TGATCGATGA GACCCGAACA CCTTCGACTT AAAATGCATC CCCTCTGCCA AGAGGGCGGT TCAACCCGTC ACCCAGGGTG AGGGGTCCTG GCGTTCTACG AGCTTCCTGC CGCAGCGCTC AGGAGCTGGT AGCTCCTGCC CCATAGCGGC TATCCCCCGA GACTTTGCCA TGCCCTGCAG <br><br> 2 5 pMON13182 <br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC <br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC <br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA <br><br> 3 0 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG <br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC <br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA <br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT <br><br> 3 51 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC <br><br> 3 5 401 ACAAGCTGTG CCACCCCGAG GAGCTGGTGC TGCTCGGACA <br><br> 451 ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC <br><br> 501 AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC <br><br> 551 TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC <br><br> 601 CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC <br><br> 40 651 AGAACTGGGA ATGGCCCCTG CCCTGCAGCC CACCCAGGGT <br><br> 701 CCTTCGCCTC TGCTTTCCAG CGCCGGGCAG GAGGGGTCCT <br><br> 751 CATCTGCAGA GCTTCCTGGA GGTGTCGTAC CGCGTTCTAC <br><br> 801 GCAGCCCTCT GGCGGCTCTG GCGGCTCTCA GAGCTTCCTG <br><br> 851 TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT <br><br> 45 901 CTGTGTGCCA CCTAATAA (SEQ ID NO:94) <br><br> CGTTCTATCT TCTGGCGGTG AATTATACAT ACCTCAATGA CCAAACCTGG AGGTATTGAG CGGCCGCACC GGAGGCTCCC TCCTCCGTCT CCATGCCGGC GTTGCTAGCC CCACCTTGCG TCAAGTCTTT CAGGAGAAGC GCTGCTCGGA CCAGCCAGGC CTTTTCCTCT GTTGGGTCCC CCACCATCTG CCCTAATAA <br><br> ACTTAAAGAG GAAGACGTCT GAGCTTCGTA CAATTCTTCG TCTCGACATC AAAACTGACG ACGTAGAGGG AACATGGCTT CTCTCTGGGC TGCAGCTGGC CAGGGGCTCC CTTGGACACA AGCAGATGGA GCCATGCCGG GGTTGCTAGC GCCACCTTGC CTCAAGTCTT CCAGGAGAAG <br><br> PMON13183 <br><br> 50 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG <br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT <br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 94 <br><br> PCT/US96/15774 <br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG <br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC <br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG <br><br> 3 01 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG <br><br> 5 3 51 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC <br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTACAAG <br><br> 451 CTGTGCCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC <br><br> 501 CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT <br><br> 551 GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG <br><br> 10 601 GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA <br><br> 651 GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC <br><br> 701 TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GCCGGCCTTC <br><br> 751 GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT <br><br> 801 GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC <br><br> 15 851 CCTCTGGCGG CTCTGGCGGC TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG <br><br> 901 CAAGTGAGAA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG <br><br> 951 TGCCACCTAA TAA (SEQ ID NO:95) <br><br> 20 pMONl3184 <br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG <br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT <br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA <br><br> 25 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG <br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC <br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG <br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG <br><br> 351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC <br><br> 30 401 CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT <br><br> 451 GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT <br><br> 501 GCAGCCCACC CAGGGTGCCA TGCCGGCCTT CGCCTCTGCT TTCCAGCGCC <br><br> 551 GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT CCTGGAGGTG <br><br> 601 TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCTCTGGCG GCTCTGGCGG <br><br> 3 5 651 CTCTCAGAGC TTCCTGCTCA AGTCTTTAGA GCAAGTGAGA AAGATCCAGG <br><br> 701 GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CAAGCTGTGC <br><br> 751 CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC <br><br> 801 TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA <br><br> 851 GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG 40 901 GAAGGGATAT CCTAATAA (SEQ ID NO:96) <br><br> PMON13185 <br><br> 45 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG <br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT <br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA <br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG <br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC <br><br> 50 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG <br><br> 3 01 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG <br><br> 3 51 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 95 PCT/US96/15774 <br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCCCGAG <br><br> 451 TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC <br><br> 501 CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC <br><br> 551 CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA <br><br> 5 601 GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA <br><br> 651 CCGCGTTCTA CGCCACCTTG CGCAGCCCTC TGGCGGCTCT GGCGGCTCTC <br><br> 701 AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG TGAGAAAGAT CCAGGGCGAT <br><br> 751 GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC <br><br> 801 CGAGGAGCTG GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC <br><br> 10 851 TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA <br><br> 901 CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG 951 GATATCCTAA TAA (SEQ ID NO:97) <br><br> 15 pMONl3186 <br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG <br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT <br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA <br><br> 20 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG <br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC <br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG <br><br> 3 01 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG <br><br> 3 51 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA <br><br> 25 401 TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CTTCGCCTCT <br><br> 451 GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC ATCTGCAGAG <br><br> 501 CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG CAGCCCTCTG <br><br> 551 GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG <br><br> 601 AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC <br><br> 3 0 651 CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG <br><br> 701 GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG <br><br> 751 GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT ACCAGGGGCT <br><br> 801 CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC ACCTTGGACA <br><br> 851 CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG <br><br> 3 5 901 GAAGAACTGG GATAATAA (SEQ ID NO:98) <br><br> PMON13187 <br><br> 40 <br><br> 1 <br><br> ATGGCTAACT <br><br> 51 <br><br> ACCACCTGCA <br><br> 101 <br><br> CTATCCTGAT <br><br> 151 <br><br> AGGGCTGTCA <br><br> 201 <br><br> TAATCTCCAA <br><br> 45 <br><br> 251 <br><br> CAATCATCAT <br><br> 301 <br><br> TTCTATCTGG <br><br> 351 <br><br> CGGTGGAGGC <br><br> 401 <br><br> CGTCTCCTCC <br><br> 451 <br><br> CCTGCCCTGC <br><br> 50 <br><br> 501 <br><br> CCAGCGCCGG <br><br> 551 <br><br> TGGAGGTGTC <br><br> 601 <br><br> TCTGGCGGCT <br><br> GCTCTATAAT GATCGATGAA CCTTTGCTGG ACCCGAACAA GGACCGAAAC CTTCGACTTC AGAACTTAGA AAATGCATCA CCATGTCTGC CCTCTGCCAC CAAGGCAGGT GACTGGCAAG TTACCCTTGA GCAAGCGCAG TCCCCGGGTG AACCGTCTGG GTCTAAAGAA TCTCATAAAT AGCCCACCCA GGGTGCCATG GCAGGAGGGG TCCTGGTTGC GTACCGCGTT CTACGCCACC CTCAGAGCTT CCTGCTCAAG <br><br> ATTATACATC ACTTAAAGAG CCTCAATGAC GAAGACGTCT CAAACCTGGA GAGCTTCGTA GGTATTGAGG CAATTCTTCG GGCCGCACCC TCTCGACATC AATTCCGGGA AAAACTGACG GAACAACAGT ACGTAGAGGG TCCAATCTCT ACTATCAACC CTCCAAACAT GGCTATGGCC CCGGCCTTCG CCTCTGCTTT TAGCCATCTG CAGAGCTTCC TTGCGCAGCC CTCTGGCGGC TCTTTAGAGC AAGTGAGAAA <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 96 <br><br> PCT/US96/15774 <br><br> 651 GATCCAGGGC <br><br> 701 AGCTGTGCCA <br><br> 751 CCCTGGGCTC <br><br> 801 CTGCTTGAGC <br><br> 851 AGGCCCTGGA <br><br> 901 CAGCTGGACG <br><br> 951 ACTGGGATAA <br><br> GATGGCGCAG CCCCGAGGAG CCCTGAGCTC CAACTCCATA AGGGATATCC TCGCCGACTT <br><br> CGCTCCAGGA CTGGTGCTGC CTGCCCCAGC GCGGCCTTTT CCCGAGTTGG TGCCACCACC <br><br> GAAGCTGTGT TCGGACACTC CAGGCCCTGC CCTCTACCAG GTCCCACCTT ATCTGGCAGC <br><br> GCCACCTACA TCTGGGCATC AGCTGGCAGG GGGCTCCTGC GGACACACTG AGATGGAAGA <br><br> TAA (SEQ ID NO:99] <br><br> 10 pMONl3188 <br><br> 1 <br><br> ATGGCTAACT <br><br> 51 <br><br> ACCACCTGCA <br><br> 101 <br><br> CTATCCTGAT <br><br> 15 <br><br> 151 <br><br> AGGGCTGTCA <br><br> 201 <br><br> TAATCTCCAA <br><br> 251 <br><br> CAATCATCAT <br><br> 301 <br><br> TTCTATCTGG <br><br> 351 <br><br> CGGTGGAGGC <br><br> 20 <br><br> 401 <br><br> CCCAGGGTGC <br><br> 451 <br><br> GGGGTCCTGG <br><br> 501 <br><br> CGTTCTACGC <br><br> 551 <br><br> GCTTCCTGCT <br><br> 601 <br><br> GCAGCGCTCC <br><br> 25 <br><br> 651 <br><br> GGAGCTGGTG <br><br> 701 <br><br> GCTCCTGCCC <br><br> 751 <br><br> CATAGCGGCC <br><br> 801 <br><br> ATCCCCCGAG <br><br> 851 <br><br> ACTTTGCCAC <br><br> 30 <br><br> 901 <br><br> GCCCTGCAGC <br><br> GCTCTATAAT GATCGATGAA CCTTTGCTGG ACCCGAACAA GGACCGAAAC CTTCGACTTC AGAACTTAGA AAATGCATCA CCATGTCTGC CCTCTGCCAC CAAGGCAGGT GACTGGCAAG TTACCCTTGA GCAAGCGCAG TCCCCGGGTG GTGGTTCTGG CATGCCGGCC TTCGCCTCTG TTGCTAGCCA TCTGCAGAGC CACCTTGCGC AGCCCTCTGG CAAGTCTTTA GAGCAAGTGA AGGAGAAGCT GTGTGCCACC CTGCTCGGAC ACTCTCTGGG CAGCCAGGCC CTGCAGCTGG TTTTCCTCTA CCAGGGGCTC TTGGGTCCCA CCTTGGACAC CACCATCTGG CAGCAGATGG CCTAATAA (SEQ ID NO:l <br><br> ATTATACATC ACTTAAAGAG CCTCAATGAC GAAGACGTCT CAAACCTGGA GAGCTTCGTA GGTATTGAGG CAATTCTTCG GGCCGCACCC TCTCGACATC AATTCCGGGA AAAACTGACG GAACAACAGT ACGTAGAGGG CGGCGGCTCC AACATGGCTA CTTTCCAGCG CCGGGCAGGA TTCCTGGAGG TGTCGTACCG CGGCTCTGGC GGCTCTCAGA GAAAGATCCA GGGCGATGGC TACAAGCTGT GCCACCCCGA CATCCCCTGG GCTCCCCTGA CAGGCTGCTT GAGCCAACTC CTGCAGGCCC TGGAAGGGAT ACTGCAGCTG GACGTCGCCG AAGAACTGGG AATGGCCCCT <br><br> &gt;0) <br><br> PMON13189 <br><br> 35 <br><br> 1 <br><br> ATGGCTAACT <br><br> 51 <br><br> ACCACCTGCA <br><br> 101 <br><br> CTATCCTGAT <br><br> 151 <br><br> AGGGCTGTCA <br><br> 201 <br><br> TAATCTCCAA <br><br> 40 <br><br> 251 <br><br> CAATCATCAT <br><br> 301 <br><br> TTCTATCTGG <br><br> 351 <br><br> CGGTGGAGGC <br><br> 401 <br><br> CGTCTCCTCC <br><br> 451 <br><br> GGTGCCATGC <br><br> 45 <br><br> 501 <br><br> CCTGGTTGCT <br><br> 551 <br><br> TACGCCACCT <br><br> 601 <br><br> CTGCTCAAGT <br><br> 651 <br><br> GCTCCAGGAG <br><br> 701 <br><br> TGGTGCTGCT <br><br> 50 <br><br> 751 <br><br> TGCCCCAGCC <br><br> 801 <br><br> CGGCCTTTTC <br><br> 851 <br><br> CCGAGTTGGG <br><br> GCTCTATAAT GATCGATGAA CCTTTGCTGG ACCCGAACAA GGACCGAAAC CTTCGACTTC AGAACTTAGA AAATGCATCA CCATGTCTGC CCTCTGCCAC CAAGGCAGGT GACTGGCAAG TTACCCTTGA GCAAGCGCAG TCCCCGGGTG AACCGTCTGG GTCTAAAGAA TCTCATAAAT CGGCCTTCGC CTCTGCTTTC AGCCATCTGC AGAGCTTCCT TGCGCAGCCC TCTGGCGGCT CTTTAGAGCA AGTGAGAAAG AAGCTGTGTG CCACCTACAA CGGACACTCT CTGGGCATCC AGGCCCTGCA GCTGGCAGGC CTCTACCAGG GGCTCCTGCA TCCCACCTTG GACACACTGC <br><br> ATTATACATC ACTTAAAGAG CCTCAATGAC GAAGACGTCT CAAACCTGGA GAGCTTCGTA GGTATTGAGG CAATTCTTCG GGCCGCACCC TCTCGACATC AATTCCGGGA AAAACTGACG GAACAACAGT ACGTAGAGGG TCCAATCTCT ACTATCAACC CTCCAAACAT GGCTACCCAG CAGCGCCGGG CAGGAGGGGT GGAGGTGTCG TACCGCGTTC CTGGCGGCTC TCAGAGCTTC ATCCAGGGCG ATGGCGCAGC GCTGTGCCAC CCCGAGGAGC CCTGGGCTCC CCTGAGCTCC TGCTTGAGCC AACTCCATAG GGCCCTGGAA GGGATATCCC AGCTGGACGT CGCCGACTTT <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 97 <br><br> PCT/US96/1S774 <br><br> 901 GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT 951 GCAGCCCTAA TAA (SEQ ID NO:101) <br><br> 5 pMONl3190 <br><br> 1 <br><br> ATGGCTAACT <br><br> 51 <br><br> ACCACCTGCA <br><br> 101 <br><br> CTATCCTGAT <br><br> 10 <br><br> 151 <br><br> AGGGCTGTCA <br><br> 201 <br><br> TAATCTCCAA <br><br> 251 <br><br> CAATCATCAT <br><br> 301 <br><br> TTCTATCTGG <br><br> 351 <br><br> CGGTGGAGGC <br><br> 15 <br><br> 401 <br><br> CTGCTTTCCA <br><br> 451 <br><br> AGCTTCCTGG <br><br> 501 <br><br> TGGCGGCTCT <br><br> 551 <br><br> TGAGAAAGAT <br><br> 601 <br><br> ACCTACAAGC <br><br> 20 <br><br> 651 <br><br> GGGCATCCCC <br><br> 701 <br><br> TGGCAGGCTG <br><br> 751 <br><br> CTCCTGCAGG <br><br> 801 <br><br> CACACTGCAG <br><br> 851 <br><br> TGGAAGAACT <br><br> 25 <br><br> 901 <br><br> CCGGCCTTCG <br><br> GCTCTATAAT GATCGATGAA CCTTTGCTGG ACCCGAACAA GGACCGAAAC CTTCGACTTC AGAACTTAGA AAATGCATCA CCATGTCTGC CCTCTGCCAC CAAGGCAGGT GACTGGCAAG TTACCCTTGA GCAAGCGCAG TCCCCGGGTG GTGGTTCTGG GCGCCGGGCA GGAGGGGTCC AGGTGTCGTA CCGCGTTCTA GGCGGCTCTC AGAGCTTCCT CCAGGGCGAT GGCGCAGCGC TGTGCCACCC CGAGGAGCTG TGGGCTCCCC TGAGCTCCTG CTTGAGCCAA CTCCATAGCG CCCTGGAAGG GATATCCCCC CTGGACGTCG CCGACTTTGC GGGAATGGCC CCTGCCCTGC CCTAATAA (SEQ ID NO:1 <br><br> ATTATACATC ACTTAAAGAG CCTCAATGAC GAAGACGTCT CAAACCTGGA GAGCTTCGTA GGTATTGAGG CAATTCTTCG GGCCGCACCC TCTCGACATC AATTCCGGGA AAAACTGACG GAACAACAGT ACGTAGAGGG CGGCGGCTCC AACATGGCTT TGGTTGCTAG CCATCTGCAG CGCCACCTTG CGCAGCCCTC GCTCAAGTCT TTAGAGCAAG TCCAGGAGAA GCTGTGTGCC GTGCTGCTCG GACACTCTCT CCCCAGCCAG GCCCTGCAGC GCCTTTTCCT CTACCAGGGG GAGTTGGGTC CCACCTTGGA CACCACCATC TGGCAGCAGA AGCCCACCCA GGGTGCCATG )2&gt; <br><br> PMON13191 <br><br> 30 <br><br> 1 <br><br> ATGGCTAACT <br><br> 51 <br><br> ACCACCTGCA <br><br> 101 <br><br> CTATCCTGAT <br><br> 151 <br><br> AGGGCTGTCA <br><br> 201 <br><br> TAATCTCCAA <br><br> 35 <br><br> 251 <br><br> CAATCATCAT <br><br> 301 <br><br> TTCTATCTGG <br><br> 351 <br><br> CGGTGGAGGC <br><br> 401 <br><br> CGTCTCCTCC <br><br> 451 <br><br> TTCCAGCGCC <br><br> 40 <br><br> 501 <br><br> CCTGGAGGTG <br><br> 551 <br><br> GCTCTGGCGG <br><br> 601 <br><br> AAGATC C AGG <br><br> 651 <br><br> CAAGCTGTGC <br><br> 701 <br><br> TCCCCTGGGC <br><br> 45 <br><br> 751 <br><br> GGCTGCTTGA <br><br> 801 <br><br> GCAGGCCCTG <br><br> 851 <br><br> TGCAGCTGGA <br><br> 901 <br><br> GAACTGGGAA <br><br> 951 <br><br> CTTCGCCTAA <br><br> 50 <br><br> PMON13192 <br><br> GCTCTATAAT GATCGATGAA CCTTTGCTGG ACCCGAACAA GGACCGAAAC CTTCGACTTC AGAACTTAGA AAATGCATCA CCATGTCTGC CCTCTGCCAC CAAGGCAGGT GACTGGCAAG TTACCCTTGA GCAAGCGCAG TCCCCGGGTG AACCGTCTGG GTCTAAAGAA TCTCATAAAT GGGCAGGAGG GGTCCTGGTT TCGTACCGCG TTCTACGCCA CTCTCAGAGC TTCCTGCTCA GCGATGGCGC AGCGCTCCAG CACCCCGAGG AGCTGGTGCT TCCCCTGAGC TCCTGCCCCA GCCAACTCCA TAGCGGCCTT GAAGGGATAT CCCCCGAGTT CGTCGCCGAC TTTGCCACCA TGGCCCCTGC CCTGCAGCCC TAA (SEQ ID NO:103) <br><br> ATTATACATC ACTTAAAGAG CCTCAATGAC GAAGACGTCT CAAACCTGGA GAGCTTCGTA GGTATTGAGG CAATTCTTCG GGCCGCACCC TCTCGACATC AATTCCGGGA AAAACTGACG GAACAACAGT ACGTAGAGGG TCCAATCTCT ACTATCAACC CTCCAAACAT GGCTTCTGCT GCTAGCCATC TGCAGAGCTT CCTTGCGCAG CCCTCTGGCG AGTCTTTAGA GCAAGTGAGA GAGAAGCTGT GTGCCACCTA GCTCGGACAC TCTCTGGGCA GCCAGGCCCT GCAGCTGGCA TTCCTCTACC AGGGGCTCCT GGGTCCCACC TTGGACACAC CCATCTGGCA GCAGATGGAA ACCCAGGGTG CCATGCCGGC <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 98 <br><br> PCT/US96/15774 <br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG <br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT <br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA <br><br> 5 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG <br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC <br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG <br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG <br><br> 351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT <br><br> 10 401 ACAAGCTGTG CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC <br><br> 451 ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC <br><br> 501 AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC <br><br> 551 TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA <br><br> 601 CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA <br><br> 15 651 AGAACTGGGA ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG <br><br> 701 CCTTCGCCTC TGCTTTCCAG CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC <br><br> 751 CATCTGCAGA GCTTCCTGGA GGTGTCGTAC CGCGTTCTAC GCCACCTTGC <br><br> 801 GCAGCCCACA CCATTGGGCC CTGCCAGCTC CCTGCCCCAG AGCTTCCTGC <br><br> 851 TCAAGTCTTT AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC <br><br> 20 901 CAGGAGAAGC TGTGTGCCAC CTAATAA (SEQ ID NO:104) <br><br> pMONl3193 <br><br> 25 <br><br> 30 <br><br> 35 <br><br> 40 <br><br> 45 <br><br> 1 51 101 151 201 251 301 351 401 451 501 551 601 651 701 751 801 851 901 951 <br><br> ATGGCTAACT ACCACCTGCA CTATCCTGAT AGGGCTGTCA TAATCTCCAA CAATCATCAT TTCTATCTGG CGGTGGAGGC CGTCTCCTCC CTGTGCCACC CTGGGCTCCC GCTTGAGCCA GCCCTGGAAG GCTGGACGTC TGGGAATGGC GCCTCTGCTT GCAGAGCTTC CCACACCATT TCTTTAGAGC GAAGCTGTGT <br><br> GCTCTATAAT CCTTTGCTGG GGACCGAAAC AGAACTTAGA CCATGTCTGC CAAGGCAGGT TTACCCTTGA TCCCCGGGTG GTCTAAAGAA CCGAGGAGCT CTGAGCTCCT ACTCCATAGC GGATATCCCC GCCGACTTTG CCCTGCCCTG TCCAGCGCCG CTGGAGGTGT GGGCCCTGCC AAGTGAGAAA GCCACCTAAT <br><br> GATCGATGAA ACCCGAACAA CTTCGACTTC AAATGCATCA CCTCTGCCAC GACTGGCAAG GCAAGCGCAG AACCGTCTGG TCTCATAAAT GGTGCTGCTC GCCCCAGCCA GGCCTTTTCC CGAGTTGGGT CCACCACCAT CAGCCCACCC GGCAGGAGGG CGTACCGCGT AGCTCCCTGC GATCCAGGGC AA (SEQ ID <br><br> ATTATACATC CCTCAATGAC CAAACCTGGA GGTATTGAGG GGCCGCACCC AATTCCGGGA GAACAACAGT TCCAATCTCT CTCCAAACAT GGACACTCTC GGCCCTGCAG TCTACCAGGG CCCACCTTGG CTGGCAGCAG AGGGTGCCAT GTCCTGGTTG TCTACGCCAC CCCAGAGCTT GATGGCGCAG NO:105) <br><br> ACTTAAAGAG GAAGACGTCT GAGCTTCGTA CAATTCTTCG TCTCGACATC AAAACTGACG ACGTAGAGGG ACTATCAACC GGCTTACAAG TGGGCATCCC CTGGCAGGCT GCTCCTGCAG ACACACTGCA ATGGAAGAAC GCCGGCCTTC CTAGCCATCT CTTGCGCAGC CCTGCTCAAG CGCTCCAGGA <br><br> pMON2 5190 <br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG <br><br> 50 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT <br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA <br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 99 <br><br> PCT/US96/15774 <br><br> 201 <br><br> TAATCTCCAA <br><br> 251 <br><br> CAATCATCAT <br><br> 301 <br><br> TTCTATCTGG <br><br> 351 <br><br> CGGTGGAGGC <br><br> 5 <br><br> 401 <br><br> CCGAGTTGGG <br><br> 451 <br><br> GCCACCACCA <br><br> 501 <br><br> GCAGCCCACC <br><br> 551 <br><br> GGGCAGGAGG <br><br> 601 <br><br> TCGTACCGCG <br><br> 10 <br><br> 651 <br><br> CAGCTCCCTG <br><br> 701 <br><br> AGATCCAGGG <br><br> 751 <br><br> AAGCTGTGCC <br><br> 801 <br><br> CCCCTGGGCT <br><br> 851 <br><br> GCTGCTTGAG <br><br> 15 <br><br> 901 <br><br> CAGGCCCTGG <br><br> CCATGTCTGC CCTCTGCCAC CAAGGCAGGT GACTGGCAAG TTACCCTTGA GCAAGCGCAG TCCCCGGGTG GTGGTTCTGG TCCCACCTTG GACACACTGC TCTGGCAGCA GATGGAAGAA CAGGGTGCCA TGCCGGCCTT GGTCCTGGTT GCTAGCCATC TTCTACGCCA CCTTGCGCAG CCCCAGAGCT TCCTGCTCAA CGATGGCGCA GCGCTCCAGG ACCCCGAGGA GCTGGTGCTG CCCCTGAGCT CCTGCCCCAG CCAACTCCAT AGCGGCCTTT AAGGGATATC CTAATAA <br><br> GGCCGCACCC TCTCGACATC AATTCCGGGA AAAACTGACG <br><br> GAACAACAGT ACGTAGAGGG <br><br> CGGCGGCTCC AACATGGCTC <br><br> AGCTGGACGT CGCCGACTTT <br><br> CTGGGAATGG CCCCTGCCCT <br><br> CGCCTCTGCT TTCCAGCGCC TGCAGAGCTT CCTGGAGGTG CCCACACCAT TGGGCCCTGC GTCTTTAGAG CAAGTGAGAA <br><br> AGAAGCTGTG TGCCACCTAC CTCGGACACT CTCTGGGCAT CCAGGCCCTG CAGCTGGCAG TCCTCTACCA GGGGCTCCTG !Q ID NO: 106) <br><br> pMON2 5191 <br><br> 20 <br><br> 1 <br><br> ATGGCTAACT <br><br> 51 <br><br> ACCACCTGCA <br><br> 101 <br><br> CTATCCTGAT <br><br> 151 <br><br> AGGGCTGTCA <br><br> 201 <br><br> TAATCTCCAA <br><br> 25 <br><br> 251 <br><br> CAATCATCAT <br><br> 301 <br><br> TTCTATCTGG <br><br> 351 <br><br> CGGTGGAGGC <br><br> 401 <br><br> CGTCTCCTCC <br><br> 451 <br><br> TTGGCTCCCA <br><br> 30 <br><br> 501 <br><br> CACCATCTGG <br><br> 551 <br><br> CCACCCAGGG <br><br> 601 <br><br> GGAGGGGTCC <br><br> 651 <br><br> CCGCGTTCTA <br><br> 701 <br><br> CCCTGCCCCA <br><br> 35 <br><br> 751 <br><br> CAGGGCGATG <br><br> 801 <br><br> GTGCCACCCC <br><br> 851 <br><br> GGGCTCCCCT <br><br> 901 <br><br> TTGAGCCAAC <br><br> 951 <br><br> CCTGGAAGGG <br><br> 40 <br><br> pMONl3194 <br><br> 1 <br><br> ATGGCTAACT <br><br> 45 <br><br> 51 <br><br> ACCACCTGCA <br><br> 101 <br><br> CTATCCTGAT <br><br> 151 <br><br> AGGGCTGTCA <br><br> 201 <br><br> TAATCTCCAA <br><br> 251 <br><br> CAATCATCAT <br><br> 50 <br><br> 301 <br><br> TTCTATCTGG <br><br> 351 <br><br> CGGTGGAGGC <br><br> 401 <br><br> TGGCCCCTGC <br><br> GCTCTATAAT GATCGATGAA CCTTTGCTGG ACCCGAACAA GGACCGAAAC CTTCGACTTC AGAACTTAGA AAATGCATCA CCATGTCTGC CCTCTGCCAC CAAGGCAGGT GACTGGCAAG TTACCCTTGA GCAAGCGCAG TCCCCGGGTG AACCGTCTGG GTCTAAAGAA TCTCATAAAT CCTTGGACAC ACTGCAGCTG CAGCAGATGG AAGAACTGGG TGCCATGCCG GCCTTCGCCT TGGTTGCTAG CCATCTGCAG CGCCACCTTG CGCAGCCCAC GAGCTTCCTG CTCAAGTCTT GCGCAGCGCT CCAGGAGAAG GAGGAGCTGG TGCTGCTCGG GAGCTCCTGC CCCAGCCAGG TCCATAGCGG CCTTTTCCTC ATATCCTAAT AA (SEQ ID <br><br> GCTCTATAAT GATCGATGAA CCTTTGCTGG ACCCGAACAA GGACCGAAAC CTTCGACTTC AGAACTTAGA AAATGCATCA CCATGTCTGC CCTCTGCCAC CAAGGCAGGT GACTGGCAAG TTACCCTTGA GCAAGCGCAG TCCCCGGGTG GTGGTTCTGG CCTGCAGCCC ACCCAGGGTG <br><br> ATTATACATC ACTTAAAGAG CCTCAATGAC GAAGACGTCT CAAACCTGGA GAGCTTCGTA GGTATTGAGG CAATTCTTCG GGCCGCACCC TCTCGACATC AATTCCGGGA AAAACTGACG GAACAACAGT ACGTAGAGGG TCCAATCTCT ACTATCAACC CTCCAAACAT GGCTCCCGAG GACGTCGCCG ACTTTGCCAC AATGGCCCCT GCCCTGCAGC CTGCTTTCCA GCGCCGGGCA AGCTTCCTGG AGGTGTCGTA ACCATTGGGC CCTGCCAGCT TAGAGCAAGT GAGAAAGATC CTGTGTGCCA CCTACAAGCT ACACTCTCTG GGCATCCCCT CCCTGCAGCT GGCAGGCTGC TACCAGGGGC TCCTGCAGGC NO:107) <br><br> ATTATACATC ACTTAAAGAG CCTCAATGAC GAAGACGTCT CAAACCTGGA GAGCTTCGTA GGTATTGAGG CAATTCTTCG GGCCGCACCC TCTCGACATC AATTCCGGGA AAAACTGACG GAACAACAGT ACGTAGAGGG CGGCGGCTCC AACATGGCTA CCATGCCGGC CTTCGCCTCT <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 100 <br><br> PCT/US96/15774 <br><br> 451 <br><br> GCTTTCCAGC <br><br> 501 <br><br> CTTCCTGGAG <br><br> 551 <br><br> CATTGGGCCC <br><br> 601 <br><br> GAGCAAGTGA <br><br> 5 <br><br> 651 <br><br> GTGTGCCACC <br><br> 701 <br><br> ACTCTCTGGG <br><br> 751 <br><br> CTGCAGCTGG <br><br> 801 <br><br> CCAGGGGCTC <br><br> 851 <br><br> CCTTGGACAC <br><br> 10 <br><br> 901 <br><br> CAGCAGATGG <br><br> GCCGGGCAGG AGGGGTCCTG GTGTCGTACC GCGTTCTACG TGCCAGCTCC CTGCCCCAGA GAAAGATCCA GGGCGATGGC TACAAGCTGT GCCACCCCGA CATCCCCTGG GCTCCCCTGA CAGGCTGCTT GAGCCAACTC CTGCAGGCCC TGGAAGGGAT ACTGCAGCTG GACGTCGCCG AAGAACTGGG ATAATAA ( <br><br> GTTGCTAGCC ATCTGCAGAG CCACCTTGCG CAGCCCACAC GCTTCCTGCT CAAGTCTTTA GCAGCGCTCC AGGAGAAGCT GGAGCTGGTG CTGCTCGGAC GCTCCTGCCC CAGCCAGGCC CATAGCGGCC TTTTCCTCTA ATCCCCCGAG TTGGGTCCCA ACTTTGCCAC CACCATCTGG :Q ID NO: 108) <br><br> pMONl3195 <br><br> 15 <br><br> 1 <br><br> ATGGCTAACT <br><br> 51 <br><br> ACCACCTGCA <br><br> 101 <br><br> CTATCCTGAT <br><br> 151 <br><br> AGGGCTGTCA <br><br> 201 <br><br> TAATCTCCAA <br><br> 20 <br><br> 251 <br><br> CAATCATCAT <br><br> 301 <br><br> TTCTATCTGG <br><br> 351 <br><br> CGGTGGAGGC <br><br> 401 <br><br> CGTCTCCTCC <br><br> 451 <br><br> CCTGCCCTGC <br><br> 25 <br><br> 501 <br><br> CCAGCGCCGG <br><br> 551 <br><br> TGGAGGTGTC <br><br> 601 <br><br> GGCCCTGCCA <br><br> 651 <br><br> AGTGAGAAAG <br><br> 701 <br><br> CCACCTACAA <br><br> 30 <br><br> 751 <br><br> CTGGGCATCC <br><br> 801 <br><br> GCTGGCAGGC <br><br> 851 <br><br> GGCTCCTGCA <br><br> 901 <br><br> GACACACTGC <br><br> 951 <br><br> GATGGAAGAA <br><br> 35 <br><br> PMON13196 <br><br> 1 <br><br> ATGGCTAACT <br><br> 40 <br><br> 51 <br><br> ACCACCTGCA <br><br> 101 <br><br> CTATCCTGAT <br><br> 151 <br><br> AGGGCTGTCA <br><br> 201 <br><br> TAATCTCCAA <br><br> 251 <br><br> CAATCATCAT <br><br> 45 <br><br> 301 <br><br> TTCTATCTGG <br><br> 351 <br><br> CGGTGGAGGC <br><br> 401 <br><br> CCCAGGGTGC <br><br> 451 <br><br> GGGGTCCTGG <br><br> 501 <br><br> CGTTCTACGC <br><br> 50 <br><br> 551 <br><br> TGCCCCAGAG <br><br> 601 <br><br> GGCGATGGCG <br><br> 651 <br><br> CCACCCCGAG <br><br> GCTCTATAAT GATCGATGAA CCTTTGCTGG ACCCGAACAA GGACCGAAAC CTTCGACTTC AGAACTTAGA AAATGCATCA CCATGTCTGC CCTCTGCCAC CAAGGCAGGT GACTGGCAAG TTACCCTTGA GCAAGCGCAG TCCCCGGGTG AACCGTCTGG GTCTAAAGAA TCTCATAAAT AGCCCACCCA GGGTGCCATG GCAGGAGGGG TCCTGGTTGC GTACCGCGTT CTACGCCACC GCTCCCTGCC CCAGAGCTTC ATCCAGGGCG ATGGCGCAGC GCTGTGCCAC CCCGAGGAGC CCTGGGCTCC CCTGAGCTCC TGCTTGAGCC AACTCCATAG GGCCCTGGAA GGGATATCCC AGCTGGACGT CGCCGACTTT CTGGGATAAT AA (SEQ ID <br><br> GCTCTATAAT GATCGATGAA CCTTTGCTGG ACCCGAACAA GGACCGAAAC CTTCGACTTC AGAACTTAGA AAATGCATCA CCATGTCTGC CCTCTGCCAC CAAGGCAGGT GACTGGCAAG TTACCCTTGA GCAAGCGCAG TCCCCGGGTG GTGGTTCTGG CATGCCGGCC TTCGCCTCTG TTGCTAGCCA TCTGCAGAGC CACCTTGCGC AGCCCACACC CTTCCTGCTC AAGTCTTTAG CAGCGCTCCA GGAGAAGCTG GAGCTGGTGC TGCTCGGACA <br><br> ATTATACATC ACTTAAAGAG CCTCAATGAC GAAGACGTCT CAAACCTGGA GAGCTTCGTA GGTATTGAGG CAATTCTTCG GGCCGCACCC TCTCGACATC AATTCCGGGA AAAACTGACG GAACAACAGT ACGTAGAGGG TCCAATCTCT ACTATCAACC CTCCAAACAT GGCTATGGCC CCGGCCTTCG CCTCTGCTTT TAGCCATCTG CAGAGCTTC C TTGCGCAGCC CACACCATTG CTGCTCAAGT CTTTAGAGCA GCTCCAGGAG AAGCTGTGTG TGGTGCTGCT CGGACACTCT TGCCCCAGCC AGGCCCTGCA CGGCCTTTTC CTCTACCAGG CCGAGTTGGG TCCCACCTTG GCCACCACCA TCTGGCAGCA NO:109) <br><br> ATTATACATC ACTTAAAGAG CCTCAATGAC GAAGACGTCT CAAACCTGGA GAGCTTCGTA GGTATTGAGG CAATTCTTCG GGCCGCACCC TCTCGACATC AATTCCGGGA AAAACTGACG GAACAACAGT ACGTAGAGGG CGGCGGCTCC AACATGGCTA CTTTCCAGCG CCGGGCAGGA TTCCTGGAGG TGTCGTACCG ATTGGGCCCT GCCAGCTCCC AGCAAGTGAG AAAGATCCAG TGTGCCACCT ACAAGCTGTG CTCTCTGGGC ATCCCCTGGG <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 101 <br><br> 701 CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG <br><br> 751 AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC TGCAGGCCCT <br><br> 801 GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA CTGCAGCTGG <br><br> 851 ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AGAACTGGGA <br><br> 901 ATGGCCCCTG CCCTGCAGCC CTAATAA (SEQ ID NO:110) <br><br> PMON13197 <br><br> 10 <br><br> 1 <br><br> ATGGCTAACT <br><br> 51 <br><br> ACCACCTGCA <br><br> 101 <br><br> CTATCCTGAT <br><br> 151 <br><br> AGGGCTGTCA <br><br> 201 <br><br> TAATCTCCAA <br><br> 15 <br><br> 251 <br><br> CAATCATCAT <br><br> 301 <br><br> TTCTATCTGG <br><br> 351 <br><br> CGGTGGAGGC <br><br> 401 <br><br> CGTCTCCTCC <br><br> 451 <br><br> GGTGCCATGC <br><br> 20 <br><br> 501 <br><br> CCTGGTTGCT <br><br> 551 <br><br> TACGCCACCT <br><br> 601 <br><br> CAGAGCTTCC <br><br> 651 <br><br> TGGCGCAGCG <br><br> 701 <br><br> CCGAGGAGCT <br><br> 25 <br><br> 751 <br><br> CTGACOTCCT <br><br> 801 <br><br> ACTCCATAGC <br><br> 851 <br><br> GGATATCCCC <br><br> 901 <br><br> GCCGACTTTG <br><br> 951 <br><br> CCCTGCCCTG <br><br> 30 <br><br> pMON13198 <br><br> 1 <br><br> ATGGCTAACT <br><br> 35 <br><br> 51 <br><br> ACCACCTGCA <br><br> 101 <br><br> CTATCCTGAT <br><br> 151 <br><br> AGGGCTGTCA <br><br> 201 <br><br> TAATCTCCAA <br><br> 251 <br><br> CAATCATCAT <br><br> 40 <br><br> 301 <br><br> TTCTATCTGG <br><br> 351 <br><br> CGGTGGAGGC <br><br> 401 <br><br> CTGCTTTCCA <br><br> 451 <br><br> AGCTTCCTGG <br><br> 501 <br><br> ACCATTGGGC <br><br> 45 <br><br> 551 <br><br> TAGAGCAAGT <br><br> 601 <br><br> CTGTGTGCCA <br><br> 651 <br><br> ACACTCTCTG <br><br> 701 <br><br> CCCTGCAGCT <br><br> 751 <br><br> TACCAGGGGC <br><br> 50 <br><br> 801 <br><br> CACCTTGGAC <br><br> 851 <br><br> GGCAGCAGAT <br><br> 901 <br><br> GGTGCCATGC <br><br> GCTCTATAAT GATCGATGAA CCTTTGCTGG ACCCGAACAA GGACCGAAAC CTTCGACTTC AGAACTTAGA AAATGCATCA CCATGTCTGC CCTCTGCCAC CAAGGCAGGT GACTGGCAAG TTACCCTTGA GCAAGCGCAG TCCCCGGGTG AACCGTCTGG GTCTAAAGAA TCTCATAAAT CGGCCTTCGC CTCTGCTTTC AGCCATCTGC AGAGCTTCCT TGCGCAGCCC ACACCATTGG TGCTCAAGTC TTTAGAGCAA CTCCAGGAGA AGCTGTGTGC GGTGCTGCTC GGACACTCTC GCCCCAGCCA GGCCCTGCAG GGCCTTTTCC TCTACCAGGG CGAGTTGGGT CCCACCTTGG CCACCACCAT CTGGCAGCAG CAGCCCTAAT AA (SEQ ID <br><br> GCTCTATAAT GATCGATGAA CCTTTGCTGG ACCCGAACAA GGACCGAAAC CTTCGACTTC AGAACTTAGA AAATGCATCA CCATGTCTGC CCTCTGCCAC CAAGGCAGGT GACTGGCAAG TTACCCTTGA GCAAGCGCAG TCCCCGGGTG GTGGTTCTGG GCGCCGGGCA GGAGGGGTCC AGGTGTCGTA CCGCGTTCTA CCTGCCAGCT CCCTGCCCCA GAGAAAGATC CAGGGCGATG CCTACAAGCT GTGCCACCCC GGCATCCCCT GGGCTCCCCT GGCAGGCTGC TTGAGCCAAC TCCTGCAGGC CCTGGAAGGG ACACTGCAGC TGGACGTCGC GGAAGAACTG GGAATGGCCC CGGCCTTCGC CTAATAA (S! <br><br> ATTATACATC ACTTAAAGAG CCTCAATGAC GAAGACGTCT CAAACCTGGA GAGCTTCGTA GGTATTGAGG CAATTCTTCG GGCCGCACCC TCTCGACATC AATTCCGGGA AAAACTGACG GAACAACAGT ACGTAGAGGG TCCAATCTCT ACTATCAACC CTCCAAACAT GGCTACCCAG CAGCGCCGGG CAGGAGGGGT GGAGGTGTCG TACCGCGTTC GCCCTGCCAG CTCCCTGCCC GTGAGAAAGA TCCAGGGCGA CACCTACAAG CTGTGCCACC TGGGCATCCC CTGGGCTCCC CTGGCAGGCT GCTTGAGCCA GCTCCTGCAG GCCCTGGAAG ACACACTGCA GCTGGACGTC ATGGAAGAAC TGGGAATGGC NO:111) <br><br> ATTATACATC ACTTAAAGAG CCTCAATGAC GAAGACGTCT CAAACCTGGA GAGCTTCGTA GGTATTGAGG CAATTCTTCG GGCCGCACCC TCTCGACATC AATTCCGGGA AAAACTGACG GAACAACAGT ACGTAGAGGG CGGCGGCTCC AACATGGCTT TGGTTGCTAG CCATCTGCAG CGCCACCTTG CGCAGCCCAC GAGCTTCCTG CTCAAGTCTT GCGCAGCGCT CCAGGAGAAG GAGGAGCTGG TGCTGCTCGG GAGCTCCTGC CCCAGCCAGG TCCATAGCGG CCTTTTCCTC ATATCCCCCG AGTTGGGTCC CGACTTTGCC ACCACCATCT CTGCCCTGCA GCCCACCCAG :Q ID NO: 112) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 102 <br><br> PCT/US96/15774 <br><br> PMON13199 <br><br> 10 <br><br> 15 <br><br> 20 <br><br> 25 <br><br> 30 <br><br> 35 <br><br> 40 <br><br> 45 <br><br> 50 <br><br> 1 51 101 151 201 251 301 351 401 451 501 551 601 651 701 751 801 851 901 951 <br><br> ATGGCTAACT ACCACCTGCA CTATCCTGAT AGGGCTGTCA TAATCTCCAA CAATCATCAT TTCTATCTGG CGGTGGAGGC CGTCTCCTCC TTCCAGCGCC CCTGGAGGTG TGGGCCCTGC CAAGTGAGAA TGCCACCTAC CTCTGGGCAT CAGCTGGCAG GGGGCTCCTG TGGACACACT CAGATGGAAG CATGCCGGCC <br><br> GCTCTATAAT CCTTTGCTGG GGACCGAAAC AGAACTTAGA CCATGTCTGC CAAGGCAGGT TTACCCTTGA TCCCCGGGTG GTCTAAAGAA GGGCAGGAGG TCGTACCGCG CAGCTCCCTG AGATCCAGGG AAGCTGTGCC CCCCTGGGCT GCTGCTTGAG CAGGCCCTGG GCAGCTGGAC AACTGGGAAT TTCGCCTAAT <br><br> GATCGATGAA ACCCGAACAA CTTCGACTTC AAATGCATCA CCTCTGCCAC GACTGGCAAG GCAAGCGCAG AACCGTCTGG TCTCATAAAT GGTCCTGGTT TTCTACGCCA CCCCAGAGCT CGATGGCGCA ACCCCGAGGA CCCCTGAGCT CCAACTCCAT AAGGGATATC GTCGCCGACT GGCCCCTGCC AA (SEQ ID <br><br> ATTATACATC CCTCAATGAC CAAACCTGGA GGTATTGAGG GGCCGCACCC AATTCCGGGA GAACAACAGT TCCAATCTCT CTCCAAACAT GCTAGCCATC CCTTGCGCAG TCCTGCTCAA GCGCTCCAGG GCTGGTGCTG CCTGCCCCAG AGCGGCCTTT CCCCGAGTTG TTGCCACCAC CTGCAGCCCA NO:113) <br><br> ACTTAAAGAG GAAGACGTCT GAGCTTCGTA CAATTCTTCG TCTCGACATC AAAACTGACG ACGTAGAGGG ACTATCAACC GGCTTCTGCT TGCAGAGCTT CCCACACCAT GTCTTTAGAG AGAAGCTGTG CTCGGACACT CCAGGCCCTG TCCTCTACCA GGTCCCACCT CATCTGGCAG CCCAGGGTGC <br><br> pMON31112 <br><br> 1 51 101 151 201 251 301 351 401 451 501 551 601 651 701 751 801 851 901 951 <br><br> ATGGCTAACT <br><br> GCCACCGCTG <br><br> ATATCCTAAT <br><br> CGTGCTGTCA <br><br> AAATCTCCTG <br><br> CAATCCATAT <br><br> TTCTATCTGA <br><br> CGGTGGAGGC <br><br> CGTCTCCTCC <br><br> GGTGCCATGC <br><br> CCTGGTTGCT <br><br> TACGCCACCT <br><br> CTGCTCAAGT <br><br> GCTCCAGGAG <br><br> TGGTGCTGCT <br><br> TGCCCCAGCC <br><br> CGGCCTTTTC <br><br> CCGAGTTGGG <br><br> GCCACCACCA <br><br> GCAGCCCTAA <br><br> GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG GGACAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA CCATGTCTGC CGCTAGCCAC GGCCGCACCC ACGCGACATC CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT TAA (SEQ ID NO:114) <br><br> pMON31113 <br><br> 1 ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA 51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 103 <br><br> PCT/US96/15774 <br><br> 101 <br><br> ATATCCTGAT <br><br> 151 <br><br> CGTGCTGTCA <br><br> 201 <br><br> AAATCTCCTG <br><br> 251 <br><br> CAATCATCAT <br><br> 5 <br><br> 301 <br><br> TTCTATCTGA <br><br> 351 <br><br> CGGTGGAGGC <br><br> 401 <br><br> CGTCTCCTCC <br><br> 451 <br><br> GGTGCCATGC <br><br> 501 <br><br> CCTGGTTGCT <br><br> 10 <br><br> 551 <br><br> TACGCCACCT <br><br> 601 <br><br> CAGAGCTTCC <br><br> 651 <br><br> TGGCGCAGCG <br><br> 701 <br><br> CCGAGGAGCT <br><br> 751 <br><br> CTGAGCTCCT <br><br> 15 <br><br> 801 <br><br> ACTCCATAGC <br><br> 851 <br><br> GGATATCCCC <br><br> 901 <br><br> GCCGACTTTG <br><br> 951 <br><br> CCCTGCCCTG <br><br> 20 <br><br> pMON31114 <br><br> 1 <br><br> ATGGCTAACT <br><br> 51 <br><br> GCCACCGCTG <br><br> 101 <br><br> ATATCCTGAT <br><br> 25 <br><br> 151 <br><br> CGTGCTGTCA <br><br> 201 <br><br> AAATCTCCTG <br><br> 251 <br><br> CAATCATCAT <br><br> 301 <br><br> TTCTATCTGA <br><br> 351 <br><br> CGGTGGAGGC <br><br> 30 <br><br> 401 <br><br> CGTCTCCTCC <br><br> 451 <br><br> GGTGCCATGC <br><br> 501 <br><br> CCTGGTTGCT <br><br> 551 <br><br> TACGCCACCT <br><br> 601 <br><br> CTGCTCAAGT <br><br> 35 <br><br> 651 <br><br> GCTCCAGGAG <br><br> 701 <br><br> TGGTGCTGCT <br><br> 751 <br><br> TGCCCCAGCC <br><br> 801 <br><br> CGGCCTTTTC <br><br> 851 <br><br> CCGAGTTGGG <br><br> 40 <br><br> 901 <br><br> GCCACCACCA <br><br> 951 <br><br> GCAGCCCTAA <br><br> pMON31115 <br><br> 1 <br><br> ATGGCTAACT <br><br> 51 <br><br> GCCACCGCTG <br><br> 101 <br><br> ATATCCTAAT <br><br> 151 <br><br> CGTGCTGTCA <br><br> 201 <br><br> AAATCTCCTG <br><br> 251 <br><br> CAATCCATAT <br><br> 301 <br><br> TTCTATCTGA <br><br> GGAAAATAAC CTTCGTCGTC AGTCTCTGCA GAATGCATCA CCATGTCTGC CCCTGGCCAC CCGTGACGGT GACTGGAATG AAACCTTGGA GAACGCGCAG TCCCCGGGTG AACCGTCTGG GTCTAAAGAA TCTCATAAAT CGGCCTTCGC CTCTGCTTTC AGCCATCTGC AGAGCTTCCT TGCGCAGCCC ACACCATTGG TGCTCAAGTC TTTAGAGCAA CTCCAGGAGA AGCTGTGTGC GGTGCTGCTC GGACACTCTC GCCCCAGCCA GGCCCTGCAG GGCCTTTTCC TCTACCAGGG CGAGTTGGGT CCCACCTTGG CCACCACCAT CTGGCAGCAG CAGCCCTAAT AA (SEQ ID <br><br> GCTCTAACAT GATCGATGAA CCGCTGCTGG ACTTCAACAA GGAAAATAAC CTTCGTCGTC AGTCTCTGCA GAATGCATCA CCATGTCTGC CCCTGGCCAC CCGTGACGGT GACTGGAATG AAACCTTGGA GAACGCGCAG TCCCCGGGTG AACCGTCTGG GTCTAAAGAA TCTCATAAAT CGGCCTTCGC CTCTGCTTTC AGCCATCTGC AGAGCTTCCT TGCGCAGCCC TCTGGCGGCT CTTTAGAGCA AGTGAGAAAG AAGCTGTGTG CCACCTACAA CGGACACTCT CTGGGCATCC AGGCCCTGCA GCTGGCAGGC CTCTACCAGG GGCTCCTGCA TCCCACCTTG GACACACTGC TCTGGCAGCA GATGGAAGAA TAA (SEQ ID NO:116) <br><br> GCTCTAACAT GATCGATGAA CCGCTGCTGG ACTTCAACAA GGACAATAAC CTTCGTCGTC AGTCTCTGCA GAATGCATCA CCATGTCTGC CGCTAGCCAC CAAGGACGGT GACTGGAATG AAACCTTGGA GAACGCGCAG <br><br> CAAACCTCGA GGCATTCAAC GCAATTGAGA GCATTCTTAA GGCCGCACCC ACGCGACATC AATTCCGTCG TAAACTGACC GCTCAACAGT ACGTAGAGGG TCCAATCTCT ACTATCAACC CTCCAAACAT GGCTACCCAG CAGCGCCGGG CAGGAGGGGT GGAGGTGTCG TACCGCGTTC GCCCTGCCAG CTCCCTGCCC GTGAGAAAGA TCCAGGGCGA CACCTACAAG CTGTGCCACC TGGGCATCCC CTGGGCTCCC CTGGCAGGCT GCTTGAGCCA GCTCCTGCAG GCCCTGGAAG ACACACTGCA GCTGGACGTC ATGGAAGAAC TGGGAATGGC NO:115) <br><br> ATCATCACCC ACCTGAAGCA CCTCAATGGT GAAGACCAAG CAAACCTCGA GGCATTCAAC GCAATTGAGA GCATTCTTAA GGCCGCACCC ACGCGACATC AATTCCGTCG TAAACTGACC GCTCAACAGT ACGTAGAGGG TCCAATCTCT ACTATCAACC CTCCAAACAT GGCTACCCAG CAGCGCCGGG CAGGAGGGGT GGAGGTGTCG TACCGCGTTC CTGGCGGCTC TCAGAGCTTC ATCCAGGGCG ATGGCGCAGC GCTGTGCCAC CCCGAGGAGC CCTGGGCTCC CCTGAGCTCC TGCTTGAGCC AACTCCATAG GGCCCTGGAA GGGATATCCC AGCTGGACGT CGCCGACTTT CTGGGAATGG CCCCTGCCCT <br><br> ATCATCACCC ACCTGAAGCA CCTCAATGGT GAAGACCAAG CAAACCTCGA GGCATTCAAC GCAATTGAGA GCATTCTTAA GGCCGCACCC ACGCGACATC AATTCCGTCG TAAACTGACC GCTCAACAGT ACGTAGAGGG <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 104 <br><br> PCT/US96/15774 <br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC <br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG <br><br> 451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT <br><br> 501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC <br><br> 5 551 TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC <br><br> 601 CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA <br><br> 651 TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC <br><br> 701 CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC CTGGGCTCCC <br><br> 751 CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA <br><br> 10 801 ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG <br><br> 851 GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC <br><br> 901 GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC <br><br> 951 CCCTGCCCTG CAGCCCTAAT AA (SEQ ID NO:117) <br><br> 15 <br><br> PMON28505 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT 2 0 CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT <br><br> 2 5 CATAAATCTCCAAACATGGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTG <br><br> GACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTG GGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACT TGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTG CAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCC <br><br> 3 0 AATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTT <br><br> GTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCG CCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGC AGACTGAGCCAGTGCCCA (SEQ ID NO:118) <br><br> 3 5 pMON28506 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT <br><br> 4 0 ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT <br><br> CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTG <br><br> 4 5 GGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACC <br><br> CTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCC CTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT GGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTC CTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCC <br><br> 5 0 ACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGAC <br><br> CTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAG TGCCCAGAGGTTCACCCT (SEQ ID NO:119) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 105 <br><br> PCT/US96/15774 <br><br> pMON2 8507 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT 5 TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC 10 CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAA ACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAG GGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAG CTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTT 15 CCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAA CACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTC AGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTC AGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTT CACCCTTTGCCTACACCT (SEQ ID NO:120) <br><br> 20 <br><br> PMON28508 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT 25 CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT 3 0 CATAAATCTCCAAACATGGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAG GAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCA GCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAG GTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGC AGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA <br><br> 3 5 GGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC <br><br> GGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTT CGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCT ACACCTGTCCTGCTGCCT (SEQ ID NO:121) <br><br> 40 pMON28509 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT <br><br> 4 5 ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT <br><br> CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACC <br><br> 5 0 AAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGG <br><br> GGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGT CTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACC <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 106 <br><br> PCT/US96/15774 <br><br> ACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAG GTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAAC ATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGAC TCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCT 5 GTCCTGCTGCCTGCTGTG (SEQ ID NO:122) <br><br> pMON2 8510 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT 10 TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCC 15 CGGGGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCA TAAACTCCAAACATGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATT CTGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCA CTTGCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCT GCAGGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCC <br><br> 2 0 AATGCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTG <br><br> TAGGGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCC TGCTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGA CTGACCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACT TTAGTTG (SEQ ID NO:123) <br><br> 25 <br><br> PMON28511 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT <br><br> 3 0 CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT <br><br> ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT 3 5 CATAAATCTCCAAACATGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGA CAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAG GGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTC CGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTC GGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTG 40 CTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTG CCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATG GAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATG GCAGCACGGGGACAACTG (SEQ ID NO:124) <br><br> 45 pMON2 8512 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT 50 ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 107 <br><br> PCT/US96/15774 <br><br> CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG GATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTG ATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCC 5 GCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTT CACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCT GCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGAC ATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGA CCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGG 10 GCCCTGCAGAGCCTCCTT (SEQ ID NO:125) <br><br> PMON28513 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT 15 TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC 20 CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTG AGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACC CTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTC CGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGC 25 CCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGA GAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTT CTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTC CTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGA ACCCAGCTTCCTCCACAG (SEQ ID NO:126) <br><br> 30 <br><br> PMON28514 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT <br><br> 3 5 CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT <br><br> ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT 40 CATAAATCTCCAAACATGGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACAC CTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG GAATTCGGCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGT AAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCAC CCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACC <br><br> 4 5 CAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGA <br><br> GTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTT TCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCT CCACAGGGCAGGACCACA (SEQ ID NO:127) <br><br> 50 pMON2 8515 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 108 <br><br> PCT/US96/15774 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT 5 CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA GGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC 10 GGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTT CGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCT ACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAG GAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCA GCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAG 15 GTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGC AGGACCACAGCTCACAAG (SEQ ID NO:128) <br><br> pMON2 8516 <br><br> 2 0 GCTAACTGCTCTATAATGATCGATGAAATTATACATC ACTTAAAGAGACCACCTGC ACCT <br><br> TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCC AAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC 25 TATCTGGTTAC.rCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTG CGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATG GCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCC 30 CATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTC CTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAG GCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGA CAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTC CTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACA <br><br> 3 5 GCTCACAAGGATCCCAAT (SEQ ID NO:129) <br><br> pMON2 8519 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT <br><br> 4 0 TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT <br><br> CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC 45 CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTG GACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTG GGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACT TGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTG 50 CAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCC AATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTT GTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCT <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 109 <br><br> PCT/US96/15774 <br><br> GCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGA CTGAGCCAGTGCCCA (SEQ ID NO:130) <br><br> PMON28520 <br><br> 5 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT 10 CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTG GGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACC 15 CTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCC CTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT GGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTC CTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCC ACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTC 20 CGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGC CCAGAGGTTCACCCT (SEQ ID NO:131) <br><br> pMON2 8521 <br><br> 2 5 GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT <br><br> TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC 30 TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAA ACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAG GGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAG <br><br> 3 5 CTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCC CTGCAGAGCCTCCTTGGAACCCAGCTT <br><br> CCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAA CACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTC AGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGT AAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCAC 40 CCTTTGCCTACACCT (SEQ ID NO:132) <br><br> pMON2 8522 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT <br><br> 4 5 TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT <br><br> CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC <br><br> 5 0 CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT <br><br> CATAAATCTCCAAACATGGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAG GAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCA <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 110 <br><br> PCT/US96/15774 <br><br> GCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAG GTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGC AGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA GGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC 5 AACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGT GACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACA CCTGTCCTGCTGCCT (SEQ ID NO:13 3) <br><br> pMON2 8523 <br><br> 10 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATC ACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT 15 CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACC AAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGG 2 0 GGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGT CTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACC ACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAG GTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATG GCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCC <br><br> 2 5 CATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTC <br><br> CTGCTGCCTGCTGTG (SEQ ID NO:134) <br><br> PMON28524 <br><br> 3 0 GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT <br><br> TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC <br><br> 3 5 TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC <br><br> CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGAC ATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGA CCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGG <br><br> 4 0 GCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG <br><br> GATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTG ATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCT CCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCAC AGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCT 45 GTGGACTTTAGCTTG (SEQ ID NO:135) <br><br> PMON2852 5 <br><br> GCTAACTGCTCT AT AATGATCGATGAAATTATACATC ACTTAAAGAGACCACCTGCACCT <br><br> 5 0 TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT <br><br> CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 111 <br><br> PCT7US96/15774 <br><br> CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGA 5 CAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAG GGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTC CGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTC GGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTT CGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCT 10 ACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAG GAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCA GCACGGGGACAACTG (SEQ ID NO:13 6) <br><br> PMON2 8526 <br><br> 15 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT 20 CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG GATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTG <br><br> 2 5 ATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC^ AC ATGGCGTCTCCCGCT <br><br> CCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCAC AGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCT GTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATT CTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCC 30 ACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCC CTGCAGAGCCTCCTT (SEQ ID NO:137) <br><br> PMON2 8527 <br><br> 3 5 GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT <br><br> TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTT CCAAAC CTGGAGAGCTTC GTAAGG GCTGTCAAGAAC T TAGAAAATGCAT CAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC 40 TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTG AGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACC CTCTGCGTCAGGGAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGA <br><br> 4 5 GTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCA <br><br> GAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAA TGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTG CTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTG GGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACC 50 CAGCTTCCTCCACAG (SEQ ID NO:138) <br><br> PMON28528 <br><br> Printed from Mimosa 08:37-.19 <br><br> WO 97/12985 <br><br> 112 <br><br> PCT/US96/15774 <br><br> GCTAACTGCTCT AT AATGATCGATGAAATTATACATC ACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCC AAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT 5 ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACAC 10 CTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG GAATTCGGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAA CTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCT TTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAG ATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTG 15 ATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCT GGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCA CAGGGCAGGACCACA (SEQ ID NO:13 9) <br><br> pMON2 8529 <br><br> 20 <br><br> GCTAACTGCTCT AT AATGATCGATGAAATTATACATC ACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT <br><br> 2 5 CGAC ATCC AATC ATCATC AAGGC AGGTGACTGGCAAG AATTCCGGGAAAAACTGACGTTC <br><br> TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA GGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC <br><br> 3 0 AACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGT <br><br> GACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACA CCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAG ACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCA CGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTC <br><br> 3 5 CGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGG <br><br> ACCACAGCTCACAAG (SEQ ID NO:140) <br><br> pMON2 853 0 <br><br> 4 0 GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT <br><br> TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC 4 5 TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTG CGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCG TCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT 50 GTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTG CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCA CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAA <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 113 <br><br> PCT/US96/15774 <br><br> CTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCT CACAAGGATCCCAAT (SEQ ID NO:141) <br><br> 5 pMON2 8533 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATC ACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT GACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGTA 10 TGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCTCG CATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTCTAT TGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCCCCGG TAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCTCATAAA TCTCCAAACATGGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTT 15 AGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCA GTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTC TCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGC CTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCC ATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGA <br><br> 2 0 GGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCG <br><br> CCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCAC AGCAGACTGAGCCAGTGCCCA (SEQ ID NO:142) <br><br> pMON2 8534 <br><br> 25 <br><br> GCTAACTGCT v. 7 AT AATGATCGATGAAATTATACATC ACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCC AAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT <br><br> 3 0 CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC <br><br> TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTG GGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACC <br><br> 3 5 CTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCC <br><br> CTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTT GGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTC CTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCC ACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCT <br><br> 4 0 GCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGA <br><br> CTGAGCCAGTGCCCAGAGGTTCACCCT (SEQ ID NO:143) <br><br> PMON2853 5 <br><br> 45 GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC 50 TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAA <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 114 <br><br> PCT/US96/15774 <br><br> ACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAG GGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAG CTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTT CCTCCACAGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAA 5 CACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTC AGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTC CGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGC CCAGAGGTTCACCCTTTGCCTACACCT (SEQ ID NO:144) <br><br> 10 pMON2 853 6 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT 15 ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAG 20 GAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCA GCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAG GTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGC AGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA GGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC 25 GGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGT AAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCAC CCTTTGCCTACACCTGTCCTGCTGCCT (SEQ ID NO:145) <br><br> PMON28537 <br><br> 30 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT 3 5 CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACC AAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGG 40 GGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGT CTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACC ACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAG GTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAAC GGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTG 45 CTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTG CCTACACCTGTCCTGCTGCCTGCTGTG (SEQ ID NO:146) <br><br> PMON2853 8 <br><br> 50 GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 115 <br><br> PCT/US96/15774 <br><br> ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT 5 CATAAATCTCCAAACATGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGAC ATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGA CCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGG GCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG GATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTG 10 ATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATG GCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCC CATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTC CTGCTGCCTGCTGTGGACTTTAGCTTG (SEQ ID NO:147) <br><br> 15 pMON28539 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT 20 ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGA <br><br> 2 5 CAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAG <br><br> GGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTC CGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTC GGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTC AGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTT <br><br> 3 0 CACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAA <br><br> ACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAG GGAGTGATGGCAGCACGGGGACAACTG (SEQ ID NO:148) <br><br> pMON2 8540 <br><br> 35 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT 40 CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG GATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTG <br><br> 4 5 ATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATG <br><br> GCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCC CATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTC CTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAG GCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGA <br><br> 5 0 CAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTC <br><br> CTCCTTGGGGCCCTGCAGAGCCTCCTT (SEQ ID NO:149) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 116 <br><br> PCT/US96/15774 <br><br> pMON28541 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT 5 CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT 10 CATAAATCTCCAAACATGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTG AGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACC CTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCT TGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTG AGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTT 15 AGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCA GTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTC TCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGC CTCCTTGGAACCCAGCTTCCTCCACAG (SEQ ID NO:150) <br><br> 20 pMON2 8542 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT <br><br> 2 5 ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT <br><br> CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACAC <br><br> 3 0 CTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTC AGG <br><br> GAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGA GTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCA GAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAA TGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTG <br><br> 3 5 CTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTG <br><br> GGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACC CAGCTTCCTCCACAGGGCAGGACCACA (SEQ ID NO:151) <br><br> pMON2 8543 <br><br> 40 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT <br><br> 4 5 CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC <br><br> TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA GGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC 50 GGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGT AAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCAC CCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACC <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 117 <br><br> PCT/US96/15774 <br><br> CAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGA GTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTT TCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCT CCACAGGGCAGGACCACAGCTCACAAG (SEQ ID NO:152) <br><br> 5 <br><br> pMON2 8544 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT 10 CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT 15 CATAAATCTCCAAACATGGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTG CGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGC GGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTT CGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCT ACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAG <br><br> 2 0 GAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCA <br><br> GCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAG GTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGC AGGACCACAGCTCACAAGGATCCCAAT (SEQ ID NO:153) <br><br> 25 pMON2 8545 <br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT <br><br> 3 0 ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT <br><br> CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA <br><br> 3 5 GGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC <br><br> GGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTT CGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCT ACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAG GAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCA <br><br> 4 0 GCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAG <br><br> GTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGGGCAGGACCACAGCT CACAAG (SEQ ID NO:154) <br><br> 45 pMONl59 81 <br><br> 1 <br><br> ATGGCTAACT <br><br> 51 <br><br> ACCACCTGCA <br><br> 101 <br><br> CTATCCTGAT <br><br> 151 <br><br> AGGGCTGTCA <br><br> 201 <br><br> TAATCTCCAA <br><br> 251 <br><br> CAATCATCAT <br><br> GCTCTATAAT GATCGATGAA CCTTTGCTGG ACCCGAACAA GGATCGAAAC CTTCGACTTC AGAACTTAGA AAATGCATCA CCATGTCTGC CCTCTGCCAC CAAGGCAGGT GACTGGCAAG <br><br> ATTATACATC ACTTAAAGAG CCTCAATGAC GAAGACGTCT CAAACCTGGA GAGCTTCGTA GGTATTGAGG CAATTCTTCG GGCCGCACCC TCTCGACATC AATTCCGGGA AAAACTGACG <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 118 <br><br> PCT/US96/15774 <br><br> 10 <br><br> 15 <br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG <br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC <br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTTACAAG <br><br> 451 CTGTGLCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC <br><br> 501 CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT <br><br> 551 GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG <br><br> 601 GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA <br><br> 651 GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC <br><br> 701 TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GCCGGCCTTC <br><br> 751 GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT <br><br> 801 GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC <br><br> 851 CCGGCGGCGG CTCTGACATG GCTACACCAT TAGGCCCTGC CAGCTCCCTG <br><br> 901 CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGGA AGATCCAGGG <br><br> 951 CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAA TAA; <br><br> (SEQ ID NO:155) <br><br> 20 <br><br> 25 <br><br> 30 <br><br> 35 <br><br> 40 <br><br> PMON15982 <br><br> 1 ATGGCTAACT GCTCTATAAT <br><br> 51 ACCACCTGCA CCTTTGCTGG <br><br> 101 CTATCCTGAT GGATCGAAAC <br><br> 151 AGGGCTGTCA AGAACTTAGA <br><br> 201 TAATCTCCAA CCATGTCTGC <br><br> 251 CAATCATCAT CAAGGCAGGT <br><br> 301 TTCTATCTGG TTACCCTTGA <br><br> 3 51 CGGTGGAGGC TCCCCGGGTG <br><br> 401 CGTCTCCTCC GTCTAAAGAA <br><br> 451 TTGGGTCCCA CCTTGGACAC <br><br> 501 CACCATCTGG CAGCAGATGG <br><br> 551 CCACCCAGGG TGCCATGCCG <br><br> 601 GGAGGGGTCC TGGTTGCTAG <br><br> 651 CCGCGTTCTA CGCCACCTTG <br><br> 701 CACCATTAGG CCCTGCCAGC <br><br> 751 TTAGAGCAAG TGAGGAAGAT <br><br> 801 GCTGTGTGCC ACCTACAAGC <br><br> 851 GACACTCTCT GGGCATCCCC <br><br> 901 GCCCTGCAGC TGGCAGGCTG <br><br> 951 CTACCAGGGG CTCCTGCAGG (SEQ ID NO:156) <br><br> PMON15965 <br><br> GATCGATGAA ACCCGAACAA CTTCGACTTC AAATGCATCA CCTCTGCCAC GACTGGCAAG GCAAGCGCAG AACCGTCTGG TCTCATAAAT ACTGCAGCTG AAGAACTGGG GCCTTCGCCT CCATCTGCAG CGCAGCCCGG TCCCTGCCCC CCAGGGCGAT TGTGCCACCC TGGGCTCCCC CTTGAGCCAA CCCTGGAAGG <br><br> ATTATACATC CCTCAATGAC CAAACCTGGA GGTATTGAGG GGCCGCACCC AATTCCGGGA GAACAACAGT TCCAATCTCT CTCCAAACAT GACGTCGCCG AATGGCCCCT CTGCTTTCCA AGCTTCCTGG CGGCGGCTCT AGAGCTTCCT GGCGCAGCGC CGAGGAGCTG TGAGCTCCTG CTCCATAGCG GATATCCTAA <br><br> ACTTAAAGAG GAAGACGTCT GAGCTTCGTA CAATTCTTCG TCTCGACATC AAAACTGACG ACGTAGAGGG ACTATCAACC GTCTCCCGAG ACTTTGCCAC GCCCTGCAGC GCGCCGGGCA AGGTGTCGTA GACATGGCTA GCTCAAGTCT TCCAGGAGAA GTGCTGCTCG CCCCAGCCAG GCCTTTTCCT TAA; <br><br> 1 <br><br> ATGGCTAACT <br><br> 51 <br><br> ACCACCTGCA <br><br> 45 <br><br> 101 <br><br> CTATCCTGAT <br><br> 151 <br><br> AGGGCTGTCA <br><br> 201 <br><br> TAATCTCCAA <br><br> 251 <br><br> CAATCATCAT <br><br> 301 <br><br> TTCTATCTGG <br><br> 50 <br><br> 351 <br><br> CGGTGGAGGC <br><br> 401 <br><br> CGTCTCCTCC <br><br> 451 <br><br> TTCCAGCGCC <br><br> GCTCTATAAT CCTTTGCTGG GGATCGAAAC AGAACTTAGA CCATGTCTGC CAAGGCAGGT TTACCCTTGA TCCCCGGGTG GTCTAAAGAA GGGCAGGAGG <br><br> GATCGATGAA ACCCGAACAA CTTCGACTTC AAATGCATCA CCTCTGCCAC GACTGGCAAG GCAAGCGCAG AACCGTCTGG TCTCATAAAT GGTCCTGGTT <br><br> ATTATACATC CCTCAATGAC CAAACCTGGA GGTATTGAGG GGCCGCACCC AATTCCGGGA GAACAACAGT TCCAATCTCT CTCCAAACAT GCTAGCCATC <br><br> ACTTAAAGAG GAAGACGTCT GAGCTTCGTA CAATTCTTCG TCTCGACATC AAAACTGACG ACGTAGAGGG ACTATCAACC GTCTTCTGCT TGCAGAGCTT <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 119 <br><br> PCT/US96/15774 <br><br> 10 <br><br> 15 <br><br> 20 <br><br> 25 <br><br> 30 <br><br> 35 <br><br> 501 551 601 651 701 751 801 851 901 951 <br><br> cctggaggtg gctctgacat ttcctgctca agcgctccag agctggtgct tcctgcccca tagcggcctt cccccgagtt tttgccacca cctgcagccc (seq id no tcgtaccgcg ggctacacca agtctttaga gagaagctgt gctcggacac gccaggccct ttcctctacc gggtcccacc ccatctggca acccagggtg : 157) <br><br> pMONl5966 <br><br> 1 atggctaact gctctataat <br><br> 51 accacctgca cctttgctgg <br><br> 101 ctatcctgat ggatcgaaac <br><br> 151 agggctgtca agaacttaga <br><br> 201 taatctccaa ccatgtctgc <br><br> 251 caatcatcat caaggcaggt <br><br> 301 ttctatctgg ttacccttga <br><br> 351 cggtggaggc tccccgggtg <br><br> 401 cgtctcctcc gtctaaagaa <br><br> 451 cctgccctgc agcccaccca <br><br> 501 ccagcgccgg gcaggagggg <br><br> 551 tggaggtgtc gtaccgcgtt <br><br> 601 tctgacatgg ctacaccatt <br><br> 651 cctgctcaag tctttagagc <br><br> 701 cgctccagga gaagctgtgt <br><br> 751 ctggtgctgc tcggacactc <br><br> 801 ctgccccagc caggccctgc <br><br> 851 gcggcctttt cctctaccag <br><br> 901 cccgagttgg gtcccacctt <br><br> 951 tgccaccacc atctggcagc (seq id no:158) <br><br> ttctacgcca ttaggccctg gcaagtgagg gtgccaccta tctctgggca gcagctggca aggggctcct ttggacacac gcagatggaa ccatgccggc gatcgatgaa acccgaacaa cttcgacttc aaatgcatca cctctgccac gactggcaag gcaagcgcag aaccgtctgg tctcataaat gggtgccatg tcctggttgc ctacgccacc aggccctgcc aagtgaggaa gccacctaca tctgggcatc agctggcagg gggctcctgc ggacacactg agatggaaga ccttgcgcag ccagctccct aagatccagg caagctgtgc tcccctgggc ggctgcttga gcaggccctg tgcagctgga gaactgggaa cttcgcctaa cccggcggcg gccccagagc gcgatggcgc caccccgagg tcccctgagc gccaactcca gaagggatat cgtcgccgac tggcccctgc taa pMONl5967 <br><br> 1 <br><br> atggctaact <br><br> 40 <br><br> 51 <br><br> accacctgca <br><br> 101 <br><br> ctatcctgat <br><br> 151 <br><br> agggctgtca <br><br> 201 <br><br> taatctccaa <br><br> 251 <br><br> caatcatcat <br><br> 45 <br><br> 301 <br><br> ttctatctgg <br><br> 351 <br><br> cggtggaggc <br><br> 401 <br><br> cgtctcctcc <br><br> 451 <br><br> ggtgccatgc <br><br> 501 <br><br> cctggttgct <br><br> 50 <br><br> 551 <br><br> tacgccacct <br><br> 601 <br><br> ggccctgcca <br><br> 651 <br><br> agtgaggaag gctctataat cctttgctgg ggatcgaaac agaacttaga ccatgtctgc caaggcaggt ttacccttga tccccgggtg gtctaaagaa cggccttcgc agccatctgc tgcgcagccc gctccctgcc atccagggcg gatcgatgaa acccgaacaa cttcgacttc aaatgcatca cctctgccac gactggcaag gcaagcgcag aaccgtctgg tctcataaat ctctgctttc agagcttcct ggcggcggct ccagagcttc atggcgcagc attatacatc cctcaatgac caaacctgga ggtattgagg ggccgcaccc aattccggga gaacaacagt tccaatctct ctccaaacat ccggccttcg tagccatctg ttgcgcagcc agctccctgc gatccagggc agctgtgcca ccctgggctc ctgcttgagc aggccctgga cagctggacg actgg gataa attatacatc cctcaatgac caaacctgga ggtattgagg ggccgcaccc aattccggga gaacaacagt tccaatctct ctccaaacat cagcgccggg ggaggtgtcg ctgacatggc ctgctcaagt gctccaggag acttaaagag gaagacgtct gagcttcgta caattcttcg tctcgacatc aaaactgacg acgtagaggg actatcaacc gtctatggcc cctctgcttt cagagcttcc cggcggcggc cccagagctt gatggcgcag ccccgaggag ccctgagctc caactccata agggatatcc tcgccgactt taa acttaaagag gaagacgtct gagcttcgta caattcttcg tctcgacatc aaaactgacg acgtagaggg actatcaacc gtctacccag caggaggggt taccgcgttc tacaccatta ctttagagca aagctgtgtg <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 120 <br><br> PCT/US96/15774 <br><br> 701 CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CGGACACTCT <br><br> 751 CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA <br><br> 801 GCTGGCAGGC TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG <br><br> 851 GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TCCCACCTTG <br><br> 5 901 GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA <br><br> 951 GATGGAAGAA CTGGGAATGG CCCCTGCCCT GCAGCCCTAA TAA (SEQ ID NO:159) <br><br> 10 <br><br> pMONl5960 <br><br> 1 ATGGCTACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT <br><br> 51 CAAGTCTTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC <br><br> 101 AGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTG <br><br> 151 CTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCC <br><br> 15 201 CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCC <br><br> 251 TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG <br><br> 3 01 TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC <br><br> 3 51 CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC <br><br> 401 CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA <br><br> 20 451 GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA <br><br> 501 CCGCGTTCTA CGCCACCTTG CGCAGCCCGG CGGCGGCTCT GACATGGCTA <br><br> 551 CACCATTGGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT <br><br> 601 TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA <br><br> 651 GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG <br><br> 25 701 GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG <br><br> 751 GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT <br><br> 801 CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC <br><br> 851 CCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATC <br><br> 901 TGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCA <br><br> 30 1001 TCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTT <br><br> 1051 CTACGCCACC TTGCGCAGCC CTGATAA (SEQ ID NO:160) <br><br> PMON32132 <br><br> 3 5 TCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT <br><br> GTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTG CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCA CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAA CTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC <br><br> 4 0 CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCT <br><br> CACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGT TTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG (SEQ ID NO:249) <br><br> 45 <br><br> PMON32133 <br><br> TCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT GTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTG CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCA CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAA 50 CTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGGGCAGGACCACAGCTCACAAGGATCCC <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 121 <br><br> PCT/US96/15774 <br><br> AATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTT GTAGGAGGGTCCACCCTCTGCGTCAGG (SEQ ID NO:250) <br><br> pmon32134 <br><br> 10 <br><br> TCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT GTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTG CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCA CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAA CTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC CTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCT CACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGT TTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG (SEQ ID NO:251) <br><br> 15 <br><br> Pmonl3181 <br><br> 1 <br><br> ccatggctaa <br><br> 51 <br><br> agaccacctg <br><br> 101 <br><br> ctctatcctg <br><br> 20 <br><br> 151 <br><br> taagggctgt <br><br> 201 <br><br> cgtaatctcc <br><br> 251 <br><br> tccaatcatc <br><br> 301 <br><br> cgttctatct <br><br> 351 <br><br> ggcggtggag <br><br> 25 <br><br> 401 <br><br> cccgtctcct <br><br> 451 <br><br> ccgcatgcaa <br><br> Pmonl3180.Seg <br><br> 30 <br><br> 1 <br><br> ccatggctaa <br><br> 51 <br><br> agaccacctg <br><br> 101 <br><br> ctctatcctg <br><br> 151 <br><br> taagggctgt <br><br> 201 <br><br> cgtaatctcc <br><br> 35 <br><br> 251 <br><br> tccaatcatc <br><br> 301 <br><br> cgttctatct <br><br> 351 <br><br> ggcggtggag <br><br> 401 <br><br> aggtaccgca ctgctctata cacctttgct atggatcgaa caagaactta aaccatgtct atcaaggcag ggttaccctt gctcCCCGGG CCGTCTAAAG gctt (seq <br><br> ATGATCGATG GGACCCGAAC ACCTTCGACT GAAAATGCAT GCCCTCTGCC GTGACTGGCA GAGCAAGCGC TGAACCGTCT AATCTCATAA ID NO:257) <br><br> AAATTATACA AACCTCAATG TCCAAACCTG CAGGTATTGA ACGGCCGCAC AGAATTCCGG AGGAACAACA GGTCCAATCT ATCTCCAAAC <br><br> CTGCTCTATA CACCTTTGCT ATGGATCGAA CAAGAACTTA AACCATGTCT ATCAAGGCAG GGTTACCCTT gctcCCCGGG TGCAAGCTT <br><br> ATGATCGATG GGACCCGAAC ACCTTCGACT GAAAATGCAT GCCCTCTGCC GTGACTGGCA GAGCAAGCGC TGGTGGTTCT (seq id no: <br><br> AAATTATACA AACCTCAATG TCCAAACCTG CAGGTATTGA ACGGCCGCAC AGAATTCCGG AGGAACAACA GGCGGCGGCT 258) <br><br> TCACTTAAAG ACGAAGACGT GAGAGCTTCG GGCAATTCTT CCTCTCGACA GAAAAACTGA GTACGTAgag CTACTATCAA ATGTAAGGTA <br><br> TCACTTAAAG ACGAAGACGT GAGAGCTTCG GGCAATTCTT CCTCTCGACA GAAAAACTGA GTACGTAgag CCAACATGTA <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 122 <br><br> PCT/US96/15774 <br><br> TAPLE 3 <br><br> PROTEIN SROITRNCES <br><br> 5 pMON26458pep <br><br> SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla 10 GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla HisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg PheLeuMeCLeuValGlyGlySerThrLeuCysValArgGluPhe 15 (SEQ ID NO:161) <br><br> pMON28548pep <br><br> SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis 20 ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValHetAlaAlaArgGlyGln LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla 25 HisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg PheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAla SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu Le-uProAlaValAspPheSerLeuGlyGluTrpLysThrGlriMetGluGluThrLysAla 30 GluAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnGlyArgThrThrAlaHisLysAspPro AsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysvalArgPheLeuMetLeu ValGlyGlySerThrLeuCysValArg (SEQ ID NO:162) <br><br> 35 <br><br> pMON2 8500 <br><br> SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu 40 LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla HisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg 45 PheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSer ProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisVal LeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeu ProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGln AspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeu 50 GlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeu GlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHis <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 123 <br><br> PCT/US96/15774 <br><br> LysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPhe LeuMetLeuValGlyGlySerThrLeuCysValArg (SEQ ID NO:163) <br><br> pM0N2 8501 <br><br> 5 <br><br> SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln 10 LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla HisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg PheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAla SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis 15 ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla GlrvAspIleLeuGlyAlaValThrLeuLeuLeuGluG lyValMetAlaAlaArgGlyGln LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla 20 HisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg PheLeuMetLeuValGlyGlySerThrLeuCysValArg (SEQ ID NO:164) <br><br> PMON28502 <br><br> 25 SerProAlaProProAlaCysAspLeuArgvalLeuSerLysLeuLeuArgAspSerHis ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu 3 0 LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla HisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg PheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGly AsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArg AspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThr <br><br> 3 5 ProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu <br><br> ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAla ArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnVal ArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArg ThrThrAlaHisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGly <br><br> 4 0 LysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg <br><br> (SEQ ID NO:165) <br><br> 13182.Pept <br><br> 45 <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser <br><br> He <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> 50 <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 124 <br><br> PCT/US96/15774 <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> (s: <br><br> EQ ID NO: <br><br> : 166) <br><br> 15 <br><br> 13183.Pept <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> (SEQ ID <br><br> NO: <br><br> 167) <br><br> 40 <br><br> 13184.Pept <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> 45 <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala Gly <br><br> Asp <br><br> Trp <br><br> 50 <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 125 <br><br> PCT/US96/15774 <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> (SEQ ID <br><br> NO:: <br><br> 168) <br><br> 15 13185.Pept <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> 20 <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> 25 <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> 30 <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> 35 <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly <br><br> lie <br><br> Ser <br><br> (SEQ ID <br><br> NO:: <br><br> 169) <br><br> 40 <br><br> 13186.Pept <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> 45 <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> 50 <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 126 <br><br> PCT/US96/15774 <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr Gin Gly Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> (SEQ ID <br><br> NO: <br><br> 170) <br><br> 13187.pept <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Sei <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> GlU <br><br> Leu <br><br> Gly <br><br> (SEQ ID <br><br> NO: <br><br> 171) <br><br> 40 13188.pept <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 127 <br><br> PCT/US96/15774 <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID <br><br> NO:! <br><br> 172) <br><br> 13189.Pept <br><br> 15 <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala <br><br> Il._ <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> 20 <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> 25 <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> 30 <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly <br><br> lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> 35 <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID <br><br> NO:: <br><br> 173) <br><br> 13190.Pept <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 128 <br><br> PCT/US96/15774 <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> 5 <br><br> Ser <br><br> Gly <br><br> Len <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly <br><br> lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> 10 <br><br> Phe <br><br> Ala <br><br> (SEQ ID <br><br> NO:174) <br><br> 13191.Pept <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> 15 <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly Asp <br><br> Trp <br><br> 20 <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> 25 <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Alf. <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> 30 <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu Gly <br><br> lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> 35 <br><br> Phe <br><br> Ala <br><br> (SEQ ID <br><br> NO: <br><br> 175) <br><br> 13192.Pept <br><br> 40 <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> 45 <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> 50 <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 129 <br><br> PCT/US96/15774 <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> (SEQ ID <br><br> NO: <br><br> 176) <br><br> 10 <br><br> 13193.Pept <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> (SEQ ID <br><br> NO:: <br><br> 177) <br><br> 35 <br><br> 25190.pept <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> 40 <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> 45 <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> 50 <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin Gly Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 130 <br><br> PCT/US96/15774 <br><br> Pro <br><br> Leu <br><br> Gl&gt; <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin Gly Asp Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> 5 <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> (SEQ ID <br><br> NO:178) <br><br> 10 <br><br> pMON2 5191.Pep <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> 15 <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu Gly Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> 20 <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu Gly Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thi <br><br> Gin Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> 25 <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly Gly Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> 30 <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> (SEQ ID <br><br> NO: <br><br> 179) <br><br> 35 <br><br> 13194.Pept <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> 40 <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> 45 <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> 50 <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 131 <br><br> PCT/US96/15774 <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> (SEQ ID <br><br> NO:; <br><br> 180) <br><br> 13195.pept <br><br> 10 <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> 15 <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> 20 <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> 25 <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> 30 <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> (SEQ ID <br><br> NO:: <br><br> 181) <br><br> 35 13196.Pept <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> 40 <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> 45 <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> 50 <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 132 <br><br> PCT/US96/15774 <br><br> Ala <br><br> Leu <br><br> Gill <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID <br><br> NO: <br><br> 182) <br><br> 13197.Pept <br><br> 10 <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> 15 <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> 20 <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> 25 <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> 30 <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID <br><br> NO:: <br><br> 183) <br><br> 13198.Pept <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly Gly Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 133 <br><br> PCT/US96/15774 <br><br> Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin Pro Thr Gin Gly Ala Met Pro Ala Phe Ala (SEQ ID NO:184) <br><br> 5 <br><br> 13199.Pept <br><br> 10 Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr 15 Ala Ala Pro Ser Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Ser Ala Phe Gin 20 Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu 25 Leu Val Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met 3 0 Glu Glu Leu Gly Met Ala Pro Ala Leu Gin Pro Thr Gin Gly Ala Met Pro Ala Phe Ala (SEQ ID NO:185) <br><br> 31104.Pep <br><br> 35 <br><br> Leu Asp Pro Asn Asn Leu Asp Arg Asn Leu Arg Leu Val Lys Asn Leu Glu Asn Asn Leu Gin Pro Cys Leu 40 His Pro lie lie lie Lys Lys Leu Thr Phe Tyr Leu Gin Gly Gly Gly Ser Asn His His Leu Lys Arg Pro Gly Gly Ser Pro Gly Glu 45 Pro Ser Pro Pro Ser Lys Thr Gin Gly Ala Met Pro Ala Gly Gly Val Leu Val Val Ser Tyr Arg Val Leu Ser Gly Gly Ser Gin Ser 50 Arg Lys lie Gin Gly Asp Ala Thr Tyr Lys Leu Cys His Ser Leu Gly lie Pro <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Gly Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 134 <br><br> Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin Pro (SEQ ID NO:186) <br><br> 31105.Pep <br><br> 10 <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> 15 <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Va^ <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> 20 <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin Gly Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> 25 <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> 30 <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID NO <br><br> : 187) <br><br> 31106.Pep <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 135 <br><br> PCT/US96/15774 <br><br> Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala <br><br> Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met 5 Ala Pro Ala Leu Gin Pro (SEQ ID NO:188) <br><br> 31107.Pep <br><br> 10 <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> 15 <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> 20 <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> 25 <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Lev. <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> 30 <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID NO <br><br> :189) <br><br> 31108.pep <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> PCT/US96/15774 <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> 5 <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID NO: <br><br> 190) <br><br> 31109.Pep <br><br> 10 <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser Gly Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> 15 <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> 20 <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> 25 <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu Gin Leu Ala Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> 30 <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID NO:191) <br><br> 31110.Pep <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 137 <br><br> PCT/US96/15774 <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID NO:192) <br><br> 31111.Pep <br><br> 10 <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu <br><br> lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> 15 <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie <br><br> lie lie <br><br> Lys <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> 20 <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lyi: <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> 25 <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> 30 <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID NO:193) <br><br> pMONl5981 <br><br> 35 <br><br> MetAlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAla ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer GlylleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro 40 SerArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaTyrLysLeuCysHisProGluGluLeuValLeuLeu GlyHisSerLeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln 45 LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln AlaLeuGluGlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVal AlaAspPheAlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu GlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGly ValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHis 50 LeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeu ProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAla AlaLeuGlnGluLysLeuCysAlaThr (SEQ ID NO:194) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 138 <br><br> PCT/US96/15774 <br><br> PMON15982 <br><br> MetAlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAla 5 ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer GlylleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro SerArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly 10 SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaProGluLeuGlyProThrLeuAspThrLeuGlnLeu AspValAlaAspPheAlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaPro AlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAla GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeu 15 ArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSer SerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAsp GlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeu ValLeuLeuGlyHisSerLeuGlylleProTrpAlaProLeuSerSerCysProSerGln AlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGly 20 LeuLeuGlnAlaLeuGluGlylleSer (SEQ ID NO:195) <br><br> pMONl5965 <br><br> MetAlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAla 25 ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer GlylleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro SerArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly 30 SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaSerAlaPheGlriArgArgAlaGlyGlyValLeuVal AlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGln ProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSer PheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGln 35 GluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHis SerLeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAla GlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeu GluGlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAsp PheAlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro 40 ThrGlnGlyAlaMetProAlaPheAla (SEQ ID NO:196) <br><br> pMONl5966 <br><br> MetAlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAla 45 ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer GlylleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro SerArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly 50 SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaMetAlaProAlaLeuGlnProThrGlnGlyAlaMet ProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeu <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> PCT/US96/15774 <br><br> GlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGly SerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLys SerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCys AlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlylle 5 ProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer GlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlylleSer ProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThr IleTrpGlnGlnMetGluGluLeuGly (SEQ ID NO:197) <br><br> 10 pMONl5967 <br><br> MetAlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAla ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer 15 GlylleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro SerArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysScrProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe 20 GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer TyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeu GlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLys HeGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHis ProGluGluLeuValLeuLeuGlyHisSerLeuGlylleProTrpAlaProLeuSerSer 25 CysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyL.euPhe LeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlylleSerProGluLeuGlyProThrLeu AspThrLeuGlnLeuAspValAlaAspPheAlaThrThrlleTrpGlnGlnMetGluGlu LeuGlyMetAlaProAlaLeuGlnPro (SEQ ID NO:198) <br><br> 30 <br><br> pMON31112.pep <br><br> MetAlaAsnCysSerAsnMetlleAspGluIlelleThrHisLeuLysGlnProProLeu 3 5 ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsn LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer AlalleGluSerlleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro ThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThr PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly 40 SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer TyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPhe LeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu 45 LysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSer LeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGlu GlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPhe AlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro 50 (SEQ ID NO:199) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 140 <br><br> PCT/US96/15774 <br><br> PMON31113.pep <br><br> MetAlaAsnCysSerAsnMetlleAspGluIlelleThrHisLeuLysGlnProProLeu ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsn 5 LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer AlalleGluSerlleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro ThrArgHisProIlellelleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThr PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu 10 SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer TyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuPro GlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla LeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeu 15 GlyHisSerLeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln AlaLeuGluGlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVal AlaAspPheAlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu GlnPro (SEQ ID N0:200) <br><br> 20 <br><br> pMON31114.pep <br><br> MetAlaAsnCysSerAsnMetlleAspGluIlelleThrHisLeuLysGlnProProLeu 25 ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsn LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer AlalleGluSerlleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro ThrArgHisPi c. IlellelleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThr PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly 30 serProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer TyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPhe LeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu 3 5 LysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSer LeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGlu GlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPhe AlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro 40 (SEQ ID NO:201) <br><br> pMON31115.pep <br><br> 45 MetAlaAsnCysSerAsnMetlleAspGluIlelleThrHisLeuLysGlnProProLeu ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsn LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer AlalleGluSerlleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro ThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThr <br><br> 50 PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 141 <br><br> PCT/US96/15774 <br><br> GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer TyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuPro GlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla LeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeu 5 GlyHisSerLeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln AlaLeuGluGlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVal AlaAspPheAlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu GlnPro (SEQ ID NO:202) <br><br> 10 <br><br> pMON28505 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro 15 LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer 20 ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGluValHisProLeuProThrProValLeuLeuProAlaVal AspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeu GlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThr CysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeu 25 GlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspPro AsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeu ValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaPro ProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSer ArgLeuSerGlnCysPro (SEQ ID NO:203) <br><br> 30 <br><br> PMON28506 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu 35 ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly HeGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIiellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer 40 HisLysSerProAsriMetLeuProThrProValLeuLeuProAlaValAspPheSerLeu GlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThr LeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSer LeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeu GlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlallePhe 45 LeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySer ThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAsp LeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGln CysProGluValHisPro (SEQ ID NO:204) <br><br> 50 pMON28507 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 142 <br><br> PCT/US96/15774 <br><br> LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsr\LeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly HeGluAlaIleLeuArgAsnLeuGlnProCysI.euProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe 5 TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLys ThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGlu GlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGln 10 LeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeu ProProGlnGlyArgThrThrAlaHisLysAspProAsnAlallePheLeuSerPheGln HisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal ArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeu SerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluVal 15 HisProLeuProThrPro (SEQ ID N0:205) <br><br> pMON2 8508 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro 20 LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer 2 5 ProGlyGluPzoSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly 30 ArgThrThrAlaHisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArg GlyLy sVa1Arg PheLeuMetLeuValGlyGlyS erThrLeuCysValAr gGluPheGly GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro ThrProValLeuLeuPro (SEQ ID NO:206) <br><br> 35 <br><br> PMON2 8509 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspvalSerlleLeuMetAspArgAsnLeu 40 ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlallelieuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer 45 HisLysSerProAsnMetAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThr LysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArg GlyGlnLeuGlyProThrCysLieuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArg LeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThr ThrAlaHisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLys 50 ValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsn MetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAsp SerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 143 <br><br> PCT/US96/15774 <br><br> ValLeuLeuProAlaVal (SEQ ID NO:207) <br><br> PMON2 8510 <br><br> 5 AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe 10 TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAsp IleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGly ProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGly 15 AlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys AspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMetAlaSerPro AlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeu HisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuPro 20 AlaValAspPheSerLeu (SEQ ID NO:208) <br><br> pMON2 8511 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro 25 LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer 30 ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsriMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln GlyArgThrThrAlaHisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeu ArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe 3 5 GlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeu LeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeu ProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMet GluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMet AlaAlaArgGlyGlnLeu (SEQ ID NO:209) <br><br> 40 <br><br> pMON2 8512 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu 45 ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer 50 HisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys AspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsriMetAlaSerPro <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 144 <br><br> PCT/US96/15774 <br><br> AlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeu HisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuPro AlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAsp IleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGly 5 ProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGly AlaLeuGlnSerLeuLeu (SEQ ID NO-.210) <br><br> pMON2 8513 <br><br> 10 AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe 15 TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGlyArgThrThrAlaHisLysAspProAsnAlallePheLeu SerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThr LeuCysValArgGluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspIieu 20 ArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCys ProGluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGly GluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeu LeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeu LeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGly 25 ThrGlnLeuProProGln (SEQ ID NO-.211) <br><br> PMON28514 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro 30 LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer 3 5 ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAlaHisLysAspProAsnAlallePheLeuSerPheGlnHis LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg GluPheGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSer LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis 40 ProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThr GlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGly ValMetAlaAiaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeu SerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuPro ProGlnGlyArgThrThr (SEQ ID NO:212} <br><br> 45 <br><br> pMON2 8515 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu 50 ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 145 <br><br> PCT/US96/15774 <br><br> TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArg GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly 5 GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu ArgAspSerHifValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlriMetGlu GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln 10 ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly ArgThrThrAlaHisLys (SEQ ID NO-.213) <br><br> PMON28516 <br><br> 15 AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe 20 TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysVal ArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnMet AlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer <br><br> 2 5 HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVal <br><br> LeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLys AlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGly GlnLeuGlyF-oThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeu LeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThr 30 AlaHisLysAspProAsn (SEQ ID NO:214) <br><br> PMON2 8519 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuIiysArgProProAlaPro <br><br> 3 5 LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu <br><br> ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer 40 ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGluValHisProLeuProThrProValLeuLeuProAlaVal AspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeu GlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThr CysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeu <br><br> 4 5 GlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspPro <br><br> AsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeu ValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAlaProPro AlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArg LeuSerGlnCysPro (SEQ ID NO:215) <br><br> 50 <br><br> PMQN28520 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 146 <br><br> PCT/US96/15774 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer 5 ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetLeuProThrProValLeuLeuProAlaValAspPheSerLeu GlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThr 10 LeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSer LeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeu GlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlallePhe LeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySer ThrLeuCysVaiArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeu 15 ArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCys ProGluValHisPro (SEQ ID NO:216) <br><br> pMON2 8521 <br><br> 20 AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe 25 TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLys ThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGlu GlyValMetAlaAlaArgGlyGInLeuGly ProThrCy sLeuS erS erLeuLeuGlyGIn 30 LeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeu ProProGlnGlyArgThrThrAlaHisLysAspProAsnAlallePheLeuSerPheGln HisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal ArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSer LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis 35 ProLeuProThrPro (SEQ ID NO:217) <br><br> PMON28522 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro 40 LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGInAlaGInGluGInGInTyrVa1GluGlyGlyGlyGlyS er 45 ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly 50 ArgThrThrAlaHisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArg GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly AsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArg <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 147 <br><br> PCT/US96/15774 <br><br> AspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThr ProValLeuLeuPro (SEQ ID NO:218) <br><br> PMON28523 <br><br> 5 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisIieuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer 10 ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThr LysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArg 15 GlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArg LeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThr ThrAlaHisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLys ValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnHet AlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer 20 HisValLeuHisSerArgLeuSerGlnCysProGluValHisF-roLeuProThrProVal LeuLeuProAlaVal (SEQ ID NO:219) <br><br> pMON2 8524 <br><br> 25 AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe 30 TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAsp IleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGly ProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGly 35 AlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys AspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAla ProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHis SerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAla 40 ValAspPheSerLeu (SEQ ID N0:220) <br><br> PMON28525 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro 45 LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer 50 ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 148 <br><br> PCT/US96/15774 <br><br> GlyArgThrThrAlaHisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeu ArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro 5 ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla AlaArgGlyGlnLeu (SEQ ID NO:221) <br><br> PMON28526 <br><br> 10 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer 15 ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGl'uGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys AspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu 20 MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAla ProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHis SerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeuLeuProAla ValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIle LeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyPro 25 ThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAla LeuGlnSerLeuLeu (SEQ ID NO:222) <br><br> pmon28527 <br><br> 30 AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaP'roSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe 35 TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGlyArgThrThrAlaHisLysAspProAsnAlallePheLeu SerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThr LeuCysValArgGluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArg 40 ValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysPro GluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGlu TrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeu LeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeu GlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThr 45 GlnLeuProProGln (SEQ ID NO:223) <br><br> pMON2 8528 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro 50 LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 149 <br><br> PCT/US96/15774 <br><br> ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAlaHisLysAspProAsnAlallePheLeuSerPheGlnHis 5 LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg GluPheGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLys LeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisPro LeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGln MetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyVal 10 MetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSer GlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProPro GlnGlyArgThrThr (SEQ ID NO:224) <br><br> pMON2 8529 <br><br> 15 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer 20 ArgHisProII-ellelleliysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArg GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly 25 AsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArg AspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThr ProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAla ArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnVal 30 ArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArg ThrThrAlaHisLys (SEQ ID NO:22 5) <br><br> pMON2 853 0 <br><br> 35 AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe 40 TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysVal ArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAla SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis 45 ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla 50 HisLysAspProAsn (SEQ ID NO:226) <br><br> pmon28533 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 150 <br><br> PCT/US96/15774 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly 5 IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGl-uPioSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGluValHisProLeuProThrProValLeuLeuProAlaVal 10 AspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeu GlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThr CysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeu GlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspPro AsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeu 15 ValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSer FroAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisVal LeuHisSerArgLeuSerGlnCysPro (SEQ ID NO:227) <br><br> pMON2 8534 <br><br> 20 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer 25 ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetLeuProThrProValLeuLeuProAlaValAspPheSerLeu GlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThr 30 LeuLeuLeuGauGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSer LeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeu GlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLysAspProAsnAlallePhe LeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySer ThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProPro 35 AlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArg LeuSerGlnCysProGluValHisPro (SEQ ID NO:228) <br><br> pMON2 853 5 <br><br> 40 AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe 45 TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLys ThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGlu GlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGln 50 LeuSerGlyGlnValArgLeuLeuLeuGlyAlaLieuGlnSerljeuLeuGlyThrGlnLeu ProProGlnGlyArgThrThrAlaHisLysAspProAsnAlallePheLeuSerPheGln HisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 151 <br><br> PCT/US96/15774 <br><br> ArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeu ArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCys ProGluValHisProLeuProThrPro (SEQ ID NO:229) <br><br> 5 pMON28536 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly 10 IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProllellelleLysAlaGlyAspTrpGlnGluPheArgGluLysIjeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu 15 GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly ArgThrThrAlaHisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArg GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly 20 GlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSer LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis ProLeuProThrProValLeuLeuPro (SEQ ID NO:230) <br><br> pMON2 8537 <br><br> 25 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer 30 ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrlieuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProlleserThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThr LysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArg 35 GlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArg LeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThr ThrAlaHisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLys ValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsn GlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeu 40 LeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeu ProThrProValLeuLeuProAlaVal (SEQ ID NO:231) <br><br> pMON2 8538 <br><br> 45 AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe 50 TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAsp <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 152 <br><br> PCT/US96/15774 <br><br> IleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGly ProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGly AlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys AspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu 5 MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMet AlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVal LeuLeuProAlaValAspPheSerLeu (SEQ ID NO:232) <br><br> 10 pMON28539 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnlieuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly 15 IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 20 GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln GlyArgThrThrAlaHisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeu ArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe GlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeu SerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluVal 25 HisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLys ThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGlu GlyValMetAlaAlaArgGlyGlnLeu (SEQ ID NO:233) <br><br> PMON28540 <br><br> 30 <br><br> AlaAsnCysSe^IleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLjeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly HeGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer 35 ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys AspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu 40 MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMet AlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVal LeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLys AlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGly 45 GlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeu LeuLeuGlyAlaLeuGlnSerLeuLeu (SEQ ID NO:234) <br><br> pMON2 8541 <br><br> 50 AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 153 <br><br> PCT/US96/15774 <br><br> IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer 5 HisLysSerProAsnMetGlyArgThrThrAlaHisLysAspProAsnAlallePheLeu SerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThr LeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAla CysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeu SerGlnCysProGluValHisProLeuProThrProValLeuLeuProAlaValAspPhe 10 SerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAla ValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeu SerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSer LeuLeuGlyThrGlnLeuProProGln (seq ID NO:235) <br><br> 15 pMON28542 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly 20 IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAlaHisLysAspProAsnAlallePheLeuSerPheGlnHis 25 LeuLeuArgGlyLysValArgPheLeuMetLe-uValGlyGlySerThrLeuCysValArg GluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArg ValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysPro GluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGlu TrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeu 30 LeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeu GlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeubeuGlyThr GlnLeuProProGlnGlyArgThrThr (SEQ ID NO:236) <br><br> PMON28543 <br><br> 35 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer 40 ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAspProAsnAlaliePheLeuSerPheGlnHisLeuLeuArg GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly 45 GlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSer LysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis ProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThr GlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGly ValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeu 50 SerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuPro ProGlnGlyArgThrThrAlaHisLys (SEQ ID NO:237) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 154 <br><br> PCT/US96/15774 <br><br> pM0N2 8544 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu 5 ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer 10 HisLysSerProAsriMetAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysVal ArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGly GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu 15 GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly ArgThrThrAlaHisLysAspProAsn (SEQ ID NO:238) <br><br> 20 pMON28545 <br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly 25 IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThtLeuGluGlnAlaGlnGluGlnGInTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArg 30 GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly GlyAsnMeCAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu ArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuPro ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 3 5 AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnGlyArgThrThrAla HisLys (SEQ ID NO-.239) <br><br> 40 pMON3 2132 <br><br> SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla 45 GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGln LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla HisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg PheLeuMetLeuValGlyGlySerThrLeuCysValArg (SEQ ID NO:252) <br><br> 50 <br><br> PMON3 2133 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/11985 <br><br> 155 <br><br> PCT/US96/15774 <br><br> SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla 5 GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluG lyValMetAlaAlaArgGlyGln LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnGlyArgThrThrAlaHisLysAspPro AsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeu ValGlyGlySerThrLeuCysValArg (SEQ id NO:253) <br><br> 10 <br><br> pmon32134 <br><br> SerProAlaPrc.ProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHis 15 ValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProValLeu LeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAla GlnAspIleLeuGlyAlaValThrLeuLeuLeuGluG lyValMetAlaAlaArgGlyGln LeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeuLeu LeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGlyArgThrThrAla 20 HisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArg PheLeuMetLeuValGlyGlySerThrLeuCysValArg (SEQ ID NO:254) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 156 <br><br> PCT/US96/15774 <br><br> The following examples will illustrate the invention in greater detail although it will be understood that the invention is not limited to these specific examples. <br><br> EXAMPLE 1 <br><br> Construction of parental BHK expression vector <br><br> A. Removal of AflHI site from mammalian expression plasmid. <br><br> A new mammalian expression vector was constructed to accept Ncol-Hindlll or Afllll-Hindlll gene fragments in-frame and 3' to the hIL-3 receptor agonist pMON13146 (WO 94/1263 8) gene and a mouse IgG2b linker fragment. First, the single AflHI site was removed from pMON393 4, which is a derivative of pMON3 3 59. pMON3 3 59 is a pUC18~based vector containing a mammalian expression cassette. The cassette includes a herpes simplex viral promoter IE110 (-800 to +120) followed by a modified human IL-3 signal peptide sequence and an SV40 late poly-adenylation (poly-A) signal which has been subcloned into the pUC18 polylinker (See Hippenmeyer et al., Bio/Technology, 1993, pp.1037-1041). The modified human IL-3 signal sequence, which facilitates secretion of gene products outside of the cell, is flanked by a BamHI site on the 5' end and a unique Ncol site on the 3' end. A unique Hindlll site is 3' to the Ncol site and 5' to the poly-A sequence. The DNA sequence encoding the signal peptide is shown below (restriction enzyme sites are indicated above). The ATG (methionine) codon within the Ncol site is in-frame with the initiator ATG of the signal peptide (underlined); <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 157 <br><br> PCT/US96/15774 <br><br> BamHI Ncol <br><br> 5' GGATCCACCATGAGCCGCCTGCCCGTCCTGCTCCTGCTCCAACTCCTGGTCCGCCCCGCCATGG <br><br> (SEQ ID NO:255! <br><br> The single AflHI site was removed from pMON3934 by 5 digestion with AflHI followed by filling in the overhangs by addition of a DNA polymerase and nucleotides. The digested DNA fragment was purified via Magic PCR Clean up kit (Promega) and ligated with T4 DNA ligase. The ligation reaction was transformed into DH5a™ and the cells were <br><br> 10 plated onto LB-agar plus ampicillin. Individual colonies were screened for the loss of the AflHI site by restriction analysis with AflHI and Hindlll which results in a single fragment if the AflHI site was removed. The resulting plasmid was designated pMON30275. <br><br> 15 <br><br> B. Transfer of hIL-3 receptor agonist pMON13416/IgG2b cassette into pMON30275. <br><br> The Ncol-Hindlll fragment (ca. 425 bp) from pMON30245 20 was ligated to the Ncol-Hindlll fragment (ca. 3800 bp) of the pMON30275. pMON30245 (WO 94/12638) contains the gene coding for hIL-3 receptor agonist pMON13416 joined to a mouse IgG2b hinge fragment. Immediately 3' to the lgG2b hinge and 5' to the Hindlll site is an AflHI site. Genes 25 can be cloned into the Afllll-Hindlll sites as Ncol-Hindlll or AfIIII-Hindlll fragments in frame with the hIL-3 variant pMON13416/IgG2b hinge to create novel chimeras. The Ncol site and the AflHI site have compatible overhangs and will ligate but both recognition sites are lost. The plasmid, 30 pMON30304 containing the DNA sequence of (SEQ ID NO:78), <br><br> coding for hIL-3 variant pMON13416 joined with a mouse IgG2b hinge region, was a result of this cloning. <br><br> 35 EXAMPLE 2 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 158 <br><br> PCT/US96/15774 <br><br> Construction of an intermediate plasmid containing one copy of the c-mpl liaand (1-1531 aene of the dimer template in order to generate a plasmid DNA with the coding sequence of c-mpl (1-153) ligand followed by a unique EcoRI restriction site, the gene is isolated via reverse transcriptase/polymerase chain reaction (RT/PCR). Human fetal (lot #38130) and adult liver (lot #46018) A+ RNA are obtained from Clontech (Palo Alto, CA) for source of c-mpl ligand messenger RNA (mRNA). The first strand cDNA reactions are carried out using a cDNA Cycle™ Kit obtained from Invitrogen (San Diego, CA). In the RT reaction, random primers and oligo dT primer are used to generate cDNA from a combination of human and fetal liver mRNA. For amplification of c-mpl ligand gene fragment encoding amino acids 1-153, the RT product serves as the template for PCR with a combination of the primers, Forward primer: c-mplNcol (SEQ ID NO:13) and Reverse primer: Ecompl. The c-mplNcol primer anneals to the c-mpl ligand gene (bases #279-311 based on c-mpl ligand sequence from Gene bank accession #L33410 or de Sauvage et al., Nature 369: 533-538 (1994)) and encodes a Ncol restriction enzyme site immediately 5' to the first codon (Ser+1) of c-mpl ligand. The Ncol restriction enzyme site codes for methionine and alanine codons prior to Ser+1 and includes codon degeneracy for the Ala codon and the first four codons (Ser, Pro, Ala, &amp; Pro) of c-mpl ligand. The Ecompl primer anneals to bases #720-737 of c-mpl ligand and encodes an EcoRI site (GAATTC) in-frame with the c-mpl ligand gene immediately following Arg-153. The EcoRI site creates Glu and Phe codons following Arg-153. The ca. 480 bp PCR product was purified, digested with Ncol and EcoRI and ligated to the NcoI-EcoRI vector fragment of pMON3993 (ca. 4550 bp.). pMON3993 was a derivative of pMON3359 (described in Example 1). The human <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 159 <br><br> PCT/US96/15774 <br><br> IL-3 signal peptide sequence, which had been subcloned as a BamHI fragment into the unique BamHI site between the IE110 promoter and poly-A signal, contains an Ncol site at its 3' end and is followed by a unique EcoRI site. The plasmid, pMON26458 containing the DNA sequence of (SEQ ID NO:79), coding for c-mpl ligand amino acids 1-153 (SEQ ID N0-.161), was the result of this cloning. <br><br> example 3 <br><br> Construction of the parental plasmids containing the second genes of the dimer templates <br><br> For amplification of c-mpl ligand gene fragments starting at amino acid 1 (Ser) with a termination codon following amino acid 153 (Arg), the RT reaction from Example 2 serves as the template for PCR with a combination of the following primers; c-mplNcol (SEQ id NO:13) (forward primer) and c-mplHindlll (SEQ id NO:15) (reverse primer). The c-mplNcol (SEQ id NO:13) primer is described in Example 2. The c-mplHindiu (SEQ id NO:15) primer, which anneals to bases #716-737 of c-mpl ligand, adds both a termination codon and a Hindlll restriction enzyme site immediately following the final codon, Arg^-53 <br><br> Two types of pcr products are generated from the rt cDNA samples, one with a deletion of the codons for amino acids 112-115 and one without the deletion of these codons. The c-mpl ligand pcr products (ca. 480 bp) are digested with Ncol and Hindlll restriction enzymes for transfer to a mammalian expression vector, pMON3934. pMON3934 is digested with Ncol and Hindlll (ca. 3800 bp) and will accept the pcr products. <br><br> Plasmid, pMON32132 (SEQ id NO:249), coding for c-mpl ligand amino acids 1-153 (SEQ id NO:252) was a result of <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 160 <br><br> PCT/US96/15774 <br><br> this cloning. Plasmid, pMON32134 (SEQ ID NO:250), coding for c-mpl ligand amino acids 1-153 (SEQ ID NO:253) was a result of this cloning. Plasmid, pMON32133 (SEQ ID NO:251), coding for c-mpl ligand amino acids 1-153 with a deletion of codons 112-115 (A112-115) (SEQ ID NO:254) was also a result of this cloning. <br><br> EXAMPLE 4 <br><br> Generation of PCR dimer template 5L with a A112-115 deletion in the second c-mpl liaand aene <br><br> A PCR template for generating novel forms of c-mpl ligand is constructed by ligating the 3.7 Kbp BstXI/EcoRI fragment of pMON26458 to the 1 Kbp NcoI/BstXI fragment from PMON32133 (containing a deletion of amino acids 112-115) along with the EcoRI/AflHI 5L synthetic oligonucleotide linker 5L-5' (SEQ ID NO:18) and 5L-3' (SEQ ID NO:19). <br><br> The EcoRI end of the linker will ligate to the EcoRI end of pMON26458. The AflHI end of the linker will ligate to the Ncol site of pMON32133, and neither restriction site will be retained upon ligation. The BstXI sites of pMON26458 and pMON32133 will ligate as well. Plasmid, pMON28548, is a result of the cloning and contains the DNA sequence of (SEQ ID N0:80) which encodes amino acids 1-153 c-mpl ligand fused via a GluPheGlyGlyAsnMetAla (SEQ ID NO:222) linker to amino acids 1-153 c-mpl ligand that contains a deletion of amino acids 112-115 (SEQ ID NO-.162). <br><br> example 5 <br><br> Generation of PCR dimer template 4L <br><br> A PCR template for generating novel forms of c-mpl ligand is constructed by ligating the 3.7 Kbp BstXI/EcoRI <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 161 <br><br> PCT/US96/15774 <br><br> fragment of pMON26458 to the 1 Kbp NcoI/BstXI fragment from pMON32132 along with the EcoRI/AflHI 4L synthetic oligonucleotide linker 4L-5' (SEQ ID NO:16) and 4L-3' (SEQ ID NO:17). <br><br> 5 The EcoRI end of the linker will ligate to the EcoRI <br><br> end of pMON26458. The AflHI end of the linker will ligate to the Ncol site of pMON32132, and neither restriction site will be retained upon ligation. The BstXI sites of pM0N26458 and pMON32132 will ligate as well. The plasmid, 10 pMON28SOO, is a result of the cloning and contains the DNA <br><br> sequence of (SEQ ID NO:82) which encodes amino acids 1-153 c-mpl ligand fused via a GluPheGlyAsnMetAla (SEQ ID NO:223) linker (4L) to amino acids 1-153 c-mpl ligand (SEQ ID NO:163). <br><br> 15 <br><br> EXAMPLE 6- <br><br> Generation of PCR dimer template 5L <br><br> 20 A PCR template for generating novel forms of c-mpl ligand is constructed by ligating the 3.7 Kbp BstXI/EcoRI fragment of pMON26458 to the 1 Kbp NcoI/BstXI fragment from pMON32132 along with the EcoRI/AflHI 5L synthetic oligonucleotide linker 5L-5' (SEQ ID NO:18) and 5L-3' (SEQ 25 ID NO:19). <br><br> The EcoRI end of the linker will ligate to the EcoRI end of pMON26458. The AfHII end of the linker will ligate to the Ncol site of pMON32132, and neither restriction site will be retained upon ligation. The BstXI sites of 30 pMON26458 and pMON32132 will ligate as well. Plasmid, <br><br> pMON28501 is a result of the cloning and contains the DNA sequence of (SEQ ID NO: 82) which encodes amino acids 1-153 c-mpl ligand fused via a GluPheGlyGlyAsnMetAla (SEQ ID N0:222) linker (5L) to amino acids 1-153 c-mpl ligand (SEQ 3 5 ID NO:164) . <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 162 <br><br> PCT/US96/15774 <br><br> EXAMPLE 7 <br><br> Generation of PCR dimer templates 81. <br><br> A PCR template for generating novel forms of c-mpl ligand is constructed by ligating the 3.7 Kbp BstXI/EcoRI fragment of pMON26458 to the 1 Kbp NcoI/BstXI fragment from pMON32134 along with the EcoRI/AflHI 8L synthetic oligonucleotide linker 8L-5' (SEQ ID N0:20) and 8L-3' (SEQ ID NO:21). <br><br> The EcoRI end of the linker will ligate to the EcoRI end of pMON26458. The AflHI end of the linker will ligate to the Ncol site of pM0N32134, and neither restriction site will be retained upon ligation. The BstXI sites of pM0N26458 and pM0N32134 will ligate as well. Plasmid, PMON28502 is a result of the cloning which contains the DNA sequence ot (SEQ ID NO:83) and encodes amino acids 1-153 c-mpl ligand fused via a GluPheGlyGlyAsnGlyGlyAsnMetAla (SEQ ID NO:224) linker (8L) to amino acids 1-153 c-mpl ligand (SEQ ID NO:165). <br><br> EXAMPLES S-44 <br><br> Generation of novel c-mpl liaand aenes with new N-terminus and C-terminus <br><br> A. PCR generation of genes encoding novel c-mpl ligand receptor agonists. <br><br> Genes encoding novel c-mpl ligand receptor agonists were generated using Method III (Horlick et al., Proc. Eng. 5:427-433, 1992 ). The PCR reactions were carried out using dimer templates, pMONs 28500, 28501, 28502 or 28548 and one of the sets of synthetic primer sets below (The first number <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 163 <br><br> PCT/US96/15774 <br><br> refers to the position of the first amino acid in the original sequence. For example, the 31-5' and 31-3' refers to the 5' and 3' oligo primers, receptively, for the sequence beginning at the codon corresponding to residue 31 5 of the original sequence.). <br><br> 31-5' (SEQ ID NO:22) and 31-3' (SEQ ID NO:23), 35-5' (SEQ ID NO:24) and 35-3' (SEQ ID NO:25), 39-5' (SEQ ID NO:26&gt; and 39-3' (SEQ ID NO:27), 43-5' (SEQ ID NO:28) and 43-3' (SEQ ID 10 NO:29), 45-5' (SEQ ID N0:30) and 45-3' (SEQ ID NO:31), 49-5' <br><br> (SEQ ID NO.-32) and 49-3' (SEQ ID NO:33), 82-5' (SEQ ID NO:34) and 82-3' (SEQ ID NO:35), 109-5' (SEQ ID NO:36) and 109-3' (SEQ ID NO:37), 115-5' (SEQ IDNO:38) and 115-3' (SEQ ID NO:3 9) , 120-5' (SEQ ID NO:40) and 120-3' (SEQ ID NO:41), 15 123-5' (SEQ ID NO:42) and 123-3' (SEQ IDNO:43), 126-5' (SEQ <br><br> ID NO:44) and 126-3' (SEQ ID NO:45). <br><br> The templates and oligonucleotide sets used in the PCR reactions are shown in Table 4. The products that were generated were about 480 bp and were purified via Magic PCR 20 Clean up kits (Promega). <br><br> B. Subcloning of novel c-mpl receptor agonist gene products into mammalian expression vector for generation of chimeras. <br><br> 25 <br><br> The c-mpl receptor agonist gene PCR products were digested with Ncol and Hindlll or AflHI and Hindlll restriction enzymes (ca. 470 bp) for transfer to a mammalian expression vector. The expression vector, pMON30304, was 3 0 digested with Ncol and Hindlll (ca. 4200 bp) and accepts the <br><br> PCR products as Ncol-Hindlll or AflIII-Hindlll fragments. The restriction digest of the PCR product and the resulting plasmids are shown in Table 4. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 164 <br><br> PCT/US96/15774 <br><br> table 4 <br><br> PCR Produce <br><br> PCR Product <br><br> Resulting <br><br> Breakpoint <br><br> Example <br><br> PCR_ template <br><br> Primer set <br><br> Restriction <br><br> Linker <br><br> Flasmid in c-mpl <br><br> Digest <br><br> pMON <br><br> ligand <br><br> Example <br><br> 6 <br><br> PMON28501 <br><br> 31 <br><br> Ncol/Hindlll <br><br> 51 <br><br> 28505 <br><br> 30-31 <br><br> Example <br><br> 9 <br><br> PMON28501 <br><br> 35 <br><br> Afllll/Hindlll <br><br> SL <br><br> 28506 <br><br> 34-35 <br><br> Example <br><br> 10 <br><br> PMON2 8501 <br><br> 39 <br><br> Ncol/Hindlll <br><br> 5L <br><br> 28507 <br><br> 36-39 <br><br> Example <br><br> 11 <br><br> PMON28501 <br><br> 43 <br><br> Ncol/Hlndlll <br><br> 5L <br><br> 28508 <br><br> 42-43 <br><br> Example <br><br> 12 <br><br> PMON28S01 <br><br> 45 <br><br> Ncol/Hindlll <br><br> 5L <br><br> 28509 <br><br> 44-45 <br><br> Example <br><br> 13 <br><br> pMON2 8501 <br><br> 49 <br><br> Ncol/Hindlll <br><br> 5L <br><br> 28510 <br><br> 48-49 <br><br> Example <br><br> 14 <br><br> pMON29SO: <br><br> 82 <br><br> Ncol/Hindlll <br><br> 5L <br><br> 2851! <br><br> 81-S2 <br><br> Example <br><br> 15 <br><br> PMON2B501 <br><br> 109 <br><br> Ncol/Hindlll <br><br> 5L <br><br> 28512 <br><br> 108-109 <br><br> Example <br><br> 16 <br><br> pl'.;'.28501 <br><br> 116 <br><br> Ncol/Hindlll <br><br> 5L <br><br> 28513 <br><br> 115-116 <br><br> Example <br><br> 17 <br><br> PMON28501 <br><br> 120 <br><br> Ncol/Hindlll <br><br> 5L <br><br> 28514 <br><br> 119-120 <br><br> Example <br><br> IS <br><br> PMON28501 <br><br> 123 <br><br> Ncol/Hindlll <br><br> 5L <br><br> 28515 <br><br> 122-123 <br><br> Example iy <br><br> PMON28501 <br><br> 126 <br><br> Ncol/Hindlll <br><br> 5L <br><br> 28516 <br><br> 125-126 <br><br> Example <br><br> 20 <br><br> PMON28500 <br><br> 31 <br><br> Ncol/Hindlll <br><br> 4L <br><br> 28519 <br><br> 3C-31 <br><br> Example <br><br> 21 <br><br> PMON28SOO <br><br> 35 <br><br> Af 1III/Hindi11 <br><br> 4L <br><br> 28520 <br><br> 34-35 <br><br> Example <br><br> 22 <br><br> PMON2 8500 <br><br> 39 <br><br> Ncol/Hindll1 <br><br> 4L <br><br> 28521 <br><br> 38-39 <br><br> Example <br><br> 23 <br><br> PMON28SOO <br><br> 43 <br><br> Ncol/Hindlll <br><br> 4L <br><br> 28522 <br><br> 42-43 <br><br> Example <br><br> 24 <br><br> PMON28500 <br><br> 45 <br><br> Ncol/Hindll I <br><br> 4 L <br><br> 28523 <br><br> 44-45 <br><br> Example <br><br> 25 <br><br> PMON28500 <br><br> 49 <br><br> Ncol/Hindlll <br><br> 4L <br><br> 28524 <br><br> 48-49 <br><br> Example <br><br> 26 <br><br> PMON2&amp;5C0 <br><br> 82 <br><br> Ncol/Hindlll <br><br> 4 L <br><br> 2&amp;525 <br><br> 81-82 <br><br> Example <br><br> 27 <br><br> pMC&gt;N28500 <br><br> 109 <br><br> Ncol/Hindlll <br><br> 4L <br><br> 28526 <br><br> 108-109 <br><br> Example <br><br> 28 <br><br> PMON28500 <br><br> 116 <br><br> Ncol/Hindlll <br><br> 4L <br><br> 28527 <br><br> 115-116 <br><br> Example <br><br> 29 <br><br> PMON285D0 <br><br> 120 <br><br> Ncol/Hindlll <br><br> 4L <br><br> 28528 <br><br> 119-120 <br><br> Example <br><br> 30 <br><br> PMQN26500 <br><br> 123 <br><br> Ncol/Hindi!I <br><br> 4 L <br><br> 28529 <br><br> 122-123 <br><br> Example <br><br> 31 <br><br> P«:1M28500 <br><br> 126 <br><br> Ncol/HindllI <br><br> 4 L <br><br> 28530 <br><br> 125-126 <br><br> Example <br><br> 32 <br><br> PMQN28502 <br><br> 31 <br><br> Nccl/Hindlll <br><br> 8L <br><br> 28533 <br><br> 30-31 <br><br> Example <br><br> 33 <br><br> PMON28502 <br><br> 35 <br><br> Afllll/Hindlll <br><br> 8L <br><br> 28534 <br><br> 34-35 <br><br> Example <br><br> 3 4 <br><br> PMON28502 <br><br> 39 <br><br> Ncol/KindllI <br><br> 8L <br><br> 28535 <br><br> 38-39 <br><br> Example <br><br> 35 <br><br> pMQN28502 <br><br> 43 <br><br> Ncol/Hindlll <br><br> SL <br><br> 26536 <br><br> 42-43 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> PCT/US96/15774 <br><br> 165 <br><br> TABLE 4 cont. <br><br> PCR Product <br><br> PCR Product <br><br> Resulting <br><br> Breakpoint <br><br> Example <br><br> « <br><br> PCE template <br><br> Primer set <br><br> Restrict ior. <br><br> Linker <br><br> Plasmid in c-mpl <br><br> Digest <br><br> pMON <br><br> ligand <br><br> Example <br><br> 36 <br><br> pt*'. W28502 <br><br> 45 <br><br> Ncol/Hindlll <br><br> BL <br><br> 28537 <br><br> 44-45 <br><br> Example <br><br> 37 <br><br> PMON2S502 <br><br> 49 <br><br> Ncol/Hindlll <br><br> 8L <br><br> 28538 <br><br> 48-49 <br><br> Example <br><br> 38 <br><br> pMON2 9 5 C 2 <br><br> 82 <br><br> Ncol/Hindlll <br><br> 31 <br><br> 28539 <br><br> 81-82 <br><br> Example <br><br> 39 <br><br> PMON28SQ2 <br><br> 109 <br><br> Ncol/Hindlll <br><br> 8L <br><br> 28540 <br><br> 108-109 <br><br> Example <br><br> 40 <br><br> PMDN28S02 <br><br> 116 <br><br> NcoT/Hindlll <br><br> 8L <br><br> 28541 <br><br> 115-116 <br><br> EXAMPLE <br><br> 41 <br><br> PMON28502 <br><br> 120 <br><br> Ncol/Hindlir <br><br> 8L <br><br> 28542 <br><br> 119-120 <br><br> Example <br><br> 42 <br><br> PMON28502 <br><br> 123 <br><br> Ncol/Hindlll <br><br> 8L <br><br> 28543 <br><br> 122-123 <br><br> Example <br><br> 43 <br><br> PMON28502 <br><br> 126 <br><br> Ncol/Hindlll <br><br> 8L <br><br> 28544 <br><br> 125-126 <br><br> Examp1e <br><br> 44 <br><br> PMON28S48' <br><br> 123 <br><br> Ncol/Hindlll <br><br> SL <br><br> 28545 <br><br> 122-123 <br><br> 5 <br><br> example 45 <br><br> Construction of PMON159 6Q <br><br> Construction of pMON15960, an intermediate plasmid used for 10 constructing plasmids containing DNA sequences encoding G- <br><br> CSF Ser^ with a new N-terminus and C-terminus. Plasmid pACYC177 (Chang, A.C.Y. and Cohen, S.N. J". Bacteriol. 134:1141-1156, 1978) DNA was digested with restriction enzymes Hindlll and BamHI, resulting in a 3 092 base pair 15 Hindlll, BamHI fragment. Plasmid, pMON13Q37 (WO 95/21254), <br><br> DNA was digested with BglH and Fspl, resulting in a 616 base pair BglH, Fspl fragment. A second sample of plasmid, pMON13037, DNA was digested with Ncol and Hindlll, <br><br> resulting in a 556 base pair Ncol, Hindlll fragment. The 20 synthetic DNA oligonucleotides lGGGSfor (SEQ ID NO:76) and lGGGSrev (SEQ ID NO:77) were annealed to each other, and then digested with AflHI and Fspl, resulting in a 21 base pair AflHI, Fspl fragment. The restriction fragments were ligated, and the ligation reaction mixture was used to <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 166 <br><br> PCT/US96/15774 <br><br> transform E, coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and analyzed by restriction analysis to confirm the correct insert. <br><br> EXAMPT.K 4 6 <br><br> Construction of PMON159 81 <br><br> Construction of pMONl5981, a plasmid containing DNA sequences encoding a multi-functional hematopoietic receptor agonist. Plasmid, pMONl5960, DNA was digested with restriction enzyme Smal and used as template in a PCR reaction using synthetic DNA oligonucleotides 3 8 stop (SEQ ID NO:65) and 39 start (SEQ ID NO:64) as primers, resulting in the amplification of a DNA fragment of 57 6 base pairs. The amplified fragment was digested with restriction enzymes Hindlll and Ncol, resulting in a Hindlll, Ncol fragment of 558 base pairs. Plasmid, pMON13181, DNA was digested with Hindlll and AflHI, resulting in a Hindlll, AflHI fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm the correct insert. The plasmid, pMONl5981, contains the" DNA sequence of (SEQ ID NO:155) which encodes the following amino acid sequence: <br><br> MetAlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAla ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer GlylleGluAlalleLieuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro SerArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaTyrLysLeuCysHisProGluGluLeuValLeuLeu GlyHisSerLeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln AlaLeuGluGlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVal <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 167 <br><br> PCT/US96/15774 <br><br> AlaAspPheAlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu GlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGly ValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHis LeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeu 5 ProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAla <br><br> AlaLeuGlnGluLysLeuCysAlaThr (SEQ ID NO:195) <br><br> EXAMPLE 47 <br><br> Construction of PMQN15.282 <br><br> 10 <br><br> Construction of pMONl5982, a plasmid containing DNA sequences encoding a multi-functional hematopoietic receptor agonist. Plasmid, pMON15960, DNA was digested with restriction enzyme Smal and used as template in a PCR 15 reaction using synthetic DNA oligonucleotides 96 stop (SEQ <br><br> ID NO:67) and 97 start (SEQ ID NO:66) as primers, resulting in the amplification of a DNA fragment of 576 base pairs. The amplified fragment was digested with restriction enzymes Hindlll and Ncol, resulting in a Hindlll, Ncol fragment of 20 558 base pairs. Plasmid, pMON13181, DNA was digested with <br><br> Hindlll and AflHI, resulting in a Hindlll, AflHI fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected 25 on ampicillin-containing plates. Plasmid DNA was isolated, <br><br> analyzed by restriction analysis, and sequenced to confirm the correct insert. The plasmid, pMONl5982, contains the DNA sequence of (SEQ ID NO:157) which encodes the following amino acid sequence: <br><br> 30 <br><br> MetAlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAla ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer GlylleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro 3 5 SerArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr <br><br> PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaProGluLeuGlyProThrLeuAspThrLeuGlnLeu AspValAlaAspPheAlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaPro 40 AlaLeuGlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAla <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 168 <br><br> PCT/US96/15774 <br><br> GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeu ArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSer SerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAsp GlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeu ValLeuLeuGlyHisSerLeuGlylleProTrpAlaProLeuSerSerCysProSerGln AlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGly LeuLeuGlriAlaLeuGluGlylleSer (SEQ ID NO: 196) <br><br> EXAMPLE 48 <br><br> Construction of PMON159 65 <br><br> Construction of pMON15965, a plasmid containing DNA sequences encoding a multi-functional hematopoietic receptor agonist. Fiasmid, pMON15960, DNA was digested with restriction enzyme Smal and used as template in a PCR reaction using synthetic DNA oligonucleotides 142 stop (SEQ ID NO:73) and 141 start (SEQ ID NO:72) as primers, resulting in the amplification of a DNA fragment of 576 base pairs. The amplified fragment was digested with restriction enzymes Hindlll and Ncol, resulting in a Hindlll, Ncol fragment of 558 base pairs. Plasmid, pMON13181, DNA was digested with Hindlll and AflHI, resulting in a Hindlll, AflHI fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm the correct insert. The plasmid, pMONl5965, contains the DNA sequence of (SEQ ID NO:157) which encodes the following amino acid sequence: <br><br> MetAlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAla ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer GlylleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro SerArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuVal <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 1S9 <br><br> PCT/US96/15774 <br><br> AlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGln ProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSer PheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGln GluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHis 5 SerLeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAla <br><br> GlyCysLeuSeiGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeu GluGlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAsp PheAlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro ThrGlnGlyAlaMetProAlaPheAla (SEQ ID NO:196) <br><br> 10 <br><br> EXAMPLE 49 <br><br> construction of PMON15966 <br><br> 15 Construction of pMONl5966, a plasmid containing DNA <br><br> sequences encoding a multi-functional hematopoietic receptor agonist. Plasmid, pMON15960, DNA was digested with restriction enzyme Smal and used as template in a PCR reaction using synthetic DNA oligonucleotides 126 stop (SEQ 20 ID NO-.68) and 125 start (SEQ ID NO-.69) as primers, <br><br> resulting in the amplification of a DNA fragment of 576 base pairs. The amplified fragment was digested with restriction enzymes Hindlll and Ncol, resulting in a Hindlll, Ncol fragment of 558 base pairs. Plasmid, pMON13181, DNA was 25 digested with Hindlll and AflHI, resulting in a Hindlll, <br><br> AflHI fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. <br><br> Transformant bacteria were selected on ampicillin-containing 30 plates. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm the correct insert. The plasmid, pMON15966, contains the DNA sequence of (SEQ ID NO:158) which encodes the following amino acid sequence: <br><br> 35 MetAlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAla <br><br> ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer GlylleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro SerArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysIjeuThr 4 0 PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly <br><br> Printed from Mimosa 08:37:19 <br><br> 170 <br><br> SerProGlyGluProS erGlyProIleS erThr11eAsnProS erProProS erLysGlu SerHisLysSerProAsnMetAlaMetAlaProAlaLeuGlnProThrGlnGlyAlaMet ProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeu GlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGly SerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheL.euLeuLys SerLeuGluGlriValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCys AlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlylle ProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer GlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlylleSer ProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThr IleTrpGlnGlnMetGluGluLeuGly (SEQ ID NO:197) <br><br> EXAMPLE 50 <br><br> Construction of PMON159 67 <br><br> Construction of pMON15967, a plasmid containing DNA sequences encoding a multi-functional hematopoietic receptor agonist. Plasmid, pMONl5960, DNA was digested with restriction enzyme Smal and used as template in a PCR reaction using synthetic DNA oligonucleotides 132 stop (SEQ ID NO:71) and 133 start (SEQ ID N0:70) as primers, resulting in the amplification of a DNA fragment of 576 base pairs. The amplified fragment was digested with restriction enzymes Hindlll and Ncol, resulting in a Hindlll, Ncol fragment of 558 base pairs. Plasmid, pMONl3181, DNA was digested with Hindlll and Afllll, resulting in a Hindlll, Afllll fragment of 4068 base pairs. The restriction fragments were ligated, and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm the correct insert. The plasmid, pMON15967, contains the DNA sequence of (SEQ ID NO: 159) which encodes the following amino acid sequence: <br><br> MetAlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAla ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer GlylleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro <br><br> 171 <br><br> SerArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer TyrArgValLeuArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeu GlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlriValArgLys IleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHis ProGluGluLeuValLeuLeuGlyHisSerLeuGlylleProTrpAlaProLeuSerSer Cy s Pro S erGInAlaLeuGlnLeuAlaGlyCysLeuSerGlnL euHisS erGlyLeuPhe LeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlylleSerProGluLeuGlyProThrLeu AspThrLeuGlnLeuAspValAlaAspPheAlaThrThrlleTrpGlnGlnMetGluGlu LeuGlyMetAlaProAlaLeuGlnPro (SEQ ID NO: 198) <br><br> EXAMPLE 51 <br><br> Construction of PMON1318Q, an intermediate plasmid used for constructing plasmids that contain DNA sequence encoding multi-functional hematopoietic receptor agonists. <br><br> Plasmid, pMONl3046 (WO 95/21254), DNA was digested with restriction endonucleases Xmal and SnaBI, resulting in a 4018 base pair vector fragment. The 4018 base pair Xmal-SnaBI fragment was purified using a Magic DNA Clean-up System kit (Promega, Madison, WI) in which the 25 base pair Xmal-SnaBI insert fragment is not retained. The complimentary pair of synthetic oligonucleotides, glyxal (SEQ ID NO:74) arid glyxa2 (SEQ ID NO:75), were designed to remove sequence encoding a factor Xa cleavage site. When properly assembled these oligonucleotides also result in Xmal and SnaBI ends. The primers, Glyxal and glyxa2, were annealed in annealing buffer (20mM Tris-HCl pH7.5, 10 mM MgCl2r 50 mM NaCl) by heating at 70°c for ten minutes and allowed to slow cool. The 4018 base pair Xmal-SnaBI fragment from p&gt;MON13046 was ligated with the assembled oligonucleotides using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life <br><br> Technologies, Gaithersburg, MD). Transformant bacteria were <br><br> 172 <br><br> selected on ampicillin-containing plates. Plasmid DNA was isolated from the transformants and analyzed using a PCR based assay. Plasmid DNA from selected transformants was sequenced to confirm the correct insertion of the 5 oligonucleotides. The resulting plasmid was designated <br><br> PMON13180 and contains the DNA sequence of (SEQ ID NO: 258). <br><br> EXAMPLE 52 <br><br> Construction of PMON13181. an intermediate plasmid fnr <br><br> 10 constructing plasmids that contain DNA sequences encoding multi-functional hematopoietic receptor agonihi-.&lt;=i. <br><br> I <br><br> Plasmid, pMON13047 (WO 95/21254), DNA was digested with restriction endonucleases Xmal and SnaBI, resulting in a 15 4063 base pair vector fragment. The 4063 base pair Xmal-SnaBl fragment was purified using a Magic DNA Clean-up System kit (Promega, Madison, WI) in which the 25 base pair Xmal-SnaBI insert fragment is not retained. The complimentary pair of synthetic oligonucleotides, glyxal 20 (SEQ ID NO:74) and glyxa2 (SEQ ID NO:75), were designed to remove sequence encoding the factor Xa cleavage site. When properly assembled these oligonucleotides also result in Xmal and SnaBI ends. Glyxal and glyxa2 were annealed in annealing buffer by heating at 70°C for ten minutes and 25 allowed to slow cool. The 4063 base pair Xmal-SnaBI <br><br> fragment from pMONl3047 was ligated with the assembled oligonucleotides using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life <br><br> 30 Technologies, Gaithersburg, MD). Transformant bacteria were <br><br> \ <br><br> selected on ampicillin-containing plates. Plasmid DNA was isolated from the transformants and analyzed using a PCR based assay. Plasmid DNA from selected transformants was sequenced to confirm the correct insertion of the <br><br> 173 <br><br> ^ oligonucleotides. The resulting plasmid was designated <br><br> It pMON13181 and contains the DNA sequence of (SEQ ID NO:257). <br><br> 5 EXAMPLE 53 <br><br> Construction of PMON13182 -* <br><br> The new N-terminus/C-terminus gene in pMONl3182 was 10 created using Method I as described in Materials and <br><br> Methods. Fragment Start was created and amplified from G-CSF Ser^-7 sequence in pMONl3037 using, the primer set, 39 start (SEQ ID NO: 64) and L-ll start (SEQ ID N0:60) . <br><br> Fragment Stop was created and amplified from G-CSF Ser^7 15 sequence i;, pMONl3037 using the primer set, 38 stop (SEQ ID <br><br> NO:65) and L-ll stop (SEQ ID NO:61) . The full-length new N terminus/C-terminus G-CSF Ser^-? gene was created and amplified from the annealed Fragments Start and Stop using primers 39 start and 38 stop. <br><br> 20 The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and Hindlll and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid, pMON13180, was digested with restriction endonucleases Hindlll and Afllll, 25 resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI) . The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). A portion of the ligation reaction was <br><br> 30 used to transform E. coli strain DH5a cells (Life <br><br> A <br><br> Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13182. <br><br> WO 97/12985 <br><br> 174 <br><br> PCT/US96/15774 <br><br> E. coli strain JM101 was transformed with pMON13182 for protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMONl3182, contains the DNA sequence of (SEQ ID NO:94) which encodes the following amino acid sequence: <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser <br><br> He <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> (SEQ ID <br><br> NO: <br><br> 166) <br><br> EXAMPLE 54 <br><br> Construction of PMON13183 <br><br> The new N-terminus/C-terminus gene in pMONl3183 was created using Method I as described in Materials and Methods. "Fragment Start" was created and amplified from G-CSF Ser^ sequence in pMONl3037 using the primer set, 39 start (SEQ ID NO-.64) and L-ll start (SEQ ID N0:60). <br><br> Fragment Stop was created and amplified from G-CSF Ser1"^ sequence in pMONl3037 using the primer set, 38 stop (SEQ ID NO-.65) and L-ll stop (SEQ ID NO:61). The full-length new N <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 175 <br><br> PCT/US96/15774 <br><br> terminus/C-terminus G-CSF Ser^7 gene was created and amplified from the annealed Fragments Start and Stop using 39 start and 38 stop. <br><br> The resulting DNA fragment which contains the new gene 5 was digested with restriction endonucleases Ncol and Hindlll and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid, pMON13181, was digested with restriction endonucleases Hindlll and AflHI, resulting in a 4068 base pair vector fragment, and purified <br><br> 10 using a Magic DNA Clean-up System kit (Promega, Madison, <br><br> WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life <br><br> 15 Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13183. <br><br> E. coli strain JM101 was transformed with pMON13183 for <br><br> 20 protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMON13183, contains the DNA sequence of (SEQ ID NO:95) which encodes the following amino acid sequence: <br><br> 25 <br><br> Asn Pro Val Ser <br><br> 3 0 Glu <br><br> Ala Gin Gin Gly <br><br> 3 5 Ser <br><br> His Trp Gly Leu <br><br> 40 Leu <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 176 <br><br> PCT/US96/15774 <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu Gly Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyx <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> (SEQ ID NO: <br><br> : 167 ) <br><br> EXAMPLE 55 <br><br> Construction of PMON13184 <br><br> The new N-terminus/C-terminus gene in pMON13184 was created using Method I as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 97 start (SEQ ID NO:66) and L-ll start (SEQ ID NO:60). <br><br> Fragment Stop was created and amplified from G-CSF Ser^7 sequence in pMON13D37 using the primer set, 9 6 stop (SEQ ID NO:67) and L-ll stop (SEQ ID N0:61). The full-length new N terminus/C-terminus G-CSF Ser^7 gene was created and amplified from the annealed Fragments Start and Stop using 97 start and 9 6 stop. <br><br> The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and Hindlll and purified using a Magic DNA clean-up System kit (Promega, Madison, WI). The intermediate plasmid, pMDN13180, was digested with restriction endonucleases Hindlll and Afllll, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5oc cells (Life <br><br> Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 177 <br><br> PCT/US96/15774 <br><br> isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMONl3184. <br><br> E. coli strain JM101 was transformed with pMONl3184 for protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMON13184, contains the DNA sequence of (SEQ ID NO:96) which encodes the following amino acid sequence: <br><br> 10 <br><br> 15 <br><br> 20 <br><br> 25 <br><br> 30 <br><br> example 5 6 <br><br> 35 Construction of PMON13185 <br><br> The new N-terminus/C-terminus gene in pMON13185 was created using Method I as described in Materials and Methods. Fragment Start was created and amplified from G-40 CSF Ser^-7 sequence in pMON13037 using the primer set, 97 <br><br> start (SEQ id NO:66) and L-ll start (SEQ id N0:60). Fragment Stop was created and amplified from G-CSF Ser^-7 <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> (SEQ ID <br><br> NO:: <br><br> 168) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 178 <br><br> PCT/US96/15774 <br><br> sequence in pMON13C&gt;37 using the primer set, 96 stop (SEQ ID NO:67 and L-ll stop (SEQ ID NO:61). The full-length new N terminus/C-terminus G-CSF Ser^7 gene was created and amplified from the annealed Fragments Start and Stop using 97 start and 9 6 stop. <br><br> The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and Hindlll and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid, pMON13181, was digested with restriction endonucleases Hindlll and AflHI, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMONl3185. <br><br> E. coli strain JM101 was transformed with pMONl3185 for protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMON13185, contains the DNA sequence of (SEQ ID NO:67) which encodes the following amino acid sequence: <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 179 <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> Hi£ <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> (SEQ ID <br><br> NO: <br><br> 169) <br><br> 10 <br><br> lie Ser (SEQ ID NO:169) <br><br> EXAMPLE 57 <br><br> 15 Construction of PMON13186 <br><br> The new N-terminus/C-terminus gene in pMON13186 was created using Method I as described in Materials and Methods. Fragment Start was created and amplified from G-20 CSF Ser^-7 sequence in pMON13037 using the primer set, 126 <br><br> start (SEQ ID NO:68) and L-ll start (SEQ ID NO:60). <br><br> Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMONl3037 using the primer set, 125 stop (SEQ ID NO:69) and L-ll stop (SEQ ID NO:61). The full-length new N 25 terminus/C-terminus G-CSF Ser17 gene was created and amplified from the annealed Fragments Start and stop using 126 start and 125 stop. <br><br> The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and Hindlll 30 and purified using a Magic DNA Clean-up System kit (Promega, <br><br> Madison, WI). The intermediate plasmid, pMON13180, was digested with restriction endonucleases Hindlll and AflHI, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, 3 5 WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 180 <br><br> PCMJS96/15774 <br><br> Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMONl3186. <br><br> E. coli strain JM101 was transformed with pMONl3186 for protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMONl3186, contains the DNA sequence of (SEQ ID NO:98) which encodes the following amino acid sequence: <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> (SEQ ID <br><br> NO: <br><br> 170) <br><br> EXAMPLE 5 8 <br><br> construction of PMON13187 <br><br> The new N-terminus/C-terminus gene in pMONl3187 was created using Method I as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser^-7 sequence in pMON13 037 using the primer set, 12 6 start (SEQ ID NO:68) and L-ll start (SEQ ID N0:60). <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 181 <br><br> Fragment Stop was created and amplified from G-CSF Ser^7 sequence in pMONl3 037 using the primer set, 125 stop (SEQ ID NO:69) and L-ll stop (SEQ ID N0:61). The full-length new N terminus/c-terminus G-CSF Ser^7 gene was created and 5 amplified from the annealed Fragments Start and Stop using 126 start and 125 stop. <br><br> The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and Hindlll and purified using a Magic DNA Clean-up System kit (Promega, 10 Madison, WI). The intermediate plasmid, pM0N13181, was digested with restriction endonucleases Hindlll and Afllll, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were combined and 15 ligated using T4 DNA ligase (Boehringer Mannheim, <br><br> Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life <br><br> Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was 20 isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON13187. <br><br> E. coli strain JM101 was transformed with pMONl3187 for protein expression and protein isolation from inclusion bodies. <br><br> 25 <br><br> The plasmid, pMONl3187, contains the DNA sequence of (SEQ ID NO:99) which encodes the following amino acid sequence: <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 182 <br><br> PCT/US96/15774 <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> (SEQ ID NO: <br><br> : 17i; <br><br> &gt; <br><br> EXAMPLE 59 <br><br> Construction of PMON13188 <br><br> The new N-terminus/C-terminus gene in pMON13188 was created using Method I as described in Materials and Methods. Fragment start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 133 start (SEQ ID N0:70) and L-ll start (SEQ ID N0:60). <br><br> Fragment Stop was created and amplified from G-CSF Ser-'-7 sequence in pMON13 037 using the primer set, 132 stop (SEQ ID NO: 71) and L-ll stop (SEQ ID N0:61). The full-length new N terminus/C-terminus G-CSF Ser17 gene was created and amplified from the annealed Fragments Start and Stop using 133 start and 132 stop. <br><br> The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and Hindlll and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid, pMONl3180, was digested with restriction endonucleases Hindlll and AflHI, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 183 <br><br> PCT/US96/15774 <br><br> Technologies, Gaithersburg, MD). Transformant bacteria were selected or. ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMONl3188. <br><br> 5 E. coli strain JM101 was transformed with pMON13188 for protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMON13188, contains the DNA sequence of 10 (SEQ ID NO:100) which encodes the following amino acid sequence: <br><br> 15 <br><br> 20 <br><br> 25 <br><br> 30 <br><br> 35 <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Glr, <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID <br><br> NO:. <br><br> 172) <br><br> Construction of PMON131B9 <br><br> The new N-terminus/C-terminus gene in pMONl3189 was created using Method I as described in Materials and 40 Methods. Fragment Start was created and amplified from G-CSF Ser^7 sequence in pMON13037 using the primer set, 133 start (SEQ ID NO:70) and L-ll start (SEQ ID N0:60). <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 184 <br><br> PCT/US96/15774 <br><br> Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMONl3037 using the primer set, 132 stop (SEQ ID NO:71) and L-ll stop (SEQ ID N0:61). The full-length new N terminus/C-terminus G-CSF Ser*7 gene was created and amplified from the annealed Fragments Start and Stop using 133 start and 132 stop. <br><br> The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and Hindlll and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid, pMONl3181, was digested with restriction endonucleases Hindlll and Afllll, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life <br><br> Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMONl3189. <br><br> E. coli strain JM101 was transformed with pMON13189 for protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMONl3189, contains the DNA sequence of (SEQ ID NO:101) which encodes the following amino acid sequence: <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 185 <br><br> Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Met Pro Ala Phe Ala Ser Ala Phe Gin Arg Arg Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu Val Leu Arg His Leu Ala Gin Pro Ser Gly Gly 5 Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin Val <br><br> Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly 10 Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser <br><br> Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Gin Pro (SEQ ID NO:173) <br><br> EXAMPLE 61 <br><br> 15 <br><br> Construction of PMON1319Q <br><br> The new N-terminus/C-terminus gene in pMON13190 was created using Method I as described in Materials and 20 Methods. Fragment Start was created and amplified from G- <br><br> CSF Ser^-7 sequence in pMON13037 using the primer set, 142 start (SEQ ID NO:72) and L-ll start (SEQ ID N0:60). <br><br> Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 141 stop (SEQ ID 25 NO:73) and L-ll stop (SEQ ID NO:61). The full-length new N <br><br> terminus/C-terminus G-CSF Ser17 gene was created and amplified from the annealed Fragments Start and Stop using 142 start and 141 stop. <br><br> The resulting DNA fragment which contains the new gene 3 0 was digested with restriction endonucleases Ncol and Hindlll and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid, pMONl3180, was digested with restriction endonucleases Hindlll and AflHI, resulting in a 4023 base pair vector fragment, and purified 3 5 using a Magic DNA Clean-up System kit (Promega, Madison, <br><br> WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life <br><br> PCT/US96/15774 <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Printed from Mimosa 08:37.19 <br><br> WO 97/12985 <br><br> 18S <br><br> PCT/US96/15774 <br><br> Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMONl3190. <br><br> E. coli strain JM101 was transformed with pMONl3190 for protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMON13190, contains the DNA sequence of (SEQ ID NO:102) which encodes the following amino acid sequence: <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly <br><br> He <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> (SEQ ID <br><br> NO: <br><br> 174) <br><br> EXAMPLE 62 <br><br> Construction of PMON13191 <br><br> The new N-terminus/C-terminus gene in pMON13191 was created using Method I as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser^7 sequence in pMQNl3 03 7 using the primer set, 142 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 187 <br><br> start (SEQ ID NO:72) and L-ll start (SEQ ID NO:60). <br><br> Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMONl3037 using the primer set, 141 stop (SEQ ID NO:73) and L-ll stop (SEQ ID NO:61). The full-length new N 5 terminus/C-terminus G-CSF Ser^7 gene was created and amplified from the annealed Fragments Start and Stop using 142 start and 141 stop. <br><br> The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and Hindlll 10 and purified using a Magic DNA Clean-up System kit (Promega, <br><br> Madison, WI). The intermediate plasmid, pMON13181, was digested with restriction endonucleases Hindlll and Afllll, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, 15 WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life <br><br> Technologies, Gaithersburg, MD). Transformant bacteria were 20 selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMONl3191. <br><br> E. coli strain JM101 was transformed with pMONl3191 for protein expression and protein isolation from inclusion 25 bodies. <br><br> The plasmid, pMON13191, contains the DNA sequence of (SEQ ID NO:103) which encodes the following amino acid sequence: <br><br> 30 <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser <br><br> He <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 188 <br><br> PCT/US96/15774 <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> (SEQ ID <br><br> NO: <br><br> 175) <br><br> EXAMPLE 63 <br><br> Construction of PMON13192 <br><br> The new N-terminus/C-terminus gene in pMON13192 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF sequence in pMONl3037 using the primer set, 39 start (SEQ ID NO:64) and P-bl start (SEQ ID NO:62). Fragment Stop was created and amplified from G-CSF Ser^7 sequence in pMONl3037 using the primer set, 38 stop (SEQ ID NO:65) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease Ncol, and Fragment Stop was digested with restriction endonuclease Hindlll. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair Ncol-Hindlll vector fragment of pMON3 93 4. <br><br> The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser17 gene and was digested with restriction endonucleases Ncol and Hindlll. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser^-7 gene was isolated using Geneclean (BiolOl, Vista, CA). The intermediate plasmid, <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 189 <br><br> PCT/US96/15774 <br><br> pMONl3180, was digested with restriction endonucleases Hindlll and AflHI, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments 5 were combined and ligated using T4 DNA ligase (Boehringer <br><br> Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells <br><br> (Life Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. 10 Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMONl3192. <br><br> E. coli strain JM101 was transformed with pMON13192 for protein expression and protein isolation from inclusion 15 bodies. <br><br> The plasmid, pMON13192, contains the DNA sequence of (SEQ ID NO:104) which encodes the following amino acid sequence: <br><br> 20 13192.Pept <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> 25 <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> 30 <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> 35 <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> 40 <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> (SEQ ID <br><br> NO: <br><br> 176) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 190 <br><br> PCT/US96/15774 <br><br> EXAMPLE 6 4 <br><br> Construction of PMON13193 <br><br> The new N-terminus/C-terminus gene in pMON13193 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser-'-7 sequence in pMONl3G37 using the primer set, 3 9 start (SEQ ID NO:64) and P-bl start (SEQ ID NO:62&gt;. <br><br> Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 38 stop (SEQ ID NO:65) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease Ncol, and Fragment Stop was digested with restriction endonuclease Hindlll. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3 800 base pair Hcol-Hindlll vector fragment of pMON3 93 4. <br><br> The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser^7 gene and was digested with restriction endonucleases Ncol and Hindlll. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser17 gene was isolated using Geneclean (BiolOl, Vista, CA). The intermediate plasmid, pMON13181, was digested with restriction endonucleases Hindlll and AflHI, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells <br><br> (Life Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 151 <br><br> PCT/US96/15774 <br><br> correct insertion of the new gene. The resulting plasmid was designated pMONl3193. <br><br> E. coli strain JM101 was transformed with pMONl3193 for protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMONl3193, contains the DNA sequence of (SEQ ID NO:105) encodes the following amino acid sequence: <br><br> 10 <br><br> 15 <br><br> 20 <br><br> 25 <br><br> 30 <br><br> EXAWPT.K 65 <br><br> 35 Construction of PMON2519Q <br><br> The new N-terminus/C-terminus gene in pMON25190 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-40 CSF sequence in pMON13037 using the primer set, 97 start <br><br> (SEQ ID NO:66) and P-bl start (SEQ ID NO:62). Fragment Stop was created and amplified from G-CSF Ser^-7 sequence in <br><br> Asn <br><br> Cys <br><br> Sei lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> (SEQ ID <br><br> NO: <br><br> 177) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 192 <br><br> PCT/US96/15774 <br><br> PMON13037 using the primer set, 96 stop (SEQ ID NO:67) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease Ncol, and Fragment Stop was digested with restriction endonuclease Hindlll. After 5 purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair Ncol-Hindlll vector fragment of pMON3934. <br><br> The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser17 gene and 10 was digested with restriction endonucleases Ncol and <br><br> Hindlll. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser^7 gene was isolated using Geneclean (BiolOl, Vista, CA). The intermediate plasmid, 15 pMON13180, was digested with restriction endonucleases <br><br> Hindlll and Afllll, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer 20 Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells <br><br> (Life Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the 25. correct insertion of the new gene. The resulting plasmid was designated pMON25190. <br><br> E. coli strain JM101 was transformed with pMON25190 for protein expression and protein isolation from inclusion bodies. <br><br> 30 <br><br> The plasmid, pMON25190, contains the DNA sequence of (SEQ ID NO:106) which encodes the following amino acid sequence: <br><br> 35 Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 193 <br><br> PCT/US96/15774 <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> (SEQ ID NO <br><br> -J <br><br> 00 <br><br> 20 <br><br> EXAMPLE 6fi <br><br> Construction of PMON25191 <br><br> 25 <br><br> The new N-terminus/C-terminus gene in pMON2 5191 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMONl3037 using the primer set, 97 30 start (SEQ ID NO:66) and P-bl start (SEQ ID NO:62). <br><br> Fragment Stop was created and amplified from G-CSF Ser^7 sequence in pMONl3 037 using the primer set, 96 stop (SEQ ID NO:98) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease Ncol, and Fragment 35 Stop was digested with restriction endonuclease Hindlll. <br><br> After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair Ncol-Hindlll vector fragment of pMON3934. <br><br> The intermediate plasmid described above contained the 40 full length new N-terminus/C-terminus G-CSF Ser17 gene and was digested with restriction endonucleases Ncol and <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 194 <br><br> PCT/US96/15774 <br><br> Hindlll. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser^7 gene was isolated using Geneclean (BiolOl, Vista, CA). The intermediate plasmid, pMON13181, was digested with restriction endonucleases Hindlll and AflHI, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up system kit (Promega, Madison, WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells <br><br> (Life Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON25191. <br><br> E. coli strain JM101 was transformed with pMON25191 for protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMON25191, contains the DNA sequence of (SEQ ID NO:107) which encodes the following amino acid sequence: <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 195 <br><br> PCT/US96/15774 <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> (SEQ ID <br><br> NO: <br><br> 179) <br><br> EXAMPLE 67 <br><br> Construction of PMON13194 <br><br> The new N-terminus/C-terminus gene in pMON13194 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser^-7 sequence in pMON13037 using the primer set, 126 start (SEQ ID NO:68) and P-bl start (SEQ ID NO:62). <br><br> Fragment Stop was created and amplified from G-CSF Ser^7 sequence in pMON13 037 using the primer set, 125 stop (SEQ ID NO:67) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease Ncol, and Fragment Stop was digested with restriction endonuclease Hindlll. After purification, the digested Fragments Start and stop were combined with and ligated to the approximately 3 800 base pair Ncol-Hindlll vector fragment of pMON3934. <br><br> The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser^-7 gene and was digested with restriction endonucleases Ncol and Hindlll. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-0 terminus/C-terminus G-CSF Ser-'-7 gene was isolated using <br><br> Geneclean (BiolOl, Vista, CA). The intermediate plasmid, PMON13180, was digested with restriction endonucleases Hindlll and AflHI, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit 5 (Promega, Madison, WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 196 <br><br> PCT/US96/15774 <br><br> Mannheim, Indianapolis, IN), A portion of the ligation reaction was used to transform E. coli strain DH5a cells <br><br> (Life Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid was designated pMON13194. <br><br> E. coli strain JM101 was transformed with pMONl3194 for protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMON13194, contains the DNA sequence of (SEQ ID NO:108) which encodes the following amino acid sequence: <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> (SEQ ID <br><br> NO: <br><br> 180) <br><br> EXAMPLE 68 <br><br> Construction of PMON13195 <br><br> The new N-terminus/C-terminus gene in pMON13195 was created using Method II as described in Materials and <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 197 <br><br> PCT/US96/15774 <br><br> Methods. Fragment Start was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 126 stare (SEQ ID NO:68) and P-bl start (SEQ ID NO:62). <br><br> Fragment Si_op was created and amplified from G-CSF Ser17 5 sequence in pMONl3(D37 using the primer set, 125 stop (SEQ ID <br><br> NO:69) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease Ncol, and Fragment Stop was digested with restriction endonuclease Hindlll. After purification, the digested Fragments Start and Stop 10 were combined with and ligated to the approximately 3800 base pair Ncol-Hindlll vector fragment of pMON3934. <br><br> The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser^7 gene and was digested with restriction endonucleases Ncol and 15 Hindlll. The digested DNA was resolved on a 1% TAE gel, <br><br> stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser17 gene was isolated using Geneclean (BiolOl, Vista, CA). The intermediate plasmid, pMON13181, vas digested with restriction endonucleases 20 Hindlll and AflHI, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). A portion of the ligation 25 reaction was used to transform E. coli strain DH5a cells <br><br> (Life Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insertion of the new gene. The resulting plasmid 30 was designated pMONl3195. <br><br> E. coli strain JM101 was transformed with pMON1319 5 for protein expression and protein isolation from inclusion bodies. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 198 <br><br> PCT/US96/15774 <br><br> The plasmid, pMON13195, contains the DNA sequence of (SEQ ID NO:109) which encodes the following amino acid sequence: <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> (SEQ ID <br><br> NO: <br><br> 181) <br><br> EXAMPLE 69 <br><br> 30 Construction of PMQN1319 6 <br><br> The new N-terminus/C-terminus gene in pMON13196 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-35 CSF sequence in pMC)Nl3037 using the primer set, 133 start <br><br> (SEQ ID NO:70) and P-bl start (SEQ ID NO:62). Fragment Stop was created and amplified from G-CSF Ser17 sequence in pMON13037 using the primer set, 132 stop (SEQ ID NO:71) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with 40 restriction endonuclease Ncol, and Fragment Stop was digested with restriction endonuclease Hindlll. After purification, the digested Fragments Start and Stop were <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 199 <br><br> PCT/US96/15774 <br><br> combined with and ligated to the approximately 3 800 base pair Ncol-Hindlll vector fragment of pMON3 9 34. <br><br> The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser^-7 gene and 5 was digested with restriction endonucleases Ncol and <br><br> Hindlll. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser^7 gene was isolated using Geneclean (BiolOl, Vista, CA). The intermediate plasmid, 10 pMC)N13180, was digested with restriction endonucleases <br><br> Hindlll and AflHI, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer 15 Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells <br><br> (Life Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the 20 correct insertion of the new gene. The resulting plasmid was designated pMON13196. <br><br> E. coli strain JM101 was transformed with pMONl3196 for protein expression and protein isolation from inclusion bodies. <br><br> 25 <br><br> The plasmid, pMONl3196, contains the DNA sequence of (SEQ ID NO:110) which encodes the following amino acid sequence: <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 200 <br><br> PCT/US96/15774 <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID <br><br> NO: <br><br> 182) <br><br> EXAMPLE 70 <br><br> Construction of PMON13197 <br><br> The new N-terminus/C-terminus gene in pMON13197 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF Ser-*-7 sequence in pMON13037 using the primer set, 133 start (SEQ ID NO:70) and P-bl start (SEQ ID NO:62). <br><br> Fragment Stop was created and amplified from G-CSF Ser^7 sequence in pMON13037 using the primer set, 132 stop (SEQ ID NO:71) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease Ncol, and Fragment Stop was digested with restriction endonuclease Hindlll. After purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair Ncol-Hindlll vector fragment of pMON3934. <br><br> The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser-^-7 gene and was digested with restriction endonucleases Ncol and Hindlll. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser^7 gene was isolated using Geneclean (BiolOl, Vista, CA). The intermediate plasmid, PMON13181, was digested with restriction endonucleases <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 201 <br><br> PCT/US96/15774 <br><br> Hindlll and AflHI, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer 5 Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells <br><br> (Life Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the 10 correct insertion of the new gene. The resulting plasmid was designated pMONl3197. <br><br> E. coli strain JM101 was transformed with pMONl3197 for protein expression and protein isolation from inclusion bodies. <br><br> 15 <br><br> 20 <br><br> 25 <br><br> 30 <br><br> 35 <br><br> 40 <br><br> The plasmid, pMON13197, contains the DNA sequence of (SEQ ID NO:111) which encodes the following amino acid sequence: <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> (SEQ ID <br><br> NO:: <br><br> 183) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 202 <br><br> PCT/US96/15774 <br><br> EXAMPLE 71 <br><br> Construction of PMON13198 <br><br> 5 The new N-terminus/C-terminus gene in pMON13198 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-CSF sequence in pMON13037 using the primer set, 142 start (SEQ ID NO:72) and P-bl start (SEQ ID NO:62). Fragment Stop 10 was created and amplified from G-CSF Ser^7 sequence in <br><br> PMON13037 using the primer set, 141 stop (SEQ ID NO:73) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease Ncol, and Fragment Stop was digested with restriction endonuclease Hindlll. After 15 purification, the digested Fragments Start and Stop were combined with and ligated to the approximately 3800 base pair Ncol-Hindlll vector fragment of pMON3934. <br><br> The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser^7 gene and 20 was digested with restriction endonucleases Ncol and <br><br> Hindlll. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser17 gene was isolated using Geneclean (BiolOl, Vista, CA). The intermediate plasmid, 25 pMONl3180, was digested with restriction endonucleases <br><br> Hindlll and AflHI, resulting in a 4023 base pair vector fragment, and purified using a Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer 30 Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells <br><br> (Life Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was.isolated and sequenced to confirm the <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 203 <br><br> PCT/US96/15774 <br><br> correct insertion of the new gene. The resulting plasmid was designated pMON13198. <br><br> E. coli strain JM101 was transformed with pMON13198 for protein expression and protein isolation from inclusion 5 bodies. <br><br> The plasmid, pMONl3198, contains the DNA sequence of (SEQ ID NO:112) which encodes the following amino acid sequence: <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Met <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> (SEQ ID <br><br> NO:: <br><br> 184) <br><br> EXAMPLE 72 <br><br> 35 Construction of PMON13199 <br><br> The new N-terminus/C-terminus gene in pMON13199 was created using Method II as described in Materials and Methods. Fragment Start was created and amplified from G-40 CSF Ser^-7 sequence in pMONl3037 using the primer set, 142 <br><br> start (SEQ ID NO:72) and P-bl start (SEQ ID NO:62). Fragment Stop was created and amplified from G-CSF Ser17 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 204 <br><br> PCT/US96/15774 <br><br> sequence in pMON13037 using the primer set, 141 stop (SEQ ID NO:73) and P-bl stop (SEQ ID NO:63). Fragment Start was digested with restriction endonuclease Ncol. and Fragment Stop was digested with restriction endonuclease Hindlll. 5 After purification, the digested Fragments Start and Stop were combirid with and ligated to the approximately 3800 base pair Ncol-Hindlll vector fragment of pMON3934. <br><br> The intermediate plasmid described above contained the full length new N-terminus/C-terminus G-CSF Ser17 gene and 10 was digested with restriction endonucleases Ncol and <br><br> Hindlll. The digested DNA was resolved on a 1% TAE gel, stained with ethidium bromide and the full-length new N-terminus/C-terminus G-CSF Ser17 gene was isolated using Geneclean (BiolOl, Vista, CA). The intermediate plasmid, 15 pMON13181, was digested with restriction endonucleases <br><br> Hindlll and Afllll, resulting in a 4068 base pair vector fragment, and purified using a Magic DNA clean-up System kit (Promega, Madison, WI). The purified restriction fragments were combined and ligated using T4 DNA ligase (Boehringer 20 Mannheim, Indianapolis, IN). A portion of the ligation reaction was used to transform E. coli strain DH5a cells <br><br> (Life Technologies, Gaithersburg, MD). Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the 25 correct insertion of the new gene. The resulting plasmid was designated pMON13199. <br><br> E. coli strain JM101 was transformed with pMON13199 for protein expression and protein isolation from inclusion bodies. <br><br> 30 <br><br> The plasmid, pMONl3199, contains the DNA sequence of (SEQ ID NO:113) which encodes the following amino acid sequence: <br><br> 35 Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 205 <br><br> PCT/US96/15774 <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Pro <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Ala <br><br> Ser <br><br> Ser <br><br> Leu <br><br> Pro <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> (SEQ ID <br><br> NO: <br><br> 185) <br><br> EXAMPLE 73 <br><br> 2 5 Construction of tandemly-duplicated plasmid template. <br><br> Svntanl <br><br> To create the tandemly-duplicated hIL-3 receptor agonist pMON13416 template, Syntanl, three DNAs were joined <br><br> 3 0 by means of ligation using T4 DNA ligase (Boehringer <br><br> Mannheim). The three DNAs are: 1) pMONl3C)46, containing hIL-3 receptor agonist pMON13416, digested with BstEll and SnaBI; 2) the annealed complimentary pair of synthetic oligonucleotides, Llsyn.for (SEQ ID NO:48) and Llsyn.rev 35 (SEQ ID NO:49), which contain sequence encoding the linker that connects the C-terminal and N-terminal ends of the original protein and a small amount of surrounding pMONl3416 sequence and which when properly assembled result in BstEII and Clal ends; and 3) a portion of hIL-3 receptor agonist 40 pMON13416 digested from pMONl3046 with Clal (DNA had been grown in the dam- cells, DMl (Life Technologies)) and SnaBI. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 206 <br><br> PCT/US96/15774 <br><br> The digested DNAs were resolved on a 0.9% TAE gel, stained with ethidium bromide and isolated using Geneclean (BiolOl). <br><br> A portion cf the ligation reaction was used to transform E. 5 coli strain DH5a cells (Life Technologies, Gaithersburg, <br><br> MD). Miniprep DNA was isolated from the transformants, and the transformants were screened using a PCR based assay. Plasmid DNA from selected transformants was sequenced to obtain the correct template. The resulting plasmid was 10 designated syntanl and contains the DNA sequence of (SEQ ID <br><br> NO:84) . <br><br> EXAMPLE 7 4 <br><br> 15 Construction of tandemlv-duplicated template. svntan3. <br><br> To create the tandemly-duplicated hIL-3 receptor agonist pMONl3416 template, syntan3, three DNAs were joined by means or ligation using T4 DNA ligase (Boehringer 20 Mannheim). The three DNAs are: 1) pMONl3046, containing hIL-3 receptor agonist pMONl3416, digested with BstEII and SnaBI; 2) the annealed complimentary pair of synthetic oligonucleotides, L3syn.for (SEQ ID NO:50) and L3syn.rev (SEQ ID NO:51), which contain sequence encoding the linker 25 that connects the C-terminal and N-terminal ends of the original protein and a small amount of surrounding pMON13416 sequence and which when properly assembled result in BstEII and SnaBI ends; and 3) a portion of hIL-3 receptor agonist pMON13416 digested from pMONl3046 with Clal (DNA had been 30 grown in the dam- cells, DM1 (Life Technologies)) and SnaBI. <br><br> The digested DNAs were resolved on a 0.9% TAE gel, stained with ethidium bromide and isolated using Geneclean (BiolOl). <br><br> A portion of the ligation reaction was used to transform E. 35 coli strain DH5a cells (Life Technologies, Gaithersburg, <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 207 <br><br> PCT/US96/15774 <br><br> MD). Miniprep DNA was isolated from the transformants, and the transformants were screened using a PCR based assay. Plasmid DNA from selected transformants was sequenced to obtain the correct template. The resulting plasmid was 5 designated syntan3 and contains the DNA sequence of (SEQ ID <br><br> NO:8 5 ) . <br><br> EXAMPLE 7 5 <br><br> 10 Construction of PMON311Q4 <br><br> The new N-terminus/C-terminus gene in pMON31104 was created using Method III as described in Materials and Methods. The full length new N-terminus/C-terminus gene of 15 hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntanl, using the primer set 35 start (SEQ ID NO:52) and 34 rev (SEQ ID NO:53). <br><br> The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and SnaBI. 20 The digested DNA fragment was resolved on a 1% TAE gel, <br><br> stained with ethidium bromide and isolated using Geneclean (BiolOl, Vista, CA). The purified digested DNA fragment was ligated into the expression vector,pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). The 25 pMON13189 DNA had been previously digested with Ncol and <br><br> SnaBI to remove the hIL3 receptor agonist pMON13 416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (BiolOl, Vista, CA) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion 30 of the ligation reaction was used to transform E. coli strain DH5a cells (Life Technologies, Gaithersburg, MD). <br><br> Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated 35 pMON31104. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 208 <br><br> PCT/US96/15774 <br><br> E. coli strain JM101 was transformed with pMON31104 for protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMON311()4, contains the DNA sequence of (SEQ ID NO:86) which encodes the following amino acid sequence: <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID <br><br> NO: <br><br> 186) <br><br> EXAMPLE 7 6 <br><br> Construction of PMON311Q5 <br><br> The new N-terminus/C-terminus gene in pMON31105 was created using Method III as described in Materials and Methods. The full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntanl, using the primer set 70 start (SEQ ID NO:54) and 69 rev (SEQ ID NO:55). <br><br> The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and SnaBI. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 209 <br><br> PCT/US96/15774 <br><br> The digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (BiolOl, Vista, CA). The purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA 5 ligase (Boehringer Mannheim, Indianapolis, IN). The <br><br> PMON13189 DNA had been previously digested with Ncol and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pa.ir vector fragment was isolated using Geneclean (BiolOl, Vista, CA) after resolution on a 10 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life Technologies, Gaithersburg, MD). <br><br> Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm 15 the correct insert. The resulting plasmid was designated pMON31105. <br><br> E. coli strain JM101 was transformed with pMON31105 for protein expression and protein isolation from inclusion bodies. <br><br> 20 <br><br> 25 <br><br> 30 <br><br> 35 <br><br> 40 <br><br> The plasmid, pMON31105, contains the DNA sequence of (SEQ ID NO:87) which encodes the protein with the following amino acid sequence: <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 210 <br><br> PCT/US96/15774 <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID <br><br> NO: <br><br> 187) <br><br> EXAMPLE 77 <br><br> Construction of pMON311Q6 <br><br> The new N-terminus/C-terminus gene in pMON31106 was created using Method III as described in Materials and Methods. The full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntanl, using the primer set 91 start (SEQ ID NO:56) and 90 rev (SEQ ID NO:57). <br><br> The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and SnaBI. The digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (BiolOl, Vista, CA). The purified digested DNA fragment was ligated into the expression vector pMONl3189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). The pMONl3189 DNA had been previously digested with Ncol and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (BiolOl, Vista, CA) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli 0 strain DH5a cells (Life Technologies, Gaithersburg, MD). <br><br> Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31106. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 211 <br><br> E. coli strain JM101 was transformed with pMON31106 for protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMON311(36, contains the DNA sequence of (SEQ ID NO:80) which encodes the protein with the following amino acid sequence: <br><br> 10 <br><br> 15 <br><br> 20 <br><br> 25 <br><br> 30 <br><br> Ala <br><br> Pro <br><br> Sei <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> GlU <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID NO <br><br> : 188: <br><br> ) <br><br> EXAMPLE 78 <br><br> 35 Construction of PMON31107 <br><br> The new N-terminus/C-terminus gene in pMON311G7 was created using Method III as described in Materials and Methods. The full length new N-terminus/C-terminus gene of 40 hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntanl, using the primer set 101 start (SEQ ID NO:58) and 100 rev (SEQ ID NO:59). <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 212 <br><br> PCT/US96/15774 <br><br> The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and SnaBI. The digested The DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean 5 (BiolOl, Vista, CA). The purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). The pMONl3189 DNA had been previously digested with Ncol and SnaBI to remove the hIL3 receptor agonist pMON13 416 coding 10 sequence and the 4254 base pair vector fragment was isolated using Geneclean (BiolOl, Vista, CA) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life Technologies, Gaithersburg, MD). <br><br> 15 Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correc'". insert. The resulting plasmid was designated pMON31107. <br><br> E. coli strain JM101 was transformed with pMON31107 for 20 protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMON31107, contains the DNA sequence of (SEQ ID NO:89) which encodes the following amino acid sequence: <br><br> 25 <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 213 <br><br> PCT/US96/15774 <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ ID <br><br> NO: <br><br> 189) <br><br> 10 EXAMPLE 79 <br><br> Construction of PMON311Q8 <br><br> The new N-terminus/C-terminus gene in pMON31108 15 was created using Method III as described in Materials and <br><br> Methods. The full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan3, using the primer set 35 start (SEQ ID NO:52) and 34 rev (SEQ ID NO:53). 20 The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and SnaBI. The digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (BiolOl, Vista, CA). The purified digested DNA fragment was 25 ligated into the expression vector pMON13189, using T4 DNA <br><br> ligase (Boehringer Mannheim, Indianapolis, IN). The PMON13189 DNA had been previously digested with Ncol and SnaBI to remove the hIL3 receptor agonist pMON13416 coding sequence and the 4254 base pair vector fragment was isolated 30 using Geneclean (BiolOl, Vista, CA) after resolution on a <br><br> 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life Technologies, Gaithersburg, MD). <br><br> Transformant bacteria were selected on ampicillin-containing 35 plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated PMON31108. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 214 <br><br> PCT/US96/15774 <br><br> E. coli strain JM101 was transformed with pMON311C)8 for protein expression and protein isolation from inclusion bodies. <br><br> 5 The plasmid, pMON311C)8, contains the DNA sequence of (SEQ ID NO:90) which encodes the following amino acid sequence: <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ <br><br> 30 ID NO:190) <br><br> EXAMPLE 80 <br><br> 35 <br><br> Construction of PMON311Q9 <br><br> The new N-terminus/C-terminus gene in pMON31109 was created using Method III as described in Materials and 40 Methods. The full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan3, using the primer set 70 start (SEQ ID NO:54) and 69 rev (SEQ ID NO:55). <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 215 <br><br> PCT/US96/15774 <br><br> The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and SnaBI. The digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean 5 (BiolOl, Vista, CA). The purified digested DNA fragment was ligated into the expression vector pMON13189, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). The pMONl3189 DNA had been previously digested with Ncol and SnaBI to remove the hIL3 receptor agonist pMON13416 coding 10 sequence and the 4254 base pair vector fragment was isolated using Geneclean (BiolOl, Vista, CA) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life Technologies, Gaithersburg, MD). <br><br> 15 Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31109. <br><br> E. coli strain JM101 was transformed with pMON31109 for 20 protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMON31109, contains the DNA sequence of (SEQ ID NO:91) which encodes the following amino acid sequence: <br><br> 25 <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Ly^ <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 216 <br><br> PCT/US96/15774 <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ <br><br> ID NO:191) <br><br> EXAMPLE 81 <br><br> Construction of PM0N3111Q <br><br> The new N-terminus/C-terminus gene in pMON31HO was created using Method III as described in Materials and Methods. The full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Syntan3, using the primer set 91 start (SEQ ID NO:56) and 90 rev (SEQ ID NO:57). <br><br> The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and SnaBI. The digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (BiolOl, Vista, CA). The purified digested DNA fragment was ligated into the expression vector pMONl318 9, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). The PMON13189 DNA had been previously digested with Ncol and SnaBI to remove the hIL3 receptor agonist pMONl3416 coding 0 sequence and the 4254 base pair vector fragment was isolated using Geneclean (BiolOl, Vista, CA) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life Technologies, Gaithersburg, MD). <br><br> 5 Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 217 <br><br> PCT/US96/15774 <br><br> the correct insert. The resulting plasmid was designated PMON31HO . <br><br> E. coli strain JM101 was transformed with pMON31110 for protein expression and protein isolation from inclusion 5 bodies. <br><br> The plasmid, pMON31HO, contains the DNA sequence of (SEQ ID NO:92) which encodes the following amino acid sequence: <br><br> 10 <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> 15 <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly- <br><br> lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Tyr val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> 20 <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly Gly <br><br> Val <br><br> Leu <br><br> Val <br><br> Ala <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyi <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> 25 <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> 30 <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ <br><br> ID NO:192) <br><br> 35 EXAMPLE 8 2 <br><br> Construction of PM0N31111 <br><br> The new N-terminus/C-terminus gene in pMON31111 was 40 created using Method III as described in Materials and <br><br> Methods. The full length new N-terminus/C-terminus gene of hIL-3 receptor agonist pMON13416 was created and amplified <br><br> Printed from Mimosa 08:37.19 <br><br> WO 97/12985 <br><br> 218 <br><br> PCT/US96/15774 <br><br> from the intermediate plasmid, Syntan3, using the primer set 101 start (SEQ ID NO:58) and 100 rev (SEQ ID NO:59). <br><br> The resulting DNA fragment which contains the new gene was digested with restriction endonucleases Ncol and SnaBI. The digested DNA fragment was resolved on a 1% TAE gel, stained with ethidium bromide and isolated using Geneclean (BiolOl, Vista, CA). The purified digested DNA fragment was ligated into the expression vector pMON131S9, using T4 DNA ligase (Boehringer Mannheim, Indianapolis, IN). The pMON13189 DNA had been previously digested with Ncol and SnaBI to remove the hIL3 receptor agonist pMONl3 416 coding sequence and the 4254 base pair vector fragment was isolated using Geneclean (BiolOl, Vista, CA) after resolution on a 0.8% TAE gel and staining with ethidium bromide. A portion of the ligation reaction was used to transform E. coli strain DH5a cells (Life Technologies, Gaithersburg, MD). <br><br> Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31111. <br><br> E. coli strain JM101 was transformed with pMON31111 for protein expression and protein isolation from inclusion bodies. <br><br> The plasmid, pMON31111, contains the DNA sequence of (SEQ ID NO:93) which encodes the following amino acid sequence: <br><br> Ala <br><br> Gly <br><br> Asp <br><br> Trp <br><br> Gin <br><br> Glu <br><br> Phe <br><br> Arg <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Thr <br><br> Phe <br><br> Tyr <br><br> Leu <br><br> Val <br><br> Thr <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Ala <br><br> Gin <br><br> Glu <br><br> Gin <br><br> Gin <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Asn <br><br> Cys <br><br> Ser lie <br><br> Met lie <br><br> Asp <br><br> Glu lie lie <br><br> His <br><br> His <br><br> Leu <br><br> Lys <br><br> Arg <br><br> Pro <br><br> Pro <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Leu <br><br> Asp <br><br> Pro <br><br> Asn <br><br> Asn <br><br> Leu <br><br> Asn <br><br> Asp <br><br> Glu <br><br> Asp <br><br> Val <br><br> Ser lie <br><br> Leu <br><br> Met <br><br> Asp <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Arg <br><br> Leu <br><br> Pro <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Ser <br><br> Phe <br><br> Val <br><br> Arg <br><br> Ala <br><br> Val <br><br> Lys <br><br> Asn <br><br> Leu <br><br> Glu <br><br> Asn <br><br> Ala <br><br> Ser <br><br> Gly lie <br><br> Glu <br><br> Ala lie <br><br> Leu <br><br> Arg <br><br> Asn <br><br> Leu <br><br> Gin <br><br> Pro <br><br> Cys <br><br> Leu <br><br> Pro <br><br> Ser <br><br> Ala <br><br> Thr <br><br> Ala <br><br> Ala <br><br> Pro <br><br> Ser <br><br> Arg <br><br> His <br><br> Pro lie lie lie <br><br> Lys <br><br> Tyr <br><br> Val <br><br> Glu <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Pro <br><br> Gly <br><br> Glu <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Pro lie <br><br> Ser <br><br> Thr lie <br><br> Asn <br><br> Pro <br><br> Ser <br><br> Pro <br><br> Pro <br><br> Ser <br><br> Lys <br><br> Glu <br><br> Ser <br><br> His <br><br> Lys <br><br> Ser <br><br> Pro <br><br> Asn <br><br> Met <br><br> Ala <br><br> Thr <br><br> Gin <br><br> Gly <br><br> Ala <br><br> Met <br><br> Pro <br><br> Ala <br><br> Phe <br><br> Ala <br><br> Ser <br><br> Ala <br><br> Phe <br><br> Gin <br><br> Arg <br><br> Arg <br><br> Ala <br><br> Gly <br><br> Gly <br><br> Val <br><br> Leu val <br><br> Ala <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 219 <br><br> PCT/US96/15774 <br><br> Ser <br><br> His <br><br> Leu <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Glu <br><br> Val <br><br> Ser <br><br> Tyr <br><br> Arg <br><br> Val <br><br> Leu <br><br> Arg <br><br> His <br><br> Leu <br><br> Ala <br><br> Gin <br><br> Pro <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gly <br><br> Gly <br><br> Ser <br><br> Gin <br><br> Ser <br><br> Phe <br><br> Leu <br><br> Leu <br><br> Lys <br><br> Ser <br><br> Leu <br><br> Glu <br><br> Gin <br><br> Val <br><br> Arg <br><br> Lys lie <br><br> Gin <br><br> Gly <br><br> Asp <br><br> Gly <br><br> Ala <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Glu <br><br> Lys <br><br> Leu <br><br> Cys <br><br> Ala <br><br> Thr <br><br> Tyr <br><br> Lys <br><br> Leu <br><br> Cys <br><br> His <br><br> Pro <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Val <br><br> Leu <br><br> Leu <br><br> Gly <br><br> His <br><br> Ser <br><br> Leu <br><br> Gly lie <br><br> Pro <br><br> Trp <br><br> Ala <br><br> Pro <br><br> Leu <br><br> Ser <br><br> Ser <br><br> Cys <br><br> Pro <br><br> Ser <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Ala <br><br> Gly <br><br> Cys <br><br> Leu <br><br> Ser <br><br> Gin <br><br> Leu <br><br> His <br><br> Ser <br><br> Gly <br><br> Leu <br><br> Phe <br><br> Leu <br><br> Tyr <br><br> Gin <br><br> Gly <br><br> Leu <br><br> Leu <br><br> Gin <br><br> Ala <br><br> Leu <br><br> Glu <br><br> Gly lie <br><br> Ser <br><br> Pro <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Pro <br><br> Thr <br><br> Leu <br><br> Asp <br><br> Thr <br><br> Leu <br><br> Gin <br><br> Leu <br><br> Asp <br><br> Val <br><br> Ala <br><br> Asp <br><br> Phe <br><br> Ala <br><br> Thr <br><br> Thr lie <br><br> Trp <br><br> Gin <br><br> Gin <br><br> Met <br><br> Glu <br><br> Glu <br><br> Leu <br><br> Gly <br><br> Met <br><br> Ala <br><br> Pro <br><br> Ala <br><br> Leu <br><br> Gin <br><br> Pro <br><br> (SEQ <br><br> ID NO:193) <br><br> EXAMPLE S3 <br><br> 15 <br><br> Cnnsr.rncr.ion of PMON31112 <br><br> Construction of pMON31112, a plasmid containing DNA sequence encoding a multi-functional hematopoietic receptor 20 agonist which activates the hIL-3 receptor and G-CSF <br><br> receptor. Plasmid, pMONl3189 DNA was digested with restriction enzymes Ncol and Xmal resulting in an Ncol, Xmal vector fragment that was isolated and purified from a 0.8% agarose gel. The DNA from a second plasmid, pMON13222 (WO 25 94/12639, US serial # 08/411,796) was digested with Ncol and <br><br> EcoRI resulting in a 281 base pair Ncol, EcoRI fragment. <br><br> This fragment was isolated and purified from a 1.0% agarose gel. Two oligonucleotides SYNNOXA1.REQ (SEQ ID N0;240) and SYNNOXA2.REQ (SEQ ID NO:241) were annealed and ligated with 30 the 281 base pair DNA fragment from pMON13222 to the DNA <br><br> vector fragment from pMON13189. A portion of the ligation mixture was then transformed into E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction 3 5 analysis to show the presence of an EcoRV fragment, and sequenced to confirm the correct inserts. <br><br> Printed from Mimosa 08:37.19 <br><br> WO 97/12985 <br><br> 220 <br><br> PCT/US96/15774 <br><br> The plasmid, pMON31112, contains the DNA sequence of (SEQ ID NO:114) which encodes the following amino acid sequence: <br><br> 5 <br><br> MetAlaAsnCysSerAsnMetlleAspGluIlelleThrHisLeuLysGlnProProLeu ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsn LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer AlalleGluSerlleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro 10 ThrArgHisPielleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThr PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer 15 TyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPhe LeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu LysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSer LeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGlu 20 GlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPhe <br><br> AlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro (SEQ ID NO:199) <br><br> Construction of PMON31113 <br><br> 25 <br><br> Construction of pMON31113, a plasmid containing DNA sequence encoding a multi-functional hematopoietic receptor agonist which activates the hIL-3 receptor and G-CSF receptor. Plasmid, pMONl3197 DNA was digested with restriction enzymes 3 0 Ncol and Xmal resulting in an Ncol, Xmal vector fragment that was isolated and purified from a 0.8% agarose gel. The DNA from a second plasmid, pMONl3239 (WO 94/12639, US serial # 08/411,796) was digested with Ncol and EcoRI resulting in a 281 base pair Ncol, EcoRI fragment. This fragment was 35 isolated and purified from a 1.0% agarose gel. Two oligonucleotides SYNNOXAl.REQ (SEQ ID NO:240) and SYNNOXA2.REQ (SEQ ID NO:241) were annealed and ligated with the 281 base pair DNA fragment from pMON13239 to the DNA vector fragment from pMON13197. A portion of the ligation 40 mixture was then transformed into B. coli K-12 strain JM101. <br><br> Transformant bacteria were selected on ampicillin-containing <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 221 <br><br> PCT/US96/15774 <br><br> plates. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of an EcoRV fragment, and sequenced to confirm the correct inserts. <br><br> 5 The plasmid, pMON31113, contains the DNA sequence of (SEQ <br><br> ID NO:115) which encodes the following amino acid sequence: <br><br> MetAlaAsnCysSerAsnMetlleAspGlullelleThrHisLeuLysGlnProProLeu ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsn 10 LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer <br><br> AlalleGluSerlleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro ThrArgHisProIlellelleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThr PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu 15 SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe <br><br> GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer TyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuPro GlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla LeuGlnGluLyrLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeu 20 GlyHisSerLeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln <br><br> LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln AlaLeuGluGlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVal AlaAspPheAlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu GlnPro (SEQ ID NO:200) <br><br> 25 <br><br> EXAMPLE 85 <br><br> Construction of PMON31114 <br><br> 30 Construction of pMON31114, a plasmid containing DNA sequence encoding a multi-functional hematopoietic receptor agonist which activates the hIL-3 receptor and G-CSF receptor. Plasmid, pMONl3189 DNA was digested with restriction enzymes Ncol and Xmal resulting in an Ncol, Xmal vector fragment 3 5 that was isolated and purified from a 0.8% agarose gel. The <br><br> DNA from a second plasmid, pMONl3239 (WO 94/12639, US serial # 08/411,796), was digested with Ncol and EcoRI resulting in a 281 base pair Ncol, EcoRI fragment. This fragment was isolated and purified from a 1.0% agarose gel. Two 40 oligonucleotides SYNNOXAl.REQ (SEQ ID NO:240) and <br><br> SYNNQXA2.REQ (SEQ ID NO:241) were annealed and ligated with <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 222 <br><br> PCT/US96/15774 <br><br> the 281 base pair DNA fragment from pMON13 23 9 to the DNA vector fragment from pMON13189. A portion of the ligation mixture was then transformed into E. coli K-12 strain JM101. Transformant bacteria were selected on ampicillin-containing 5 plates. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of an EcoRV fragment, and sequenced to confirm the correct inserts. <br><br> 10 The plasmid, pMON31114, contains the DNA sequence of <br><br> (SEQ ID NO:116) which encodes the following amino acid sequence: <br><br> 15 MetAlaAsnCysSerAsnMetlleAspGlullelleThrHisLeuLysGlnProProLeu <br><br> ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsn LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlriAsnAlaSer AlalleGluSerlleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro ThrArgHi sProllelleIle ArgAspGlyAspTrpAsnGluPheArgArgLysL euThr 20 PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly <br><br> SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer TyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPhe 25 LeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu <br><br> LysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSer LeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGlu GlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPhe 30 AlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro <br><br> (SEQ ID NO:201) <br><br> EXAMPLE 8 6 <br><br> 35 <br><br> Construction ot PMQN31115 <br><br> Construction of pMON31115, a plasmid containing DNA sequence encoding a multi-functional hematopoietic receptor agonist 40 which activates the hIL-3 receptor and G-CSF receptor. <br><br> Plasmid, pMON13197 DNA was digested with restriction enzymes <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 223 <br><br> PCT/US96/15774 <br><br> Ncol and Xmal resulting in an Ncol, Xmal vector fragment that was isolated and purified from a 0.8% agarose gel. The DNA from a second plasmid, pMONl3222, was digested with Ncol and EcoRI resulting in a 281 base pair Ncol, EcoRI fragment. <br><br> 5 This fragment was isolated and purified from a 1.0% agarose gel. Two oligonucleotides SYNNOXAl.REQ (SEQ ID NO:240) and SYNNOXA2.REQ (SEQ ID NO:241) were annealed and ligated with the 281 base pair DNA fragment from pMON13222 to the DNA vector fragment from pMON13197. A portion of the ligation 10 mixture was then transformed into E. coli K-12 strain JM101. <br><br> Transformant bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of an EcoRV fragment, and sequenced to confirm the correct inserts. <br><br> 15 <br><br> The plasmid, pMON31115, contains the DNA sequence of (SEQ ID NO:117) which encodes the following amino acid sequence: <br><br> 20 MetAlaAsnCysSerAsnMetlleAspGluIlelleThrHisLeuLysGlnProProLeu <br><br> ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsn LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer AlalleGluSerlleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro ThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThr 25 PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly <br><br> SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer TyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuPro 3 0 GlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla <br><br> LeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeu GlyHisSerLeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln AlaLeuGluGlylleSerProGluLeuGlyProThrLeuAspTnrLeuGlnLeuAspVal 3 5 AlaAspPheAlaThrThrIleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu <br><br> GlnPro (SEQ ID NO:202) <br><br> EXAMPLE 9,1 <br><br> 40 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 224 <br><br> PCT/US96/15774 <br><br> Determination of the in vitro activity of multi-functional hematopoietic receptor agonist nrnr.fiins <br><br> The protein concentration of the multi-functional 5 hematopoietic receptor agonist protein can be determined using a sandwich ELISA based on an affinity purified polyclonal antibody. Alternatively the protein concentration can be determined by amino acid composition analysis. The bioactivity of the multi-functional hematopoietic receptor 10 agonist can be determined in a number of in vitro assays. <br><br> For example a multi-functional hematopoietic receptor agonist which binds the hIL-3 receptor and G-CSF receptor can be assayed in cell proliferation assays using cell lines expressing the hIL-3 and/or G-CSF receptors. One such assay 15 is the AML-193 cell proliferation assay. AML-193 cells respond to IL-3 and G-CSF which allows for the combined bioactivity of the IL-3/G-CSF multi-functional hematopoietic receptor agonist to be determined. Another such assay is the TFl cell proliferation assay. <br><br> 20 In addition other factor dependent cell lines, such as <br><br> M-NFS-60 (ATCC. CRL 183 8) or 32D which are murine IL-3 dependent cell line, may be used. The activity of IL-3 is species specific whereas G-CSF is not, therefore the bioactivity of the G-CSF component of the IL-3/G-CSF multi-25 functional hematopoietic receptor agonist can be determined independently. Cell lines, such as BHK or murine Baf/3, which do not express the receptor for a given ligand can be transfected with a plasmid containing a gene encoding the desired receptor. An example of such a cell line is BaF3 30 transfected with the hG-CSF receptor (BaF3/hG-CSF). The activity of the multi-functional hematopoietic receptor agonist in these cell lines can be compared with hIL-3 or G-CSF alone or together. The bioactivity of examples of multifunctional hematopoietic receptor agonists of the present 35 invention assayed in the BaF3/hG-CSF cell proliferation and <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 225 <br><br> PCT/US96/15774 <br><br> TF1 cell proliferation assays is shown in Table 5 and Table 6. The bioactivity of the multi-functional hematopoietic receptor agonist is expressed as relative activity compared with a standard protein pMONl3056 (WO 95/21254). The bioactivity of examples of multi-functional hematopoietic receptor agonists of the present invention assayed in the BaF3/c-mpl cell proliferation and TF1 cell proliferation assays is shown in Table 7 and Table 8. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 226 <br><br> PCT/US96/15774 <br><br> TABLE 5 CELL PROLIFERATIVE ACTIVITY OF DUAL IL-3/G-CSF RECEPTOR AGONISTS <br><br> BaF3/hG-CSF receptor <br><br> TF1 <br><br> pMON <br><br> call proliferation c»ll proliferation <br><br> assay assay <br><br> relative activity* <br><br> relative activity* <br><br> 13182 <br><br> 0.015 <br><br> 1.1 <br><br> 13183 <br><br> 0.02 <br><br> nd <br><br> 13184 <br><br> 0.01 <br><br> 0.3 <br><br> 13185 <br><br> 0.023 <br><br> 0.36 <br><br> 13186 <br><br> 0.36 <br><br> 0.45 <br><br> 13187 <br><br> 0.07 <br><br> 0.26 <br><br> 13188 <br><br> 0.64 <br><br> 1.3 <br><br> 13189 <br><br> 0.58 <br><br> 1.37 <br><br> 13190 <br><br> 0.045 <br><br> 1.2 <br><br> 13191 <br><br> 0.14 <br><br> 2.7 <br><br> 13192 <br><br> 0.09 <br><br> 2.2 <br><br> 13193 <br><br> 0.06 <br><br> 3.0 <br><br> 25190 <br><br> nd nd <br><br> 25191 <br><br> 0.43 <br><br> 1.2 <br><br> 13194 <br><br> nd nd <br><br> 13195 <br><br> 1.3 <br><br> 4.3 <br><br> 13196 <br><br> 0.66 <br><br> 0.5 <br><br> 13197 <br><br> 0.6 <br><br> 0 .77 <br><br> 13198 <br><br> 0.6 <br><br> 0.5 <br><br> 13199 <br><br> nd nd <br><br> 15982 <br><br> 0.7 <br><br> 1.9 <br><br> 15981 <br><br> 0.068 <br><br> 1.2 <br><br> 15965 <br><br> 0.7 <br><br> 0 . 82 <br><br> 15966 <br><br> 0.36 <br><br> 1.48 <br><br> 15967 <br><br> 0. 62 <br><br> 1.37 <br><br> nd = not determined <br><br> * The bioactivity of the multi-functional hematopoietic receptor agonist is expressed as relative activity compared with a standard protein pMON13056. n=3 or greater <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 227 <br><br> PCT/US96/15774 <br><br> TABLE 6 <br><br> CELL PROLIFERATIVE ACTIVITY OF DUAL IL-3/G-CSF RECEPTOR AGONISTS <br><br> pMON <br><br> BaF3/hG-CSF receptor cell proliferation a ssay relative activity <br><br> TP 1 <br><br> call proliferation assay relative activity <br><br> 31104 <br><br> + <br><br> + <br><br> 31105 <br><br> + <br><br> + <br><br> 31106 <br><br> + <br><br> + <br><br> 31107 <br><br> nd nd <br><br> 31108 <br><br> + <br><br> + <br><br> 31109 <br><br> + <br><br> + <br><br> 31110 <br><br> nd nd <br><br> 31111 <br><br> nd nd <br><br> 31112 <br><br> + <br><br> + <br><br> 31113 <br><br> + <br><br> + <br><br> 31114 <br><br> + <br><br> 31115 <br><br> + <br><br> + <br><br> 31116 <br><br> nd nd <br><br> 31117 <br><br> nd nd nd = not determined t The bioactivity (n=l or 2) of the multi-functional hematopoietic receptor agonist is expressed as relative activity compared with a standard protein pMONl3056. "+" indicates that the molecule was comparable to pMONl3Q56. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 228 <br><br> PCT/US96/15774 <br><br> TABLE 7 CELL PROLIFERATION ACTIVITY <br><br> pMON <br><br> Baf3/c-mpl receptor cell proliferation aBsay act ivity* <br><br> TFl cell proliferation assay act ivity <br><br> 28505 <br><br> - <br><br> + <br><br> 28506 <br><br> - <br><br> + <br><br> 28507 <br><br> + <br><br> 28508 <br><br> - <br><br> + <br><br> 28509 <br><br> - <br><br> + <br><br> 28510 <br><br> - <br><br> + <br><br> 28511 <br><br> + <br><br> + <br><br> 28512 <br><br> + <br><br> + <br><br> 28513 <br><br> + <br><br> + <br><br> 28514 <br><br> + <br><br> + <br><br> 28519 <br><br> - <br><br> + <br><br> 28520 <br><br> - <br><br> + <br><br> 28521 <br><br> - <br><br> + <br><br> 28522 <br><br> - <br><br> + <br><br> 28523 <br><br> - <br><br> + <br><br> 28524 <br><br> - <br><br> + <br><br> 28525 <br><br> + <br><br> + <br><br> 28526 <br><br> + <br><br> + <br><br> 28533 <br><br> - <br><br> + <br><br> 28534 <br><br> - <br><br> + <br><br> 28535 <br><br> - <br><br> + <br><br> 28536 <br><br> - <br><br> + <br><br> 28537 <br><br> - <br><br> + <br><br> 28538 <br><br> - <br><br> + <br><br> 28539 <br><br> + <br><br> + <br><br> 28540 <br><br> + <br><br> + <br><br> 28541 <br><br> + <br><br> + <br><br> 28542 <br><br> + <br><br> + <br><br> 28543 <br><br> + <br><br> + <br><br> 28544 <br><br> + <br><br> + <br><br> 28545 <br><br> + <br><br> + <br><br> * Activity measured in the Baf3 cell line transfected with the c-mpl receptor, relative to c-mpl ligand (1-153). t Activity measured relative to pMON13056. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 229 <br><br> PCT/US96/15774 <br><br> In a similar mariner other factor dependent cell lines known to those skilled in the art can be used to measure the bioactivity of the desired multi-functional hematopoietic 5 receptor agonist. The methylcellulose assay can be used to determine the effect of the multi-functional hematopoietic receptor agonists on the expansion of the hematopoietic progenitor cells and the pattern of the different types of hematopoietic colonies in vitro. The methylcellulose assay 10 can provide an estimate of precursor frequency since one measures the frequency of progenitors per 100,000 input cells. Long term, stromal dependent cultures have been used to delineate primitive hematopoietic progenitors and stem cells. This assay can be used to determine whether the 15 multi-functional hematopoietic receptor agonist stimulates the expansion of very primitive progenitors and/or stem cells. In addition, limiting dilution cultures can be performed which will indicate the frequency of primitive progenitors stimulated by the multi-functional hematopoietic 20 receptor agonist. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 230 <br><br> PCT/US96/15774 <br><br> Table 8 <br><br> pMON # <br><br> IL-3 agonist activity <br><br> (AML cell proliferation assay) <br><br> c-mol reecptor agonist activity (Baf/3-c-ir\pl cell proliferation assay <br><br> 28505 <br><br> + <br><br> - <br><br> 28506 <br><br> + <br><br> - <br><br> 28507 <br><br> + <br><br> - <br><br> 28508 <br><br> + <br><br> - <br><br> 28509 <br><br> + <br><br> - <br><br> 28510 <br><br> + <br><br> - <br><br> 28511 <br><br> + <br><br> + <br><br> 28512 <br><br> + <br><br> + <br><br> 28513 <br><br> + <br><br> + <br><br> 28514 <br><br> + <br><br> + <br><br> 28515 <br><br> + <br><br> + <br><br> 28519 <br><br> + <br><br> - <br><br> 28520 <br><br> + <br><br> - <br><br> 28521 <br><br> + <br><br> - <br><br> 28522 <br><br> + <br><br> - <br><br> 28523 <br><br> + <br><br> - <br><br> 28524 <br><br> + <br><br> - <br><br> 28525 <br><br> + <br><br> + <br><br> 28526 <br><br> + <br><br> + <br><br> 28527 <br><br> -»■ <br><br> 28528 <br><br> + <br><br> + <br><br> 28529 <br><br> + <br><br> + <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 231 <br><br> PCT/US96/15774 <br><br> Table 8 (cont) <br><br> 28535 <br><br> + <br><br> _ <br><br> 28539 <br><br> + <br><br> + <br><br> 28540 <br><br> + <br><br> + <br><br> 285*1 <br><br> + <br><br> 28542 <br><br> + <br><br> + <br><br> 28545 <br><br> + <br><br> + <br><br> 28551 <br><br> + <br><br> + <br><br> 28571 <br><br> + <br><br> + <br><br> 5 EXAMPLE 8a <br><br> G-CSF variants which contain single or multiple amino acid substitutions were made using PCR mutagenesis techniques as described in WO 94/12639 and WO 94/12638. 10 These and other variants (i.e. amino acid substitutions, <br><br> insertions or deletions and N-terminal or C-terminal extensions) could also be made, by one skilled in the art, using a variety of other methods including synthetic gene assembly or site-directed mutagenesis (see Taylor et al., 15 Nucl. Acids Res., 13: 7864-8785 [1985]; Kunkel et al., Proc. <br><br> Natl. Acad. Sci. USA, 82: 488-492 [1985]; Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, [1989], (WO 94/12639) and (WO 94/12638)). These substitutions can be 20 made one at a time or in combination with other amino acid substitutions, and/or deletions, and/or insertions and/or extensions. After sequence verification of the changes, the plasmid DNA can be transfected into an appropriate mammalian cell, insect cell or bacterial strain such as E. coli for 25 production. Known variants of G-CSF, which are active, <br><br> include substitutions at positions 1 (Thr to Ser, Arg or <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 232 <br><br> PCT/US96/15774 <br><br> Gly, 2 (Pro to Leu), 3 (Leu to Arg or Ser) and 17 (Cys to Ser) and deletions of amino acids 1-11 (Kuga et al. Biochemicla and Biophysical Research Comm. 159:103-111 (1989)). These G-CSF amino acid substitution variants can be used as the template to create the G-CSF receptor agonists in which a new N-terminus and new C-terminys are created. Examples of G-CSF amino acid substitution variants are shown in Table 9. <br><br> EXAMPLE 39 <br><br> Bioactivity determination of G-CSF amino acid substitution variants <br><br> The G-CSF amino acid substitution variants can be assayed for cell proliferation activity using the Baf/3 cell line transfected with the human G-CSF receptor. The bioactvity of examples of G-CSF amino acid substitution variants is shown in Table 9 relative to native human G-CSF. A "+" indicates a comparable activity to native and a indicates significantly reduced or no measurable activity. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 233 <br><br> PCT/US96/15774 <br><br> TAgLE 9 <br><br> CF.T.L PROLIFERATION ACTTVTTY OF G-CSF VARIANTS TN BAF3 CELT, LINE TRANSFECTED WITH THE HUMAN K-CSF RECF.PTOR <br><br> aa position native aa mutant aa activity * <br><br> 13 <br><br> Phe <br><br> Ser <br><br> + <br><br> 13 <br><br> Phe <br><br> His <br><br> + <br><br> 13 <br><br> Phe <br><br> Thr <br><br> + <br><br> 13 <br><br> Phe <br><br> Pro <br><br> + <br><br> 16 <br><br> Lys <br><br> Pro <br><br> + <br><br> 16 <br><br> Lys <br><br> Ser <br><br> 4- <br><br> 16 <br><br> Lys <br><br> Thr <br><br> + <br><br> 16 <br><br> Lys <br><br> His <br><br> + <br><br> 18 <br><br> Leu <br><br> Pro <br><br> + <br><br> 18 <br><br> Leu <br><br> Thr <br><br> + <br><br> 18 <br><br> Leu <br><br> His <br><br> + <br><br> 18 <br><br> Leu <br><br> Cys <br><br> + <br><br> 18 <br><br> Leu lie <br><br> + <br><br> 19 <br><br> Glu <br><br> Ala <br><br> - <br><br> 19 <br><br> Glu <br><br> Thr <br><br> - <br><br> 19 <br><br> Glu <br><br> Arg <br><br> - <br><br> 19 <br><br> Glu <br><br> Pro <br><br> " <br><br> 19 <br><br> Glu <br><br> Leu <br><br> - <br><br> 19 <br><br> Glu <br><br> Ser <br><br> " <br><br> 22 <br><br> Arg <br><br> Tyr <br><br> + <br><br> 22 <br><br> Arg <br><br> Ser <br><br> + <br><br> 22 <br><br> Arg <br><br> Ala <br><br> + <br><br> 22 <br><br> Arg <br><br> Thr <br><br> + <br><br> 24 <br><br> He <br><br> Pro <br><br> + <br><br> 24 <br><br> lie <br><br> Leu <br><br> + <br><br> 24 <br><br> lie <br><br> Tyr <br><br> + <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 234 <br><br> PCT/US96/15774 <br><br> TA.BLE 9 coat. <br><br> aa position native aa mutant aa act ivity <br><br> 27 <br><br> Asp <br><br> Gly <br><br> + <br><br> 30 <br><br> Ala lie <br><br> + <br><br> 30 <br><br> Ala <br><br> Leu <br><br> + <br><br> 34 <br><br> Lys <br><br> Ser <br><br> + <br><br> 43 <br><br> His <br><br> Gly <br><br> + <br><br> 43 <br><br> His <br><br> Thr <br><br> + <br><br> 43 <br><br> His <br><br> Val <br><br> + <br><br> 43 <br><br> His <br><br> Lys <br><br> + <br><br> 43 <br><br> His <br><br> Trp <br><br> + <br><br> 43 <br><br> His <br><br> Ala <br><br> + <br><br> 43 <br><br> His <br><br> Arg <br><br> + <br><br> 43 <br><br> His <br><br> Cys <br><br> + <br><br> 43 <br><br> His <br><br> Leu <br><br> + <br><br> 44 <br><br> Pro <br><br> Arg <br><br> + <br><br> 44 <br><br> Pro <br><br> Asp <br><br> + <br><br> 44 <br><br> Pro <br><br> Val <br><br> + <br><br> 44 <br><br> Pro <br><br> Ala <br><br> + <br><br> 44 <br><br> Pro <br><br> His <br><br> + <br><br> 44 <br><br> Pro <br><br> Gin <br><br> + <br><br> 44 <br><br> Pro <br><br> Trp <br><br> + <br><br> 44 <br><br> Pro <br><br> Gly <br><br> •*- <br><br> 44 <br><br> Pro <br><br> Thr <br><br> + <br><br> 46 <br><br> Glu <br><br> Ala <br><br> + <br><br> 46 <br><br> Glu <br><br> Arg <br><br> 47 <br><br> Leu <br><br> Thr <br><br> + <br><br> 49 <br><br> Leu <br><br> Phe <br><br> 49 <br><br> Leu <br><br> Arg <br><br> - <br><br> 49 <br><br> Leu <br><br> Ser <br><br> + <br><br> 50 <br><br> Leu <br><br> His <br><br> + <br><br> 54 <br><br> Leu <br><br> His <br><br> + <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 235 <br><br> PCT/US96/15774 <br><br> TABLE 8 conc. <br><br> aa position native aa mutant aa activity <br><br> 67 <br><br> Gin <br><br> Lys <br><br> + <br><br> 67 <br><br> Gin <br><br> Leu <br><br> + <br><br> 67 <br><br> Gin <br><br> Cys <br><br> + <br><br> 70 <br><br> Gin <br><br> Pro <br><br> 70 <br><br> Gin <br><br> Leu <br><br> + <br><br> 70 <br><br> Gin <br><br> Arg <br><br> + <br><br> 70 <br><br> Gin <br><br> Ser <br><br> + <br><br> 104 <br><br> Asp <br><br> Gly <br><br> -f <br><br> 104 <br><br> Asp <br><br> Val <br><br> + <br><br> 108 <br><br> Leu <br><br> Ala <br><br> + <br><br> 108 <br><br> Leu <br><br> Val <br><br> + <br><br> 108 <br><br> Leu <br><br> Arg <br><br> + <br><br> 108 <br><br> Leu <br><br> Gly <br><br> + <br><br> 108 <br><br> Leu <br><br> Trp <br><br> + <br><br> 108 <br><br> Leu <br><br> Gin <br><br> + <br><br> 115 <br><br> Thr <br><br> His <br><br> •f <br><br> 115 <br><br> Thr <br><br> Leu <br><br> + <br><br> 115 <br><br> Thr <br><br> Ala <br><br> + <br><br> 144 <br><br> Phe <br><br> His <br><br> + <br><br> 144 <br><br> Phe <br><br> Arg <br><br> + <br><br> 144 <br><br> Phe <br><br> Pro <br><br> + <br><br> 144 <br><br> Phe <br><br> Leu <br><br> 144 <br><br> Phe <br><br> Glu <br><br> -h <br><br> 146 <br><br> Arg <br><br> Gin <br><br> + <br><br> 147 <br><br> Arg <br><br> Gin <br><br> + <br><br> 156 <br><br> His <br><br> Asp <br><br> " <br><br> 156 <br><br> His <br><br> Ser <br><br> + <br><br> 156 <br><br> His <br><br> Gly <br><br> + <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> PCT/US96/15774 <br><br> 236 <br><br> TABLE 8 cont. <br><br> aa position native aa mutant aa activity <br><br> 159 <br><br> Ser <br><br> Arg <br><br> + <br><br> 159 <br><br> Ser <br><br> Thr <br><br> + <br><br> 159 <br><br> Ser <br><br> Tyr <br><br> + <br><br> 159 <br><br> Ser <br><br> Val <br><br> + <br><br> 159 <br><br> Ser <br><br> Gly <br><br> + <br><br> 162 <br><br> Glu <br><br> Gly <br><br> - <br><br> 162 <br><br> Glu <br><br> Trp <br><br> + <br><br> 162 <br><br> Glu <br><br> Leu <br><br> 163 <br><br> Val <br><br> Arg <br><br> + <br><br> 163 <br><br> Val <br><br> Ala <br><br> + <br><br> 163 <br><br> Val <br><br> Gly <br><br> + <br><br> 165 <br><br> Tyr <br><br> Cys nd <br><br> 169 <br><br> Ser <br><br> Leu <br><br> + <br><br> 169 <br><br> Ser <br><br> Cys <br><br> + <br><br> 169 <br><br> Ser <br><br> Arg <br><br> + <br><br> 17 0 <br><br> His <br><br> Arg <br><br> + <br><br> 170 <br><br> His <br><br> Ser <br><br> + <br><br> * activity relative to native hG-CSF nd = not determined <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> PCT/US96/15774 <br><br> 237 <br><br> Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to 5 be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. <br><br> More details concerning the molecular biology techniques, protein purification and bioassays can be found 10 in WO 94/12639, WO 94/12638, WO 95/20976, WO 95/21197, WO <br><br> 95/20977, WO 95/21254, are hereby incorporated by reference in their entirety. <br><br> All references, patents or applications cited herein 15 are incorporated by reference in their entirety as if written herein. <br><br> Various other examples will be apparent to the person skilled in the art after reading the present disclosure 20 without departing from the spirit and scope of the invention. It is intended that all such other examples be included within the scope of the appended claims. <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 238 <br><br> PCT/US96/15774 <br><br> SEQUENCE LISTING <br><br> (1) GENERAL INFORMATION: <br><br> (i) APPLICANT: <br><br> (A) NAME: G. D. Searle &amp; Co. <br><br> (B) STREET: P. 0. Box 5110 <br><br> (C) CITY: Chicago <br><br> (D) STATE: Illinois <br><br> (E) COUNTRY: United States o£ America <br><br> (F) POSTAL CODE (ZIP): 60680 <br><br> (G) TELEPHONE: (708)470-6501 <br><br> (H) TELEFAX: (708)470-6881 <br><br> (A) NAME: Monsanto Company <br><br> (B) STREET: 800 North Lindbergh Boulevard <br><br> (C) CITY: St. Louis <br><br> (D) STATE: Missouri <br><br> (E) COUNTRY: United States of America <br><br> (F) POSTAL CODE (ZIP): 63167 <br><br> (G) TELEPHONE: (314)647-3131 <br><br> (H) TELEFAX: (314)694-5435 <br><br> (ii) TITLE OF INVENTION: Multi-Functional Hematopoietic Receptor Agonists <br><br> (iii) NUMBER OF SEQUENCES: 258 <br><br> (iv) COMPUTER READABLE FORM: <br><br> (A) MEDIUM TYPE: Floppy disk <br><br> (B) COMPUTER: IBM PC compatible <br><br> (C) OPERATING SYSTEM: PC-DOS/MS-DOS <br><br> (D) SOFTWARE: Patentln Release #1.0, Version #1.30 (EPO) <br><br> (v) CURRENT APPLICATION DATA: <br><br> APPLICATION NUMBER: US 2910 (vi) PRIOR APPLICATION DATA: <br><br> (A) APPLICATION NUMBER: US 60/004,834 <br><br> (B) FILING DATE: Q5-0CT-1995 <br><br> (2) INFORMATION FOR SEQ ID NO: 1: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 174 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: unknown <br><br> (D) TOPOLOGY: unknown <br><br> (ii) MOLECULE TYPE: protein <br><br> (ix) FEATURE: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 239 <br><br> PCT/US96/15774 <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:1 <br><br> (D) OTHER INFORMATION:/note= "Xaa aC position 1 is Thr, Ser, Arg, Tyr or Gly;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:2 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 2 is Pro or Leu;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:3 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 3 is Leu, Arg, Tyr or Ser;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:13 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 13 is Phe, Ser, His, Thr or Pro,-" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:16 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 16 is Lys, Pro, Ser, thr or His;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:17 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 17 is Cys, Ser, Gly, Ala, lie, Tyr or Arg;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:IB <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 18 is Leu, Thr, Pro, His, lie or Cys;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:22 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:24 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 24 is lie, Pro, Tyr or Leu;" <br><br> (ix) FEATURE: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 240 <br><br> PCT/US96/15774 <br><br> (A) NAME/KEY: Modified-site (3) LOCATION:27 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 27 is Asp, or Gly;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:30 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 30 is Ala, lie. Leu or Gly;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:34 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 34 is Lys or Ser;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:36 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 36 is Cys or Ser;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:42 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 42 is Cys or Ser,-" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:43 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:44 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gin, or Thr;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:46 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 46 is Glu, Arg, Phe, Arg, lie or Ala;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:47 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 47 is Leu or Thr;" <br><br> (ix) FEATURE: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 241 <br><br> PCT/US96/15774 <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:49 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 49 is Leu, Phe, Arg or Ser;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:50 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 50 is Leu, lie. His, Pro or Tyr;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:54 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 54 is Leu or His;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:64 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 64 is Cys or Ser;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:67 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 67 is Gin, Lys, Leu or Cys;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:70 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 70 is Gin, Pro, Leu, Arg or Ser;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:74 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 74 is Cys or Ser;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:104 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 104 is Asp, Gly or Val;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:108 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gin or Gly;" <br><br> (ix) FEATURE: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 242 <br><br> PCT/US96/15774 <br><br> (A) NAME/KEY: Modified-site &lt;B) LOCATION:115 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 115 is Thr, His, Leu or Ala;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:120 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 120 is Gin, Gly, Arg, Lys or His" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:123 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 123 is Glu, Arg, Phe or Thr" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:144 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gin or Glu;" <br><br> (ix) FEATURE-. <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:146 <br><br> (D) OTHER INFORMATION:/note= "Xaa at positionl46 is Arg or Gin;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:147 <br><br> (D) OTHER INFORMATION:/note= "Xaa ap position 147 is Arg or Gin;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:156 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 156 is His, Gly or Ser;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:159 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION;162 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 162 is Glu, Leu, Gly or Trp;" <br><br> (ix) FEATURE: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 243 <br><br> PCT/US96/15774 <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION: 163 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 163 is Val, Gly, Arg or Ala;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:169 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 169 is Arg, Ser, Leu, Arg or Cys;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:170 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 170 is His, Arg or Ser;" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 1: <br><br> Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gin Ser Xaa Leu Leu Xaa 15 10 15 <br><br> Xaa Xaa Glu Gin Val Xaa Lys Xaa Gin Gly Xaa Gly Ala Xaa Leu Gin 20 25 30 <br><br> Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa Xaa Glu Xaa Xaa Val 35 40 45 <br><br> Xaa Xaa Gly His Ser Xaa Gly lie Pro Trp Ala Pro Leu Ser Ser Xaa 50 55 60 <br><br> Pro Ser Xaa Ala Leu Xaa Leu Ala Gly Xaa Leu Ser Gin Leu His Ser 65 70 75 80 <br><br> Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser 85 90 95 <br><br> Pro Glu Leu Gly Pro Thr Leu Xaa Thr Leu Gin Xaa Asp Val Ala Asp 100 105 110 <br><br> Phe Ala Xaa Thr lie Trp Gin Gin Met Glu Xaa Xaa Gly Met Ala Pro 115 120 125 <br><br> Ala Leu Gin Pro Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa 130 135 140 <br><br> Gin Xaa Xaa Ala Gly Gly Val Leu Val Ala Ser Xaa Leu Gin Xaa Phe 145 150 155 160 <br><br> Leu Xaa Xaa Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gin Pro 165 170 <br><br> (2) INFORMATION FOR SEQ ID NO: 2: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 244 <br><br> PCT/US96/15774 <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 133 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:17 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gin, or Arg;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:18 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 18 is Asn, His, Leu, lie, Phe, Arg, or Gin;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:19 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 19 is Met, Phe, lie, Arg, Gly, Ala, or Cys;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:20 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 20 is lie, Cys, Gin, Glu, Arg, Pro, or Ala;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:21 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 21 is Asp, <br><br> Phe, Lys, Arg, Ala, Gly, Glu, Gin, Asn, Thr, Ser or <br><br> Val; " <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:22 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 22 is Glu, <br><br> Trp, Pro, Ser, Ala, His, Asp, Asn, Gin, Leu, Val or <br><br> Gly; " <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:23 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 23 is lie, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 245 <br><br> PCT/US96/15774 <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:24 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 24 is lie, Gly, Val, Arg, Ser, Phe, Leu;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:25 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 25 is Thr, His, Gly, Gin, Arg, Pro, or Ala," <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:26 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, Trp;" <br><br> (ix) FEATURE: <br><br> [A) NAME/KEY: Modified-site <br><br> (B) LOCATION:27 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:28 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 28 is Lys, Arg, Leu, Gin, Gly, Pro, Val or Trpr" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:29 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 29 is Gin, Asn, Leu, Pro, Arg, or Val;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:30 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gin, Ser, Leu, or L..." <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:31 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gin;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:32 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 32 is Leu, Val, Arg, Gin, Asn, Gly, Ala, or Glu;" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 246 <br><br> PCT/US96/15774 <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:33 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 33 is Pro, Leu, Gin, Ala, Thr, or Glu;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:34 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 34 is Leu, <br><br> Val, Gly, Ser, Lys, Glu, Gin, Thr, Arg, Ala, Phe, lie or Met;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:35 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gin, or Val;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:3 6 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 36 is Asp, Leu, or Val;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:37 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 37 is Phe, Ser, Pro, Trp, or lie;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:38 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 38 is Asn, or Ala;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:40 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 40 is Leu, Trp, or Arg;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:41 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or pro;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:42 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 42 is Gly, <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 247 <br><br> PCT/US96/15774 <br><br> lie. Met <br><br> Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, or Ala;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:43 <br><br> (D) OTHER INFORMATION;/note= "Xaa at position 43 is Glu, <br><br> Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gin, Arg, Thr, Gly, <br><br> or Ser;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:44 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 44 is Asp, <br><br> Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gin, Ala or Pro; " <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:45 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 45 is Gin, <br><br> Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, <br><br> Ser, Ala, <br><br> lie, Glu or His;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:46 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 46 is Asp, <br><br> Phe, Ser, Thr, Cys, Glu, Asn, Gin, Lys, His, Ala, Tyr, <br><br> lie, Val or Gly;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:47 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 47 is lie, Gly, Val, Ser, Arg, Pro, or His;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:48 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 48 is Leu, <br><br> Ser, Cys, Arg, lie. His, Phe, Glu, Lys, Thr, Ala, Met, <br><br> Val or <br><br> Asn; " <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:49 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 248 <br><br> PCT/US96/15774 <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:50 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 50 is Glu, <br><br> Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, lie, Val, His, <br><br> Phe, Met or Gin;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:51 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or his;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:52 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:53 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 53 is Le-u, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or M..." <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:54 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 54 is Arg, <br><br> Asp, lie, Ser, Val, Thr, Gin, Asn, Lys, His, Ala or <br><br> Leu; " <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:55 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:56 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 56 is Pro, <br><br> Gly, Cys, Ser, Gin, Glu, Arg, His, Thr, Ala, Tyr, Phe, <br><br> Leu, Val or Lys;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:57 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 57 is Asn or Gly;" <br><br> (ix) FEATURE: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 249 <br><br> PCT/US96/15774 <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:58 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 58 is Leu, Ser, Asp, Arg, Gin, Val, or Cys;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:59 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:60 <br><br> (D) OTHER INFORMATION:/n.ote= "Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:61 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:62 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or lie;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:63 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:64 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:65 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:66 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 66 is Lys, lie, Arg, Val, Asn, Glu, or Ser;" <br><br> (ix) FEATURE: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 250 <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:67 <br><br> (D) OTHER INFORMATION:/note= "Xaa at postion 67 is Ser, Ala, Phe, Val, Gly, Asn, lie, Pro, or His;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:68 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 68 is Leu, Val, Trp, Ser, lie, Phe, Thr, or His;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:69 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 69 is Gin, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or L..." <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:70 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 70 is Asn, Leu, Val, Trp, pro, or Ala; " <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:71 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gin, Trp, or Asn;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:72 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:73 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site (B&gt; LOCATION:74 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 74 is lie. Met, Thr, Pro, Arg, Gly, Ala;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:75 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gin, or Leu;" <br><br> (ix) FEATURE: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 251 <br><br> PCT/US96/15774 <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:76 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or A..." <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:77 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 77 is lie, Ser, Arg, Thr, or Leu;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:78 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:79 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 79 is Lys, Thr, Asn, Met, Arg, lie, Gly, or Asp;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:80 <br><br> (D) OTHER INFORMATION:/note= "Xaa position at 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:81 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 81 is Leu, Gin, Gly, Ala, Trp, Arg, Val, or Lys;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:82 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 82 is Leu, <br><br> Gin, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, <br><br> Tyr, Phe, <br><br> lie. Met or Val;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:83 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:84 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 252 <br><br> PCT/US96/15774 <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:85 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 85 is Leu, Asn, Val, or Gin," <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:86 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:87 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 87 is Leu, Ser, Trp, or Gly;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:88 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:89 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or S..." <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:90 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, lie, or .Met;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:91 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:92 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, lie or Leu;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:93 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 253 <br><br> PCT/US96/15774 <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:94 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 94 is Arg, <br><br> lie, Ser, Glu, Leu, Val, Gin, Lys, His, Ala, or Pro;1' <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:95 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 95 is His, <br><br> Gin, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, <br><br> Trp, Phe, <br><br> lie, or Tyr;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:96 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 96 is Pro, Lys, Tyr, Gly, lie, or Thr;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:97 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 97 is lie, Val, Lys, Ala, or Asn;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:98 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 98 is His, <br><br> lie, Asn, Leu, Asp, Ala, Thr, Glu, Gin, Ser, Phe, Met, <br><br> Val, Lys, <br><br> Arg, Tyr, or Pro," <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:99 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 99 is lie, <br><br> Leu, Arg, Asp, Val, Pro, Gin, Gly, Ser, Phe, or His;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-sice <br><br> (B) LOCATION:100 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 100 is Lys, Tyr, Leu, His, Arg, lie, Ser, Gin, or ..." <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:101 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position is Asp, <br><br> Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, <br><br> Gly, lie, <br><br> Leu, or Gin;" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 254 <br><br> PCT/US96/15774 <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:102 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:103 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 103 is Asp, or Ser;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:104 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 104 is Trp, <br><br> Val, Cys, Tyr, Thr, Met, Pro, Leu, Gin, Lys, Ala, Phe, <br><br> or Gly;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:105 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 105 is Asn, <br><br> Pro, Ala, Phe, Ser, Trp, Gin, Tyr, Leu, Lys, lie. Asp, <br><br> or His;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:106 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, lie, Gly, or Pro;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:108 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 108 is Arg, <br><br> Lys, Asp, Leu, Thr, lie. Gin, His, Ser, Ala or Pro;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:109 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:110 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 110 is Lys, <br><br> Ala, Asn, Thr, Leu, Arg, Gin, His, Glu, Ser, or Trp;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:111 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 255 <br><br> PCT/US96/15774 <br><br> (D) OTHER INFORMATION:/note= 'Xaa at position 111 is Leu, lie, Arg, Asp, or Met;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:112 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 112 is Thr, Val, Gin, Tyr, Glu, His, Ser, or Phe;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION-.113 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 113 is Phe, <br><br> Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, lie, Val or Asn;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:114 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:115 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:116 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 116 is Lys, <br><br> Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, <br><br> His, Ala, <br><br> Tyr, Phe, Gin, or lie;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:117 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 117 is Thr, Ser, Asn, lie, Trp, Lys, or Pro;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:118 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:119 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 119 is Glu, Ser, Lys, Pro, leu, Thr, Tyr, or Arg;" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 256 <br><br> PCT/US96/15774 <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:120 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gin;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:121 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 121 is Ala, Ser, lie, Asn, Pro, Lys, Asp, or Gly; " <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:122 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 122 is Gin, <br><br> Ser, Met, Trp, Arg, Phe, Pro, His, lie, Tyr, or Cys;" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:123 <br><br> (D) OTHER INFORMATION:/note= "Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 2: <br><br> Ala Pro Met Thr Gin Thr Thr Ser Leu Lys Thr Ser Trp Val Asn Cys 15 10 15 <br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa <br><br> 20 25 30 <br><br> Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 <br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 50 55 60 <br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65 70 75 80 <br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 85 90 95 <br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Phe Xaa Xaa Xaa Xaa Xaa 100 105 110 <br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gin Gin Thr Thr Leu 115 120 125 <br><br> Ser Leu Ala lie Phe 130 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 257 <br><br> PCT/US96/15774 <br><br> (2) INFORMATION FOR SEQ ID NO: 3: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 332 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: unknown <br><br> (D) TOPOLOGY: unknown <br><br> (ii) MOLECULE TYPE: protein <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:112 <br><br> (D) OTHER INFORMATION:/note= "position 112 is deleted or Leu, Ala, Val, lie. Pro, Phe, Trp, or M..." <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:113 <br><br> (D) OTHER INFORMATION:/note= "position 113 is deleted or Pro, Phe, Ala, Leu, lie, Trp, or Met" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:114 <br><br> (D) OTHER INFORMATION:/note= "position 114 is deleted or Pro, Phe, Ala, Val, Leu, lie, Trp or Met" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:115 <br><br> (D) OTHER INFORMATION:/note= "position 115 is deleted or Gin, Gly, Ser, Thr, Tyr or Asn" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 3: <br><br> Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu 15 10 15 <br><br> Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val 20 25 30 <br><br> His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 35 40 45 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 50 55 60 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 65 70 75 80 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 258 <br><br> PCT /US96/15774 <br><br> 85 90 95 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Xaa 100 105 110 <br><br> Xaa Xaa Xaa Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe 115 120 125 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu 130 135 140 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg Arg Ala Pro Pro Thr Thr Ala 145 150 155 160 <br><br> Val Pro Ser Arg Thr Ser Leu Val Leu Thr Leu Asn Glu Leu Pro Asn 165 170 175 <br><br> Arg Thr Ser Gly Leu Leu Glu Thr Asn Phe Thr Ala Ser Ala Arg Thr 180 185 190 <br><br> Thr Gly Ser Gly Leu Leu Lys Trp Gin Gin Gly Phe Arg Ala Lys lie 195 200 205 <br><br> Pro Gly Leu Leu Asn Gin Thr Ser Arg Ser Leu Asp Gin lie Pro Gly 210 215 220 <br><br> Tyr Leu Asn Arg He His Glu Leu Leu Asn Gly Thr Arg Gly Leu Phe 225 230 235 240 <br><br> Pro Gly Pro Ser Arg Arg Thr Leu Gly Ala Pro Asp lie Ser Ser Gly 245 250 255 <br><br> Thr Ser Asp Thr Gly Ser Leu Pro Pro Asn Leu Gin Pro Gly Tyr Ser 260 265 270 <br><br> Pro Ser Pro Thr His Pro Pro Thr Gly Gin Tyr Thr Leu Phe Pro Leu 275 280 285 <br><br> Pro Pro Thr Leu Pro Thr Pro Val Val Gin Leu His Pro Leu Leu Pro 290 295 300 <br><br> Asp Pro Ser Ala Pro Thr Pro Thr Pro Thr Ser Pro Leu Leu Asn Thr 305 310 315 320 <br><br> Ser Tyr Thr His Ser Gin Asn Leu Ser Gin Glu Gly 325 330 <br><br> (2) INFORMATION FOR SEQ ID NO: 4: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 1 amino acids {B&gt; TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 259 <br><br> PCT/US96/15774 <br><br> (ii) MOLECULE TYPE: protein <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Protein <br><br> (B) LOCATION:1 <br><br> (D) OTHER INFORMATION:/note= "where x=(glyglyglyser)n and where n is an integer" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 4: <br><br> Xaa 1 <br><br> (2) INFORMATION FOR SEQ ID NO: 5: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 1 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Peptide <br><br> (B) LOCATION:! <br><br> (D) OTHER INFORMATION:/note= "where x=(glyglyglyglyser) n and where n is an integer" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 5: <br><br> Xaa <br><br> 1 <br><br> (2) INFORMATION FOR SEQ ID NO: 6: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 1 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Protein <br><br> (B) LOCATION:1 <br><br> (D) OTHER INFORMATION:/note= "where x= <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 260 <br><br> PCT/US96/15774 <br><br> (glyglyglyglyglyser)n and where n is an integer" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 6: <br><br> Xaa 1 <br><br> (2) INFORMATION FOR SEQ ID NO: 7: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: I amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Protein <br><br> (B) LOCATION:1 <br><br> (D) OTHER INFORMATION:/note= "where x= (gly n ser)n and where n is an integer" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 7: <br><br> Xaa <br><br> 1 <br><br> (2) INFORMATION FOR SEQ ID NO: 8: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 1 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Protein <br><br> (B) LOCATION:1 <br><br> (D) OTHER INFORMATION:/note= "where x=(alaglyser)n and where n is an integer" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 8: <br><br> Xaa 1 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 261 <br><br> PCT/US96/15774 <br><br> (2) INFORMATION FOR SEQ ID NO: 9 : <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 35 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 9: <br><br> Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Gly Gly Ser 15 10 15 <br><br> Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Gly 20 25 30 <br><br> Gly Gly Ser 35 <br><br> (2) INFORMATION FOR SEQ ID NO: 10: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 24 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 10: <br><br> lie Ser Glu Pro Ser Gly Pro lie Ser Thr lie Asn Pro Ser Pro Thr 15 10 15 <br><br> Ser Lys Glu Ser His Lys Ser Pro 20 <br><br> (2) INFORMATION FOR SEQ ID NO: 11: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 2 8 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 262 <br><br> PCT/US96/15774 <br><br> (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 11: <br><br> lie Glu Gly Arg lie Ser Glu Pro Ser Gly Pro lie Ser Thr lie Asn 15 10 15 <br><br> Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro <br><br> 20 25 <br><br> (2) INFORMATION FOR SEQ ID NO: 12: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 4 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 12: <br><br> Gly Gly Gly Ser 1 <br><br> (2) INFORMATION FOR SEQ ID NO: 13: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 45 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic) <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13: <br><br> ACGTCCATGG CNTCNCCNGC NCCNCCTGCT TGTGCACTCC GAGTC 45 <br><br> (2) INFORMATION FOR SEQ ID NO: 14: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 30 base pairs <br><br> (B) TYPE: nucleic acid <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 263 <br><br> PCT/US96/15774 <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 14: <br><br> ATGCACGAAT TCCCTGACGC AGAGGGTGGA 30 <br><br> (2) INFORMATION FOR SEQ ID NO: 15: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (Al LENGTH: 33 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 15: <br><br> TGACAAGCTT ACCTGACGCA GAGGGTGGAC CCT 33 <br><br> (2) INFORMATION FOR SEQ ID NO: 16: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 10 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 16: <br><br> AATTCGGCAA 10 <br><br> (2) INFORMATION FOR SEQ ID NO: 17: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> PCT/US96/15774 <br><br> 264 <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 10 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 17: <br><br> CATGTTGCCG 10 <br><br> (2) INFORMATION FOR SEQ ID NO: 18: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 13 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 18: <br><br> AATTCGGCGG CAA 13 <br><br> (2) INFORMATION FOR SEQ ID NO: 19: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 13 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 19: <br><br> CATGTTGCCG CCG <br><br> 13 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 265 <br><br> PCT/US96/15774 <br><br> (2) INFORMATION FOR SEQ ID NO: 20: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 22 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 20: <br><br> AATTCGGCGG CAACGGCGGC AA 22 <br><br> (2) INFORMATION FOR SEQ ID NO; 21: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 22 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 21: <br><br> CATGTTGCCG CCGTTGCCGC CG 22 <br><br> (2) INFORMATION FOR SEQ ID NO: 22: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 27 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 22: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 266 <br><br> PCT/US96/15774 <br><br> CGATCCATGG AGGTTCACCC TTTGCCT 27 <br><br> (2) INFORMATION FOR SEQ ID NO: 23: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 29 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic) " <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 23: <br><br> GATCAAGCTT ATGGGCACTG GCTCAGTCT 29 <br><br> (2) INFORMATION FOR SEQ ID NO: 24: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 27 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 24: <br><br> CGATACATGT TGCCTACACC TGTCCTG 27 <br><br> (2) INFORMATION FOR SEQ ID NO: 25: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 29 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 267 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 25: <br><br> GATCAAGCTT AAGGGTGAAC CTCTGGGCA 29 <br><br> (2) INFORMATION FOR SEQ ID NO: 26: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 27 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 26: <br><br> CGATCCATGG TCCTGCTGCC TGCTGTG 27 <br><br> (2) INFORMATION FOR SEQ ID NO: 27: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 29 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 27: <br><br> GATCAAGCTT AAGGTGTAGG CAAAGGGTG 29 <br><br> (2) INFORMATION FOR SEQ ID NO: 28: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 30 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 268 <br><br> PCT/US96/15774 <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 28: <br><br> CGATCCATGG CTGTGGACTT TAGCTTGGGA 30 <br><br> (2) INFORMATION FOR SEQ ID NO: 29: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 2 9 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 29: <br><br> GATCAAGCTT AAGGCAGCAG GACAGGTGT 29 <br><br> (2) INFORMATION FOR SEQ ID NO: 30: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 27 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 30: <br><br> CGATCCATGG ACTTTAGCTT GGGAGAA 27 <br><br> (2) INFORMATION FOR SEQ ID NO: 31: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 29 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 269 <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 31: <br><br> GATCAAGCTT ACACAGCAGG CAGCAGGAC 29 <br><br> (2) INFORMATION FOR SEQ ID NO: 32: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 27 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 32: <br><br> CGATCCATGG GAGAATGGAA AACCCAG <br><br> 27 <br><br> (2) INFORMATION FOR SEQ ID NO: 33: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 29 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 33: <br><br> GATCAAGCTT ACAAGCTAAA GTCCACAGC 29 <br><br> (2) INFORMATION FOR SEQ ID NO: 34: (i) SEQUENCE CHARACTERISTICS: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 270 <br><br> PCT/US96/15774 <br><br> (A) LENGTH: 27 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 34: <br><br> CGATCCATGG GACCCACTTG CCTCTCA 27 <br><br> (2) INFORMATION FOR SEQ ID NO: 35: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 29 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 35: <br><br> GATCAAGCTT ACAGTTGTCC CCGTGCTGC 29 <br><br> (2) INFORMATION FOR SEQ ID NO: 36: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 27 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 36: <br><br> CAGTCCATGG GAACCCAGCT TCCTCCA 27 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 271 <br><br> PCT/US96/15774 <br><br> (2) INFORMATION FOR SEQ ID NO: 37: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 29 base pairs <br><br> (B) TYPE: nucleic acid <br><br> &lt; C) STRANDEDNESS: single (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 37: <br><br> GATCAAGCTT AAAGGAGGCT CTGCAGGGC 29 <br><br> (2) INFORMATION FOR SEQ ID NO: 38: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 27 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TO POLOGY: 1inear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 38: <br><br> CGATCCATGG GCAGGACCAC AGCTCAC 27 <br><br> (2) INFORMATION FOR SEQ ID NO: 39: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 0 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 39: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> PCT/US96/15774 <br><br> 272 <br><br> GATCAAGCTT ACTGTGGAGG AAGCTGGGTT 30 <br><br> (2) INFORMATION FOR SEQ ID NO: 40: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 30 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 40: <br><br> CGATCCATGG CTCACAAGGA TCCCAATGCC 30 <br><br> (2) INFORMATION FOR SEQ ID NO: 41: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 29 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 41: <br><br> GATCAAGCTT ATGTGGTCCT GCGCTGTGG 29 <br><br> (2) INFORMATION FOR SEQ ID NO: 42: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 30 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 273 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 42: <br><br> CGATCCATGG ATCCCAATGC CATCTTCCTG 30 <br><br> (2) INFORMATION FOR SEQ ID NO: 43: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 29 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 43: <br><br> GATCAAGCTT ACTTGTGAGC TGTGGTCCT 29 <br><br> (2) INFORMATION FOR SEQ ID NO: 44: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 30 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic) <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 44: <br><br> CGATCCATGG CCATCTTCCT GAGCTTCCAA 30 <br><br> (2) INFORMATION FOR SEQ ID NO: 45: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 32 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 274 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 45: <br><br> GATCAAGCTT AATTGGGATC CTTGTGAGCT GT 32 <br><br> (2) INFORMATION FOR SEQ ID NO: 46: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 83 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 46: <br><br> AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT 60 <br><br> ACGTAGAGGG CGGTGGAGGC TCC 83 <br><br> (2) INFORMATION FOR SEQ ID NO: 47: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 83 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 47: <br><br> CCGGGGAGCC TCCACCGCCC TCTACGTACT GTTGAGCCTG CGCGTTCTCC AAGGTTTTCA 60 <br><br> GATAGAAGGT CAGTTTACGA CGG 83 <br><br> (2) INFORMATION FOR SEQ ID NO: 48: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 275 <br><br> PCT/US96/15774 <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 59 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 48: <br><br> GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT CTAACTGCTC TATAATGAT 59 <br><br> (2) INFORMATION FOR SEQ ID NO: 49: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 56 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 49: <br><br> CGATCATTAT AGAGCAGTTA GAGCCACCAC CCTGTTGTTC CTGCGCTTGC TCAAGG 56 <br><br> (2) INFORMATION FOR SEQ ID NO: 50: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 80 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 50: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 276 <br><br> PCT/US96/15774 <br><br> GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT CTGGCGGTGG CAGCGGCGGC 60 <br><br> GGTTCTAACT GCTCTATAAT 80 <br><br> (2) INFORMATION FOR SEQ ID NO: 51: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: BO base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 51: <br><br> CGATCATTAT AGAGCAGTTA GAACCGCCGC CGCTGCCACC GCCAGAGCCA CCACCCTGTT 60 <br><br> GTTCCTGCGC TTGCTCAAGG 80 <br><br> (2) INFORMATION FOR SEQ ID NO: 52: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 0 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 52: <br><br> GATCGACCAT GGCTCTGGAC CCGAACAACC 30 <br><br> (2) INFORMATION FOR SEQ ID NO: 53: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 28 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 277 <br><br> PCT/US96/15774 <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 53: <br><br> CTCGATTACG TACAAAGGTG CAGGTGGT 28 <br><br> (2) INFORMATION FOR SEQ ID NO: 54: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 32 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 54: <br><br> GATCGACCAT GGCTAATGCA TCAGGTATTG AG 32 <br><br> (2) INFORMATION FOR SEQ ID NO: 55: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 2 8 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 55: <br><br> CTCGATTACG TATTCTAAGT TCTTGACA 28 <br><br> (2) INFORMATION FOR SEQ ID NO: 56: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 32 base pairs <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 278 <br><br> PCT/US96/15774 <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 56: <br><br> GATCGACCAT GGCTGCACCC TCTCGACATC CA 32 <br><br> (2) INFORMATION FOR SEQ ID NO: 57: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 28 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 57: <br><br> CTCGATTACG TAGGCCGTGG CAGAGGGC 28 <br><br> (2) INFORMATION FOR SEQ ID NO: 58: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 32 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 58: <br><br> GATCGACCAT GGCTGCAGGT GACTGGCAAG AA 32 <br><br> (2) INFORMATION FOR SEQ ID NO: 59: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 279 <br><br> PCT/US96/15774 <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 28 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 59: <br><br> CTCGATTACG TACTTGATGA TGATTGGA 28 <br><br> (2) INFORMATION FOR SEQ ID NO: 60: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 54 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 60: <br><br> GCTCTGAGAG CCGCCAGAGC CGCCAGAGGG CTGCGCAAGG TGGCGTAGAA CGCG 54 <br><br> (2) INFORMATION FOR SEQ ID NO: 61: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 54 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 61: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 280 <br><br> PCT/US96/15774 <br><br> CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAG 54 <br><br> (2) INFORMATION FOR SEQ ID NO: 62: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 18 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 62: <br><br> GGGCTGCGCA AGGTGGCG 18 <br><br> (2) INFORMATION FOR SEQ ID NO: 63: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 21 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 63: <br><br> ACACCATTGG GCCCTGCCAG C 21 <br><br> (2) INFORMATION FOR SEQ ID NO: 64: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 32 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 281 <br><br> PCIYUS96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 64: <br><br> GATCGACCAT GGCTTACAAG CTGTGCCACC CC 32 <br><br> (2) INFORMATION FOR SEQ ID NO: 65: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 36 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 65: <br><br> CGATCGAAGC TTATTAGGTG GCACACAGCT TCTCCT 36 <br><br> (2) INFORMATION FOR SEQ ID NO: 66: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 32 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 66: <br><br> GATCGACCAT GGCTCCCGAG TTGGGTCCCA CC 32 <br><br> (2) INFORMATION FOR SEQ ID NO: 67: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 36 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic) <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 282 <br><br> PCT/US96/15774 <br><br> (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 67: <br><br> CGATCGAAGC TTATTAGGAT ATCCCTTCCA GGGCCT 36 <br><br> (2) INFORMATION FOR SEQ ID NO: 68: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 2 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 68: <br><br> GATCGACCAT GGCTATGGCC CCTGCCCTGC AG 32 <br><br> (2) INFORMATION FOR SEQ ID NO: 69: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 36 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 69: <br><br> CGATCGAAGC TTATTATCCC AGTTCTTCCA TCTGCT 36 <br><br> (2) INFORMATION FOR SEQ ID NO: 70: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 32 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 283 <br><br> PCT/US96/15774 <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 70: <br><br> GATCGACCAT GGCTACCCAG GGTGCCATGC CG 32 <br><br> (2) INFORMATION FOR SEQ ID NO: 71: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 36 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 71: <br><br> CGATCGAAGC TTATTAGGGC TGCAGGGCAG GGGCCA 36 <br><br> (2) INFORMATION FOR SEQ ID NO: 72: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 6 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 72: <br><br> CGATCGAAGC TTATTAGGGC TGCAGGGCAG GGGCCA 36 <br><br> (2) INFORMATION FOR SEQ ID NO: 73: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 36 base pairs <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 284 <br><br> PCT/US96/15774 <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 73: <br><br> CGATCGAAGC TTATTAGGCG AAGGCCGGCA TGGCAC 36 <br><br> (2) INFORMATION FOR SEQ ID NO: 74: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 21 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 74: <br><br> GTAGAGGGCG GTGGAGGCTC C 21 <br><br> (2) INFORMATION FOR SEQ ID NO: 75: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 25 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION; /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 75: <br><br> CCGGGGAGCC TCCACCGCCC TCTAC 25 <br><br> (2) INFORMATION FOR SEQ ID NO: 76: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 285 <br><br> PCT/US96/15774 <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 53 base pairs <br><br> (B) TYPE: nucleic acid tC) STRANDEDNESS: single (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE; other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic) <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 76: <br><br> TTCTACGCCA CCTTGCGCAG CCCGGCGGCG GCTCTGACAT GTCTACACCA TTG 53 <br><br> (2) INFORMATION FOR SEQ ID NO: 77: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 53 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 77: <br><br> CAATGGTGTA GACATGTCAG AGCCGCCGCC GGGCTGCGCA AGGTGGCGTA GAA 53 <br><br> (2) INFORMATION FOR SEQ ID NO: 78: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 43 9 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 7 8: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 286 <br><br> PCT/US96/15774 <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGT 439 <br><br> (2) INFORMATION FOR SEQ ID NO: 79: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 465 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 79: <br><br> TCCCCAGCTC CACCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT 60 <br><br> GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG 120 <br><br> CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA 180 <br><br> CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA 240 <br><br> CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC 300 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 287 <br><br> PCT/US96/15774 <br><br> CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT 360 <br><br> CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT 420 <br><br> TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGGG AATTC 465 <br><br> (2) INFORMATION FOR SEQ ID NO: 80: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 80: <br><br> TCCCCAGCTC CACCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT 60 <br><br> GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG 120 <br><br> CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA 180 <br><br> CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA 240 <br><br> CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC 300 <br><br> CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT 360 <br><br> CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT 420 <br><br> TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGGG AATTCGGCGG CAACATGGCG 480 <br><br> TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT 540 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 288 <br><br> PCT/US96/15774 <br><br> GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG 600 <br><br> CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA 660 <br><br> CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA 720 <br><br> CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC 780 <br><br> CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGGGCAGGA CCACAGCTCA CAAGGATCCC 840 <br><br> AATGCCATCT TCCTGAGCTT CCAACACCTG CTCCGAGGAA AGGTGCGTTT CCTGATGCTT 900 <br><br> GTAGGAGGGT CCACCCTCTG CGTCAGG 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 81: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 936 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 81: <br><br> TCCCCAGCTC CACCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT 60 <br><br> GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG 120 <br><br> CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA 180 <br><br> CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA 240 <br><br> CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC 300 <br><br> CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT 360 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 289 <br><br> PCT/US96/15774 <br><br> CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT 420 <br><br> TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGGG AATTCGGCAA CATGGCGTCT 480 <br><br> CCCGCTCCGC CTGCTTGTGA CCTCCGAGTC CTCAGTAAAC TGCTTCGTGA CTCCCATGTC 540 <br><br> CTTCACAGCA GACTGAGCCA GTGCCCAGAG GTTCACCCTT TGCCTACACC TGTCCTGCTG 600 <br><br> CCTGCTGTGG ACTTTAGCTT GGGAGAATGG AAAACCCAGA TGGAGGAGAC CAAGGCACAG 660 <br><br> GACATTCTGG GAGCAGTGAC CCTTCTGCTG GAGGGAGTGA TGGCAGCACG GGGACAACTG 720 <br><br> GGACCCACTT GCCTCTCATC CCTCCTGGGG CAGCTTTCTG GACAGGTCCG TCTCCTCCTT 780 <br><br> GGGGCCCTGC AGAGCCTCCT TGGAACCCAG CTTCCTCCAC AGGGCAGGAC CACAGCTCAC 840 <br><br> AAGGATCCCA ATGCCATCTT CCTGAGCTTC CAACACCTGC TCCGAGGAAA GGTGCGTTTC 900 <br><br> CTGATGCTTG TAGGAGGGTC CACCCTCTGC GTCAGG 936 <br><br> (2) INFORMATION FOR SEQ ID NO: 82: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 93 9 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 82: <br><br> TCCCCAGCTC CACCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT 60 <br><br> GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG 120 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 290 <br><br> PCT/US96/15774 <br><br> CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA 180 <br><br> CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA 240 <br><br> CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC 300 <br><br> CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT 360 <br><br> CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT 420 <br><br> TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGGG AATTCGGCGG CAACATGGCG 480 <br><br> TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT 540 <br><br> GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG 600 <br><br> CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA 660 <br><br> CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA 720 <br><br> CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC 780 <br><br> CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT 840 <br><br> CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT 900 <br><br> TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGG 939 <br><br> (2) INFORMATION FOR SEQ ID NO: 83: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 948 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)". <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 291 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 83: <br><br> TCCCCAGCGC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT 60 <br><br> GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG 120 <br><br> CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA 180 <br><br> CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA 240 <br><br> CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC 300 <br><br> CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT 360 <br><br> CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT 420 <br><br> TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGGG AATTCGGCGG CAACGGCGGC 480 <br><br> AACATGGCGT CCCCAGCGCC GCCTGCTTGT GACCTCCGAG TCCTCAGTAA ACTGCTTCGT 540 <br><br> GACTCCCATG TCCTTCACAG CAGACTGAGC CAGTGCCCAG AGGTTCACCC TTTGCCTACA 600 <br><br> CCTGTCCTGC TGCCTGCTGT GGACTTTAGC TTGGGAGAAT GGAAAACCCA GATGGAGGAG 660 <br><br> ACCAAGGCAC AGGACATTCT GGGAGCAGTG ACCCTTCTGC TGGAGGGAGT GATGGCAGCA 720 <br><br> CGGGGACAAC TGGGACCCAC TTGCCTCTCA TCCCTCCTGG GGCAGCTTTC TGGACAGGTC 780 <br><br> CGTCTCCTCC TTGGGGCCCT GCAGAGCCTC CTTGGAACCC AGCTTCCTCC ACAGGGCAGG 840 <br><br> ACCACAGCTC ACAAGGATCC CAATGCCATC TTCCTGAGCT TCCAACACCT GCTCCGAGGA 900 <br><br> AAGGTGCGTT TCCTGATGCT TGTAGGAGGG TCCACCCTCT GCGTCAGG 948 <br><br> (2) INFORMATION FOR SEQ ID NO: 84: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 292 <br><br> PCT/US96/15774 <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 688 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 84: <br><br> CATGGCTAAC TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA GACCACCTGC 60 <br><br> ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC TCTATCCTGA TGGACCGAAA 120 <br><br> CCTTCGACTT CCAAACCTGG AGAGCTTCGT AAGGGCTGTC AAGAACTTAG AAAATGCATC 180 <br><br> AGGTATTGAG GCAATTCTTC GTAATCTCCA ACCATGTCTG CCCTCTGCCA CGGCCGCACC 240 <br><br> CTCTCGACAT CCAATCATCA TCAAGGCAGG TGACTGGCAA GAATTCCGGG AAAAACTGAC 300 <br><br> GTTCTATCTG GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT CTAACTGCTC 360 <br><br> TATAATGATC GATGAAATTA TACATCACTT AAAGAGACCA CCTGCACCTT TGCTGGACCC 420 <br><br> GAACAACCTC AATGACGAAG ACGTCTCTAT CCTGATGGAC CGAAACCTTC GACTTCCAAA 480 <br><br> CCTGGAGAGC TTCGTAAGGG CTGTCAAGAA CTTAGAAAAT GCATCAGGTA TTGAGGCAAT 540 <br><br> TCTTCGTAAT CTCCAACCAT GTCTGCCCTC TGCCACGGCC GCACCCTCTC GACATCCAAT 600 <br><br> CATCATCAAG GCAGGTGACT GGCAAGAATT CCGGGAAAAA CTGACGTTCT ATCTGGTTAC 660 <br><br> CCTTGAGCAA GCGCAGGAAC AACAGTAC 688 <br><br> (2) INFORMATION FOR SEQ ID NO: 85: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 712 base pairs <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 293 <br><br> PCT/US96/15774 <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 85: <br><br> CATGGCTAAC TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA GACCACCTGC 60 <br><br> ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC TCTATCCTGA TGGACCGAAA 120 <br><br> CCTTCGACTT CCAAACCTGG AGAGCTTCGT AAGGGCTGTC AAGAACTTAG AAAATGCATC 180 <br><br> AGGTATTGAG GCAATTCTTC GTAATCTCCA ACCATGTCTG CCCTCTGCCA CGGCCGCACC 240 <br><br> CTCTCGACAT CCAATCATCA TCAAGGCAGG TGACTGGCAA GAATTCCGGG AAAAACTGAC 300 <br><br> GTTCTATCTG GTTACCCTTG AGCAAGCGCA GGAACAACAG GGTGGTGGCT CTGGCGGTGG 360 <br><br> CAGCGGCGGC GGTTCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG 420 <br><br> ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT 480 <br><br> GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA 540 <br><br> AAATGCATCA GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC 600 <br><br> GGCCGCACCC TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA 660 <br><br> AAAACTGACG TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT AC 712 <br><br> (2) INFORMATION FOR SEQ ID NO: 86: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 975 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 294 <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 86: <br><br> ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 60 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 120 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 180 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 240 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TAACTGCTCT 300 <br><br> ATAATGATCG ATGAAATTAT ACATCACTTA AAGAGACCAC CTGCACCTTT GTACGTAGAG 360 <br><br> GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CCCGTCTCCT 420 <br><br> CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGGCTACCC AGGGTGCCAT GCCGGCCTTC 480 <br><br> GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC 540 <br><br> CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC 600 <br><br> TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CGATGGCGCA 660 <br><br> GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG 720 <br><br> CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG 780 <br><br> CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG 840 <br><br> CAGGCCCTGG AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC 900 <br><br> Printed from Mimosa 08:37.19 <br><br> WO 97/12985 <br><br> 295 <br><br> PCT/US96/15774 <br><br> GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT GGCCCCTGCC 960 <br><br> CTGCAGCCCT AATAA 975 <br><br> (2) INFORMATION FOR SEQ ID NO: 87: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 975 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 87: <br><br> ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 60 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 120 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 180 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 240 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TAACTGCTCT 300 <br><br> ATAATGATCG ATGAAATTAT ACATCACTTA AAGAGACCAC CTGCACCTTT GTACGTAGAG 360 <br><br> GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CCCGTCTCCT 420 <br><br> CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGGCTACCC AGGGTGCCAT GCCGGCCTTC 480 <br><br> GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC 540 <br><br> CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC 600 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 296 <br><br> PCT/US96/15774 <br><br> TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CGATGGCGCA 660 <br><br> GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG 720 <br><br> CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG 780 <br><br> CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG 840 <br><br> CAGGCCCTGG AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC 900 <br><br> GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT GGCCCCTGCC 960 <br><br> CTGCAGCCCT AATAA 975 <br><br> (2) INFORMATION FOR SEQ ID NO: 88; <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 975 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 88: <br><br> ATGGCTGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG 60 <br><br> GAAAAACTGA CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GGGTGGTGGC 120 <br><br> TCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 180 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 240 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 300 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CTACGTAGAG 360 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 297 <br><br> PCT/US96/15774 <br><br> GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CCCGTCTCCT 420 <br><br> CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGGCTACCC AGGGTGCCAT GCCGGCCTTC 480 <br><br> GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC 540 <br><br> CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC 600 <br><br> TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CGATGGCGCA 660 <br><br> GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG 720 <br><br> CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG 780 <br><br> CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG 840 <br><br> CAGGCCCTGG AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC 900 <br><br> GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT GGCCCCTGCC 960 <br><br> CTGCAGCCCT AATAA 975 <br><br> (2) INFORMATION FOR SEQ ID NO: 89: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 975 base pairs <br><br> (B) TYPE: nucleic acid (C&gt; STRANDEDNESS: single (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 89: <br><br> ATGGCTGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTT 60 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 298 <br><br> PCT/US96/15774 <br><br> GAGCAAGCGC AGGAACAACA GGGTGGTGGC TCTAACTGCT CTATAATGAT CGATGAAATT 120 <br><br> ATACATCACT TAAAGAGACC ACCTGCACCT TTGCTGGACC CGAACAACCT CAATGACGAA 180 <br><br> GACGTCTCTA TCCTGATGGA CCGAAACCTT CGACTTCCAA ACCTGGAGAG CTTCGTAAGG 240 <br><br> GCTGTCAAGA ACTTAGAAAA TGCATCAGGT ATTGAGGCAA TTCTTCGTAA TCTCCAACCA 300 <br><br> TGTCTGCCCT CTGCCACGGC CGCACCCTCT CGACATCCAA TCATCATCAA GTACGTAGAG 360 <br><br> GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CCCGTCTCCT 420 <br><br> CCGTCTAAAG AATCTCATAA ATCTCCAAAC ATGGCTACCC AGGGTGCCAT GCCGGCCTTC 480 <br><br> GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC 540 <br><br> CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC 600 <br><br> TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CGATGGCGCA 660 <br><br> GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG 720 <br><br> CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG 780 <br><br> CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG 840 <br><br> CAGGCCCTGG AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC 900 <br><br> GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT GGCCCCTGCC 960 <br><br> CTGCAGCCCT AATAA 975 <br><br> (2) INFORMATION FOR SEQ ID NO: 90: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 999 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 299 <br><br> PCT/US96/15774 <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 90: <br><br> ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 60 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 120 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC <br><br> iao <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 240 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TGGCGGTGGC 300 <br><br> AGCGGCGGCG GTTCTAACTG CTCTATAATG ATCGATGAAA TTATACATCA CTTAAAGAGA 360 <br><br> CCACCTGCAC CTTTGTACGT AGAGGGCGGT GGAGGCTCCC CGGGTGAACC GTCTGGTCCA 420 <br><br> ATCTCTACTA TCAACCCGTC TCCTCCGTCT AAAGAATCTC ATAAATCTCC AAACATGGCT 480 <br><br> ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG 540 <br><br> GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG 600 <br><br> CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG 660 <br><br> AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CTACAAGCTG 720 <br><br> TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GGCTCCCCTG 780 <br><br> AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC 840 <br><br> CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC 900 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 300 <br><br> PCT/US96/15774 <br><br> ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG 960 <br><br> GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA 999 <br><br> (2) INFORMATION FOR SEQ ID NO: 91: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 999 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 91: <br><br> ATGGCTAATG CATCAGGTAT TGAGGCAATT CTTCGTAATC TCCAACCATG TCTGCCCTCT 60 <br><br> GCCACGGCCG CACCCTCTCG ACATCCAATC ATCATCAAGG CAGGTGACTG GCAAGAATTC 120 <br><br> CGGGAAAAAC TGACGTTCTA TCTGGTTACC CTTGAGCAAG CGCAGGAACA ACAGGGTGGT 180 <br><br> GGCTCTGGCG GTGGCAGCGG CGGCGGTTCT AACTGCTCTA TAATGATCGA TGAAATTATA 240 <br><br> CATCACTTAA AGAGACCACC TGCACCTTTG CTGGACCCGA ACAACCTCAA TGACGAAGAC 300 <br><br> GTCTCTATCC TGATGGACCG AAACCTTCGA CTTCCAAACC TGGAGAGCTT CGTAAGGGCT 360 <br><br> GTCAAGAACT TAGAATACGT AGAGGGCGGT GGAGGCTCCC CGGGTGAACC GTCTGGTCCA 420 <br><br> ATCTCTACTA TCAACCCGTC TCCTCCGTCT AAAGAATCTC ATAAATCTCC AAACATGGCT 480 <br><br> ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG 540 <br><br> GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG 600 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 301 <br><br> PCT/US96/15774 <br><br> CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG 660 <br><br> AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CTACAAGCTG 720 <br><br> TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GGCTCCCCTG 780 <br><br> AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC 840 <br><br> CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC 900 <br><br> ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG 960 <br><br> GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA 999 <br><br> (2) INFORMATION FOR SEQ ID NO: 92: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 999 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 92: <br><br> ATGGCTGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG 60 <br><br> GAAAAACTGA CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GGGTGGTGGC 120 <br><br> TCTGGCGGTG GCAGCGGCGG CGGTTCTAAC TGCTCTATAA TGATCGATGA AATTATACAT <br><br> 180 <br><br> CACTTAAAGA GACCACCTGC ACCTTTGCTG GACCCGAACA ACCTCAATGA CGAAGACGTC 240 <br><br> TCTATCCTGA TGGACCGAAA CCTTCGACTT CCAAACCTGG AGAGCTTCGT AAGGGCTGTC 300 <br><br> AAGAACTTAG AAAATGCATC AGGTATTGAG GCAATTCTTC GTAATCTCCA ACCATGTCTG 360 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 302 <br><br> PCT/US96/15774 <br><br> CCCTCTGCCA CGGCCTACGT AGAGGGCGGT GGAGGCTCCC CGGGTGAACC GTCTGGTCCA 420 <br><br> ATCTCTACTA TCAACCCGTC TCCTCCGTCT AAAGAATCTC ATAAATCTCC AAACATGGCT 480 <br><br> ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG 540 <br><br> GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG 600 <br><br> CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG 660 <br><br> AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CTACAAGCTG 720 <br><br> TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GGCTCCCCTG 780 <br><br> AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC 840 <br><br> CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC 900 <br><br> ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG 960 <br><br> GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA 999 <br><br> (2) INFORMATION FOR SEQ ID NO: 93: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 999 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 93: <br><br> ATGGCTGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTT 60 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 303 <br><br> PCT/US96/15774 <br><br> GAGCAAGCGC AGGAACAACA GGGTGGTGGC TCTGGCGGTG GCAGCGGCGG CGGTTCTAAC 120 <br><br> TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA GACCACCTGC ACCTTTGCTG 180 <br><br> GACCCGAACA ACCTCAATGA CGAAGACGTC TCTATCCTGA TGGACCGAAA CCTTCGACTT 240 <br><br> CCAAACCTGG AGAGCTTCGT AAGGGCTGTC AAGAACTTAG AAAATGCATC AGGTATTGAG 300 <br><br> GCAATTCTTC GTAATCTCCA ACCATGTCTG CCCTCTGCCA CGGCCGCACC CTCTCGACAT 360 <br><br> CCAATCATCA TCAAGTACGT AGAGGGCGGT GGAGGCTCCC CGGGTGAACC GTCTGGTCCA 420 <br><br> ATCTCTACTA TCAACCCGTC TCCTCCGTCT AAAGAATCTC ATAAATCTCC AAACATGGCT 480 <br><br> ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG 540 <br><br> GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG 600 <br><br> CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG 660 <br><br> AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CTACAAGCTG 720 <br><br> TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GGCTCCCCTG 780 <br><br> AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC 840 <br><br> CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC 900 <br><br> ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG 960 <br><br> GAAGAACTGG GAATGGCCCC TGCCCTGCAG CCCTAATAA 999 <br><br> (2) INFORMATION FOR SEQ ID NO: 94: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 304 <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 94: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 1B0 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT ACAAGCTGTG CCACCCCGAG 420 <br><br> GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC 480 <br><br> AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC 540 <br><br> CAGGGGCTCC TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA 600 <br><br> CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AGAACTGGGA 660 <br><br> ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG CCTTCGCCTC TGCTTTCCAG 720 <br><br> CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC CATCTGCAGA GCTTCCTGGA GGTGTCGTAC 780 <br><br> CGCGTTCTAC GCCACCTTGC GCAGCCCTCT GGCGGCTCTG GCGGCTCTCA GAGCTTCCTG 840 <br><br> CTCAAGTCTT TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG 900 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 305 <br><br> PCT/US96/15774 <br><br> CTGTGTGCCA CCTAATAA 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 95: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 963 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 95: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GGCTTACAAG CTGTGCCACC CCGAGGAGCT GGTGCTGCTC 480 <br><br> GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG 540 <br><br> CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG 600 <br><br> GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC 660 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 306 <br><br> PCT/US96/15774 <br><br> GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC GCCTGCCCTG 720 <br><br> CAGCCCACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG 780 <br><br> GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC 840 <br><br> CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG 900 <br><br> CAAGTGAGAA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAA 960 <br><br> TAA <br><br> 963 <br><br> (2) INFORMATION FOR SEQ ID NO: 96: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> &lt;A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 96: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC CCGAGTTGGG TCCCACCTTG 420 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 307 <br><br> PCT/US96/15774 <br><br> GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA GATGGAAGAA 480 <br><br> CTGGGAATGG CCCCTGCCCT GCAGCCCACC CAGGGTGCCA TGCCGGCCTT CGCCTCTGCT S40 <br><br> TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT CCTGGAGGTG 600 <br><br> TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCTCTGGCG GCTCTGGCGG CTCTCAGAGC 660 <br><br> TTCCTGCTCA AGTCTTTAGA GCAAGTGAGA AAGATCCAGG GCGATGGCGC AGCGCTCCAG 720 <br><br> GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACAC 780 <br><br> TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA 840 <br><br> GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG 900 <br><br> GAAGGGATAT CCTAATAA 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 97: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 963 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 97: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 1b0 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 308 <br><br> PCT/US96/15774 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GGCTCCCGAG TTGGGTCCCA CCTTGGACAC ACTGCAGCTG 480 <br><br> GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT 540 <br><br> GCCCTGCAGC CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA 600 <br><br> GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA 660 <br><br> CGCCACCTTG CGCAGCCCTC TGGCGGCTCT GGCGGCTCTC AGAGCTTCCT GCTCAAGTCT 720 <br><br> TTAGAGCAAG TGAGAAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC 780 <br><br> ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG GACACTCTCT GGGCATCCCC 840 <br><br> TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA 900 <br><br> CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCTAA 960 <br><br> TAA <br><br> 963 <br><br> (2) INFORMATION FOR SEQ ID NO: 98: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 309 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 98: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG <br><br> 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA TGGCCCCTGC CCTGCAGCCC 420 <br><br> ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG 480 <br><br> GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG 540 <br><br> CAGCCCTCTG GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG 600 <br><br> AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC CTACAAGCTG 660 <br><br> TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG GCATCCCCTG GGCTCCCCTG 720 <br><br> AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG GCAGGCTGCT TGAGCCAACT CCATAGCGGC 780 <br><br> CTTTTCCTCT ACCAGGGGCT CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC 840 <br><br> ACCTTGGACA CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG 900 <br><br> GAAGAACTGG GATAATAA 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 99: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 310 <br><br> PCT/US96/15774 <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 963 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic) " <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 99: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GGCTATGGCC CCTGCCCTGC AGCCCACCCA GGGTGCCATG 480 <br><br> CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG 540 <br><br> CAGAGCTTCC TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CTCTGGCGGC 600 <br><br> TCTGGCGGCT CTCAGAGCTT CCTGCTCAAG TCTTTAGAGC AAGTGAGAAA GATCCAGGGC 660 <br><br> GATGGCGCAG CGCTCCAGGA GAAGCTGTGT GCCACCTACA AGCTGTGCCA CCCCGAGGAG 720 <br><br> CTGGTGCTGC TCGGACACTC TCTGGGCATC CCCTGGGCTC CCCTGAGCTC CTGCCCCAGC 780 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 311 <br><br> PCT/US96/15774 <br><br> CAGGCCCTGC AGCTGGCAGG CTGCTTGAGC CAACTCCATA GCGGCCTTTT CCTCTACCAG 840 <br><br> GGGCTCCTGC AGGCCCTGGA AGGGATATCC CCCGAGTTGG GTCCCACCTT GGACACACTG 900 <br><br> CAGCTGGACG TCGCCGACTT TGCCACCACC ATCTGGCAGC AGATGGAAGA ACTGGGATAA 960 <br><br> TAA <br><br> 963 <br><br> (2) INFORMATION FOR SEQ ID NO: 100: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 100: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA CCCAGGGTGC CATGCCGGCC 420 <br><br> TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA GGGGTCCTGG TTGCTAGCCA TCTGCAGAGC 480 <br><br> TTCCTGGAGG TGTCGTACCG CGTTCTACGC CACCTTGCGC AGCCCTCTGG CGGCTCTGGC 540 <br><br> Printed from Mimosa 08.37.19 <br><br> WO 97/12985 <br><br> 312 <br><br> PCT/US96/15774 <br><br> GGCTCTCAGA GCTTCCTGCT CAAGTCTTTA GAGCAAGTGA GAAAGATCCA GGGCGATGGC 600 <br><br> GCAGCGCTCC AGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTG 660 <br><br> CTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC 720 <br><br> CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCC TTTTCCTCTA CCAGGGGCTC 780 <br><br> CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG TTGGGTCCCA CCTTGGACAC ACTGCAGCTG 840 <br><br> GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT 900 <br><br> GCCCTGCAGC CCTAATAA 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 101: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 963 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single CD) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 101: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> Printed from Mimosa 08.37.19 <br><br> WO 97/12985 <br><br> 313 <br><br> PCT/US96/15774 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC 480 <br><br> CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG 540 <br><br> TACCGCGTTC TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC 600 <br><br> CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG 660 <br><br> AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CGGACACTCT 720 <br><br> CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC 780 <br><br> TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA 840 <br><br> GGGATATCCC CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT 900 <br><br> GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT GCAGCCCTAA 960 <br><br> TAA <br><br> 963 <br><br> (2) INFORMATION FOR SEQ ID NO: 102: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 102: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 314 <br><br> PCT/US96/15774 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT CTGCTTTCCA GCGCCGGGCA 420 <br><br> GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA 480 <br><br> CGCCACCTTG CGCAGCCCTC TGGCGGCTCT GGCGGCTCTC AGAGCTTCCT GCTCAAGTCT 540 <br><br> TTAGAGCAAG TGAGAAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC 600 <br><br> ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG GACACTCTCT GGGCATCCCC 660 <br><br> TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA 720 <br><br> CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC 780 <br><br> GAGTTGGGTC CCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATC 840 <br><br> TGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCA GGGTGCCATG 900 <br><br> CCGGCCTTCG CCTAATAA 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 103: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 963 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 315 <br><br> PCT/U S96/15774 <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 103: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GGCTTCTGCT TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT 480 <br><br> GCTAGCCATC TGCAGAGCTT CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG 540 <br><br> CCCTCTGGCG GCTCTGGCGG CTCTCAGAGC TTCCTGCTCA AGTCTTTAGA GCAAGTGAGA 600 <br><br> AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CAAGCTGTGC 660 <br><br> CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC 720 <br><br> TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA GCCAACTCCA TAGCGGCCTT 780 <br><br> TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GGGTCCCACC 840 <br><br> TTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GCAGATGGAA 900 <br><br> Printed from Mimosa 08:37.19 <br><br> WO 97/12985 <br><br> 316 <br><br> PCT/US96/15774 <br><br> GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CTTCGCCTAA 960 <br><br> TAA 963 <br><br> (2) INFORMATION FOR SEQ ID NO: 104: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 104: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT ACAAGCTGTG CCACCCCGAG 420 <br><br> GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC 480 <br><br> AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC 540 <br><br> CAGGGGCTCC TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA 600 <br><br> CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AGAACTGGGA 660 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 317 <br><br> PCT/US96/15774 <br><br> ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG CCTTCGCCTC TGCTTTCCAG 720 <br><br> CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC CATCTGCAGA GCTTCCTGGA GGTGTCGTAC 780 <br><br> CGCGTTCTAC GCCACCTTGC GCAGCCCACA CCATTGGGCC CTGCCAGCTC CCTGCCCCAG 840 <br><br> AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC 900 <br><br> CAGGAGAAGC TGTGTGCCAC CTAATAA 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 105: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 972 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic) " <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 105: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 318 <br><br> PCT/US96/15774 <br><br> TCTCATAAAT CTCCAAACAT GGCTTACAAG CTGTGCCACC CCGAGGAGCT GGTGCTGCTC 480 <br><br> GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG 540 <br><br> CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG 600 <br><br> GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC 660 <br><br> GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CCCTGCCCTG 720 <br><br> CAGCCCACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG 780 <br><br> GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC 840 <br><br> CTTGCGCAGC CCACACCATT GGGCCCTGCC AGCTCCCTGC CCCAGAGCTT CCTGCTCAAG 900 <br><br> TCTTTAGAGC AAGTGAGAAA GATCCAGGGC GATGGCGCAG CGCTCCAGGA GAAGCTGTGT 960 <br><br> GCCACCTAAT AA 972 <br><br> (2) INFORMATION FOR SEQ ID NO: 106: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 106: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> Printed from Mimosa 08:37.19 <br><br> WO 97/12985 <br><br> 319 <br><br> PCT/US96/15774 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC CCGAGTTGGG TCCCACCTTG 420 <br><br> GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA GATGGAAGAA 480 <br><br> CTGGGAATGG CCCCTGCCCT GCAGCCCACC CAGGGTGCCA TGCCGGCCTT CGCCTCTGCT 540 <br><br> TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT CCTGGAGGTG 600 <br><br> TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCACACCAT TGGGCCCTGC CAGCTCCCTG 660 <br><br> CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG CGATGGCGCA 720 <br><br> GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG 7B0 <br><br> CTCGGACACT CTCTGGGCAT CCCCTGGGCT CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG 840 <br><br> CAGCTGGCAG GCTGCTTGAG CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG 900 <br><br> CAGGCCCTGG AAGGGATATC CTAATAA 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 107: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 972 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 320 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 107: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GGCTCCCGAG TTGGGTCCCA CCTTGGACAC ACTGCAGCTG 480 <br><br> GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT 540 <br><br> GCCCTGCAGC CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA 600 <br><br> GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA 660 <br><br> CGCCACCTTG CGCAGCCCAC ACCATTGGGC CCTGCCAGCT CCCTGCCCCA GAGCTTCCTG 720 <br><br> CTCAAGTCTT TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG 780 <br><br> CTGTGTGCCA CCTACAAGCT GTGCCACCCC GAGGAGCTGG TGCTGCTCGG ACACTCTCTG 840 <br><br> GGCATCCCCT GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG CCCTGCAGCT GGCAGGCTGC 900 <br><br> TTGAGCCAAC TCCATAGCGG CCTTTTCCTC TACCAGGGGC TCCTGCAGGC CCTGGAAGGG 960 <br><br> ATATCCTAAT AA 972 <br><br> (2) INFORMATION FOR SEQ ID NO: 10B: <br><br> Printed from Mimosa 08:37.19 <br><br> WO 97/12985 <br><br> 321 <br><br> PCT/US96/15774 <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 108: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA TGGCCCCTGC CCTGCAGCCC 420 <br><br> ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG 480 <br><br> GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG 540 <br><br> CAGCCCACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTCTTTA 600 <br><br> GAGCAAGTGA GAAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC 660 <br><br> TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG 720 <br><br> GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC 780 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 322 <br><br> PCT/US96/15774 <br><br> CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG 840 <br><br> TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG 900 <br><br> CAGCAGATGG AAGAACTGGG ATAATAA 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 109: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 972 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 109: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GGCTATGGCC CCTGCCCTGC AGCCCACCCA GGGTGCCATG 480 <br><br> CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG 540 <br><br> CAGAGCTTCC TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CACACCATTG 600 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 323 <br><br> PCT/US96/15774 <br><br> GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG 660 <br><br> ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC 720 <br><br> CCCGAGGAGC TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC 780 <br><br> TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG CGGCCTTTTC 840 <br><br> CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TCCCACCTTG 900 <br><br> GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA GATGGAAGAA 960 <br><br> CTGGGATAAT AA 972 <br><br> (2) INFORMATION FOR SEQ ID NO: 110: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 110: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 324 <br><br> PCT/US96/15774 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA CCCAGGGTGC CATGCCGGCC 420 <br><br> TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA GGGGTCCTGG TTGCTAGCCA TCTGCAGAGC 480 <br><br> TTCCTGGAGG TGTCGTACCG CGTTCTACGC CACCTTGCGC AGCCCACACC ATTGGGCCCT 540 <br><br> GCCAGCTCCC TGCCCCAGAG CTTCCTGCTC AAGTCTTTAG AGCAAGTGAG AAAGATCCAG 600 <br><br> GGCGATGGCG CAGCGCTCCA GGAGAAGCTG TGTGCCACCT ACAAGCTGTG CCACCCCGAG 660 <br><br> GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC 720 <br><br> AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC 780 <br><br> CAGGGGCTCC TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA 840 <br><br> CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AGAACTGGGA 900 <br><br> ATGGCCCCTG CCCTGCAGCC CTAATAA 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 111: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 972 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 111: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 325 <br><br> PCT/US96/15774 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC 480 <br><br> CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG 540 <br><br> TACCGCGTTC TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC 600 <br><br> CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA TGGCGCAGCG 660 <br><br> CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC CCGAGGAGCT GGTGCTGCTC 720 <br><br> GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG 780 <br><br> CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG 840 <br><br> GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC 900 <br><br> GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CCCTGCCCTG 960 <br><br> CAGCCCTAAT AA 972 <br><br> (2) INFORMATION FOR SEQ ID NO: 112: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 326 <br><br> PCT/US96/15774 <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic) <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 112: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT CTGCTTTCCA GCGCCGGGCA 420 <br><br> GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA 480 <br><br> CGCCACCTTG CGCAGCCCAC ACCATTGGGC CCTGCCAGCT CCCTGCCCCA GAGCTTCCTG 540 <br><br> CTCAAGTCTT TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG 600 <br><br> CTGTGTGCCA CCTACAAGCT GTGCCACCCC GAGGAGCTGG TGCTGCTCGG ACACTCTCTG 660 <br><br> GGCATCCCCT GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG CCCTGCAGCT GGCAGGCTGC 720 <br><br> TTGAGCCAAC TCCATAGCGG CCTTTTCCTC TACCAGGGGC TCCTGCAGGC CCTGGAAGGG 780 <br><br> ATATCCCCCG AGTTGGGTCC CACCTTGGAC ACACTGCAGC TGGACGTCGC CGACTTTGCC 840 <br><br> ACCACCATCT GGCAGCAGAT GGAAGAACTG GGAATGGCCC CTGCCCTGCA GCCCACCCAG 900 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 327 <br><br> PCT/US96/15774 <br><br> GGTGCCATGC CGGCCTTCGC CTAATAA 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 113: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 972 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 113: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GGCTTCTGCT TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT 480 <br><br> GCTAGCCATC TGCAGAGCTT CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG 540 <br><br> CCCACACCAT TGGGCCCTGC CAGCTCCCTG CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG 600 <br><br> CAAGTGAGAA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC 660 <br><br> AAGCTGTGCC ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT 720 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 328 <br><br> PCT/US96/15774 <br><br> CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG CCAACTCCAT 780 <br><br> AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG AAGGGATATC CCCCGAGTTG 840 <br><br> GGTCCCACCT TGGACACACT GCAGCTGGAC GTCGCCGACT TTGCCACCAC CATCTGGCAG 900 <br><br> CAGATGGAAG AACTGGGAAT GGCCCCTGCC CTGCAGCCCA CCCAGGGTGC CATGCCGGCC 960 <br><br> TTCGCCTAAT AA 972 <br><br> (2) INFORMATION FOR SEQ ID NO: 114: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 963 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = *DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 114: <br><br> ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GCCACCGCTG 60 <br><br> CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTAAT GGACAATAAC 120 <br><br> CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GAATGCATCA 180 <br><br> GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CGCTAGCCAC GGCCGCACCC 240 <br><br> ACGCGACATC CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC 300 <br><br> TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 329 <br><br> PCT/US96/15774 <br><br> TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC 480 <br><br> CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG 540 <br><br> TACCGCGTTC TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC 600 <br><br> CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG 660 <br><br> AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CGGACACTCT 720 <br><br> CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC 780 <br><br> TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA 840 <br><br> GGGATATCCC CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT 900 <br><br> GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT GCAGCCCTAA 960 <br><br> TAA 963 <br><br> (2) INFORMATION FOR SEQ ID NO: 115: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 972 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 115: <br><br> ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GCCACCGCTG 60 <br><br> CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTGAT GGAAAATAAC 120 <br><br> CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GAATGCATCA 180 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 330 <br><br> PCT/US96/15774 <br><br> GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC 240 <br><br> ACGCGACATC CAATCATCAT CCGTGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC 300 <br><br> TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC 480 <br><br> CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG 540 <br><br> TACCGCGTTC TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC 600 <br><br> CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA TGGCGCAGCG 660 <br><br> CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC CCGAGGAGCT GGTGCTGCTC 720 <br><br> GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG 780 <br><br> CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG 840 <br><br> GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC 900 <br><br> GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CCCTGCCCTG 960 <br><br> CAGCCCTAAT AA 972 <br><br> (2) INFORMATION FOR SEQ ID NO: 116: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 963 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single &lt;D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 331 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 116: <br><br> ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GCCACCGCTG 60 <br><br> CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTGAT GGAAAATAAC 120 <br><br> CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GAATGCATCA 180 <br><br> GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC 240 <br><br> ACGCGACATC CAATCATCAT CCGTGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC 300 <br><br> TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC 480 <br><br> CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG 540 <br><br> TACCGCGTTC TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC 600 <br><br> CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG 660 <br><br> AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CGGACACTCT 720 <br><br> CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC 780 <br><br> TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA 840 <br><br> GGGATATCCC CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT 900 <br><br> GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT GCAGCCCTAA 960 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 332 <br><br> PCT/US96/15774 <br><br> TAA 963 <br><br> (2) INFORMATION FOR SEQ ID NO: 117: <br><br> {i &gt; SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 972 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 117: <br><br> ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GCCACCGCTG 60 <br><br> CCGCTGCTGG ACTTCAACAA CCTCAATGGT.GAAGACCAAG ATATCCTAAT GGACAATAAC 120 <br><br> CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GAATGCATCA 180 <br><br> GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CGCTAGCCAC GGCCGCACCC 240 <br><br> ACGCGACATC CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC 300 <br><br> TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC 480 <br><br> CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG 540 <br><br> TACCGCGTTC TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC 600 <br><br> CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA TGGCGCAGCG 660 <br><br> CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC CCGAGGAGCT GGTGCTGCTC 720 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 333 <br><br> PCT/US96/15774 <br><br> GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG 780 <br><br> CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG 840 <br><br> GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC 900 <br><br> GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CCCTGCCCTG 960 <br><br> CAGCCCTAAT AA 972 <br><br> (2) INFORMATION FOR SEQ ID NO: 118: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 118: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 334 <br><br> PCT/US96/15774 <br><br> CATAAATCTC CAAACATGGA GGTTCACCCT TTGCCTACAC CTGTCCTGCT GCCTGCTGTG 480 <br><br> GACTTTAGCT TGGGAGAATG GAAAACCCAG ATGGAGGAGA CCAAGGCACA GGACATTCTG 540 <br><br> GGAGCAGTGA CCCTTCTGCT GGAGGGAGTG ATGGCAGCAC GGGGACAACT GGGACCCACT 600 <br><br> TGCCTCTCAT CCCTCCTGGG GCAGCTTTCT GGACAGGTCC GTCTCCTCCT TGGGGCCCTG 660 <br><br> CAGAGCCTCC TTGGAACCCA GCTTCCTCCA CAGGGCAGGA CCACAGCTCA CAAGGATCCC 720 <br><br> AATGCCATCT TCCTGAGCTT CCAACACCTG CTCCGAGGAA AGGTGCGTTT CCTGATGCTT 780 <br><br> GTAGGAGGGT CCACCCTCTG CGTCAGGGAA TTCGGCGGCA ACATGGCGTC TCCCGCTCCG 840 <br><br> CCTGCTTGTG ACCTCCGAGT CCTCAGTAAA CTGCTTCGTG ACTCCCATGT CCTTCACAGC 900 <br><br> AGACTGAGCC AGTGCCCA 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 119: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 119: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 335 <br><br> PCT/US96/15774 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGTT GCCTACACCT GTCCTGCTGC CTGCTGTGGA CTTTAGCTTG 480 <br><br> GGAGAATGGA AAACCCAGAT GGAGGAGACC AAGGCACAGG ACATTCTGGG AGCAGTGACC 540 <br><br> CTTCTGCTGG AGGGAGTGAT GGCAGCACGG GGACAACTGG GACCCACTTG CCTCTCATCC 600 <br><br> CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT 660 <br><br> GGAACCCAGC TTCCTCCACA GGGCAGGACC ACAGCTCACA AGGATCCCAA TGCCATCTTC 720 <br><br> CTGAGCTTCC AACACCTGCT CCGAGGAAAG GTGCGTTTCC TGATGCTTGT AGGAGGGTCC 780 <br><br> ACCCTCTGCG TCAGGGAATT CGGCGGCAAC ATGGCGTCTC CCGCTCCGCC TGCTTGTGAC 840 <br><br> CTCCGAGTCC TCAGTAAACT GCTTCGTGAC TCCCATGTCC TTCACAGCAG ACTGAGCCAG 900 <br><br> TGCCCAGAGG TTCACCCT 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 120: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid tC) STRANDEDNESS: single (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 120: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 336 <br><br> PCT/US96/15774 <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGT CCTGCTGCCT GCTGTGGACT TTAGCTTGGG AGAATGGAAA 480 <br><br> ACCCAGATGG AGGAGACCAA GGCACAGGAC ATTCTGGGAG CAGTGACCCT TCTGCTGGAG 540 <br><br> GGAGTGATGG CAGCACGGGG ACAACTGGGA CCCACTTGCC TCTCATCCCT CCTGGGGCAG 600 <br><br> CTTTCTGGAC AGGTCCGTCT CCTCCTTGGG GCCCTGCAGA GCCTCCTTGG AACCCAGCTT 660 <br><br> CCTCCACAGG GCAGGACCAC AGCTCACAAG GATCCCAATG CCATCTTCCT GAGCTTCCAA 720 <br><br> CACCTGCTCC GAGGAAAGGT GCGTTTCCTG ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC 780 <br><br> AGGGAATTCG GCGGCAACAT GGCGTCTCCC GCTCCGCCTG CTTGTGACCT CCGAGTCCTC 840 <br><br> AGTAAACTGC TTCGTGACTC CCATGTCCTT CACAGCAGAC TGAGCCAGTG CCCAGAGGTT 900 <br><br> CACCCTTTGC CTACACCT 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 121: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 337 <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 121: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CCAGATGGAG 4B0 <br><br> GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AGTGATGGCA 540 <br><br> GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TTCTGGACAG 600 <br><br> GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TCCACAGGGC 660 <br><br> AGGACCACAG CTCACAAGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CCTGCTCCGA 720 <br><br> GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GGAATTCGGC 780 <br><br> GGCAACATGG CGTCTCCCGC TCCGCCTGCT TGTGACCTCC GAGTCCTCAG TAAACTGCTT 840 <br><br> CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CCCTTTGCCT 900 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 338 <br><br> PCT/US96/15774 <br><br> ACACCTGTCC TGCTGCCT 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 122: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 122: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGA CTTTAGCTTG GGAGAATGGA AAACCCAGAT GGAGGAGACC 480 <br><br> AAGGCACAGG ACATTCTGGG AGCAGTGACC CTTCTGCTGG AGGGAGTGAT GGCAGCACGG 540 <br><br> GGACAACTGG GACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT 600 <br><br> CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC TTCCTCCACA GGGCAGGACC 660 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 339 <br><br> PCT/US96/15774 <br><br> ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCC AACACCTGCT CCGAGGAAAG 720 <br><br> GTGCGTTTCC TGATGCTTGT AGGAGGGTCC ACCCTCTGCG TCAGGGAATT CGGCGGCAAC 780 <br><br> ATGGCGTCTC CCGCTCCGCC TGCTTGTGAC CTCCGAGTCC TCAGTAAACT GCTTCGTGAC 840 <br><br> TCCCATGTCC TTCACAGCAG ACTGAGCCAG TGCCCAGAGG TTCACCCTTT GCCTACACCT 900 <br><br> GTCCTGCTGC CTGCTGTG 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 123: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 907 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 123: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCGGTTAC CCTTGAGCAA GCGCAGGAAC AACAGTACGT AGAGGGCGGT GGAGGCTCCC 360 <br><br> CGGGGAACCG TCTGGTCCAA TCTCTACTAT CAACCCGTCT CCTCCGTCTA AAGAATCTCA 420 <br><br> TAAACTCCAA ACATGGGAGA ATGGAAAACC CAGATGGAGG AGACCAAGGC ACAGGACATT 480 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 340 <br><br> PCT/US96/15774 <br><br> CTGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA CTGGGACCCA 540 <br><br> CTTGCTCTCA TCCCTCCTGG GGCAGCTTTC TGGACAGGTC CGTCTCCTCC TTGGGGCCCT 600 <br><br> GCAGGCCTCC TTGGAACCCA GCTTCCTCCA CAGGGCAGGA CCACAGCTCA CAAGGATCCC 660 <br><br> AATGCATCTT CCTGAGCTTC CAACACCTGC TCCGAGGAAA GGTGCGTTTC CTGATGCTTG 720 <br><br> TAGGGGGTCC ACCCTCTGCG TCAGGGAATT CGGCGGCAAC ATGGCGTCTC CCGCTCCGCC 780 . <br><br> TGCTGTGACC TCCGAGTCCT CAGTAAACTG CTTCGTGACT CCCATGTCCT TCACAGCAGA 840 <br><br> CTGACCAGTG CCCAGAGGTT CACCCTTTGC CTACACCTGT CCTGCTGCCT GCTGTGGACT 900 <br><br> TTAGTTG 907 <br><br> [2) INFORMATION FOR SEQ ID NO: 124: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 124: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 341 <br><br> PCT/US96/15774 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGG ACCCACTTGC CTCTCATCCC TCCTGGGGCA GCTTTCTGGA 480 <br><br> CAGGTCCGTC TCCTCCTTGG GGCCCTGCAG AGCCTCCTTG GAACCCAGCT TCCTCCACAG 540 <br><br> GGCAGGACCA CAGCTCACAA GGATCCCAAT GCCATCTTCC TGAGCTTCCA ACACCTGCTC 600 <br><br> CGAGGAAAGG TGCGTTTCCT GATGCTTGTA GGAGGGTCCA CCCTCTGCGT CAGGGAATTC 660 <br><br> GGCGGCAACA TGGCGTCTCC CGCTCCGCCT GCTTGTGACC TCCGAGTCCT CAGTAAACTG 720 <br><br> CTTCGTGACT CCCATGTCCT TCACAGCAGA CTGAGCCAGT GCCCAGAGGT TCACCCTTTG 780 <br><br> CCTACACCTG TCCTGCTGCC TGCTGTGGAC TTTAGCTTGG GAGAATGGAA AACCCAGATG 840 <br><br> GAGGAGACCA AGGCACAGGA CATTCTGGGA GCAGTGACCC TTCTGCTGGA GGGAGTGATG 900 <br><br> GCAGCACGGG GACAACTG 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 125: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 848 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 125: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 342 <br><br> PCT/US96/15774 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AGCTCACAAG 480 <br><br> GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GCGTTTCCTG 540 <br><br> ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCGGCAACAT GGCGTCTCCC 600 <br><br> GCTCCGCCTG CTTGTGACCT CCGAGTCCTC AGTAAACTGC TTCGTGACTC CCATGTCCTT 660 <br><br> CACAGCAGAC TGAGCCAGTG CCCAGAGGTT CACCCTTTGC CTACACCTGT CCTGCTGCCT 720 <br><br> GCTGTGGACT TTAGCTTGGG AGAATGGAAA ACCCAGATGG AGGAGACCAA GGCACAGGAC 780 <br><br> ATTCTGGGAG CAGTGACCCT TCTGCTGGAG GGAGTGATGG CAGCACGGGG ACAACTGGGA B40 <br><br> CCCACTTG 848 <br><br> (2) INFORMATION FOR SEQ ID NO: 126: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 343 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 126: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGG CAGGACCACA GCTCACAAGG ATCCCAATGC CATCTTCCTG 480 <br><br> AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG CGTTTCCTGA TGCTTGTAGG AGGGTCCACC 540 <br><br> CTCTGCGTCA GGGAATTCGG CGGCAACATG GCGTCTCCCG CTCCGCCTGC TTGTGACCTC 600 <br><br> CGAGTCCTCA GTAAACTGCT TCGTGACTCC CATGTCCTTC ACAGCAGACT GAGCCAGTGC 660 <br><br> CCAGAGGTTC ACCCTTTGCC TACACCTGTC CTGCTGCCTG CTGTGGACTT TAGCTTGGGA 720 <br><br> GAATGGAAAA CCCAGATGGA GGAGACCAAG GCACAGGACA TTCTGGGAGC AGTGACCCTT 780 <br><br> CTGCTGGAGG GAGTGATGGC AGCACGGGGA CAACTGGGAC CCACTTGCCT CTCATCCCTC 840 <br><br> CTGGGGCAGC TTTCTGGACA GGTCCGTCTC CTCCTTGGGG CCCTGCAGAG CCTCCTTGGA 900 <br><br> ACCCAGCTTC CTCCACAG 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 127: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 344 <br><br> PCT/US96/15774 <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 127: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60. <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGC TCACAAGGAT CCCAATGCCA TCTTCCTGAG CTTCCAACAC 480 <br><br> CTGCTCCGAG GAAAGGTGCG TTTCCTGATG CTTGTAGGAG GGTCCACCCT CTGCGTCAGG 540 <br><br> . GAATTCGGCG GCAACATGGC GTCTCCCGCT CCGCCTGCTT GTGACCTCCG AGTCCTCAGT 600 <br><br> AAACTGCTTC GTGACTCCCA TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AGAGGTTCAC 660 <br><br> CCTTTGCCTA CACCTGTCCT GCTGCCTGCT GTGGACTTTA GCTTGGGAGA ATGGAAAACC 720 <br><br> CAGATGGAGG AGACCAAGGC ACAGGACATT CTGGGAGCAG TGACCCTTCT GCTGGAGGGA 780 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 345 <br><br> PCT/US96/15774 <br><br> GTGATGGCAG CACGGGGACA ACTGGGACCC ACTTGCCTCT CATCCCTCCT GGGGCAGCTT 840 <br><br> TCTGGACAGG TCCGTCTCCT CCTTGGGGCC CTGCAGAGCC TCCTTGGAAC CCAGCTTCCT 900 <br><br> CCACAGGGCA GGACCACA 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 128: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 128: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CCTGCTCCGA 480 <br><br> GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GGAATTCGGC 540 <br><br> GGCAACATGG CGTCTCCCGC TCCGCCTGCT TGTGACCTCC GAGTCCTCAG TAAACTGCTT 600 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 346 <br><br> PCT/US96/15774 <br><br> CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CCCTTTGCCT 660 <br><br> ACACCTGTCC TGCTGCCTGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CCAGATGGAG 720 <br><br> GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AGTGATGGCA 780 <br><br> GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TTCTGGACAG 840 <br><br> GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TCCACAGGGC 900 <br><br> AGGACCACAG CTCACAAG 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 129: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 918 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 129: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 347 <br><br> PCT/US96/15774 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGC CATCTTCCTG AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG 480 <br><br> CGTTTCCTGA TGCTTGTAGG AGGGTCCACC CTCTGCGTCA GGGAATTCGG CGGCAACATG 540 <br><br> GCGTCTCCCG CTCCGCCTGC TTGTGACCTC CGAGTCCTCA GTAAACTGCT TCGTGACTCC 600 <br><br> CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC TACACCTGTC 660 <br><br> CTGCTGCCTG CTGTGGACTT TAGCTTGGGA GAATGGAAAA CCCAGATGGA GGAGACCAAG 720 <br><br> GCACAGGACA TTCTGGGAGC AGTGACCCTT CTGCTGGAGG GAGTGATGGC AGCACGGGGA 780 <br><br> CAACTGGGAC CCACTTGCCT CTCATCCCTC CTGGGGCAGC TTTCTGGACA GGTCCGTCTC 840 <br><br> CTCCTTGGGG CCCTGCAGAG CCTCCTTGGA ACCCAGCTTC CTCCACAGGG CAGGACCACA 900 <br><br> GCTCACAAGG ATCCCAAT 918 <br><br> (2) INFORMATION FOR SEQ ID NO: 130: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 915 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 130: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 348 <br><br> PCT/US96/15774 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGA GGTTCACCCT TTGCCTACAC CTGTCCTGCT GCCTGCTGTG 480 <br><br> GACTTTAGCT TGGGAGAATG GAAAACCCAG ATGGAGGAGA CCAAGGCACA GGACATTCTG 540 <br><br> GGAGCAGTGA CCCTTCTGCT GGAGGGAGTG ATGGCAGCAC GGGGACAACT GGGACCCACT 600 <br><br> TGCCTCTCAT CCCTCCTGGG GCAGCTTTCT GGACAGGTCC GTCTCCTCCT TGGGGCCCTG 660 <br><br> CAGAGCCTCC TTGGAACCCA GCTTCCTCCA CAGGGCAGGA CCACAGCTCA CAAGGATCCC 720 <br><br> AATGCCATCT TCCTGAGCTT CCAACACCTG CTCCGAGGAA AGGTGCGTTT CCTGATGCTT 780 <br><br> GTAGGAGGGT CCACCCTCTG CGTCAGGGAA TTCGGCAACA TGGCGTCTCC CGCTCCGCCT 840 <br><br> GCTTGTGACC TCCGAGTCCT CAGTAAACTG CTTCGTGACT CCCATGTCCT TCACAGCAGA 900 <br><br> CTGAGCCAGT GCCCA 915 <br><br> (2) INFORMATION FOR SEQ ID NO: 131: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 915 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 349 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 131: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGTT GCCTACACCT GTCCTGCTGC CTGCTGTGGA CTTTAGCTTG 480 <br><br> GGAGAATGGA AAACCCAGAT GGAGGAGACC AAGGCACAGG ACATTCTGGG AGCAGTGACC 540 <br><br> CTTCTGCTGG AGGGAGTGAT GGCAGCACGG GGACAACTGG GACCCACTTG CCTCTCATCC 600 <br><br> CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT 660 <br><br> GGAACCCAGC TTCCTCCACA GGGCAGGACC ACAGCTCACA AGGATCCCAA TGCCATCTTC 720 <br><br> CTGAGCTTCC AACACCTGCT CCGAGGAAAG GTGCGTTTCC TGATGCTTGT AGGAGGGTCC 780 <br><br> ACCCTCTGCG TCAGGGAATT CGGCAACATG GCGTCTCCCG CTCCGCCTGC TTGTGACCTC 840 <br><br> CGAGTCCTCA GTAAACTGCT TCGTGACTCC CATGTCCTTC ACAGCAGACT GAGCCAGTGC 900 <br><br> CCAGAGGTTC ACCCT 915 <br><br> (2) INFORMATION FOR SEQ ID NO: 132: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 915 base pairs <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 350 <br><br> PCT/US96/15774 <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 132: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGT CCTGCTGCCT GCTGTGGACT TTAGCTTGGG AGAATGGAAA 480 <br><br> ACCCAGATGG AGGAGACCAA GGCACAGGAC ATTCTGGGAG CAGTGACCCT TCTGCTGGAG 540 <br><br> GGAGTGATGG CAGCACGGGG ACAACTGGGA CCCACTTGCC TCTCATCCCT CCTGGGGCAG 600 <br><br> CTTTCTGGAC AGGTCCGTCT CCTCCTTGGG GCCCTGCAGA GCCTCCTTGG AACCCAGCTT 660 <br><br> CCTCCACAGG GCAGGACCAC AGCTCACAAG GATCCCAATG CCATCTTCCT GAGCTTCCAA 720 <br><br> CACCTGCTCC GAGGAAAGGT GCGTTTCCTG ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC 780 <br><br> AGGGAATTCG GCAACATGGC GTCTCCCGCT CCGCCTGCTT GTGACCTCCG AGTCCTCAGT 840 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 351 <br><br> PCT/US96/15774 <br><br> AAACTGCTTC GTGACTCCCA TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AGAGGTTCAC 900 <br><br> CCTTTGCCTA CACCT 915 <br><br> (2) INFORMATION FOR SEQ ID NO: 133: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 915 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 133: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CCAGATGGAG 480 <br><br> GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AGTGATGGCA 540 <br><br> GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TTCTGGACAG 600 <br><br> GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TCCACAGGGC 660 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 352 <br><br> PCT/US96/15774 <br><br> AGGACCACAG CTCACAAGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CCTGCTCCGA 720 <br><br> GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GGAATTCGGC 780 <br><br> AACATGGCGT CTCCCGCTCC GCCTGCTTGT GACCTCCGAG TCCTCAGTAA ACTGCTTCGT 840 <br><br> GACTCCCATG TCCTTCACAG CAGACTGAGC CAGTGCCCAG AGGTTCACCC TTTGCCTACA 900 <br><br> CCTGTCCTGC TGCCT 915 <br><br> (2) INFORMATION FOR SEQ ID NO: 134: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 915 base pairs <br><br> (B)* TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 134: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 353 <br><br> PCT/US96/15774 <br><br> CATAAATCTC CAAACATGGA CTTTAGCTTG GGAGAATGGA AAACCCAGAT GGAGGAGACC 480 <br><br> AAGGCACAGG ACATTCTGGG AGCAGTGACC CTTCTGCTGG AGGGAGTGAT GGCAGCACGG 540 <br><br> GGACAACTGG GACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT 600 <br><br> CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC TTCCTCCACA GGGCAGGACC 660 <br><br> ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCC AACACCTGCT CCGAGGAAAG 720 <br><br> GTGCGTTTCC TGATGCTTGT AGGAGGGTCC ACCCTCTGCG TCAGGGAATT CGGCAACATG 780 <br><br> GCGTCTCCCG CTCCGCCTGC TTGTGACCTC CGAGTCCTCA GTAAACTGCT TCGTGACTCC 840 <br><br> CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC TACACCTGTC 900 <br><br> CTGCTGCCTG CTGTG 915 <br><br> (2) INFORMATION FOR SEQ ID NO: 135: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 915 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 135: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 354 <br><br> PCT/US96/15774 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGG AGAATGGAAA ACCCAGATGG AGGAGACCAA GGCACAGGAC 480 <br><br> ATTCTGGGAG CAGTGACCCT TCTGCTGGAG GGAGTGATGG CAGCACGGGG ACAACTGGGA 540 <br><br> CCCACTTGCC TCTCATCCCT CCTGGGGCAG CTTTCTGGAC AGGTCCGTCT CCTCCTTGGG 600 <br><br> GCCCTGCAGA GCCTCCTTGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AGCTCACAAG 660 <br><br> GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GCGTTTCCTG 720 <br><br> ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCAACATGGC GTCTCCCGCT 780 <br><br> CCGCCTGCTT GTGACCTCCG AGTCCTCAGT AAACTGCTTC GTGACTCCCA TGTCCTTCAC 840 <br><br> AGCAGACTGA GCCAGTGCCC AGAGGTTCAC CCTTTGCCTA CACCTGTCCT GCTGCCTGCT 900 <br><br> GTGGACTTTA GCTTG 915 <br><br> (2) INFORMATION FOR SEQ ID NO: 13 6: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 915 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 136: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 355 <br><br> PCT/US96/15774 <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGG ACCCACTTGC CTCTCATCCC TCCTGGGGCA GCTTTCTGGA 480 <br><br> CAGGTCCGTC TCCTCCTTGG GGCCCTGCAG AGCCTCCTTG GAACCCAGCT TCCTCCACAG 540 <br><br> GGCAGGACCA CAGCTCACAA GGATCCCAAT GCCATCTTCC TGAGCTTCCA ACACCTGCTC 600 <br><br> CGAGGAAAGG TGCGTTTCCT GATGCTTGTA GGAGGGTCCA CCCTCTGCGT CAGGGAATTC 660 <br><br> GGCAACATGG CGTCTCCCGC TCCGCCTGCT TGTGACCTCC GAGTCCTCAG TAAACTGCTT 720 <br><br> CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CCCTTTGCCT 780 <br><br> ACACCTGTCC TGCTGCCTGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CCAGATGGAG 840 <br><br> GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AGTGATGGCA 900 <br><br> GCACGGGGAC AACTG 915 <br><br> (2) INFORMATION FOR SEQ ID NO: 137: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 915 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 356 <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 137: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AGCTCACAAG 480 <br><br> GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GCGTTTCCTG 540 <br><br> ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCAACATGGC GTCTCCCGCT 600 <br><br> CCGCCTGCTT GTGACCTCCG AGTCCTCAGT AAACTGCTTC GTGACTCCCA TGTCCTTCAC 660 <br><br> AGCAGACTGA GCCAGTGCCC AGAGGTTCAC CCTTTGCCTA CACCTGTCCT GCTGCCTGCT 720 <br><br> GTGGACTTTA GCTTGGGAGA ATGGAAAACC CAGATGGAGG AGACCAAGGC ACAGGACATT 780 <br><br> CTGGGAGCAG TGACCCTTCT GCTGGAGGGA GTGATGGCAG CACGGGGACA ACTGGGACCC 840 <br><br> ACTTGCCTCT CATCCCTCCT GGGGCAGCTT TCTGGACAGG TCCGTCTCCT CCTTGGGGCC 900 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 357 <br><br> PCT/US96/15774 <br><br> CTGCAGAGCC TCCTT 915 <br><br> (2) INFORMATION FOR SEQ ID NO: 138: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 915 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 138: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGG CAGGACCACA GCTCACAAGG ATCCCAATGC CATCTTCCTG 480 <br><br> AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG CGTTTCCTGA TGCTTGTAGG AGGGTCCACC 540 <br><br> CTCTGCGTCA GGGAATTCGG CAACATGGCG TCTCCCGCTC CGCCTGCTTG TGACCTCCGA 600 <br><br> GTCCTCAGTA AACTGCTTCG TGACTCCCAT GTCCTTCACA GCAGACTGAG CCAGTGCCCA 660 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 358 <br><br> PCT/US96/15774 <br><br> GAGGTTCACC CTTTGCCTAC ACCTGTCCTG CTGCCTGCTG TGGACTTTAG CTTGGGAGAA 720 <br><br> TGGAAAACCC AGATGGAGGA GACCAAGGCA CAGGACATTC TGGGAGCAGT GACCCTTCTG 780 <br><br> CTGGAGGGAG TGATGGCAGC ACGGGGACAA CTGGGACCCA CTTGCCTCTC ATCCCTCCTG 840 <br><br> GGGCAGCTTT CTGGACAGGT CCGTCTCCTC CTTGGGGCCC TGCAGAGCCT CCTTGGAACC 900 <br><br> CAGCTTCCTC CACAG 915 <br><br> (2) INFORMATION FOR SEQ ID NO: 139: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 915 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 139: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGC TCACAAGGAT CCCAATGCCA TCTTCCTGAG CTTCCAACAC 480 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 359 <br><br> PCT/US96/15774 <br><br> CTGCTCCGAG GAAAGGTGCG TTTCCTGATG CTTGTAGGAG GGTCCACCCT CTGCGTCAGG 540 <br><br> GAATTCGGCA ACATGGCGTC TCCCGCTCCG CCTGCTTGTG ACCTCCGAGT CCTCAGTAAA 600 <br><br> CTGCTTCGTG ACTCCCATGT CCTTCACAGC AGACTGAGCC AGTGCCCAGA GGTTCACCCT 660 <br><br> TTGCCTACAC CTGTCCTGCT GCCTGCTGTG GACTTTAGCT TGGGAGAATG GAAAACCCAG 720 <br><br> ATGGAGGAGA CCAAGGCACA GGACATTCTG GGAGCAGTGA CCCTTCTGCT GGAGGGAGTG 780 <br><br> ATGGCAGCAC GGGGACAACT GGGACCCACT TGCCTCTCAT CCCTCCTGGG GCAGCTTTCT 840 <br><br> GGACAGGTCC GTCTCCTCCT TGGGGCCCTG CAGAGCCTCC TTGGAACCCA GCTTCCTCCA 900 <br><br> CAGGGCAGGA CCACA 915 <br><br> (2) INFORMATION FOR SEQ ID NO: 140: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 915 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 140: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 360 <br><br> PCT/US96/15774 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CCTGCTCCGA 480 <br><br> GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GGAATTCGGC 540 <br><br> AACATGGCGT CTCCCGCTCC GCCTGCTTGT GACCTCCGAG TCCTCAGTAA ACTGCTTCGT 600 <br><br> GACTCCCATG TCCTTCACAG CAGACTGAGC CAGTGCCCAG AGGTTCACCC TTTGCCTACA 660 <br><br> CCTGTCCTGC TGCCTGCTGT GGACTTTAGC TTGGGAGAAT GGAAAACCCA GATGGAGGAG 720 <br><br> ACCAAGGCAC AGGACATTCT GGGAGCAGTG ACCCTTCTGC TGGAGGGAGT GATGGCAGCA 780 <br><br> CGGGGACAAC TGGGACCCAC TTGCCTCTCA TCCCTCCTGG GGCAGCTTTC TGGACAGGTC 840 <br><br> CGTCTCCTCC TTGGGGCCCT GCAGAGCCTC CTTGGAACCC AGCTTCCTCC ACAGGGCAGG 900 <br><br> ACCACAGCTC ACAAG 915 <br><br> (2) INFORMATION FOR SEQ ID NO: 141: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 915 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 141: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 36! <br><br> PCT/US96/15774 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGC CATCTTCCTG AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG 480 <br><br> CGTTTCCTGA TGCTTGTAGG AGGGTCCACC CTCTGCGTCA GGGAATTCGG CAACATGGCG 540 <br><br> TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT 600 <br><br> GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG 660 <br><br> CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA 720 <br><br> CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA 780 <br><br> CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC 840 <br><br> CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT 900 <br><br> CACAAGGATC CCAAT 915 <br><br> (2) INFORMATION FOR SEQ ID NO: 142: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 921 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 362 <br><br> PCT/US96/15774 <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic) <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 142: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> GACTTCCAAA CCTGGAGAGC TTCGTAAGGG CTGTCAAGAA CTTAGAAAAT GCATCAGGTA 180 <br><br> TGAGGCAATT CTTCGTAATC TCCAACCATG TCTGCCCTCT GCCACGGCCG CACCCTCTCG 240 <br><br> CATCCAATCA TCATCAAGGC AGGTGACTGG CAAGAATTCC GGGAAAAACT GACGTTCTAT 300 <br><br> TGGTTACCCT TGAGCAAGCG CAGGAACAAC AGTACGTAGA GGGCGGTGGA GGCTCCCCGG 360 <br><br> TAACCGTCTG GTCCAATCTC TACTATCAAC CCGTCTCCTC CGTCTAAAGA ATCTCATAAA 420 <br><br> TCTCCAAACA TGGAGGTTCA CCCTTTGCCT ACACCTGTCC TGCTGCCTGC TGTGGACTTT 480 <br><br> AGCTTGGGAG AATGGAAAAC CCAGATGGAG GAGACCAAGG CACAGGACAT TCTGGGAGCA 540 <br><br> GTGACCCTTC TGCTGGAGGG AGTGATGGCA GCACGGGGAC AACTGGGACC CACTTGCCTC 600 <br><br> TCATCCCTCC TGGGGCAGCT TTCTGGACAG GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC 660 <br><br> CTCCTTGGAA CCCAGCTTCC TCCACAGGGC AGGACCACAG CTCACAAGGA TCCCAATGCC 720 <br><br> ATCTTCCTGA GCTTCCAACA CCTGCTCCGA GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA 780 <br><br> GGGTCCACCC TCTGCGTCAG GGAATTCGGC GGCAACGGCG GCAACATGGC GTCCCCAGCG 840 <br><br> CCGCCTGCTT GTGACCTCCG AGTCCTCAGT AAACTGCTTC GTGACTCCCA TGTCCTTCAC 900 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 363 <br><br> PCT/US96/15774 <br><br> AGCAGACTGA GCCAGTGCCC A 921 <br><br> (2) INFORMATION FOR SEQ ID NO: 143: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 143: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGTT GCCTACACCT GTCCTGCTGC CTGCTGTGGA CTTTAGCTTG 480 <br><br> GGAGAATGGA AAACCCAGAT GGAGGAGACC AAGGCACAGG ACATTCTGGG AGCAGTGACC 540 <br><br> CTTCTGCTGG AGGGAGTGAT GGCAGCACGG GGACAACTGG GACCCACTTG CCTCTCATCC 600 <br><br> CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT 660 <br><br> GGAACCCAGC TTCCTCCACA GGGCAGGACC ACAGCTCACA AGGATCCCAA TGCCATCTTC 720 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 364 <br><br> PCT/US96/15774 <br><br> CTGAGCTTCC AACACCTGCT CCGAGGAAAG GTGCGTTTCC TGATGCTTGT AGGAGGGTCC 780 <br><br> ACCCTCTGCG TCAGGGAATT CGGCGGCAAC GGCGGCAACA TGGCGTCCCC AGCGCCGCCT 840 <br><br> GCTTGTGACC TCCGAGTCCT CAGTAAACTG CTTCGTGACT CCCATGTCCT TCACAGCAGA 900 <br><br> CTGAGCCAGT GCCCAGAGGT TCACCCT 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 144: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 144: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGT CCTGCTGCCT GCTGTGGACT TTAGCTTGGG AGAATGGAAA 480 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 365 <br><br> PCT/US96/15774 <br><br> ACCCAGATGG AGGAGACCAA GGCACAGGAC ATTCTGGGAG CAGTGACCCT TCTGCTGGAG 540 <br><br> GGAGTGATGG CAGCACGGGG ACAACTGGGA CCCACTTGCC TCTCATCCCT CCTGGGGCAG 600 <br><br> CTTTCTGGAC AGGTCCGTCT CCTCCTTGGG GCCCTGCAGA GCCTCCTTGG AACCCAGCTT 660 <br><br> CCTCCACAGG GCAGGACCAC AGCTCACAAG GATCCCAATG CCATCTTCCT GAGCTTCCAA 720 <br><br> CACCTGCTCC GAGGAAAGGT GCGTTTCCTG ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC 780 <br><br> AGGGAATTCG GCGGCAACGG CGGCAACATG GCGTCCCCAG CGCCGCCTGC TTGTGACCTC 840 <br><br> CGAGTCCTCA GTAAACTGCT TCGTGACTCC CATGTCCTTC ACAGCAGACT GAGCCAGTGC 900 <br><br> CCAGAGGTTC ACCCTTTGCC TACACCT 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 145: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 145: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 366 <br><br> PCT/US96/15774 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CCAGATGGAG 480 <br><br> GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AGTGATGGCA 540 <br><br> GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TTCTGGACAG 600 <br><br> GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TCCACAGGGC 660 <br><br> AGGACCACAG CTCACAAGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CCTGCTCCGA 720 <br><br> GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GGAATTCGGC 780 <br><br> GGCAACGGCG GCAACATGGC GTCCCCAGCG CCGCCTGCTT GTGACCTCCG AGTCCTCAGT 840 <br><br> AAACTGCTTC GTGACTCCCA TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AGAGGTTCAC 900 <br><br> CCTTTGCCTA CACCTGTCCT GCTGCCT 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 146: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 146: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 367 <br><br> PCT/US96/15774 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGA CTTTAGCTTG GGAGAATGGA AAACCCAGAT GGAGGAGACC 480 <br><br> AAGGCACAGG ACATTCTGGG AGCAGTGACC CTTCTGCTGG AGGGAGTGAT GGCAGCACGG 540 <br><br> GGACAACTGG GACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT 600 <br><br> CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC TTCCTCCACA GGGCAGGACC 660 <br><br> ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCC AACACCTGCT CCGAGGAAAG 720 <br><br> GTGCGTTTCC TGATGCTTGT AGGAGGGTCC ACCCTCTGCG TCAGGGAATT CGGCGGCAAC 780 <br><br> GGCGGCAACA TGGCGTCCCC AGCGCCGCCT GCTTGTGACC TCCGAGTCCT CAGTAAACTG 840 <br><br> CTTCGTGACT CCCATGTCCT TCACAGCAGA CTGAGCCAGT GCCCAGAGGT TCACCCTTTG 900 <br><br> CCTACACCTG TCCTGCTGCC TGCTGTG 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 147: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 368 <br><br> PCT/US96/15774 <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 147: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 1b0 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGG AGAATGGAAA ACCCAGATGG AGGAGACCAA GGCACAGGAC 480 <br><br> ATTCTGGGAG CAGTGACCCT TCTGCTGGAG GGAGTGATGG CAGCACGGGG ACAACTGGGA 540 <br><br> CCCACTTGCC TCTCATCCCT CCTGGGGCAG CTTTCTGGAC AGGTCCGTCT CCTCCTTGGG 600 <br><br> GCCCTGCAGA GCCTCCTTGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AGCTCACAAG 660 <br><br> GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GCGTTTCCTG 720 <br><br> ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCGGCAACGG CGGCAACATG 780 <br><br> GCGTCCCCAG CGCCGCCTGC TTGTGACCTC CGAGTCCTCA GTAAACTGCT TCGTGACTCC 840 <br><br> CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC TACACCTGTC 900 <br><br> CTGCTGCCTG CTGTGGACTT TAGCTTG 927 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 369 <br><br> PCT/US96/15774 <br><br> (2) INFORMATION FOR SEQ ID NO: 148: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic) <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 148: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGG ACCCACTTGC CTCTCATCCC TCCTGGGGCA GCTTTCTGGA 480 <br><br> CAGGTCCGTC TCCTCCTTGG GGCCCTGCAG AGCCTCCTTG GAACCCAGCT TCCTCCACAG 540 <br><br> GGCAGGACCA CAGCTCACAA GGATCCCAAT GCCATCTTCC TGAGCTTCCA ACACCTGCTC 600 <br><br> CGAGGAAAGG TGCGTTTCCT GATGCTTGTA GGAGGGTCCA CCCTCTGCGT CAGGGAATTC 660 <br><br> GGCGGCAACG GCGGCAACAT GGCGTCCCCA GCGCCGCCTG CTTGTGACCT CCGAGTCCTC 720 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 370 <br><br> PCT/US96/15774 <br><br> AGTAAACTGC TTCGTGACTC CCATGTCCTT CACAGCAGAC TGAGCCAGTG CCCAGAGGTT 780 <br><br> CACCCTTTGC CTACACCTGT CCTGCTGCCT GCTGTGGACT TTAGCTTGGG AGAATGGAAA 840 <br><br> ACCCAGATGG AGGAGACCAA GGCACAGGAC ATTCTGGGAG CAGTGACCCT TCTGCTGGAG 900 <br><br> GGAGTGATGG CAGCACGGGG ACAACTG 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 149: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic/" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 149: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGG AACCCAGCTT CCTCCACAGG GCAGGACCAC AGCTCACAAG 480 <br><br> GATCCCAATG CCATCTTCCT GAGCTTCCAA CACCTGCTCC GAGGAAAGGT GCGTTTCCTG 540 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 371 <br><br> PCT/US96/15774 <br><br> ATGCTTGTAG GAGGGTCCAC CCTCTGCGTC AGGGAATTCG GCGGCAACGG CGGCAACATG 600 <br><br> GCGTCCCCAG CGCCGCCTGC TTGTGACCTC CGAGTCCTCA GTAAACTGCT TCGTGACTCC 660 <br><br> CATGTCCTTC ACAGCAGACT GAGCCAGTGC CCAGAGGTTC ACCCTTTGCC TACACCTGTC 720 <br><br> CTGCTGCCTG CTGTGGACTT TAGCTTGGGA GAATGGAAAA CCCAGATGGA GGAGACCAAG 780 <br><br> GCACAGGACA TTCTGGGAGC AGTGACCCTT CTGCTGGAGG GAGTGATGGC AGCACGGGGA 840 <br><br> CAACTGGGAC CCACTTGCCT CTCATCCCTC CTGGGGCAGC TTTCTGGACA GGTCCGTCTC 900 <br><br> CTCCTTGGGG CCCTGCAGAG CCTCCTT 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 150: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single (D&gt; TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 150: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 372 <br><br> PCT/US96/15774 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGG CAGGACCACA GCTCACAAGG ATCCCAATGC CATCTTCCTG 480 <br><br> AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG CGTTTCCTGA TGCTTGTAGG AGGGTCCACC 540 <br><br> CTCTGCGTCA GGGAATTCGG CGGCAACGGC GGCAACATGG CGTCCCCAGC GCCGCCTGCT 600 <br><br> TGTGACCTCC GAGTCCTCAG TAAACTGCTT CGTGACTCCC ATGTCCTTCA CAGCAGACTG 660 <br><br> AGCCAGTGCC CAGAGGTTCA CCCTTTGCCT ACACCTGTCC TGCTGCCTGC TGTGGACTTT 720 <br><br> AGCTTGGGAG AATGGAAAAC CCAGATGGAG GAGACCAAGG CACAGGACAT TCTGGGAGCA 780 <br><br> GTGACCCTTC TGCTGGAGGG AGTGATGGCA GCACGGGGAC AACTGGGACC CACTTGCCTC 840 <br><br> TCATCCCTCC TGGGGCAGCT TTCTGGACAG GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC 900 <br><br> CTCCTTGGAA CCCAGCTTCC TCCACAG 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 151: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 151: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 373 <br><br> PCT/US96/15774 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGC TCACAAGGAT CCCAATGCCA TCTTCCTGAG CTTCCAACAC 480 <br><br> CTGCTCCGAG GAAAGGTGCG TTTCCTGATG CTTGTAGGAG GGTCCACCCT CTGCGTCAGG 540 <br><br> GAATTCGGCG GCAACGGCGG CAACATGGCG TCCCCAGCGC CGCCTGCTTG TGACCTCCGA 600 <br><br> GTCCTCAGTA AACTGCTTCG TGACTCCCAT GTCCTTCACA GCAGACTGAG CCAGTGCCCA 660 <br><br> GAGGTTCACC CTTTGCCTAC ACCTGTCCTG CTGCCTGCTG TGGACTTTAG CTTGGGAGAA 720 <br><br> TGGAAAACCC AGATGGAGGA GACCAAGGCA CAGGACATTC TGGGAGCAGT GACCCTTCTG 780 <br><br> CTGGAGGGAG TGATGGCAGC ACGGGGACAA CTGGGACCCA CTTGCCTCTC ATCCCTCCTG 840 <br><br> GGGCAGCTTT CTGGACAGGT CCGTCTCCTC CTTGGGGCCC TGCAGAGCCT CCTTGGAACC 900 <br><br> CAGCTTCCTC CACAGGGCAG GACCACA 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 152: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 374 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 152: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CCTGCTCCGA 480 <br><br> GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GGAATTCGGC 540 <br><br> GGCAACGGCG GCAACATGGC GTCCCCAGCG CCGCCTGCTT GTGACCTCCG AGTCCTCAGT 600 <br><br> AAACTGCTTC GTGACTCCCA TGTCCTTCAC AGCAGACTGA GCCAGTGCCC AGAGGTTCAC 660 <br><br> CCTTTGCCTA CACCTGTCCT GCTGCCTGCT GTGGACTTTA GCTTGGGAGA ATGGAAAACC 720 <br><br> CAGATGGAGG AGACCAAGGC ACAGGACATT CTGGGAGCAG TGACCCTTCT GCTGGAGGGA 780 <br><br> GTGATGGCAG CACGGGGACA ACTGGGACCC ACTTGCCTCT CATCCCTCCT GGGGCAGCTT 840 <br><br> TCTGGACAGG TCCGTCTCCT CCTTGGGGCC CTGCAGAGCC TCCTTGGAAC CCAGCTTCCT 900 <br><br> CCACAGGGCA GGACCACAGC TCACAAG 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 153: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 375 <br><br> PCT/US96/15774 <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 927 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 153: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGC CATCTTCCTG AGCTTCCAAC ACCTGCTCCG AGGAAAGGTG 480 <br><br> CGTTTCCTGA TGCTTGTAGG AGGGTCCACC CTCTGCGTCA GGGAATTCGG CGGCAACGGC 540 <br><br> GGCAACATGG CGTCCCCAGC GCCGCCTGCT TGTGACCTCC GAGTCCTCAG TAAACTGCTT 600 <br><br> CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CCCTTTGCCT 660 <br><br> ACACCTGTCC TGCTGCCTGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CCAGATGGAG 720 <br><br> GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AGTGATGGCA 780 <br><br> Printed from Mimosa 08:37.19 <br><br> WO 97/12985 <br><br> 376 <br><br> PCT/US96/15774 <br><br> GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TTCTGGACAG 840 <br><br> GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGCTTCC TCCACAGGGC 900 <br><br> AGGACCACAG CTCACAAGGA TCCCAAT 927 <br><br> (2) INFORMATION FOR SEQ ID NO: 154: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 906 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 154: <br><br> GCTAACTGCT CTATAATGAT CGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT 60 <br><br> TTGCTGGACC CGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT 120 <br><br> CGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT 180 <br><br> ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC CGCACCCTCT 240 <br><br> CGACATCCAA TCATCATCAA GGCAGGTGAC TGGCAAGAAT TCCGGGAAAA ACTGACGTTC 300 <br><br> TATCTGGTTA CCCTTGAGCA AGCGCAGGAA CAACAGTACG TAGAGGGCGG TGGAGGCTCC 360 <br><br> CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCCTCCGTC TAAAGAATCT 420 <br><br> CATAAATCTC CAAACATGGA TCCCAATGCC ATCTTCCTGA GCTTCCAACA CCTGCTCCGA 480 <br><br> GGAAAGGTGC GTTTCCTGAT GCTTGTAGGA GGGTCCACCC TCTGCGTCAG GGAATTCGGC 540 <br><br> GGCAACATGG CGTCTCCCGC TCCGCCTGCT TGTGACCTCC GAGTCCTCAG TAAACTGCTT 600 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 377 <br><br> PCT/US96/15774 <br><br> CGTGACTCCC ATGTCCTTCA CAGCAGACTG AGCCAGTGCC CAGAGGTTCA CCCTTTGCCT 660 <br><br> ACACCTGTCC TGCTGCCTGC TGTGGACTTT AGCTTGGGAG AATGGAAAAC CCAGATGGAG 720 <br><br> GAGACCAAGG CACAGGACAT TCTGGGAGCA GTGACCCTTC TGCTGGAGGG AGTGATGGCA 780 <br><br> GCACGGGGAC AACTGGGACC CACTTGCCTC TCATCCCTCC TGGGGCAGCT TTCTGGACAG 840 <br><br> GTCCGTCTCC TCCTTGGGGC CCTGCAGAGC CTCCTTGGAA CCCAGGGCAG GACCACAGCT 900 <br><br> CACAAG 906 <br><br> (2) INFORMATION FOR SEQ ID NO: 155: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 993 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 155: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGATCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 378 <br><br> PCT/US96/15774 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GTCTTACAAG CTGTGCCACC CCGAGGAGCT GGTGCTGCTC 480 <br><br> GGACACTCTC TGGGCATCCC CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG 540 <br><br> CTGGCAGGCT GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG 600 <br><br> GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC 660 <br><br> GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC CCCTGCCCTG 720 <br><br> CAGCCCACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG 780 <br><br> GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC 840 <br><br> CTTGCGCAGC CCGGCGGCGG CTCTGACATG GCTACACCAT TAGGCCCTGC CAGCTCCCTG 900 <br><br> CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGGA AGATCCAGGG CGATGGCGCA 960 <br><br> GCGCTCCAGG AGAAGCTGTG TGCCACCTAA TAA 993 <br><br> (2) INFORMATION FOR SEQ ID NO: 156: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 993 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 156: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGATCGAAAC 120 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 379 <br><br> PCT/US96/15774 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GTCTCCCGAG TTGGGTCCCA CCTTGGACAC ACTGCAGCTG 480 <br><br> GACGTCGCCG ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT 540 <br><br> GCCCTGCAGC CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA 600 <br><br> GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA 660 <br><br> CGCCACCTTG CGCAGCCCGG CGGCGGCTCT GACATGGCTA CACCATTAGG CCCTGCCAGC 720 <br><br> TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT 780 <br><br> GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG 840 <br><br> GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG 900 <br><br> GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CTACCAGGGG 960 <br><br> CTCCTGCAGG CCCTGGAAGG GATATCCTAA TAA 993 <br><br> (2) INFORMATION FOR SEQ ID NO: 157: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 993 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 380 <br><br> PCT/US96/15774 <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 157: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGATCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GTCTTCTGCT TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT 480 <br><br> GCTAGCCATC TGCAGAGCTT CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG 540 <br><br> CCCGGCGGCG GCTCTGACAT GGCTACACCA TTAGGCCCTG CCAGCTCCCT GCCCCAGAGC 600 <br><br> TTCCTGCTCA AGTCTTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC AGCGCTCCAG 660 <br><br> GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACAC 720 <br><br> TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA 780 <br><br> GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG 840 <br><br> GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CGTCGCCGAC 900 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 381 <br><br> PCMJS96/15774 <br><br> TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC CCTGCAGCCC 960 <br><br> ACCCAGGGTG CCATGCCGGC CTTCGCCTAA TAA 993 <br><br> (2) INFORMATION FOR SEQ ID NO: 158: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 993 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 158: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGATCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GTCTATGGCC CCTGCCCTGC AGCCCACCCA GGGTGCCATG 480 <br><br> CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG 540 <br><br> CAGAGCTTCC TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CGGCGGCGGC 600 <br><br> TCTGACATGG CTACACCATT AGGCCCTGCC AGCTCCCTGC CCCAGAGCTT CCTGCTCAAG 660 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 382 <br><br> PCT/US96/15774 <br><br> TCTTTAGAGC AAGTGAGGAA GATCCAGGGC GATGGCGCAG CGCTCCAGGA GAAGCTGTGT 720 <br><br> GCCACCTACA AGCTGTGCCA CCCCGAGGAG CTGGTGCTGC TCGGACACTC TCTGGGCATC 780 <br><br> CCCTGGGCTC CCCTGAGCTC CTGCCCCAGC CAGGCCCTGC AGCTGGCAGG CTGCTTGAGC 840 <br><br> CAACTCCATA GCGGCCTTTT CCTCTACCAG GGGCTCCTGC AGGCCCTGGA AGGGATATCC 900 <br><br> CCCGAGTTGG GTCCCACCTT GGACACACTG CAGCTGGACG TCGCCGACTT TGCCACCACC 960 <br><br> ATCTGGCAGC AGATGGAAGA ACTGGGATAA TAA 993 <br><br> (2) INFORMATION FOR SEQ ID NO: 159: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 993 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 159: <br><br> ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60 <br><br> CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGATCGAAAC 120 <br><br> CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180 <br><br> GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240 <br><br> TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300 <br><br> TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 383 <br><br> PCT/US96/15774 <br><br> TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420 <br><br> TCTCATAAAT CTCCAAACAT GTCTACCCAG GGTGCCATGC CGGCCTTCGC CTCTGCTTTC 430 <br><br> CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG 540 <br><br> TACCGCGTTC TACGCCACCT TGCGCAGCCC GGCGGCGGCT CTGACATGGC TACACCATTA 600 <br><br> GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA AGTGAGGAAG 660 <br><br> ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC 720 <br><br> CCCGAGGAGC TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC 780 <br><br> TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG CGGCCTTTTC 840 <br><br> CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TCCCACCTTG 900 <br><br> GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA GATGGAAGAA 960 <br><br> CTGGGAATGG CCCCTGCCCT GCAGCCCTAA TAA 993 <br><br> (2) INFORMATION FOR SEQ ID NO: 160: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 1027 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 160: <br><br> ATGGCTACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTCTTTA 60 <br><br> GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC 120 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 384 <br><br> PCT/US96/15774 <br><br> TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG 180 <br><br> GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC 240 <br><br> CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG 300 <br><br> TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG 360 <br><br> CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG 420 <br><br> GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG 480 <br><br> AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCGG CGGCGGCTCT 540 <br><br> GACATGGCTA CACCATTGGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT 600 <br><br> TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC 660 <br><br> ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCG GACACTCTCT GGGCATCCCC 720 <br><br> TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA 780 <br><br> CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC 840 <br><br> GAGTTGGGTC CCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATC 900 <br><br> TGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCA TCCTGGTTGC 960 <br><br> TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC 1020 <br><br> CTGATAA 1027 <br><br> (2) INFORMATION FOR SEQ ID NO: 161: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 155 amino acids <br><br> (B) TYPE: amino acid <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 385 <br><br> PCT/US96/15774 <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 161: <br><br> Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu 15 10 15 <br><br> Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val 20 25 30 <br><br> His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 35 40 45 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 50 55 60 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 65 70 75 80 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 85 90 95 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu 100 105 110 <br><br> Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe 115 120 125 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu 130 135 140 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe 145 150 155 <br><br> (2) INFORMATION FOR SEQ ID NO: 162: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 309 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 162: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 386 <br><br> PCT/US96/15774 <br><br> Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu 15 10 15 <br><br> Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val 20 25 30 <br><br> His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 35 40 45 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 50 55 60 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 65 70 75 80 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 85 90 95 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu 100 105 110 <br><br> Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe 115 120 125 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu 130 135 140 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala 145 150 155 160 <br><br> Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu 165 170 175 <br><br> Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val 180 185 190 <br><br> His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 195 200 205 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 210 215 220 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 225 230 235 240 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 245 250 255 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Gly 260 265 270 <br><br> Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe Leu Ser Phe Gin 275 280 285 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 387 <br><br> His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser 290 295 300 <br><br> Thr Leu Cys Val Arg 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 163: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 312 amino acids <br><br> (B) TYPE: amino acid <br><br> &lt;C) STRANDEDNESS: single (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 163: <br><br> Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu 15 10 15 <br><br> Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val 20 25 30 <br><br> His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 35 40 45 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 50 55 60 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 65 70 75 80 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 85 90 95 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu 100 105 110 <br><br> Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe 115 120 125 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu 130 135 140 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Asn Met Ala Ser 145 150 155 160 <br><br> Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg 165 170 175 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 388 <br><br> PCT/US96/15774 <br><br> Asp Ser His Val Leu His Ser Arg Leu Ser Glri Cys Pro Glu Val His 180 18S 190 <br><br> Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly 195 200 205 <br><br> Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu Gly 210 215 220 <br><br> Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin Leu 225 230 235 240 <br><br> Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin Val 245 250 255 <br><br> Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu Pro 260 265 270 <br><br> Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe Leu 275 280 285 <br><br> Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val 290 295 300 <br><br> Gly Gly Ser Thr Leu Cys Val Arg 305 310 <br><br> (2) INFORMATION FOR SEQ ID NO: 164: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 313 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 164: <br><br> Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu 15 10 15 <br><br> Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val 20 25 30 <br><br> His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 35 40 45 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 50 55 60 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 389 <br><br> PCT/US96/15774 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 65 70 75 80 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 85 90 95 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu 100 105 110 <br><br> Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe 115 120 125 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu 130 135 140 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala 145 150 155 160 <br><br> Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu 165 170 175 <br><br> Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val 180 185 190 <br><br> His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 195 200 205 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 210 215 220 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 225 230 235 240 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 245 250 255 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu 260 265 270 <br><br> Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe 275 280 285 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu 290 295 300 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg 305 310 <br><br> (2) INFORMATION FOR SEQ ID NO: 165: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 316 amino acids <br><br> (B) TYPE: amino acid <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 390 <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 165: <br><br> Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu 15 10 15 <br><br> Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val 20 25 30 <br><br> His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 35 40 45 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 50 55 60 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 65 70 75 80 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 85 90 95 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu 100 105 110 <br><br> Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe 115 120 125 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu 130 135 140 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gly 145 150 155 160 <br><br> Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser 165 170 175 <br><br> Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys 180 185 190 <br><br> Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp 195 200 205 <br><br> Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin 210 215 220 <br><br> Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala 225 230 235 240 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 391 <br><br> PCT/US96/15774 <br><br> Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu 245 250 255 <br><br> Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin. Ser Leu Leu Gly 260 265 270 <br><br> Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn 275 280 285 <br><br> Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe 290 295 300 <br><br> Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg 305 310 315 <br><br> (2) INFORMATION FOR SEQ ID NO: 166: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 302 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 166: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu <br><br> 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser 115 120 125 <br><br> Printed from Mimosa 08.37:19 <br><br> WO 97/12985 <br><br> 392 <br><br> PCT/US96/15774 <br><br> Asn Met Ala Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly 130 135 140 <br><br> His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin 145 150 155 160 <br><br> Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe 165 170 175 <br><br> Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu 180 185 190 <br><br> Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr 195 200 205 <br><br> Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin 210 215 220 <br><br> Pro Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gin Arg Arg 225 230 235 240 <br><br> Ala Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu Val 245 250 255 <br><br> Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro Ser Gly Gly Ser Gly 260 265 270 <br><br> Gly Ser Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie 275 280 285 <br><br> Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr 290 295 300 <br><br> (2) INFORMATION FOR SEQ ID NO: 167: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 317 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 167: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 393 <br><br> PCT/US96/15774 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser 115 120 125 <br><br> Thr He Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn 130 135 140 <br><br> Met Ala Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His 145 150 155 160 <br><br> Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin Ala 165 170 175 <br><br> Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe Leu 180 185 190 <br><br> Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly 195 200 205 <br><br> Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr Thr 210 215 220 <br><br> lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin Pro 225 230 235 240 <br><br> Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gin Arg Arg Ala 245 250 255 <br><br> Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu Val Ser 260 265 270 <br><br> Tyr Arg Val Leu Arg His Leu Ala Gin Pro Ser Gly Gly Ser Gly Gly 275 280 285 <br><br> Ser Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie Gin 290 295 300 <br><br> Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr 305 310 315 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 394 <br><br> (2) INFORMATION FOR SEQ ID NO: 168: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 302 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 168: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser 115 120 125 <br><br> Asn Met Ala Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp 130 135 140 <br><br> Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly 145 150 155 160 <br><br> Met Ala Pro Ala Leu Gin Pro Thr Gin Gly Ala Met Pro Ala Phe Ala 165 170 175 <br><br> Ser Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu 180 185 190 <br><br> Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin 195 200 205 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 395 <br><br> PCT/US96/15774 <br><br> Pro Ser Gly Gly Ser Gly Gly Ser Gin Ser Phe Leu Leu Lys Ser Leu 210 215 220 <br><br> Glu Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys 225 230 235 240 <br><br> Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu 245 250 255 <br><br> Gly His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser 260 265 270 <br><br> Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu 275 280 285 <br><br> Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser 290 295 300 <br><br> (2) INFORMATION FOR SEQ ID NO: 169: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 317 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 169: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 1 5 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu <br><br> 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 396 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser 115 120 125 <br><br> Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn 130 135 140 <br><br> Met Ala Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val 145 150 155 160 <br><br> Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met 165 170 175 <br><br> Ala Pro Ala Leu Gin Pro Thr Gin Gly Ala Met Pro Ala Phe Ala Ser 180 185 190 <br><br> Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin 195 200 205 <br><br> Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro 210 215 220 <br><br> Ser Gly Gly Ser Gly Gly Ser Gin Ser Phe Leu Leu Lys Ser Leu Glu 225 230 235 240 <br><br> Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu 245 250 255 <br><br> Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly 260 265 270 <br><br> His Ser Leu Gly He Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin 275 280 285 <br><br> Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe 290 295 300 <br><br> Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser <br><br> 305 310 315 <br><br> (2) INFORMATION FOR SEQ ID NO: 170: <br><br> ti) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 02 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 17 0: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 397 <br><br> PCT/US96/I5774 <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala He Leu 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser 115 120 125 <br><br> Asn Met Ala Met Ala Pro Ala Leu Gin Pro Thr Gin Gly Ala Met Pro 130 135 140 <br><br> Ala Phe Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala 145 150 155 160 <br><br> Ser His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His 165 170 175 <br><br> Leu Ala Gin Pro Ser Gly Gly Ser Gly Gly Ser Gin Ser Phe Leu Leu 180 185 190 <br><br> Lys Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu 195 200 205 <br><br> Gin Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu <br><br> 210 215 220 <br><br> Val Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser 225 230 235 240 <br><br> Cys Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His 245 250 255 <br><br> Ser Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie 260 265 270 <br><br> Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala 275 280 285 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 398 <br><br> Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly 290 295 300 <br><br> (2) INFORMATION FOR SEQ ID NO: 171: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 317 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 171: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser 115 120 125 <br><br> Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn 130 135 140 <br><br> Met Ala Met Ala Pro Ala Leu Gin Pro Thr Gin Gly Ala Met Pro Ala 145 150 155 160 <br><br> Phe Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser 165 170 175 <br><br> His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu 180 185 190 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 399 <br><br> PCT /US96/15774 <br><br> Ala Gin Pro Ser Gly Gly Ser Gly Gly Ser Gin Ser Phe Leu Leu Lys 195 200 205 <br><br> Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin 210 215 220 <br><br> Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val 225 230 235 240 <br><br> Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys 245 250 255 <br><br> Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser 260 265 270 <br><br> Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser 275 280 285 <br><br> Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp 290 295 300 <br><br> Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly 305 310 315 <br><br> (2) INFORMATION FOR SEQ ID NO: 172: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 302 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> &lt;ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 172: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser <br><br> 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu <br><br> 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 400 <br><br> PCT/US96/15774 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser 115 120 125 <br><br> Asn Met Ala Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gin 130 135 140 <br><br> Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe Leu 145 150 155 160 <br><br> Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro Ser Gly Gly 165 170 175 <br><br> Ser Gly Gly Ser Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin Val Arg 180 185 190 <br><br> Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr 195 200 205 <br><br> Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu 210 215 220 <br><br> Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin Ala Leu Gin 225 230 235 240 <br><br> Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin 245 250 255 <br><br> Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr 260 265 270 <br><br> Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr Thr lie Trp 275 280 285 <br><br> Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin Pro 290 295 300 <br><br> (2) INFORMATION FOR SEQ ID NO: 173: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 317 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 401 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 17 3: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser 115 120 125 <br><br> Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn 130 135 140 <br><br> Met Ala Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gin Arg 145 150 155 160 <br><br> Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu <br><br> 165 170 175 <br><br> Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro Ser Gly Gly Ser 180 185 190 <br><br> Gly Gly Ser Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin Val Arg Lys 195 200 205 <br><br> lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr Tyr 210 215 220 <br><br> Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly 225 230 235 240 <br><br> lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin Ala Leu Gin Leu 245 250 255 <br><br> Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly 260 265 270 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 402 <br><br> PCT/US96/15774 <br><br> Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu 275 280 285 <br><br> Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr Thr lie Trp Gin 290 295 300 <br><br> Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin Pro 305 310 315 <br><br> (2) INFORMATION FOR SEQ ID NO: 174: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 302 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 174: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> He Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser 115 120 125 <br><br> Asn Met Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala 130 135 140 <br><br> Ser His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His 145 150 155 160 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 403 <br><br> PCT/US96/15774 <br><br> Leu Ala Gin Pro Ser Gly Gly Ser Gly Gly Ser Gin Ser Phe Leu Leu 165 170 175 <br><br> Lys Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu .180 185 190 <br><br> Gin Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu 195 200 205 <br><br> Val Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser 210 215 220 <br><br> Cys Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His 225 230 235 240 <br><br> Ser Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie 245 250 255 <br><br> Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala 260 265 270 <br><br> Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala 275 280 285 <br><br> Pro Ala Leu Gin Pro Thr Gin Gly Ala Met Pro Ala Phe Ala 290 295 300 <br><br> (2) INFORMATION FOR SEQ ID NO: 175: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 317 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 175: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro <br><br> 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser <br><br> 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val <br><br> 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu <br><br> 50 55 60 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 404 <br><br> PCT/US96/15774 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro He Ser 115 120 125 <br><br> Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn 130 135 140 <br><br> Met Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser 145 150 155 160 <br><br> His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu 165 170 175 <br><br> Ala Gin Pro Ser Gly Gly Ser Gly Gly Ser Gin Ser Phe Leu Leu Lys 180 185 190 <br><br> Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin 195 200 205 <br><br> Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val 210 215 220 <br><br> Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys 225 230 235 240 <br><br> Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser 245 250 255 <br><br> Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser 260 265 270 <br><br> Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp 275 280 285 <br><br> Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro 290 295 300 <br><br> Ala Leu Gin Pro Thr Gin Gly Ala Met Pro Ala Phe Ala 305 310 315 <br><br> (2) INFORMATION FOR SEQ ID NO: 176: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 05 amino acids <br><br> (B) TYPE: amino acid <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 405 <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE; protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 176: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser 115 120 125 <br><br> Asn Met Ala Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly 130 135 140 <br><br> His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin 145 150 155 160 <br><br> Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe 165 170 175 <br><br> Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu 180 185 190 <br><br> Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr 195 200 205 <br><br> Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin 210 215 220 <br><br> Pro Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gin Arg Arg 225 230 235 240 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 406 <br><br> PCT/US96/15774 <br><br> Ala Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu Val 245 250 255 <br><br> Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro Thr Pro Leu Gly Pro 260 265 270 <br><br> Ala Ser Ser Leu Pro Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin Val 275 280 285 <br><br> Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala 290 295 300 <br><br> Thr 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 177: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 320 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 177: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser 115 120 125 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 407 <br><br> Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn 130 135 140 <br><br> Met Ala Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His 145 150 155 160 <br><br> Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin Ala 165 170 175 <br><br> Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe Leu 180 185 190 <br><br> Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly 195 200 205 <br><br> Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr Thr 210 215 220 <br><br> lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin Pro 225 230 235 240 <br><br> Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gin Arg Arg Ala 245 250 255 <br><br> Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu Val Ser 260 265 270 <br><br> Tyr Arg Val Leu Arg His Leu Ala Gin Pro Thr Pro Leu Gly Pro Ala 275 280 285 <br><br> Ser Ser Leu Pro Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin Val Arg 290 295 300 <br><br> Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr 305 310 315 320 <br><br> (2) INFORMATION FOR SEQ ID NO: 178: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 305 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 178: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 408 <br><br> PCT/US96/15774 <br><br> 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser 115 120 125 <br><br> Asn Met Ala Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp 130 135 140 <br><br> Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly 145 150 155 160 <br><br> Met Ala Pro Ala Leu Gin Pro Thr Gin Gly Ala Met Pro Ala Phe Ala 165 170 175 <br><br> Ser Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu 180 185 190 <br><br> Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin 195 200 205 <br><br> Pro Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gin Ser Phe Leu Leu 210 215 220 <br><br> Lys Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu 225 230 235 240 <br><br> Gin Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu 245 250 255 <br><br> Val Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser 260 265 270 <br><br> Cys Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His 275 280 285 <br><br> Ser Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 409 <br><br> PCT/US96/15774 <br><br> 290 295 300 <br><br> Ser 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 179: <br><br> &lt;i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 320 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 179: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> i <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser 115 120 125 <br><br> Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn 130 135 140 <br><br> Met Ala Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val 145 150 155 160 <br><br> Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met 165 170 175 <br><br> Ala Pro Ala Leu Gin Pro Thr Gin Gly Ala Met Pro Ala Phe Ala Ser <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 410 <br><br> 180 185 190 <br><br> Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin 195 200 205 <br><br> Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro 210 215 220 <br><br> Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gin Ser Phe Leu Leu Lys 225 230 235 240 <br><br> Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin 245 250 255 <br><br> Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val 260 265 270 <br><br> Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys 275 280 285 <br><br> Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser 290 295 300 <br><br> Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser 305 310 315 320 <br><br> (2) INFORMATION FOR SEQ ID NO: 180: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 305 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 180: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu 50 55 60 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 411 <br><br> PCI7US96/15774 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser 115 120 125 <br><br> Asn Met Ala Met Ala Pro Ala Leu Gin Pro Thr Gin Gly Ala Met Pro 130 135 140 <br><br> Ala Phe Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala 145 150 155 160 <br><br> Ser His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His 165 170 175 <br><br> Leu Ala Gin Pro Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gin Ser 180 185 190 <br><br> Phe Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp Gly 195 200 205 <br><br> Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro 210 215 220 <br><br> Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala Pro 225 230 235 240 <br><br> Leu Ser Ser Cys Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser 245 250 255 <br><br> Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu 260 265 270 <br><br> Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu 275 280 285 <br><br> Asp Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu 290 295 300 <br><br> Gly 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 181: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 320 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 412 <br><br> PCT/US96/15774 <br><br> (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein <br><br> (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 181: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser 115 120 125 <br><br> Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn 130 135 140 <br><br> Met Ala Met Ala Pro Ala Leu Gin Pro Thr Gin Gly Ala Met Pro Ala 145 150 155 160 <br><br> Phe Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser 165 170 175 <br><br> His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu 180 185 190 <br><br> Ala Gin Pro Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gin Ser Phe 195 200 205 <br><br> Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp Gly Ala 210 215 220 <br><br> Ala Leu Gin Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu 225 230 235 240 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 413 <br><br> PCT/US96/15774 <br><br> Glu Leu Val Leu Leu Gly His Ser 245 <br><br> Ser Ser Cys Pro Ser Gin Ala Leu 260 <br><br> Leu His Ser Gly Leu Phe Leu Tyr 275 280 <br><br> Gly lie Ser Pro Glu Leu Gly Pro 290 295 <br><br> Val Ala Asp Phe Ala Thr Thr lie 305 310 <br><br> Leu Gly lie Pro Trp Ala Pro Leu <br><br> 250 255 <br><br> Gin Leu Ala Gly Cys Leu Ser Gin 265 270 <br><br> Gin Gly Leu Leu Gin Ala Leu Glu 285 <br><br> Thr Leu Asp Thr Leu Gin Leu Asp 300 <br><br> Trp Gin Gin Met Glu Glu Leu Gly 315 320 <br><br> (2) INFORMATION FOR SEQ ID NO: 182: <br><br> (ij SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 05 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 182: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser 115 120 125 <br><br> Printed from Mimosa 08.37.19 <br><br> WO 97/12985 <br><br> 414 <br><br> PCT/US96/15774 <br><br> Asn Met Ala Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gin 130 135 140 <br><br> Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe Leu 145 150 155 160 <br><br> Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro Thr Pro Leu 165 170 175 <br><br> Gly Pro Ala Ser Ser Leu Pro Gin Ser Phe Leu Leu Lys Ser Leu Glu 180 185 190 <br><br> Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu 195 200 205 <br><br> Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly 210 215 220 <br><br> His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin 225 230 235 240 <br><br> Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe 245 250 255 <br><br> Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu 260 265 270 <br><br> Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr 275 280 285 <br><br> Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin 290 295 300 <br><br> Pro <br><br> 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 183: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 320 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 183: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 415 <br><br> PCT/US96/15774 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser 115 120 125 <br><br> Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn 130 135 140 <br><br> Met Ala Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gin Arg 145 150 155 160 <br><br> Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu 165 170 175 <br><br> Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro Thr Pro Leu Gly 180 185 190 <br><br> Pro Ala Ser Ser Leu Pro Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin 195 200 205 <br><br> Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys 210 215 220 <br><br> Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His 225 230 235 240 <br><br> Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin Ala 245 250 255 <br><br> Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe Leu 260 265 270 <br><br> Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly He Ser Pro Glu Leu Gly 275 280 285 <br><br> Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr Thr 290 295 300 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 416 <br><br> PCT/US96/15774 <br><br> lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin Pro 305 310 315 320 <br><br> (2) INFORMATION FOR SEQ ID NO: 184: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 305 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 184: <br><br> Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro 15 10 15 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 20 25 30 <br><br> lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val 35 40 45 <br><br> Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu 50 55 60 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser 115 120 125 <br><br> Asn Met Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala 130 135 140 <br><br> Ser His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His 145 150 155 160 <br><br> Leu Ala Gin Pro Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gin Ser 165 170 175 <br><br> Phe Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp Gly <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 417 <br><br> PCT/US96/15774 <br><br> 180 185 190 <br><br> Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro 195 200 205 <br><br> Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala Pro 210 215 220 <br><br> Leu Ser Ser Cys Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser 225 230 235 240 <br><br> Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu 245 250 255 <br><br> Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu 260 265 270 <br><br> Asp Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu 275 280 285 <br><br> Gly Met Ala Pro Ala Leu Gin Pro Thr Gin Gly Ala Met Pro Ala Phe 290 295 300 <br><br> Ala 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 185: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 320 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ II <br><br> Asn Cys Ser lie Met lie Asp Glu 1 5 <br><br> Pro Ala Pro Leu Leu Asp Pro Asn 20 <br><br> lie Leu Met Asp Arg Asn Leu Arg 35 40 <br><br> Arg Ala Val Lys Asn Leu Glu Asn 50 55 <br><br> Arg Asn Leu Gin Pro Cys Leu Pro l NO: 185: <br><br> lie lie His His Leu Lys Arg Pro 10 15 <br><br> Asn Leu Asn Asp Glu Asp Val Ser <br><br> 25 30 <br><br> Leu Pro Asn Leu Glu Ser Phe Val 45 <br><br> Ala Ser Gly lie Glu Ala lie Leu 60 <br><br> Ser Ala Thr Ala Ala Pro Ser Arg <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 418 <br><br> 65 70 75 80 <br><br> His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys 85 90 95 <br><br> Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr 100 105 110 <br><br> Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser 115 120 125 <br><br> Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn 130 135 140 <br><br> Met Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser 145 150 155 160 <br><br> His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu 165 170 175 <br><br> Ala Gin Pro Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gin Ser Phe 180 185 190 <br><br> Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp Gly Ala 195 200 205 <br><br> Ala Leu Gin Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu 210 215 220 <br><br> Glu Leu Val Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala Pro Leu 225 230 235 240 <br><br> Ser Ser Cys Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin 245 250 255 <br><br> Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu 260 265 270 <br><br> Gly lie Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp 275 280 285 <br><br> Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly 290 295 300 <br><br> Met Ala Pro Ala Leu Gin Pro Thr Gin Gly Ala Met Pro Ala Phe Ala 305 310 315 320 <br><br> (2) INFORMATION FOR SEQ ID NO: 186: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 321 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 419 <br><br> (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 186: <br><br> Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser lie Leu Met Asp 15 10 15 <br><br> Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys 20 25 30 <br><br> Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu Arg Asn Leu Gin 35 40 45 <br><br> Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg Kis Pro lie lie 50 55 60 <br><br> lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys Leu Thr Phe Tyr 65 70 75 80 <br><br> Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Gly Gly Gly Ser Asn 85 90 95 <br><br> Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro Pro 100 105 110 <br><br> Ala Pro Leu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser 115 120 125 <br><br> Gly Pro lie Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His 130 135 140 <br><br> Lys Ser Pro Asn Met Ala Thr Gin Gly Ala Met Pro Ala Phe Ala Ser 145 150 155 160 <br><br> Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin 165 170 175 <br><br> Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro 180 185 190 <br><br> Ser Gly Gly Ser Gly Gly Ser Gin Ser Phe Leu Leu Lys Ser Leu Glu 195 200 205 <br><br> Gin Val Arg Lys He Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu 210 • 215 220 <br><br> Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly 225 230 235 240 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 420 <br><br> PCT/US96/15774 <br><br> His Ser Leu Gly lie Pro Trp Ala 245 <br><br> Ala Leu Gin Leu Ala Gly Cys Leu 260 <br><br> Leu Tyr Gin Gly Leu Leu Gin Ala 275 280 <br><br> Gly Pro Thr Leu Asp Thr Leu Gin 290 295 <br><br> Thr lie Trp Gin Gin Met Glu Glu 305 310 <br><br> Pro <br><br> Pro Leu Ser Ser Cys Pro Ser Gin 250 255 <br><br> Ser Gin Leu His Ser Gly Leu Phe 265 270 <br><br> Leu Glu Gly lie Ser Pro Glu Leu 285 <br><br> Leu Asp Val Ala Asp Phe Ala Thr <br><br> 300 <br><br> Leu Gly Met Ala Pro Ala Leu Gin 315 320 <br><br> (2) INFORMATION FOR SEQ ID NO: 187: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 21 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 187: <br><br> Asn Ala Ser Gly lie Glu Ala lie Leu Arg Asn Leu Gin Pro Cys Leu 15 10 15 <br><br> Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro lie lie lie Lys Ala 20 25 30 <br><br> Gly Asp Trp Gin Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr 35 40 45 <br><br> Leu Glu Gin Ala Gin Glu Gin Gin Gly Gly Gly Ser Asn Cys Ser lie 50 55 60 <br><br> Met lie Asp Glu lie lie His His Leu Lys Arg Pro Pro Ala Pro Leu 65 70 75 80 <br><br> Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser lie Leu Met Asp 85 90 95 <br><br> Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys 100 105 110 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/XJS96/I5774 <br><br> 421 <br><br> Asn Leu Glu Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser 115 120 125 <br><br> Gly Pro lie Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His 130 135 140 <br><br> Lys Ser Pro Asn Met Ala Thr Gin Gly Ala Met Pro Ala Phe Ala Ser 145 150 155 160 <br><br> Ala Phe Gill Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin 165 170 175 <br><br> Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro 180 185 190 <br><br> Ser Gly Gly Ser Gly Gly Ser Gin Ser Phe Leu Leu Lys Ser Leu Glu 195 200 205 <br><br> Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu 210 215 220 <br><br> Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly 225 230 235 240 <br><br> His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin 245 250 255 <br><br> Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe 260 265 270 <br><br> Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu 275 280 285 <br><br> Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr 290 295 300 <br><br> Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin 305 310 315 320 <br><br> Pro <br><br> (2) INFORMATION FOR SEQ ID NO: 188: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 321 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 422 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 188: <br><br> Ala Pro Ser Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu 15 10 15 <br><br> Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin 20 25 30 <br><br> Glu Gin Gin Gly Gly Gly Ser Asn Cys Ser lie Met lie Asp Glu lie 35 40 45 <br><br> lie His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn 50 55 60 <br><br> Leu Asn Asp Glu Asp Val Ser lie Leu Met Asp Arg Asn Leu Arg Leu 65 70 75 80 <br><br> Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala 85 90 95 <br><br> Ser Gly lie Glu Ala lie Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser 100 105 110 <br><br> Ala Thr Ala Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser 115 120 125 <br><br> Gly Pro lie Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His 130 135 140 <br><br> Lys Ser Pro Asn Met Ala Thr Gin Gly Ala Met Pro Ala Phe Ala Ser 145 150 155 160 <br><br> Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin 165 170 175 <br><br> Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro 180 185 190 <br><br> Ser Gly Gly Ser Gly Gly Ser Gin Ser Phe Leu Leu Lys Ser Leu Glu 195 200 205 <br><br> Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu 210 215 220 <br><br> Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly 225 230 235 240 <br><br> His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin 245 250 255 <br><br> Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe 260 265 270 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 423 <br><br> PCT/US96/15774 <br><br> Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu 275 280 285 <br><br> Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr 290 295 300 <br><br> Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin 305 310 315 320 <br><br> Pro <br><br> (2) INFORMATION FOR SEQ ID NO: 189: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 321 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 189: <br><br> Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val 15 10 15 <br><br> Thr Leu Glu Gin Ala Gin Glu Gin Gin Gly Gly Gly Ser Asn Cys Ser 20 25 30 <br><br> lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro Pro Ala Pro <br><br> 35 40 45 <br><br> Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser lie Leu Met 50 55 60 <br><br> Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val 65 70 75 80 <br><br> Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu Arg Asn Leu 85 90 95 <br><br> Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro lie 100 105 110 <br><br> lie lie Lys Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser 115 120 125 <br><br> Gly Pro lie Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His 130 135 140 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 424 <br><br> PCT/US96/15774 <br><br> Lys Ser Pro Asn Met Ala Thr Gin Gly Ala Met Pro Ala Phe Ala Ser 145 150 155 160 <br><br> Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin 165 170 175 <br><br> Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro 180 185 190 <br><br> Ser Gly Gly Ser Gly Gly Ser Gin Ser Phe Leu Leu Lys Ser Leu Glu 195 200 205 <br><br> Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu 210 215 220 <br><br> Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly 225 230 235 240 <br><br> His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin 245 250 255 <br><br> Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe 260 265 270 <br><br> Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu 275 280 285 <br><br> Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr 290 295 300 <br><br> Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin 305 310 315 320 <br><br> Pro <br><br> (2) INFORMATION FOR SEQ 10 NO: 190: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 329 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 190: <br><br> Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser lie Leu Met Asp 15 10 15 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 425 <br><br> PCT/US96/15774 <br><br> Arg Asn Leu Arg Leu Pro Asn Leu 20 <br><br> Asn Leu Glu Asn Ala Ser Gly lie 35 40 <br><br> Pro Cys Leu Pro Ser Ala Thr Ala 50 55 <br><br> lie Lys Ala Gly Asp Trp Gin Glu 65 70 <br><br> Leu Val Thr Leu Glu Gin Ala Gin 85 <br><br> Gly Gly Ser Gly Gly Gly Ser Asn 100 <br><br> Glu Ser Phe Val Arg Ala Val Lys 25 30 <br><br> Glu Ala lie Leu Arg Asn Leu Gin 45 <br><br> Ala Pro Ser Arg His Pro lie lie 60 <br><br> Phe Arg Glu Lys Leu Thr Phe Tyr 75 80 <br><br> Glu Gin Gin Gly Gly Gly Ser Gly 90 * 95 <br><br> Cys Ser lie Met lie Asp Glu lie 105 110 <br><br> He His His Leu Lys Arg Pro Pro Ala Pro Leu Tyr Val Glu Gly Gly 115' 120 125 <br><br> Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser Thr lie Asn Pro 130 135 140 <br><br> Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gin 145 150 155 160 <br><br> Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly 165 170 175 <br><br> Val Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg 18Q . 185 190 <br><br> Val Leu Arg His Leu Ala Gin Pro Ser Gly Gly Ser Gly Gly Ser Gin <br><br> 195 i 200 205 <br><br> / <br><br> Ser Phe Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp 210 215 220 <br><br> Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His 225 230 235 240 <br><br> Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala 245 250 255 <br><br> Pro Leu Ser Ser Cys Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu 260 265 270 <br><br> Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala 275 280 285 <br><br> Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin 290 295 300 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 426 <br><br> PCT/US96/15774 <br><br> Leu Asp Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu 305 310 315 320 <br><br> Leu Gly Met Ala Pro Ala Leu Gin Pro 325 <br><br> (2) INFORMATION FOR SEQ ID NO: 191: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 329 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 191: <br><br> Asn Ala Ser Gly lie Glu Ala lie Leu Arg Asn Leu Gin Pro Cys Leu I 5 10 15 <br><br> Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro lie lie lie Lys Ala 20 25 30 <br><br> Gly Asp Trp Gin Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr 35 40 45 <br><br> Leu Glu Gin Ala Gin Glu Gin Gin Gly Gly Gly Ser Gly Gly Gly Ser 50 55 60 <br><br> Gly Gly Gly Ser Asn Cys Ser lie Met lie Asp Glu lie lie His His 65 70 75 80 <br><br> Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp 85 90 95 <br><br> Glu Asp Val Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu 100 105 110 <br><br> Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Tyr Val Glu Gly Gly 115 120 125 <br><br> Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser Thr lie Asn Pro 130 135 140 <br><br> Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gin 145 150 155 160 <br><br> Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly 165 170 175 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 427 <br><br> PCT/US96/15774 <br><br> Val Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg 180 185 190 <br><br> Val Leu Arg His Leu Ala Gin Pro Ser Gly Gly Ser Gly Gly Ser Gin 195 200 205 <br><br> Ser Phe Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp 210 215 220 <br><br> Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His 225 230 235 240 <br><br> Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala 245 250 255 <br><br> Pro Leu Ser Ser Cys Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu 260 265 270 <br><br> Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala 275 280 285 <br><br> Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin 290 295 300 <br><br> Leu Asp Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu 305 310 315 320 <br><br> Leu Gly Met Ala Pro Ala Leu Gin Pro 325 <br><br> (2) INFORMATION FOR SEQ ID NO: 192: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 329 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 192: <br><br> Ala Pro Ser Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu 15 10 15 <br><br> Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin 20 25 30 <br><br> Glu Gin Gin Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Asn 35 40 45 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 428 <br><br> PCT/US96/15774 <br><br> Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro Pro 50 55 60 <br><br> Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser lie 65 70 75 80 <br><br> Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg 85 90 95 <br><br> Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu Arg 100 105 110 <br><br> Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Tyr Val Glu Gly Gly 115 120 125 <br><br> Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser Thr lie Asn Pro 130 135 140 <br><br> Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gin 145 150 155 160 <br><br> Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly 165 170 175 <br><br> Val Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg 180 185 190 <br><br> Val Leu Arg His Leu Ala Gin Pro Ser Gly Gly Ser Gly Gly Ser Gin 195 200 205 <br><br> Ser Phe Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp 210 215 220 <br><br> Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His 225 230 235 240 <br><br> Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala 245 250 255 <br><br> Pro Leu Ser Ser Cys Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu 260 265 270 <br><br> Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala 275 280 285 <br><br> Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin 290 295 300 <br><br> Leu Asp Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu 305 310 315 320 <br><br> Leu Gly Met Ala Pro Ala Leu Gin Pro 325 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 429 <br><br> PCT/US96/15774 <br><br> (2) INFORMATION FOR SEQ ID NO: 193: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 299 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 193: <br><br> Gly Gly Ser Gly Gly Gly Ser Asn Cys Ser lie Met lie Asp Glu lie 15 10 15 <br><br> lie His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn 20 25 30 <br><br> Leu Asn Asp Glu Asp Val Ser lie Leu Met Asp Arg Asn Leu Arg Leu 35 40 45 <br><br> Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala 50 55 60 <br><br> Ser Gly lie Glu Ala lie Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser 65 70 75 80 <br><br> Ala Thr Ala Ala Pro Ser Arg His Pro lie lie lie Lys Tyr Val Glu 85 90 95 <br><br> Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser Thr lie 100 105 110 <br><br> Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala 115 120 125 <br><br> Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gin Arg Arg Ala 130 135 140 <br><br> Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu Val Ser 145 150 155 160 <br><br> Tyr Arg Val Leu Arg His Leu Ala Gin Pro Ser Gly Gly Ser Gly Gly 165 170 175 <br><br> Ser Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie Gin 180 185 190 <br><br> Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr Tyr Lys Leu 195 200 205 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 430 <br><br> PCT/US96/15774 <br><br> Cys His Pro Glu Glu Leu Val Leu 210 215 <br><br> Trp Ala Pro Leu Ser Ser Cys Pro 225 230 <br><br> Cys Leu Ser Gin Leu His Ser Gly 245 <br><br> Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr 260 265 270 <br><br> Leu Gin Leu Asp Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met 275 280 285 <br><br> Glu Glu Leu Gly Met Ala Pro Ala Leu Gin Pro 290 295 <br><br> (2) INFORMATION FOR SEQ ID NO: 194: <br><br> Leu Gly His Ser Leu Gly lie Pro 220 <br><br> Ser Gin Ala Leu Gin Leu Ala Gly 235 240 <br><br> Leu Phe Leu Tyr Gin Gly Leu Leu 250 255 <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 329 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 194: <br><br> Met Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys 15 10 15 <br><br> Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30 <br><br> Val Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45 <br><br> Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala 50 55 60 <br><br> lie Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro 65 70 75 80 <br><br> Ser Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg 85 90 95 <br><br> Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin 100 105 110 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 431 <br><br> PCT/US96/15774 <br><br> Gin Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro 115 120 125 <br><br> lie Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser 130 135 140 <br><br> Pro Asn Met Ala Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu 145 150 155 160 <br><br> Gly His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser 165 170 175 <br><br> Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu 180 185 190 <br><br> Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu 195 200 205 <br><br> Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala 210 215 220 <br><br> Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu 225 230 235 240 <br><br> Gin Pro Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gin Arg 245 250 255 <br><br> Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu 260 265 270 <br><br> Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro Gly Gly Gly Ser 275 280 285 <br><br> Asp Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gin Ser Phe 290 295 300 <br><br> Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp Gly Ala 305 310 315 320 <br><br> Ala Leu Gin Glu Lys Leu Cys Ala Thr 325 <br><br> (2) INFORMATION FOR SEQ ID NO: 195: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 329 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 432 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 195: <br><br> Met Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys 15 10 15 <br><br> Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp <br><br> 20 25 30 <br><br> Val Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45 <br><br> Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala 50 55 60 <br><br> lie Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro 65 70 75 80 <br><br> Ser Arg His Pro He lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg 85 90 95 <br><br> Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin 100 105 110 <br><br> Gin Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro 115 120 125 <br><br> lie Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser 130 135 140 <br><br> Pro Asn Met Ala Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu 145 150 155 160 <br><br> Asp Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu 165 170 175 <br><br> Gly Met Ala Pro Ala Leu Gin Pro Thr Gin Gly Ala Met Pro Ala Phe 180 185 190 <br><br> Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser His 195 200 205 <br><br> Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala 210 215 220 <br><br> Gin Pro Gly Gly Gly Ser Asp Met Ala Thr Pro Leu Gly Pro Ala Ser 225 230 235 240 <br><br> Ser Leu Pro Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin Val Arg Lys 245 250 255 <br><br> lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr Tyr 260 265 270 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 433 <br><br> PCT/US96/15774 <br><br> Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly 275 280 285 <br><br> lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin Ala Leu Gin Leu 290 295 300 <br><br> Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly 305 310 315 320 <br><br> Leu Leu Gin Ala Leu Glu Gly lie Ser 325 <br><br> (2) INFORMATION FOR SEQ ID NO: 196t <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 329 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 196: <br><br> Met Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys 15 10 15 <br><br> Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30 <br><br> Val Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45 <br><br> Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala 50 55 60 <br><br> lie Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro 65 70 75 80 <br><br> Ser Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg 85 90 95 <br><br> Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin 100 105 110 <br><br> Gin Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro 115 120 125 <br><br> lie Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser 130 135 140 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 434 <br><br> PCT/US96/15774 <br><br> Pro Asn Met Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val 145 150 155 160 <br><br> Ala Ser His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg 165 170 175 <br><br> His Leu Ala Gin Pro Gly Gly Gly Ser Asp Met Ala Thr Pro Leu Gly 180 185 190 <br><br> Pro Ala Ser Ser Leu Pro Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin 195 200 205 <br><br> Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys 210 215 220 <br><br> Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His 225 230 235 240 <br><br> Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin Ala 245 250 255 <br><br> Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe Leu 260 265 270 <br><br> Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly 275 280 285 <br><br> Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr Thr 290 295 300 <br><br> lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin Pro 305 310 315 320 <br><br> Thr Gin Gly Ala Met Pro Ala Phe Ala 325 <br><br> (2) INFORMATION FOR SEQ ID NO: 197: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 329 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 197: <br><br> Met Ala Asn Cys Ser lie Met lie Asp Glu He lie His His Leu Lys 15 10 15 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 435 <br><br> PCT/US96/15774 <br><br> Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30 <br><br> Val Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45 <br><br> Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala 50 55 60 <br><br> lie Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro 65 70 75 B0 <br><br> Ser Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg 85 90 95 <br><br> Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin 100 105 110 <br><br> Gin Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro 115 120 125 <br><br> lie Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser 130 135 140 <br><br> Pro Asn Met Ala Met Ala Pro Ala Leu Gin Pro Thr Gin Gly Ala Met 145 150 155 160 <br><br> Pro Ala Phe Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val 165 170 175 <br><br> Ala Ser His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg 180 185 190 <br><br> His Leu Ala Gin Pro Gly Gly Gly Ser Asp Met Ala Thr Pro Leu Gly 195 200 205 <br><br> Pro Ala Ser Ser Leu Pro Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin 210 215 220 <br><br> Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys 225 230 235 240 <br><br> Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His 245 250 255 <br><br> Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin Ala 260 265 270 <br><br> Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe Leu 275 280 285 <br><br> Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly 290 295 300 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 436 <br><br> PCT/US96/15774 <br><br> Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr Thr 305 310 315 320 <br><br> lie Trp Gin Gin MeC Glu Glu Leu Gly 325 <br><br> (2) INFORMATION FOR SEQ ID NO: 198: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 329 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 198: <br><br> Met Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys 15 10 15 <br><br> Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp 20 25 30 <br><br> Val Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser 35 40 45 <br><br> Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala 50 55 60 <br><br> lie Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro 65 70 75 80 <br><br> Ser Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg 85 90 95 <br><br> Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin 100 105 110 <br><br> Gin Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro 115 120 125 <br><br> lie Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser 130 135 140 <br><br> Pro Asn Met Ala Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe 145 150 155 160 <br><br> Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe 165 170 175 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 437 <br><br> PCT/US96/15774 <br><br> Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro Gly Gly 180 185 190 <br><br> Gly Ser Asp Mec Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gin 195 200 205 <br><br> Ser Phe Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp 210 215 220 <br><br> Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His 225 230 235 240 <br><br> Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala 245 250 255 <br><br> Pro Leu Ser Ser Cys Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu 260 265 270 <br><br> Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala 275 280 285 <br><br> Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin 290 295 300 <br><br> Leu Asp Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu 305 310 315 320 <br><br> Leu Gly Met Ala Pro Ala Leu Gin Pro 325 <br><br> (2) INFORMATION FOR SEQ ID NO: 199: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 319 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 199: <br><br> Met Ala Asn Cys Ser Asn Met lie Asp Glu lie lie Thr His Leu Lys 15 10 15 <br><br> Gin Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp 20 25 30 <br><br> Gin Asp lie Leu Met Asp Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala 35 40 45 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 438 <br><br> PCT/US96/15774 <br><br> Phe Asn Arg Ala Val 50 <br><br> lie Leu Lys Asn Leu 65 <br><br> Thr Arg His Pro lie 85 <br><br> Arg Lys Leu Thr Phe 100 <br><br> Gin Tyr Val Glu Gly 115 <br><br> lie Ser Thr lie Asn 130 <br><br> Pro Asn Met Ala Thr 145 <br><br> Gin Arg Arg Ala Gly 165 <br><br> Leu Glu Val Ser Tyr <br><br> 180 <br><br> Gly Ser Gly Gly Ser 195 <br><br> Arg Lys lie Gin Gly 210 <br><br> Thr Tyr Lys Leu Cys <br><br> 225 <br><br> Leu Gly lie Pro Trp 245 <br><br> Gin Leu Ala Gly Cys 260 <br><br> Gin Gly Leu Leu Gin 275 <br><br> Thr Leu Asp Thr Leu 290 <br><br> Trp Gin Gin Met Glu 305 <br><br> Lys Ser Leu Gin Asn Ala <br><br> 55 <br><br> Leu Pro Cys Leu Pro Leu 70 75 <br><br> His lie Lys Asp Gly Asp 90 <br><br> Tyr Leu Lys Thr Leu Glu <br><br> 105 <br><br> Gly Gly Gly Ser Pro Gly 120 <br><br> Pro Ser Pro Pro Ser Lys 135 <br><br> Gin Gly Ala Met Pro Ala 150 155 <br><br> Gly Val Leu Val Ala Ser 170 <br><br> Arg Val Leu Arg His Leu 185 <br><br> Gin Ser Phe Leu Leu Lys 200 <br><br> Asp Gly Ala Ala Leu Gin 215 <br><br> His Pro Glu Glu Leu Val 230 235 <br><br> Ala Pro Leu Ser Ser Cys 250 <br><br> Leu Ser Gin Leu His Ser 265 <br><br> Ala Leu Glu Gly lie Ser 280 <br><br> Gin Leu Asp Val Ala Asp <br><br> 295 <br><br> Glu Leu Gly Met Ala Pro 310 315 <br><br> Ser Ala lie Glu Ser 60 <br><br> Ala Thr Ala Ala Pro 80 <br><br> Trp Asn Glu Phe Arg 95 <br><br> Asn Ala Gin Ala Gin 110 <br><br> Glu Pro Ser Gly Pro 125 <br><br> Glu Ser His Lys Ser 140 <br><br> Phe Ala Ser Ala Phe 160 <br><br> His Leu Gin Ser Phe 175 <br><br> Ala Gin Pro Ser Gly 190 <br><br> Ser Leu Glu Gin Val 205 <br><br> Glu Lys Leu Cys Ala 220 <br><br> Leu Leu Gly His Ser 240 <br><br> Pro Ser Gin Ala Leu 255 <br><br> Gly Leu Phe Leu Tyr 270 <br><br> Pro Glu Leu Gly Pro 285 <br><br> Phe Ala Thr Thr lie 300 <br><br> Ala Leu Gin Pro <br><br> (2) INFORMATION FOR SEQ ID NO: 200: (i) SEQUENCE CHARACTERISTICS: <br><br> Printed from Mimosa 08:37:19 <br><br> &lt;1 <br><br> O 97/12985 <br><br> PCT/US96/15774 <br><br> 439 <br><br> (A) LENGTH: 322 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 200: <br><br> Met Ala Asn Cys Ser Asn Met lie Asp Glu lie lie Thr His Leu Lys 15 10 15 <br><br> Gin Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp 20 25 30 <br><br> Gin Asp lie Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala 35 40 45 <br><br> Phe Asn Arg Ala Val Lys Ser Leu Gin Asn Ala Ser Ala lie Glu Ser 50 55 60 <br><br> lie Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro 65 70 75 80 <br><br> Thr Arg His Pro lie lie lie Arg Asp Gly Asp Trp Asn Glu Phe Arg 85 90 95 <br><br> Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gin Ala Gin 100 105 110 <br><br> Gin Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro 115 120 125 <br><br> lie Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser 130 135 140 <br><br> Pro Asn Met Ala Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe 145 150 155 160 <br><br> Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe 165 170 175 <br><br> Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro Thr Pro 180 185 190 <br><br> Leu Gly Pro Ala Ser Ser Leu Pro Gin Ser Phe Leu Leu Lys Ser Leu 195 200 205 <br><br> Glu Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys 210 215 220 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 440 <br><br> PCT/US96/15774 <br><br> Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu 225 230 235 240 <br><br> Gly His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser 245 250 255 <br><br> Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu 260 265 270 <br><br> Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu 275 280 285 <br><br> Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala 290 295 300 <br><br> Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu 305 310 315 320 <br><br> Gin Pro <br><br> (2) INFORMATION FOR SEQ ID NO: 2 01: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH; 319 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 201: <br><br> Met Ala Asn Cys Ser Asn Met lie Asp Glu lie lie Thr His Leu Lys <br><br> 15 10 15 <br><br> Gin Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp <br><br> 20 25 30 <br><br> Gin Asp lie Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala <br><br> 35 40 45 <br><br> Phe Asn Arg Ala Val Lys Ser Leu Gin Asn Ala Ser Ala lie Glu Ser <br><br> 50 55 60 <br><br> lie Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro <br><br> 65 70 75 80 <br><br> Thr Arg His Pro lie lie lie Arg Asp Gly Asp Trp Asn Glu Phe Arg <br><br> 85 90 95 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 44) <br><br> PCT/US96/15774 <br><br> Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gin Ala Gin 100 105 110 <br><br> Gin Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro 115 120 125 <br><br> lie Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser 130 135 140 <br><br> Pro Asn Met Ala Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe 145 150 155 160 <br><br> Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe 165 170 175 <br><br> Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro Ser Gly 180 185 190 <br><br> Gly Ser Gly Gly Ser Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin Val 195 200 205 <br><br> Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala 210 215 220 <br><br> Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser 225 230 235 240 <br><br> Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin Ala Leu 245 250 255 <br><br> Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe Leu Tyr 260 265 270 <br><br> Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly Pro 275 280 285 <br><br> Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr Thr lie 290 295 300 <br><br> Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin Pro 305 310 315 <br><br> (2) INFORMATION FOR SEQ ID NO: 202: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 322 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 442 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 202: <br><br> Met Ala Asn Cys Ser Asn Met lie Asp Glu lie lie Thr His Leu Lys 15 10 15 <br><br> Gin Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp 20 25 30 <br><br> Gin Asp lie Leu Met Asp Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala 35 40 45 <br><br> Phe Asn Arg Ala Val Lys Ser Leu Gin Asn Ala Ser Ala lie Glu Ser <br><br> 50 55 60 <br><br> lie Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro 65 70 75 80 <br><br> Thr Arg His Pro lie His lie Lys Asp Gly Asp Trp Asn Glu Phe Arg 85 90 95 <br><br> Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gin Ala Gin 100 105 110 <br><br> Gin Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro 115 120 125 <br><br> lie Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser 130 135 140 <br><br> Pro Asn Met Ala Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe 145 150 155 160 <br><br> Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe 165 170 175 <br><br> Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro Thr Pro 180 185 190 <br><br> Leu Gly Pro Ala Ser Ser Leu Pro Gin Ser Phe Leu Leu Lys Ser Leu 195 200 205 <br><br> Glu Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys 210 215 220 <br><br> Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu 225 230 235 240 <br><br> Gly His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser 245 250 255 <br><br> Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu 260 265 270 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 443 <br><br> Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu 275 280 285 <br><br> Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala 290 295 300 <br><br> Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu 305 310 315 320 <br><br> Gin Pro <br><br> (2) INFORMATION FOR SEQ ID NO: 203: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 06 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 203: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 444 <br><br> PCT/US96/15774 <br><br> Asn Met Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val 145 150 155 160 <br><br> Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala 165 170 175 <br><br> Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala 180 185 190 <br><br> Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin 195 200 205 <br><br> Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu 210 215 220 <br><br> Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro 225 230 235 240 <br><br> Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg 245 250 255 <br><br> Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly 260 265 270 <br><br> Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu 275 280 285 <br><br> Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin 290 295 300 <br><br> Cys Pro 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 204: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 306 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single (D&gt; TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 204: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 1 5 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 445 <br><br> PCT/US96/15774 <br><br> Ser He Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly He Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 145 150 155 160 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 165 170 175 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 180 185 190 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 195 200 205 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu 210 215 220 <br><br> Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe 225 230 235 240 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu 245 250 255 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala 260 265 270 <br><br> Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu 275 2B0 285 <br><br> Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val 290 295 300 <br><br> His Pro 305 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 446 <br><br> PCT/US96/15774 <br><br> (2) INFORMATION FOR SEQ ID NO: 205: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 306 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 205: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys 145 150 155 160 <br><br> Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu Gly Ala Val Thr 165 170 175 <br><br> Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin Leu Gly Pro Thr 180 185 190 <br><br> Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin Val Arg Leu Leu 195 200 205 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 447 <br><br> PCT/US96/15774 <br><br> Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu Pro Pro Gin Gly 210 215 220 <br><br> Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe Leu Ser Phe Gin 225 230 235 240 <br><br> His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser 245 250 255 <br><br> Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Ala Pro 260 265 270 <br><br> Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His 275 280 285 <br><br> Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val His Pro Leu Pro 290 295 300 <br><br> Thr Pro <br><br> 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 206: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 306 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 206: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe <br><br> 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly He Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 448 <br><br> PCT/US96/1S774 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu 145 150 155 160 <br><br> Glu Thr Lys Ala Gin Asp He Leu Gly Ala Val Thr Leu Leu Leu Glu 165 170 175 <br><br> Gly Val Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser 180 185 190 <br><br> Leu Leu Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu 195 200 205 <br><br> Gin Ser Leu Leu Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala 210 215 220 <br><br> His Lys Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg 225 230 235 240 <br><br> Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val 245 250 255 <br><br> Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp 260 265 270 <br><br> Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser 275 280 285 <br><br> Arg Leu Ser Gin Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu 290 295 300 <br><br> Leu Pro 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 2 07: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 306 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 449 <br><br> PCMJS96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 207: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 1 5 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie <br><br> 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu Glu Thr 145 150 155 160 <br><br> Lys Ala Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val 165 170 175 <br><br> Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu 180 185 190 <br><br> Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser 195 200 205 <br><br> Leu Leu Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys 210 215 220 <br><br> Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys 225 230 235 240 <br><br> Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu 245 250 255 <br><br> Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg 260 265 270 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 450 <br><br> PCT/US96/15774 <br><br> Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu 275 280 285 <br><br> Ser Gin Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro 290 295 300 <br><br> Ala Val 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 208: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 30S amino acids (B&gt; TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 208: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp 145 150 155 160 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 451 <br><br> PCT/US96/15774 <br><br> lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg 165 170 175 <br><br> Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser 180 185 190 <br><br> Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr 195 200 205 <br><br> Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala 210 215 220 <br><br> lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu 225 230 235 240 <br><br> Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn 245 250 255 <br><br> Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys 260 265 270 <br><br> Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro 275 280 285 <br><br> Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe 290 295 300 <br><br> Ser Leu 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 209: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 306 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 209: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 452 <br><br> PCT/US96/15774 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie <br><br> 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr He Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly 145 150 155 160 <br><br> Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin 165 170 175 <br><br> Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie 180 185 190 <br><br> Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met 195 200 205 <br><br> Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met 210 215 220 <br><br> Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu 225 230 235 240 <br><br> Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu 245 250 255 <br><br> Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser 260 265 270 <br><br> Leu Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie 275 280 285 <br><br> Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly 290 295 300 <br><br> Gin Leu <br><br> 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 210: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 453 <br><br> PCT/US96/15774 <br><br> (A) LENGTH: 306 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 210: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie <br><br> 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys 145 150 155 160 <br><br> Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys 165 170 175 <br><br> Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu 180 185 190 <br><br> Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg 195 200 205 <br><br> Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu 210 215 220 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 454 <br><br> PCT/US96/15774 <br><br> Ser Glri Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro 225 230 235 240 <br><br> Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu Glu Thr 245 250 255 <br><br> Lys Ala Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val 260 265 270 <br><br> Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu 275 280 285 <br><br> Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser 290 295 300 <br><br> Leu Leu 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 211: <br><br> {i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 306 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 211: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 455 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Mec Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe Leu 145 150 155 160 <br><br> Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val 165 170 175 <br><br> Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala Ser 180 185 190 <br><br> Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg 195 200 205 <br><br> Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val His 210 215 220 <br><br> Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly 225 230 235 240 <br><br> Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu Gly 245 250 255 <br><br> Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin Leu 260 265 270 <br><br> Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin Val 275 280 285 <br><br> Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu Pro 290 295 300 <br><br> Pro Gin 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 212: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 306 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 212: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 456 <br><br> PCT/US96/15774 <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Ala His Lys Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His 145 150 155 160 <br><br> Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr 165 170 175 <br><br> Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro 180 185 190 <br><br> Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val 195 200 205 <br><br> Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val His Pro Leu Pro Thr 210 215 220 <br><br> Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr 225 230 235 240 <br><br> Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu Gly Ala Val Thr Leu 245 250 255 <br><br> Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys 260 265 270 <br><br> Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu 275 280 285 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 457 <br><br> PCT/US96/15774 <br><br> Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu Pro Pro Gin Gly Arg 290 295 300 <br><br> Thr Thr 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 213: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 306 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 213: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg 145 150 155 160 <br><br> Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val 165 170 175 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 458 <br><br> PCT/US96/15774 <br><br> Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp 180 185 190 <br><br> Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser 195 200 205 <br><br> Arg Leu Ser Gin Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu 210 215 220 <br><br> Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu 225 230 235 240 <br><br> Glu Thr Lys Ala Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu 245 250 255 <br><br> Gly Val Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser 260 265 270 <br><br> Leu Leu Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu 275 280 285 <br><br> Gin Ser Leu Leu Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala 290 295 300 <br><br> His Lys 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 214: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 306 amino acids <br><br> (B) TYPE: amino acid <br><br> &lt;C) STRANDEDNESS: single (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 214: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg <br><br> 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 459 <br><br> PCT/US96/15774 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val 145 150 155 160 <br><br> Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe 165 170 175 <br><br> Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val 180 185 190 <br><br> Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser 195 200 205 <br><br> Gin Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala 210 215 220 <br><br> Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys 225 230 235 240 <br><br> Ala Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met 245 250 255 <br><br> Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly 260 265 270 <br><br> Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu 275 280 285 <br><br> Leu Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp 290 295 300 <br><br> Pro Asn 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 215: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 05 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/1S774 <br><br> 460 <br><br> (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 215: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val 145 150 155 160 <br><br> Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala 165 170 175 <br><br> Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala 180 185 190 <br><br> Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin 195 200 205 <br><br> Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu 210 215 220 <br><br> Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro 225 230 235 240 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 461 <br><br> Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg 245 250 255 <br><br> Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly 260 265 270 <br><br> Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser 275 280 285 <br><br> Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys 290 295 300 <br><br> Pro 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 216: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 305 amino acids (B! TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 216: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg <br><br> 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 462 <br><br> PCT/US96/15774 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 145 150 155 150 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 165 170 175 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 180 185 190 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 195 200 205 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu 210 215 220 <br><br> Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala He Phe 225 230 235 240 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu 245 250 255 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Asn Met Ala Ser 260 265 270 <br><br> Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg 275 280 285 <br><br> Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val His 290 295 300 <br><br> Pro 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 217: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 305 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 217: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 1 5 10 15 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 463 <br><br> PCT/US96/15774 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala He 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys 145 150 155 160 <br><br> Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu Gly Ala Val Thr 165 170 175 <br><br> Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin Leu Gly Pro Thr 180 185 190 <br><br> Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin Val Arg Leu Leu 195 200 205 <br><br> Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu Pro Pro Gin Gly 210 215 220 <br><br> Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe Leu Ser Phe Gin 225 230 235 240 <br><br> His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser 245 250 255 <br><br> Thr Leu Cys Val Arg Glu Phe Gly Asn Met Ala Ser Pro Ala Pro Pro 260 265 270 <br><br> Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val 275 280 285 <br><br> Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val His Pro Leu Pro Thr 290 295 300 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 464 <br><br> PCT/US96/15774 <br><br> Pro 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 218: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 305 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 218: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu 145 150 155 160 <br><br> Glu Thr Lys Ala Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu 165 170 175 <br><br> Gly Val Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser 180 185 190 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 465 <br><br> PCT/US96/15774 <br><br> Leu Leu Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu 195 200 205 <br><br> Gin Ser Leu Leu Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala 210 215 220 <br><br> His Lys Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg 225 230 235 240 <br><br> Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val 245 250 255 <br><br> Arg Glu Phe Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu 260 265 270 <br><br> Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg 275 280 285 <br><br> Leu Ser Gin Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu 290 295 300 <br><br> Pro 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 219: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 305 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 219: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val <br><br> 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu,Arg Leu Pro Asn Leu Glu Ser Phe 35 40 ' 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 466 <br><br> PCT/US96/15774 <br><br> Arg His Pro He lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met: Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu Glu Thr 145 150 155 160 <br><br> Lys Ala Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val 165 170 175 <br><br> Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu 180 185 190 <br><br> Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser 195 200 205 <br><br> Leu Leu Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys 210 215 220 <br><br> Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys 225 230 235 240 <br><br> Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu 245 250 255 <br><br> Phe Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val 260 265 270 <br><br> Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser 275 280 285 <br><br> Gin Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala 290 295 300 <br><br> Val 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 220: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 05 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 467 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 220: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Eer Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp 145 150 155 160 <br><br> lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg 165 170 175 <br><br> Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser 180 185 190 <br><br> Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr 195 200 205 <br><br> Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala 210 215 220 <br><br> lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu 225 230 235 240 <br><br> Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Asn Met 245 250 255 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 468 <br><br> PCT/US96/15774 <br><br> Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu 260 265 270 <br><br> Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu 275 280 285 <br><br> Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser 290 295 300 <br><br> Leu <br><br> 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 221: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 05 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 221: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin. Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 469 <br><br> PCT/US96/15774 <br><br> Asn Met Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly 145 150 155 160 <br><br> Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin 165 170 175 <br><br> Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie 180 185 190 <br><br> Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met 195 200 205 <br><br> Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Asn Met Ala 210 215 220 <br><br> Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu 225 230 235 240 <br><br> Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val 245 250 255 <br><br> His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 260 265 270 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 275 280 285 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 290 295 300 <br><br> Leu 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 222: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 05 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 222: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 470 <br><br> PCT/US96/15774 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys 145 150 155 160 <br><br> Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys 165 170 175 <br><br> Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu 180 185 190 <br><br> Phe Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val 195 200 205 <br><br> Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser 210 215 220 <br><br> Gin Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala 225 230 235 240 <br><br> Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys 245 250 255 <br><br> Ala Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met 260 265 270 <br><br> Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly 275 280 285 <br><br> Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu 290 295 300 <br><br> Leu <br><br> 305 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 471 <br><br> PCT/US96/15774 <br><br> (2) INFORMATION FOR SEQ ID NO: 223: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 305 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single {D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 223: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu <br><br> 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe Leu 145 150 155 160 <br><br> Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val 165 170 175 <br><br> Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Asn Met Ala Ser Pro 180 185 190 <br><br> Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp 195 200 205 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 472 <br><br> PCT/US96/15774 <br><br> Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val His Pro 210 215 220 <br><br> Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu 225 230 235 240 <br><br> Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu Gly Ala 245 250 255 <br><br> Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin Leu Gly 260 265 270 <br><br> Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin Val Arg 275 2B0 285 <br><br> Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu Pro Pro 290 295 300 <br><br> Gin 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 224: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 05 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 224: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 473 <br><br> PCT/US96/15774 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe Leu 145 150 155 160 <br><br> Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val 165 170 175 <br><br> Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Asn Met Ala Ser Pro 180 185 190 <br><br> Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp 195 200 205 <br><br> Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val His Pro 210 215 220 <br><br> Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu 225 230 235 240 <br><br> Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu Gly Ala 245 250 255 <br><br> Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin Leu Gly 260 265 270 <br><br> Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin Val Arg 275 280 285 <br><br> Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu Pro Pro 290 295 300 <br><br> Gin 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 225: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 305 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 474 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 225: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg 145 150 155 160 <br><br> Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val 165 170 175 <br><br> Arg Glu Phe Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu 180 185 190 <br><br> Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg 195 200 205 <br><br> Leu Ser Gin Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu 210 215 220 <br><br> Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu Glu 225 230 235 240 <br><br> Thr Lys Ala Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly 245 250 255 <br><br> Val Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu 260 265 270 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 475 <br><br> PCT/US96/15774 <br><br> Leu Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin 275 280 285 <br><br> Ser Leu Leu Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His 290 295 300 <br><br> Lys <br><br> 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 226: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 305 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 22 6: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn. Ala Ser Gly lie Glu Ala lie <br><br> 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr 100 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser 115 120 <br><br> Ser Thr lie Asn Pro Ser Pro Pro 130 135 <br><br> Asn Met Ala lie Phe Leu Ser Phe 145 150 <br><br> Leu Glu Gin Ala Gin Glu Gin Gin 105 110 <br><br> Pro Gly Glu Pro Ser Gly Pro lie 125 <br><br> Ser Lys Glu Ser His Lys Ser Pro 140 <br><br> Gin His Leu Leu Arg Gly Lys Val 155 160 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 476 <br><br> PCT/US96/15774 <br><br> Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe 165 170 175 <br><br> Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu 180 185 190 <br><br> Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin 195 200 205 <br><br> Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val 210 215 220 <br><br> Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala 225 230 235 240 <br><br> Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala 245 250 255 <br><br> Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin 260 265 270 <br><br> Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu 275 280 2B5 <br><br> Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro 290 295 300 <br><br> Asn <br><br> 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 227: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 09 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 227: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 477 <br><br> PCT/US96/15774 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 145 150 155 160 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 165 170 175 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 180 185 190 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 195 200 205 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu 210 215 220 <br><br> Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe 225 230 235 240 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu 245 250 255 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gly 260 265 270 <br><br> Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser 275 280 285 <br><br> Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys 290 295 300 <br><br> Pro Glu Val His Pro 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 228: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 478 <br><br> (A) LENGTH: 309 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 228: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 145 150 155 160 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 165 170 175 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 180 185 190 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 195 200 205 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu 210 215 220 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 479 <br><br> PCT/US96/15774 <br><br> Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe 225 230 235 240 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu 245 250 255 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gly 260 265 270 <br><br> Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser 275 280 285 <br><br> Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys 290 295 300 <br><br> Pro Glu Val His Pro 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 229: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 309 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 229: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin' Glu Gin Gin 100 105 110 <br><br> Printed from Mimosa 08:37.19 <br><br> WO 97/12985 <br><br> 480 <br><br> PCT/US96/15774 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys 145 150 155 160 <br><br> Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu Gly Ala Val Thr 165 170 175 <br><br> Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin Leu Gly Pro Thr 180 185 190 <br><br> Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin Val Arg Leu Leu 195 200 205 <br><br> Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu Pro Pro Gin Gly 210 215 220 <br><br> Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe Leu Ser Phe Gin 225 230 235 240 <br><br> His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser 245 250 255 <br><br> Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gly Asn Met Ala Ser 260 265 270 <br><br> Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg 275 280 285 <br><br> Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val His 290 295 300 <br><br> Pro Leu Pro Thr Pro 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 230: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 09 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 230: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 481 <br><br> PCT/US96/15774 <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly He Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu 145 150 155 160 <br><br> Glu Thr Lys Ala Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu 165 170 175 <br><br> Gly Val Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser 180 185 190 <br><br> Leu Leu Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu 195 200 205 <br><br> Gin Ser Leu Leu Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala 210 215 220 <br><br> His Lys Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg 225 230 235 240 <br><br> Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val 245 250 255 <br><br> Arg Glu Phe Gly Gly Asn Gly Gly Asn Met Ala Ser Pro Ala Pro Pro 260 265 270 <br><br> Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val 275 280 285 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 482 <br><br> PCT/US96/15774 <br><br> Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val His Pro Leu Pro Thr 290 295 300 <br><br> Pro Val Leu Leu Pro 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 231: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 309 amino acids <br><br> (B) TYPE: amino acid <br><br> (C&gt; STRANDEDNESS: single (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 231: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu Glu Thr 145 150 155 160 <br><br> Lys Ala Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu. Glu Gly Val 165 170 175 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 483 <br><br> PCT/US96/15774 <br><br> Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu 180 185 190 <br><br> Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser 195 200 205 <br><br> Leu Leu Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys 210 215 220 <br><br> Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys 225 230 235 240 <br><br> Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu 245 250 255 <br><br> Phe Gly Gly Asn Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys 260 265 270 <br><br> Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His 275 280 285 <br><br> Ser Arg Leu Ser Gin Cys Pro Glu Val His Pro Leu Pro Thr Pro Val 290 295 300 <br><br> Leu Leu Pro Ala Val 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 232: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 309 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ I] <br><br> Ala Asn Cys Ser lie Met lie Asp 1 5 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro <br><br> 20 <br><br> Ser lie Leu Met Asp Arg Asn Leu 35 40 <br><br> Val Arg Ala Val Lys Asn Leu Glu 50 55 <br><br> &gt; NO: 232: <br><br> Glu lie lie His His Leu Lys Arg 10 15 <br><br> Asn Asn Leu Asn Asp Glu Asp Val 25 30 <br><br> Arg Leu Pro Asn Leu Glu Ser Phe 45 <br><br> Asn Ala Ser Gly lie Glu Ala lie 60 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 484 <br><br> PCT/US96/15774 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp 145 150 155 160 <br><br> lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg 165 170 175 <br><br> Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser 180 185 190 <br><br> Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr 195 200 205 <br><br> Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala 210 215 220 <br><br> lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu 225 230 235 240 <br><br> Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn 245 250 255 <br><br> Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val 260 265 270 <br><br> Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser 275 280 285 <br><br> Gin Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala 290 295 300 <br><br> Val Asp Phe Ser Leu 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 233: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 09 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 485 <br><br> PCT/US96/15774 <br><br> (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 233: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly 145 150 155 160 <br><br> Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin 165 170 175 <br><br> Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie 180 185 190 <br><br> Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met 195 200 205 <br><br> Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gly 210 215 220 <br><br> Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu 225 230 235 240 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 486 <br><br> Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin 245 250 255 <br><br> Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val 260 265 270 <br><br> Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala 275 280 285 <br><br> Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala 290 295 300 <br><br> Ala Arg Gly Gin Leu 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 234: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 309 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 234: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 487 <br><br> PCT/US96/15774 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys 145 150 155 160 <br><br> Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys 165 170 175 <br><br> Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu 180 185 190 <br><br> Phe Gly Gly Asn Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys 195 200 205 <br><br> Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His 210 215 220 <br><br> Ser Arg Leu Ser Gin Cys Pro Glu Val His Pro Leu Pro Thr Pro Val 225 230 235 240 <br><br> Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met 245 250 255 <br><br> Glu Glu Thr Lys Ala Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu 260 265 270 <br><br> Glu Gly Val Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser 275 280 285 <br><br> Ser Leu Leu Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala 290 295 300 <br><br> Leu Gin Ser Leu Leu 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 235: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 309 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 235: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 488 <br><br> PCT /US96/15774 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe Leu 145 150 155 160 <br><br> Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val 165 170 175 <br><br> Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gly Asn 180 185 190 <br><br> Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys 195 200 205 <br><br> Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro 210 215 220 <br><br> Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe 225 230 235 240 <br><br> Ser Leu Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp 245 250 255 <br><br> lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg 260 265 270 <br><br> Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser 275 280 285 <br><br> Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr 290 295 300 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 489 <br><br> Gin Leu Pro Pro Gin 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 23 6: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 309 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 236: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Ala His Lys Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His 145 150 155 160 <br><br> Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr 165 170 175 <br><br> Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gly Asn Met Ala Ser Pro 180 185 190 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 490 <br><br> PCT/US96/15774 <br><br> Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp 195 200 205 <br><br> Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val His Pro 210 215 220 <br><br> Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu 225 230 235 240 <br><br> Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu Gly Ala 245 250 255 <br><br> Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin Leu Gly 260 265 270 <br><br> Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin Val Arg 275 280 285 <br><br> Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu Pro Pro 290 295 300 <br><br> Gin Gly Arg Thr Thr 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 237: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 309 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 237: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 491 <br><br> PCT/US96/15774 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro He 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg 145 150 155 160 <br><br> Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val 165 170 175 <br><br> Arg Glu Phe Gly Gly Asn Gly Gly Asn Met Ala Ser Pro Ala Pro Pro 180 185 190 <br><br> Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val 195 200 205 <br><br> Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val His Pro Leu Pro Thr 210 215 220 <br><br> Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr 225 230 235 240 <br><br> Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu Gly Ala Val Thr Leu 245 250 255 <br><br> Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys 260 265 270 <br><br> Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu 275 280 285 <br><br> Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu Pro Pro Gin Gly Arg 290 295 300 <br><br> Thr Thr Ala His Lys 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 23 8: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 309 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 492 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 238: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val 145 150 155 160 <br><br> Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe 165 170 175 <br><br> Gly Gly Asn Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp 180 185 190 <br><br> Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser 195 200 205 <br><br> Arg Leu Ser Gin Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu 210 215 220 <br><br> Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu 225 230 235 240 <br><br> Glu Thr Lys Ala Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu 245 250 255 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 493 <br><br> PCT/US96/15774 <br><br> Gly Val Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser 260 265 270 <br><br> Leu Leu Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu 275 280 285 <br><br> Gin Ser Leu Leu Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala 290 295 300 <br><br> His Lys Asp Pro Asn <br><br> 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 239: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 3 02 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 239: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe <br><br> 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 494 <br><br> Asn Met Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg 145 150 155 160 <br><br> Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val 165 170 175 <br><br> Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp 180 185 190 <br><br> Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser 195 200 205 <br><br> Arg Leu Ser Gin Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu 210 215 220 <br><br> Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu 225 230 235 240 <br><br> Glu Thr Lys Ala Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu 245 250 255 <br><br> Gly Val Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser 260 265 270 <br><br> Leu Leu Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu 275 280 285 <br><br> Gin Ser Leu Leu Gly Thr Gin Gly Arg Thr Thr Ala His Lys 290 295 300 <br><br> (2) INFORMATION FOR SEQ ID NO: 240: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 83 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 240: <br><br> AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT 60 <br><br> ACGTAGAGGG CGGTGGAGGC TCC 83 <br><br> (2) INFORMATION FOR SEQ ID NO: 241: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 495 <br><br> PCT/US96/15774 <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 82 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 2 41: <br><br> CCGGGGAGCC TCCACCGCCC TCTACGTACT GTTGAGCCTG CGCGTTCTCC AAGTTTTCAG 60 <br><br> ATAGAAGGTC AGTTTACGAC GG 82 <br><br> (2) INFORMATION FOR SEQ ID NO: 242: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 8 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 242: <br><br> Gly Gly Gly Ser Gly Gly Gly Ser 1 5 <br><br> (2) INFORMATION FOR SEQ ID NO: 243: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 12 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 243: Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 496 <br><br> PCT/US96/15774 <br><br> 1 5 10 <br><br> (2) INFORMATION FOR SEQ ID NO: 244: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 7 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 244: <br><br> Ser Gly Gly Ser Gly Gly Ser 1 5 <br><br> (2) INFORMATION FOR SEQ ID NO: 245: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 6 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 245: <br><br> Glu Phe Gly Asn Met Ala 1 5 <br><br> (2) INFORMATION FOR SEQ ID NO: 246: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 7 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 246: Glu Phe Gly Gly Asn Asn Ala <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 497 <br><br> PCT/US96/15774 <br><br> 1 5 <br><br> (2) INFORMATION FOR SEQ ID NO: 247: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 10 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 247: <br><br> Glu Phe Gly Gly Asn Gly Gly Asn Met Ala <br><br> 15 10 <br><br> (2) INFORMATION FOR SEQ ID NO: 248: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 309 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 248: <br><br> Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg 15 10 15 <br><br> Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val 20 25 30 <br><br> Ser He Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe 35 40 45 <br><br> Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie 50 55 60 <br><br> Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 65 70 75 80 <br><br> Arg His Pro lie lie Leu Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu 85 90 95 <br><br> Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCT/US96/15774 <br><br> 498 <br><br> 100 105 110 <br><br> Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie 115 120 125 <br><br> Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro 130 135 140 <br><br> Asn Met Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 145 150 155 160 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Asn Asp lie Leu 165 170 175 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 180 185 190 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 195 200 205 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu 210 215 220 <br><br> Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe 225 230 235 240 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu 245 250 255 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Gly Gly 260 265 270 <br><br> Asn Met Ala Ser Pro Ala Pro Pro Ala Ser Asp Leu Arg Val Leu Ser 275 280 285 <br><br> Lys Leu Leu Lys Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys 290 295 300 <br><br> Pro Glu Val His Pro 305 <br><br> (2) INFORMATION FOR SEQ ID NO: 249: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 459 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 499 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 249: <br><br> TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT 60 <br><br> GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG 120 <br><br> CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA 180 <br><br> CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA 240 <br><br> CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC 300 <br><br> CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT 360 <br><br> CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT 420 <br><br> TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGG 459 <br><br> (2) INFORMATION FOR SEQ ID NO: 250: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 447 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 250: <br><br> TCTCCCGCTC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT 60 <br><br> GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG 120 <br><br> CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA 180 <br><br> CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA 240 <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 500 <br><br> PCT/US96/15774 <br><br> CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC 300 <br><br> CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGGGCAGGA CCACAGCTCA CAAGGATCCC 360 <br><br> AATGCCATCT TCCTGAGCTT CCAACACCTG CTCCGAGGAA AGGTGCGTTT CCTGATGCTT 420 <br><br> GTAGGAGGGT CCACCCTCTG CGTCAGG 447 <br><br> (2) INFORMATION FOR SEQ ID NO: 251: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 459 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 251: <br><br> TCCCCAGCGC CGCCTGCTTG TGACCTCCGA GTCCTCAGTA AACTGCTTCG TGACTCCCAT 60 <br><br> GTCCTTCACA GCAGACTGAG CCAGTGCCCA GAGGTTCACC CTTTGCCTAC ACCTGTCCTG 120 <br><br> CTGCCTGCTG TGGACTTTAG CTTGGGAGAA TGGAAAACCC AGATGGAGGA GACCAAGGCA 180 <br><br> CAGGACATTC TGGGAGCAGT GACCCTTCTG CTGGAGGGAG TGATGGCAGC ACGGGGACAA 240 <br><br> CTGGGACCCA CTTGCCTCTC ATCCCTCCTG GGGCAGCTTT CTGGACAGGT CCGTCTCCTC 300 <br><br> CTTGGGGCCC TGCAGAGCCT CCTTGGAACC CAGCTTCCTC CACAGGGCAG GACCACAGCT 360 <br><br> CACAAGGATC CCAATGCCAT CTTCCTGAGC TTCCAACACC TGCTCCGAGG AAAGGTGCGT 420 <br><br> TTCCTGATGC TTGTAGGAGG GTCCACCCTC TGCGTCAGG 459 <br><br> (2) INFORMATION FOR SEQ ID NO: 252: <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 501 <br><br> PCI7US96/15774 <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 153 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 252: <br><br> Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu 1 5 10 15 <br><br> Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val 20 25 30 <br><br> His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 35 40 45 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 50 55 60 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 65 70 75 80 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 85 90 95 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Leu 100 105 110 <br><br> Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe 115 120 125 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu 130 135 140 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg 145 150 <br><br> (2) INFORMATION FOR SEQ ID NO: 253: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 149 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 502 <br><br> PCT/US96/15774 <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 253: <br><br> Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu 15 10 15 <br><br> Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val 20 25 30 <br><br> His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 35 40 45 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 50 55 60 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 65 70 75 80 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 85 90 95 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Gly 100 105 110 <br><br> Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe Leu Ser Phe Gin 115 120 125 <br><br> His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser 130 135 140 <br><br> Thr Leu Cys Val Arg 145 <br><br> (2) INFORMATION FOR SEQ ID NO: 254: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 153 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: protein <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 254: <br><br> Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu 15 10 15 <br><br> Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 503 <br><br> PCT/US96/15774 <br><br> 20 25 30 <br><br> His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 35 40 45 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 50 55 60 <br><br> Gly Ala Val Thr Leu Leu Leu Glu 65 70 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser 85 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin 100 105 <br><br> Pro Pro Gin Gly Arg Thr Thr Ala His 115 120 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly 130 135 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg 145 150 <br><br> (2) INFORMATION FOR SEQ ID NO: 255: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 64 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> Gly Val Met Ala Ala Arg Gly Gin 75 80 <br><br> Leu Leu Gly Gin Leu Ser Gly Gin 90 95 <br><br> Ser Leu Leu Gly Thr Gin Leu 110 <br><br> Lys Asp Pro Asn Ala lie Phe 125 <br><br> Lys Val Arg Phe Leu Met Leu 140 <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 255: <br><br> GGATCCACCA TGAGCCGCCT GCCCGTCCTG CTCCTGCTCC AACTCCTGGT CCGCCCCGCC 60 <br><br> ATGG 64 <br><br> (2) INFORMATION FOR SEQ ID NO: 256: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 153 amino acids <br><br> (B) TYPE: amino acid <br><br> (C) STRANDEDNESS: unknown <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 504 <br><br> PCT/US96/15774 <br><br> (D) TOPOLOGY: unknown (ii) MOLECULE TYPE: protein <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:112 <br><br> (D) OTHER INFORMATION:/note= "position 112 is deleted or Leu, Ala,VAl, lie, Pro, Phe, Trp or Met" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:113 <br><br> (D) OTHER INFORMATION:/note= "positoin 113 is deleted or Pro, Phe, Ala, Val, Leu, lie, Trp or Met" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:114 <br><br> (D) OTHER INFORMATION:/note= "position 114 is deleted or Pro, Phe, Ala, Val, Leu, lie, Trp or Met" <br><br> (ix) FEATURE: <br><br> (A) NAME/KEY: Modified-site <br><br> (B) LOCATION:115 <br><br> (D) OTHER INFORMATION:/note= "positon 115 is deleted or Gin, Gly, Ser, Thr, Tyr, or Asn" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 25 6: <br><br> Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu 15 10 15 <br><br> Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val 20 25 30 <br><br> His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu 35 40 45 <br><br> Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu 50 55 60 <br><br> Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin 65 70 75 80 <br><br> Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin 85 90 95 <br><br> Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu Gly Thr Gin Xaa 100 105 110 <br><br> Xaa Xaa Xaa Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 <br><br> 505 <br><br> PCT/US96/15774 <br><br> 115 120 125 <br><br> Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu 130 135 140 <br><br> Val Gly Gly Ser Thr Leu Cys Val Arg 145 150 <br><br> (2) INFORMATION FOR SEQ ID NO: 257: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 464 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 257: <br><br> CCATGGCTAA CTGCTCTATA ATGATCGATG AAATTATACA TCACTTAAAG AGACCACCTG 60 <br><br> CACCTTTGCT GGACCCGAAC AACCTCAATG ACGAAGACGT CTCTATCCTG ATGGATCGAA 120 <br><br> ACCTTCGACT TCCAAACCTG GAGAGCTTCG TAAGGGCTGT CAAGAACTTA GAAAATGCAT 160 <br><br> CAGGTATTGA GGCAATTCTT CGTAATCTCC AACCATGTCT GCCCTCTGCC ACGGCCGCAC 240 <br><br> CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA 300 <br><br> CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GTACGTAGAG GGCGGTGGAG 360 <br><br> GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CCCGTCTCCT CCGTCTAAAG 420 <br><br> AATCTCATAA ATCTCCAAAC ATGTAAGGTA CCGCATGCAA GCTT 464 <br><br> (2) INFORMATION FOR SEQ ID NO: 258: <br><br> (i) SEQUENCE CHARACTERISTICS: <br><br> (A) LENGTH: 419 base pairs <br><br> (B) TYPE: nucleic acid <br><br> (C) STRANDEDNESS: single <br><br> Printed from Mimosa 08:37:19 <br><br> WO 97/12985 PCMJS96/15774 <br><br> 506 <br><br> (D) TOPOLOGY: linear <br><br> (ii) MOLECULE TYPE: other nucleic acid <br><br> (A) DESCRIPTION: /desc = "DNA (synthetic)" <br><br> (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 258: <br><br> CCATGGCTAA CTGCTCTATA ATGATCGATG AAATTATACA TCACTTAAAG AGACCACCTG 60 <br><br> CACCTTTGCT GGACCCGAAC AACCTCAATG ACGAAGACGT CTCTATCCTG ATGGATCGAA 120 <br><br> ACCTTCGACT TCCAAACCTG GAGAGCTTCG TAAGGGCTGT CAAGAACTTA GAAAATGCAT 1B0 <br><br> CAGGTATTGA GGCAATTCTT CGTAATCTCC AACCATGTCT GCCCTCTGCC ACGGCCGCAC 240 <br><br> CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA <br><br> 300 <br><br> CGTTCTATCT GGTTACCCTT GAGCAAGCGC AGGAACAACA GTACGTAGAG GGCGGTGGAG 360 <br><br> GCTCCCCGGG TGGTGGTTCT GGCGGCGGCT CCAACATGTA AGGTACCGCA TGCAAGCTT 419 <br><br> Printed from Mimosa 08:37:19 <br><br></p> </div>

Claims (1)

  1. <div class="application article clearfix printTableText" id="claims"> <p lang="en"> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 507<br><br> WHAT IS CLAIMED IS:<br><br> 1 A substantially pure hematopoietic protein comprising; an amino acid sequence of the formula:<br><br> RI-L1-R2, R2-L1-R1, Rl"R2, or R2-R1<br><br> wherein Ri and R2 are independently selected from the group consisting of;<br><br> (I) A polypeptide comprising; a modified human G-CSF amino acid sequence of the formula:<br><br> 1 10<br><br> Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gin Ser Xaa<br><br> 20<br><br> Leu Leu Xaa Xaa Xaa Glu Gin Val Xaa Lys Xaa Gin Gly Xaa Gly<br><br> 30 40<br><br> Ala Xaa Leu Gin Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa<br><br> 50<br><br> Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly lie Pro Trp<br><br> 60 70<br><br> Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly<br><br> 80<br><br> Xaa Leu Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu<br><br> 90 100<br><br> Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu<br><br> 110<br><br> Xaa Thr Leu Gin Xaa Asp Val Ala Asp Phe Ala Xaa Thr lie Trp<br><br> 120 130<br><br> Gin Gin Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gin Pro Thr<br><br> 140<br><br> Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gin Xaa Xaa Ala<br><br> 150 160<br><br> Gly Gly Val Leu Val Ala Ser Xaa Leu Gin Xaa Phe Leu Xaa Xaa<br><br> INTELLECTUAL PROPERTY OFFICE OF N.Z.<br><br> 2 5 JAN 2001<br><br> RECEIVED)<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 508<br><br> 170<br><br> Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gin Pro (SEQ ID NO:l) wherein<br><br> Xaa at position 1 is Thr, Ser, Arg, Tyr or Gly;<br><br> Xaa at position 2 is Pro or Leu;<br><br> Xaa at position 3 is Leu, Arg, Tyr or Ser;<br><br> Xaa at position 13 is Phe, Ser, His, Thr or Pro;<br><br> Xaa at position 16 is Lys, Pro, Ser, Thr or His;<br><br> Xaa at position 17 is Cys, Ser, Gly, Ala, lie, Tyr or Arg; Xaa at position 18 is Leu, Thr, Pro, His, lie or Cys;<br><br> Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala;<br><br> Xaa at position 24 is lie, Pro, Tyr or Leu;<br><br> Xaa at position 27 is Asp, or Gly;<br><br> Xaa at position 30 is Ala, lie. Leu or Gly;<br><br> Xaa at position 34 is Lys or Ser;<br><br> Xaa at. position 36 is Cys or Ser Xaa at position 42 is Cys or Ser;<br><br> Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala,<br><br> Arg, Cys, or Leu;<br><br> Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His,<br><br> Trp, Gin, or Thr;<br><br> Xaa at position 46 is Glu, Arg, Phe, Arg, lie or Ala;<br><br> Xaa at position 47 is Leu or Thr;<br><br> Xaa at position 49 is Leu, Phe, Arg or Ser;<br><br> Xaa at position 50 is Leu, lie, His, Pro or Tyr;<br><br> Xaa at position 54 is Leu or His;<br><br> Xaa at position 64 is Cys or Ser;<br><br> Xaa at position 67 is Gin, Lys, Leu or Cys;<br><br> Xaa at position 70 is Gin, Pro, Leu, Arg or Ser;<br><br> Xaa at position 74 is Cys or Ser;<br><br> Xaa at position 104 is Asp, Gly or Val;<br><br> Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gin or Gly;<br><br> Xaa at position 115 is Thr, His, Leu or Ala;<br><br> Xaa at position 120 is Gin, Gly, Arg, Lys or His<br><br> Xaa at position 123 is Glu, Arg, Phe or Thr<br><br> Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gin or Glu;<br><br> Xaa at position 146 is Arg or Gin;<br><br> Xaa at position 147 is Arg or Gin;<br><br> Xaa at position 156 is His, Gly or Ser;<br><br> Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly;<br><br> Xaa at position 162 is Glu, Leu, Gly or Trp;<br><br> Xaa at position 163 is Val, Gly, Arg or Ala;<br><br> Xaa at position 169 is Arg, Ser, Leu, Arg or Cys;<br><br> Xaa at position 170 is His, Arg or Ser;<br><br> wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can optionally be deleted from said modified human G-CSF amino acid sequence; and<br><br> wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;<br><br> 5<br><br> 38-39<br><br> 62-63<br><br> 123-124<br><br> 39-40<br><br> 63-64<br><br> 124-125<br><br> 40-41<br><br> 64-65<br><br> 125-126<br><br> 10<br><br> 41-42<br><br> 65-66<br><br> 126-127<br><br> 42-43<br><br> 66-67<br><br> 128-129<br><br> 43-44<br><br> 67-68<br><br> 128-129<br><br> 45-46<br><br> 68-69<br><br> 129-130<br><br> 48-49<br><br> 69-70<br><br> 130-131<br><br> 15<br><br> 49-50<br><br> 70-71<br><br> 131-132<br><br> 52-53<br><br> 71-72<br><br> 132-133<br><br> 53-54<br><br> 91-92<br><br> 133-134<br><br> 54-55<br><br> 92-93<br><br> 134-135<br><br> 55-56<br><br> 93-94<br><br> 135-136<br><br> 20<br><br> 56-57<br><br> 94-95<br><br> 136-137<br><br> 57-58<br><br> 95-96<br><br> 137-138<br><br> 58-59<br><br> 96-97<br><br> 138-139<br><br> 59-60<br><br> 97-98<br><br> 139-140<br><br> 60-61<br><br> 98-99<br><br> 140-141<br><br> 25<br><br> 61-62<br><br> 99-100<br><br> 141-142<br><br> or 142-143<br><br> respectively;<br><br> (II) A polypeptide comprising;<br><br> a modified human IL<br><br> 30<br><br> amino acid sequence of the formula:<br><br> Ala Pro Met Thr Gin Thr Thr Ser Leu Lys Thr Ser Trp Val Asn 15 10 15<br><br> 35<br><br> Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 20 25 30<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 40 35 40 45<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 50 55 60<br><br> 510<br><br> 10<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 65 70 75<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 80 85 90<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 95 100 105<br><br> Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 110 115 120<br><br> Xaa Xaa Xaa Gin Gin Thr Thr Leu Ser Leu Ala lie Phe<br><br> 15 125 130 (SEQ ID NO:2)<br><br> wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gin, or Arg;<br><br> Xaa at position 18 is Asn, His, Leu, lie, Phe, Arg, or Gin;<br><br> Xaa at position 19 is Met, Phe, lie, Arg, Gly, Ala, or Cys<br><br> 20 Xaa at position 20 is lie, Cys, Gin, Glu, Arg, Pro, or Ala;<br><br> Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gin, Asn, Thr, Ser or Val;<br><br> Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gin, Leu, Val or Gly;<br><br> 25 Xaa at position 23 is lie, Val, Ala, Gly, Trp, Lys, Phe,<br><br> Leu, Ser, or Arg;<br><br> 30<br><br> 35<br><br> Xaa at position 24<br><br> is<br><br> He,<br><br> Gly,<br><br> Val,<br><br> Arg,<br><br> Ser,<br><br> Phe, or Leu;<br><br> Xaa at position 25<br><br> is<br><br> Thr,<br><br> His,<br><br> Gly,<br><br> Gin,'<br><br> Arg,<br><br> Pro, or Ala;<br><br> Xaa at position 26<br><br> is<br><br> His,<br><br> Thr,<br><br> Phe,<br><br> Gly,<br><br> Arg,<br><br> Ala, or Trp;<br><br> Xaa at position 27<br><br> is<br><br> Leu,<br><br> Gly,<br><br> Arg,<br><br> Thr,<br><br> Ser,<br><br> or Ala;<br><br> Xaa at position 28<br><br> is<br><br> Lys,<br><br> Arg,<br><br> Leu,<br><br> Gin,<br><br> Gly,<br><br> Pro, Val or Trp;<br><br> Xaa at position 29<br><br> is<br><br> Gin,<br><br> Asn,<br><br> Leu,<br><br> Pro,<br><br> Arg,<br><br> or Val;<br><br> Xaa at position 30<br><br> is<br><br> Pro,<br><br> His,<br><br> Thr,<br><br> Gly,<br><br> Asp,<br><br> Gin, Ser, Leu, or Lys;<br><br> Xaa at position 31<br><br> is<br><br> Pro,<br><br> Asp,<br><br> Gly,<br><br> Ala,<br><br> Arg,<br><br> Leu, or Gin;<br><br> Xaa at position 32<br><br> is<br><br> Leu,<br><br> Val,<br><br> Arg,<br><br> Gin,<br><br> Asn,<br><br> Gly, Ala, or Glu;<br><br> 511<br><br> Xaa at position 33 is Pro, Leu, Gin, Ala, Thr, or Glu;<br><br> Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gin, Thr,<br><br> Arg, Ala,'Phe, lie or Met;<br><br> Xaa at position 35 is.Leu, Ala, Gly, Asn, Pro, Gin, or Val; 5 Xaa at position 36 is Asp, Leu, or Val;<br><br> Xaa at position 37 is Phe, Ser, Pro, Trp, or lie;<br><br> Xaa at position 38 is Asn, or Ala;<br><br> Xaa at position 40 is Leu, Trp, or Arg;<br><br> Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; 10 Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu,<br><br> Val, Glu, Phe, Tyr, lie, Met or Ala;<br><br> Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys,<br><br> Gin, Arg, Thr, Gly or Ser;<br><br> Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, 15 Glu, Asn, Gin, Ala or Pro;<br><br> Xaa at position 45 is Gin, Pro, Phe, Val, Met, Leu, Thr, Lys,<br><br> Trp, Asp, Asn, Arg, Ser, Ala, lie, Glu or His;<br><br> Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gin, Lys, His, Ala, Tyr, lie, Val or Gly;<br><br> 20 Xaa at position 47 is lie, Gly, Val, Ser, Arg, Pro, or His;<br><br> Xaa at position 48 is Leu, Ser, Cys, Arg, lie, His, Phe, Glu,<br><br> Lys, Thr, Ala, Met, Val or Asn;<br><br> Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, 25 Ala, lie, Val, His, Phe, Met or Gin;<br><br> Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;<br><br> Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;<br><br> Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg, Asp, lie, Ser, Val, Thr, Gin, Asn, 30 Lys, His, Ala or Leu;<br><br> Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;<br><br> Xaa at position 56 is Pro, Gly, Cys, Ser, Gin, Glu, Arg, His,<br><br> Thr, Ala, Tyr, Phe, Leu, Val or Lys;<br><br> Xaa at position 57 is Asn or Gly;<br><br> 35 Xaa at position 58 is Leu, Ser, Asp, Arg, Gin, Val, or Cys;<br><br> 512<br><br> —<br><br> Xaa at position<br><br> 59<br><br> is<br><br> Glu Tyr,<br><br> His,<br><br> Leu,<br><br> Pro, or Arg;<br><br> Xaa at position<br><br> 60<br><br> is<br><br> Ala,<br><br> Ser,<br><br> Pro,<br><br> Tyr,<br><br> Asn, or Thr;<br><br> Xaa at position<br><br> 61<br><br> is<br><br> Phe,<br><br> Asn,<br><br> Glu,<br><br> Pro,<br><br> Lys, Arg,<br><br> or Ser;<br><br> Xaa at position<br><br> 62<br><br> is<br><br> Asn,<br><br> His,<br><br> Val,<br><br> Arg,<br><br> Pro, Thr,<br><br> Asp,<br><br> or lie;<br><br> 5<br><br> Xaa at position<br><br> 63<br><br> is<br><br> Arg,<br><br> Tyr,<br><br> Trp,<br><br> Lys,<br><br> Ser, His,<br><br> Pro,<br><br> or Val;<br><br> Xaa at position<br><br> 64<br><br> is<br><br> Ala,<br><br> Asn,<br><br> Pro,<br><br> Ser,<br><br> or Lys;<br><br> Xaa at position<br><br> 65<br><br> is<br><br> Val,<br><br> Thr,<br><br> Pro,<br><br> His,<br><br> Leu, Phe,<br><br> or Ser;<br><br> Xaa at position<br><br> 66<br><br> is<br><br> Lys,<br><br> He,<br><br> Arg,<br><br> Val,<br><br> Asn, Glu,<br><br> or Ser;<br><br> Xaa at position<br><br> 67<br><br> is<br><br> Ser,<br><br> Ala,<br><br> Phe,<br><br> Val,<br><br> Gly, Asn,<br><br> lie,<br><br> Pro, or<br><br> His;<br><br> 10<br><br> Xaa at position<br><br> 68<br><br> is<br><br> Leu,<br><br> Val,<br><br> Trp,<br><br> Ser,<br><br> lie, Phe,<br><br> Thr,<br><br> or His;<br><br> Xaa at position<br><br> 69<br><br> is<br><br> Gin,<br><br> Ala,<br><br> Pro,<br><br> Thr,<br><br> Glu, Arg,<br><br> Trp,<br><br> Gly, or<br><br> Leu;<br><br> Xaa at position<br><br> 70<br><br> is<br><br> Asn,<br><br> Leu,<br><br> Val,<br><br> Trp,<br><br> Pro, or Ala;<br><br> Xaa at position<br><br> 71<br><br> is<br><br> Ala,<br><br> Met,<br><br> Leu,<br><br> Pro,<br><br> Arg, Glu,<br><br> Thr,<br><br> Gin,<br><br> Trp, or Asn ;<br><br> 15<br><br> Xaa at position 72<br><br> is<br><br> Ser,<br><br> Glu,<br><br> Met,<br><br> Ala,<br><br> His, Asn,<br><br> Arg,<br><br> or Asp;<br><br> Xaa at position<br><br> 73<br><br> is<br><br> Ala,<br><br> Glu,<br><br> Asp,<br><br> Leu,<br><br> Ser, Gly,<br><br> Thr,<br><br> or Arg;<br><br> Xaa at position 74<br><br> is lie<br><br> , Met<br><br> , Thr<br><br> , Pro<br><br> , Arg, Gly<br><br> , Ala<br><br> /<br><br> Xaa at position 75<br><br> is<br><br> Glu,<br><br> Lys,<br><br> Gly,<br><br> Asp,<br><br> Pro, Trp,<br><br> Arg,<br><br> Ser,<br><br> Gin, or Leu;<br><br> 20<br><br> Xaa at position<br><br> 76<br><br> is<br><br> Ser,<br><br> Val,<br><br> Ala,<br><br> Asn,<br><br> Trp, Glu,<br><br> Pro,<br><br> Gly, or<br><br> Asp;<br><br> Xaa at position<br><br> 77<br><br> is lie.<br><br> Ser,<br><br> Arg,<br><br> Thr,<br><br> or Leu;<br><br> Xaa at position<br><br> 78<br><br> is<br><br> Leu,<br><br> Ala,<br><br> Ser,<br><br> Glu,<br><br> Phe, Gly,<br><br> or Arg;<br><br> Xaa at position<br><br> 79<br><br> is<br><br> Lys,<br><br> Thr,<br><br> Asn,<br><br> Met,<br><br> Arg, lie.<br><br> Gly,<br><br> or Asp;<br><br> Xaa at position<br><br> 80<br><br> is<br><br> Asn,<br><br> Trp,<br><br> Val,<br><br> Gly,<br><br> Thr, Leu,<br><br> Glu,<br><br> or Arg;<br><br> 25<br><br> Xaa at position<br><br> 81<br><br> is<br><br> Leu,<br><br> Gin,<br><br> Gly,<br><br> Ala,<br><br> Trp, Arg,<br><br> Val,<br><br> or Lys;<br><br> Xaa at position<br><br> 82<br><br> is<br><br> Leu,<br><br> Gin,<br><br> Lys,<br><br> Trp,<br><br> Arg, Asp,<br><br> Glu,<br><br> Asn,<br><br> His, Thr,<br><br> Ser, Ala,<br><br> Tyr,<br><br> Phe,<br><br> He,<br><br> Met or Val<br><br> /<br><br> Xaa at position<br><br> 83<br><br> is<br><br> Pro,<br><br> Ala,<br><br> Thr,<br><br> Trp;<br><br> Arg, or Met;<br><br> Xaa at position<br><br> 84<br><br> is<br><br> Cys,<br><br> Glu,<br><br> Gly,<br><br> Arg,<br><br> Met, or Val;<br><br> 30<br><br> Xaa at position<br><br> 85<br><br> is<br><br> Leu,<br><br> Asn,<br><br> Val,<br><br> or Gin;<br><br> Xaa at position<br><br> 86<br><br> is<br><br> Pro,<br><br> Cys,<br><br> Arg,<br><br> Ala,<br><br> or Lys;<br><br> Xaa at position<br><br> 87<br><br> is<br><br> Leu,<br><br> Ser,<br><br> Trp,<br><br> or Gly;<br><br> Xaa at position<br><br> 88<br><br> is<br><br> Ala,<br><br> Lys,<br><br> Arg,<br><br> Val,<br><br> or Trp;<br><br> Xaa at position<br><br> 89<br><br> is<br><br> Thr,<br><br> Asp,<br><br> Cys,<br><br> Leu,<br><br> Val, Glu,<br><br> His,<br><br> Asn, or<br><br> Ser;<br><br> 35<br><br> Xaa at position<br><br> 90<br><br> is<br><br> Ala,<br><br> Pro,<br><br> Ser,<br><br> Thr,<br><br> Gly, Asp,<br><br> lie.<br><br> or Met;<br><br> 513<br><br> Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;<br><br> Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, lie or<br><br> Leu ;<br><br> Xaa at position 93 is.Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;<br><br> 5 Xaa at position 94 is Arg, lie, Ser, Glu, Leu, Val, Gin, Lys, His,<br><br> Ala, or Pro;<br><br> Xaa at position 95 is His, Gin, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, lie, or Tyr;<br><br> Xaa at position 96 is Pro, Lys, Tyr, Gly, lie, or Thr;<br><br> 10 Xaa at position 97 is lie, Val, Lys, Ala, or Asn;<br><br> Xaa at position 98 is His, lie, Asn, Leu, Asp, Ala, Thr,<br><br> Glu, Gin, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;<br><br> Xaa at position 99 is lie. Leu, Arg, Asp, Val, Pro, Gin,<br><br> Gly, Ser, Phe, or His;<br><br> 15 Xaa at position 100 is Lys, Tyr, Leu, His, Arg, lie, Ser, Gin, or Pro;<br><br> Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val,<br><br> Tyr, Glu, Asn, Ser, Ala, Gly, lie. Leu, or Gin;<br><br> Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;<br><br> Xaa at position 103 is Asp, or Ser;<br><br> 20 Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu,<br><br> Gin, Lys, Ala, Phe, or Gly;<br><br> Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gin, Tyr,<br><br> Leu, Lys, lie,<br><br> Asp, or His r<br><br> Xaa at position 106<br><br> is<br><br> Glu,<br><br> Ser,<br><br> Ala,<br><br> Lys,<br><br> 25<br><br> Xaa at position 108<br><br> is<br><br> Arg,<br><br> Lys,<br><br> Asp,<br><br> Leu,<br><br> Ala or Pro;<br><br> Xaa at position 109<br><br> is<br><br> Arg,<br><br> Thr,<br><br> Pro,<br><br> Glu,<br><br> Xaa at position 110<br><br> is<br><br> Lys,<br><br> Ala,<br><br> Asn,<br><br> Thr',<br><br> Ser, or Trp;<br><br> 30<br><br> Xaa at position 111<br><br> is<br><br> Leu,<br><br> lie,<br><br> Arg,<br><br> Asp,<br><br> Xaa at position 112<br><br> is<br><br> Thr,<br><br> Val,<br><br> Gin,<br><br> Tyr,<br><br> Xaa at position 113<br><br> is<br><br> Phe,<br><br> Ser,<br><br> Cys,<br><br> His,<br><br> Lys, Leu, lie, Val or Asn;<br><br> Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; 35 Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr,<br><br> 514 -<br><br> Trp, or Met;<br><br> Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp,'Ser, Asn, His, Ala, Tyr, Phe, Gin, or lie;<br><br> Ser, Asn, lie, Trp, Lys, or Pro;<br><br> Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;<br><br> Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;<br><br> Ala, Pro, Leu, His, Val, or Gin;<br><br> Ser, lie, Asn, Pro, Lys, Asp, or Gly;<br><br> Ser, Met, Trp, Arg, Phe, Pro, His,<br><br> Met, Glu, His, Ser, Pro, Tyr, or Leu;<br><br> wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human IL-3 amino acid sequence; wherein from 0 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; and wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) / capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;<br><br> 26-27<br><br> 49-50<br><br> 83-84<br><br> 27-28<br><br> 50-51<br><br> 84-85<br><br> 28-29<br><br> 51-52<br><br> 85-86<br><br> 29-30<br><br> 52-53<br><br> 86-87<br><br> 30-31<br><br> 53-54<br><br> 87-88<br><br> 31-32<br><br> 54-55<br><br> 88-89<br><br> 32-33<br><br> 64-65<br><br> 89-90<br><br> 33-34<br><br> 65-66<br><br> 90-91<br><br> 34-35<br><br> 66-67<br><br> 91-92<br><br> 35-36<br><br> 67-68<br><br> 92-93<br><br> 36-37<br><br> 68-69<br><br> 97-98<br><br> 37-38<br><br> 69-70<br><br> 98-99<br><br> 38-39<br><br> 70-71<br><br> 99-100<br><br> 39-40<br><br> 71-72<br><br> 100-101<br><br> 40-41<br><br> 72-73<br><br> 101-102<br><br> Xaa at position 117 is Thr,<br><br> Xaa at position 118 is Leu,<br><br> Xaa at position 119 is Glu,<br><br> Xaa at position 120 is Asn,<br><br> Xaa at position 121 is Ala,<br><br> Xaa at position 122 is Gin,<br><br> lie, Tyr, or Cys;<br><br> Xaa at position 123 is Ala,<br><br> 515<br><br> 41-42 82-83 102-103<br><br> or 103-104 respectively;<br><br> (III) A polypeptide comprising; a modified human c-mpl ligand amino acid sequence of the formula:<br><br> 5<br><br> SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer 15 10 15<br><br> HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 10 20 25 30 35<br><br> ValLeuLeuProAlaValAspPheSerLeuGlyGluTroLysThrGlnMetGluGlu 40 45 50 55<br><br> 15 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla<br><br> 60 65 70 75<br><br> 20<br><br> AlaArgGlyGinLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95<br><br> GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110<br><br> XaaGlyArgThrThrAlaHisLysAspProAsnAlallePheLeuSerPheGlnHis 25 115 120 125 130<br><br> LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150<br><br> 30 Arg (SEQ ID NO:256)<br><br> 153<br><br> wherein;<br><br> 35 Xaa at position 112 is deleted or Leu, Ala, Val, lie, Pro,<br><br> Phe, Trp, or Met;<br><br> Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu,<br><br> lie, Trp, or Met;<br><br> Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, 40 lie, Trp, or Met;<br><br> Xaa at position 115 is deleted or Gin, Gly, Ser, Thr, Tyr,<br><br> 516<br><br> or Asn; and wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;<br><br> 26-27<br><br> 27-28<br><br> 28-29<br><br> 29-30<br><br> 30-31<br><br> 32-33<br><br> 33-34<br><br> 34-35<br><br> 36-37<br><br> 37-38<br><br> 38-39<br><br> 40-41<br><br> 41-42<br><br> 42-43<br><br> 43-44<br><br> 44-45<br><br> 46-47<br><br> 47-48<br><br> 48-49 50-51<br><br> 51-52<br><br> 52-53<br><br> 53-54<br><br> 54-55<br><br> 55-56<br><br> 56-57<br><br> 57-58<br><br> 58-59<br><br> 59-60<br><br> 78-79<br><br> 79-80<br><br> 80-81<br><br> 81-82<br><br> 82-83<br><br> 83-84<br><br> 84-85<br><br> 85-86<br><br> 86-87<br><br> 87-88<br><br> 88-89<br><br> 108-109<br><br> 109-110<br><br> 110-111<br><br> 111-112<br><br> 112-113<br><br> 113-114<br><br> 114-115<br><br> 115-116<br><br> 116-117<br><br> 117-118<br><br> 118-119<br><br> 119-120<br><br> 120-121<br><br> 121-122<br><br> 122-123<br><br> 123-124<br><br> 124-125<br><br> 125-126<br><br> 126-127<br><br> or 127-128 respectively ;<br><br> 10 (IV) A polypeptide comprising; a modified human IL-3<br><br> amino acid sequence of the formula:<br><br> 15<br><br> Ala Pro Met Thr Gin Thr Thr Ser Leu Lys Thr Ser Trp Val Asn 15 10 15<br><br> Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 20 25 30<br><br> 20<br><br> Xaa Xaa Xaa<br><br> Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45<br><br> 517<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 50 55 60<br><br> 5 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 65 70 75<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 80 85 90<br><br> 10<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 95 100 105<br><br> Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 15 110 115 120<br><br> Xaa Xaa Xaa Gin Gin Thr Thr Leu Ser Leu Ala lie Phe<br><br> 125 130 (SEQ ID NO:2)<br><br> 20 wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gin, or Arg;<br><br> Xaa at position<br><br> 18<br><br> is<br><br> Asn,<br><br> His,<br><br> Leu,<br><br> lie,<br><br> Phe,<br><br> Arg,<br><br> or Gin;<br><br> Xaa at position<br><br> 19<br><br> is<br><br> Met,<br><br> Phe,<br><br> lie,<br><br> Arg,<br><br> Gly,<br><br> Ala,<br><br> or Cys;<br><br> Xaa at position<br><br> 20<br><br> is lie,<br><br> Cys,<br><br> Gin,<br><br> Glu,<br><br> Arg,<br><br> Pro,<br><br> or Ala;<br><br> Xaa at position<br><br> 21<br><br> is<br><br> Asp,<br><br> Phe,<br><br> Lys,<br><br> Arg,<br><br> Ala,<br><br> Gly,<br><br> Glu, Gin, Asn,<br><br> 25 Thr, Ser or Val;<br><br> Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gin,<br><br> Leu, Val or Gly;<br><br> Xaa at position 23 is lie, Val, Ala, Gly, Trp, Lys, Phe,<br><br> Leu, Ser, or Arg;<br><br> 30<br><br> Xaa at position<br><br> 24<br><br> is lie,<br><br> Gly,<br><br> Val,<br><br> Arg,<br><br> Ser,<br><br> Phe, or<br><br> Leu<br><br> Xaa at position<br><br> 25<br><br> is<br><br> Thr,<br><br> His,<br><br> Gly,<br><br> Gin,<br><br> Arg,<br><br> Pro, or<br><br> Ala<br><br> Xaa at position<br><br> 26<br><br> is<br><br> His,<br><br> Thr,<br><br> Phe,<br><br> Gly,<br><br> Arg,<br><br> Ala, or<br><br> Trp<br><br> Xaa at position<br><br> 27<br><br> is<br><br> Leu,<br><br> Gly,<br><br> Arg,<br><br> Thr,<br><br> Ser,<br><br> or Ala;<br><br> Xaa at position<br><br> 28<br><br> is<br><br> Lys,<br><br> Arg,<br><br> Leu,<br><br> Gin,<br><br> Gly,<br><br> Pro, Val or<br><br> 35<br><br> Xaa at position<br><br> 29<br><br> is<br><br> Gin,<br><br> Asn,<br><br> Leu,<br><br> Pro,<br><br> Arg,<br><br> or Val;<br><br> 518<br><br> Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gin, Ser, Leu, or Lys;<br><br> Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gin;<br><br> Xaa at position 32 is Leu, Val, Arg, Gin, Asn, Gly, Ala, or Glu;<br><br> Xaa at position 33 is Pro, Leu, Gin, Ala, Thr, or Glu;<br><br> 5 Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gin, Thr, Arg, Ala, Phe, lie or Met;<br><br> Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gin, or Val;<br><br> Xaa at position 36 is Asp, Leu, or Val;<br><br> Xaa at position 37 is Phe, Ser, Pro, Trp, or lie;<br><br> 10 Xaa at position 38,is Asn, or Ala;<br><br> Xaa at position 40 is Leu, Trp, or Arg;<br><br> Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;<br><br> Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, lie. Met or Ala;<br><br> 15 Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gin, Arg, Thr, Gly or Ser;<br><br> Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp,<br><br> Glu, Asn, Gin, Ala or Pro;<br><br> Xaa at position 45 is Gin, Pro, Phe, Val, Met, Leu, Thr, Lys, 20 Trp, Asp, Asn, Arg, Ser, Ala, lie, Glu or His;<br><br> Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gin,<br><br> Lys, His, Ala, Tyi, lie, Val or Gly;<br><br> Xaa at position 47 is lie, Gly, Val, Ser, Arg, Pro, or His;<br><br> Xaa at position 48 is Leu, Ser, Cys, Arg, lie, His, Phe, Glu, 25 Lys, Thr, Ala, Met, Val or Asn;<br><br> Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;<br><br> Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser,<br><br> Ala, lie, Val, His, Phe, Met or Gin;<br><br> Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;<br><br> 30 Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;<br><br> Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;<br><br> Xaa at position 54 is Arg, Asp, lie, Ser, Val, Thr, Gin, Asn,<br><br> Lys, His, Ala or Leu;<br><br> Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;<br><br> 35 Xaa at position 56 is Pro, Gly, Cys, Ser, Gin, Glu, Arg, His,<br><br> 519<br><br> Thr, Ala, Tyr, Phe, Leu, Val or Lys;<br><br> 10<br><br> 15<br><br> Xaa at position<br><br> 57<br><br> is<br><br> Asn or Gly;<br><br> Xaa at position<br><br> 58<br><br> is<br><br> Leu,<br><br> Ser,<br><br> Asp,<br><br> Arg,<br><br> Gin,<br><br> Val,<br><br> or Cys;<br><br> Xaa at position<br><br> 59<br><br> is<br><br> Glu<br><br> Tyr,<br><br> His,<br><br> Leu,<br><br> Pro,<br><br> or Arg;<br><br> Xaa at position<br><br> 60<br><br> is<br><br> Ala,<br><br> Ser,<br><br> Pro,<br><br> Tyr,<br><br> Asn,<br><br> or Thr;<br><br> Xaa at position<br><br> 61<br><br> is<br><br> Phe,<br><br> Asn,<br><br> Glu,<br><br> Pro,<br><br> Lys,<br><br> Arg,<br><br> or Ser;<br><br> Xaa at position<br><br> 62<br><br> is<br><br> Asn,<br><br> His,<br><br> Val,<br><br> Arg,<br><br> Pro,<br><br> Thr,<br><br> Asp, or lie;<br><br> Xaa at position<br><br> 63<br><br> is<br><br> Arg,<br><br> Tyr,<br><br> Trp,<br><br> Lys,<br><br> Ser,<br><br> His,<br><br> Pro, or Val ,-<br><br> Xaa at position<br><br> 64<br><br> is<br><br> Ala,<br><br> Asn,<br><br> Pro,<br><br> Ser,<br><br> or Lys;<br><br> Xaa at position<br><br> 65.<br><br> is<br><br> Val,<br><br> Thr,<br><br> Pro,<br><br> His,<br><br> Leu,<br><br> Phe,<br><br> or Ser;<br><br> Xaa at position<br><br> 66<br><br> is<br><br> Lys,<br><br> lie.<br><br> Arg,<br><br> Val,<br><br> Asn,<br><br> Glu,<br><br> or Ser;<br><br> Xaa at position<br><br> 67<br><br> is<br><br> Ser,<br><br> Ala,<br><br> Phe,<br><br> Val,<br><br> Gly,<br><br> Asn,<br><br> lie. Pro, or<br><br> Xaa at position<br><br> 68<br><br> is<br><br> Leu,<br><br> Val,<br><br> Trp,<br><br> Ser,<br><br> lie,<br><br> Phe,<br><br> Thr, or His;<br><br> Xaa at position<br><br> 69<br><br> is<br><br> Gin,<br><br> ■ Ala,<br><br> Pro,<br><br> Thr,<br><br> Glu,<br><br> Arg,<br><br> Trp, Gly, or<br><br> Xaa at position<br><br> 70<br><br> is<br><br> Asn,<br><br> Leu,<br><br> Val,<br><br> Trp,<br><br> Pro,<br><br> or Ala;<br><br> Xaa at position<br><br> 71<br><br> is<br><br> Ala,<br><br> Met,<br><br> Leu,<br><br> Pro,<br><br> Arg,<br><br> Glu,<br><br> Thr, Gin,<br><br> Trp, or Asn;<br><br> Xaa at position<br><br> 72<br><br> is<br><br> Ser,<br><br> Glu,<br><br> Met,<br><br> Ala,<br><br> His,<br><br> Asn,<br><br> Arg,<br><br> or Asp;<br><br> Xaa at position 73<br><br> is<br><br> Ala,<br><br> Glu,<br><br> Asp,<br><br> Leu,<br><br> Ser,<br><br> Gly,<br><br> Thr,<br><br> or Arg;<br><br> 20<br><br> Xaa at position<br><br> 74<br><br> is lie,<br><br> Met,<br><br> Thr,<br><br> Pro,<br><br> Arg,<br><br> Gly,<br><br> Ala;<br><br> Xaa at position 75 Gin, or Leu;<br><br> is<br><br> Glu,<br><br> Lys,<br><br> Gly,<br><br> Asp,<br><br> Pro,<br><br> Trp,<br><br> Arg,<br><br> Ser,<br><br> Xaa at position<br><br> 76<br><br> is<br><br> Ser,<br><br> Val,<br><br> Ala,<br><br> Asn,<br><br> Trp,<br><br> Glu,<br><br> Pro,<br><br> Gly, or<br><br> Xaa at position<br><br> 77<br><br> is lie,<br><br> Ser,<br><br> Arg,<br><br> Thr,<br><br> or Leu;<br><br> 25<br><br> Xaa at position<br><br> 78<br><br> is<br><br> Leu,<br><br> Ala,<br><br> Ser,<br><br> Glu,<br><br> Phe,<br><br> Gly,<br><br> or Arg;<br><br> Xaa at position<br><br> 79<br><br> is<br><br> Lys,<br><br> Thr,<br><br> Asn,<br><br> Met,<br><br> Arg,<br><br> lie,<br><br> Gly,<br><br> or Asp;<br><br> Xaa at position<br><br> 80<br><br> is<br><br> Asn,<br><br> Trp,<br><br> Val,<br><br> Gly,<br><br> Thr,<br><br> Leu,<br><br> Glu,<br><br> or Arg;<br><br> Xaa at position<br><br> 81<br><br> is<br><br> Leu,<br><br> Gin,<br><br> Gly,<br><br> Ala,<br><br> Trp,<br><br> Arg,<br><br> Val,<br><br> or Lys;<br><br> Xaa at position<br><br> 82<br><br> is<br><br> Leu,<br><br> Gin,<br><br> Lys,<br><br> Trp,<br><br> Arg,<br><br> Asp,<br><br> Glu,<br><br> Asn,<br><br> 30<br><br> His, Thr,<br><br> Ser, Ala,<br><br> Tyr,<br><br> Phe,<br><br> He,<br><br> Met or Val;<br><br> Xaa at position<br><br> 83<br><br> is<br><br> Pro,<br><br> Ala,<br><br> Thr,<br><br> Trp,<br><br> Arg,<br><br> or Met;<br><br> Xaa at position<br><br> 84<br><br> is<br><br> Cys,<br><br> Glu,<br><br> Gly,<br><br> Arg,<br><br> Met,<br><br> or Val;<br><br> Xaa at position<br><br> 85<br><br> is<br><br> Leu,<br><br> Asn,<br><br> Val,<br><br> or Gin;<br><br> Xaa at position<br><br> 86<br><br> is<br><br> Pro,<br><br> Cys,<br><br> Arg,<br><br> Ala,<br><br> or Lys;<br><br> 35<br><br> Xaa at position<br><br> 87<br><br> is<br><br> Leu,<br><br> Ser,<br><br> Trp,<br><br> or Gly;<br><br> 520<br><br> Xaa at position<br><br> 88<br><br> is<br><br> Ala,<br><br> Lys,<br><br> Arg,<br><br> Val,<br><br> or Trp;<br><br> Xaa at position<br><br> '89<br><br> is<br><br> Thr,<br><br> Asp,<br><br> Cys,<br><br> Leu,<br><br> Val,<br><br> Glu,<br><br> His,<br><br> Asn, or Ser;<br><br> Xaa at position<br><br> 90.<br><br> is<br><br> Ala,<br><br> Pro,<br><br> Ser,<br><br> Thr,<br><br> Gly,<br><br> Asp,:<br><br> .lie,<br><br> or Met;<br><br> Xaa at position<br><br> 91<br><br> is<br><br> Ala,<br><br> Pro,<br><br> Ser,<br><br> Thr,<br><br> Phe,<br><br> Leu,<br><br> Asp,<br><br> or His;<br><br> Xaa at position<br><br> 92<br><br> is<br><br> Pro,<br><br> Phe,<br><br> Arg,<br><br> Ser,<br><br> Lys,<br><br> His,<br><br> Ala,<br><br> Gly, lie or<br><br> Leu;<br><br> Xaa at position<br><br> 93<br><br> is<br><br> Thr,<br><br> Asp,<br><br> Ser,<br><br> Asn,<br><br> Pro,<br><br> Ala,<br><br> Leu,<br><br> or Arg;<br><br> Xaa at position<br><br> 94<br><br> is<br><br> Arg,<br><br> lie,<br><br> Ser,<br><br> Glu,<br><br> Leu,<br><br> Val,<br><br> Gin,<br><br> Lys, His,<br><br> Ala, or Pro;<br><br> Xaa at position<br><br> 95<br><br> is<br><br> His,<br><br> Gin,<br><br> Pro,<br><br> Arg,<br><br> Val,<br><br> Leu,<br><br> Gly,<br><br> Thr, Asn,<br><br> Lys, Ser, Ala, Trp, Phe, lie, or Tyr;<br><br> Xaa at position 96 is Pro, Lys, Tyr, Gly, lie, or Thr;<br><br> Xaa at position 97 is lie, Val, Lys, Ala, or Asn;<br><br> Xaa at position 98 is His, lie, Asn, Leu, Asp, Ala, Thr, 15 Glu, Gin, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;<br><br> Xaa at position 99 is lie, Leu, Arg, Asp, Val, Pro, Gin,<br><br> Gly, Ser, Phe, or His;<br><br> Xaa at position 100 is Lys, Tyr, Leu, His, Arg, lie, Ser, Gin, or Pro; Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, 20 Tyr, Glu, Asn, Ser, Ala, Gly, lie, Leu, or Gin;<br><br> Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;<br><br> Xaa at position 103 is Asp, or Ser;<br><br> Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gin, Lys, Ala, Phe, or Gly;<br><br> 25 Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gin, Tyr,<br><br> Leu, Lys, lie, Asp, or His;<br><br> Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, lie, Gly, or Pro; Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, lie, Gin, His, Ser, Ala or Pro;:<br><br> 30 Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;<br><br> Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gin, His, Glu, Ser, or Trp;<br><br> Xaa at position 111 is Leu, lie, Arg, Asp, or Met;<br><br> Xaa at position 112 is Thr, Val, Gin, Tyr, Glu, His, Ser, or Phe; 35 Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp,<br><br> 521<br><br> Lys, Leu, lie, Val or Asn;<br><br> Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;<br><br> Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, •Trp, or Met;<br><br> Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu,<br><br> Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gin, or lie;<br><br> Xaa at position 117 is Thr, Ser, Asn, lie, Trp, Lys, or Pro;<br><br> Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;<br><br> Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;<br><br> Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gin;<br><br> Xaa at position 121 is Ala, Ser, lie, Asn, Pro, Lys, Asp, or Gly;<br><br> Xaa at position 122 is Gin, Ser, Met, Trp, Arg, Phe, Pro, His,<br><br> lie, Tyr, or Cys;<br><br> Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;<br><br> wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human IL-3 amino acid sequence; and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; and<br><br> (V) a colony stimulating factor,.<br><br> and wherein Li is a linker capable of linking Ri to R2;<br><br> with the proviso that at least Ri or R2 is selected from the polypeptide of formula (I) , (II), or (III); and said hematopoietic protein can optionally be immediately preceded by (methionine-1), (alanine-1) or (methionine-^, alanine-1).<br><br> 2. The hematopoietic protein as recited in claim 1 wherein the polypeptide of (IV) is selected from the from the group consisting of;<br><br> 5<br><br> Ala<br><br> Asn<br><br> Cys<br><br> Ser lie<br><br> Met lie Asp Glu lie lie<br><br> His<br><br> His<br><br> Leu<br><br> Lys<br><br> Arg<br><br> Pro<br><br> Pro<br><br> Ala<br><br> Pro<br><br> Leu<br><br> Leu<br><br> Asp<br><br> Pro<br><br> Asn<br><br> Asn<br><br> Leu<br><br> Asn<br><br> Ala<br><br> Glu<br><br> 10<br><br> Asp Glu<br><br> Val Ser<br><br> Asp Phe lie Val<br><br> Leu Arg<br><br> Met Ala<br><br> Glu Arg Asn Val Lys Asn<br><br> Leu Leu<br><br> Arg Glu<br><br> Leu Asn<br><br> Pro Ala<br><br> Asn Ser<br><br> Leu Gly<br><br> lie<br><br> Glu<br><br> Ala lie<br><br> Leu<br><br> Arg<br><br> Asn<br><br> Leu<br><br> Gin<br><br> Pro<br><br> Cys<br><br> Leu<br><br> Pro<br><br> Ser<br><br> Ala<br><br> 15<br><br> Thr<br><br> Ala<br><br> Ala<br><br> Pro<br><br> Ser<br><br> Arg<br><br> His<br><br> Pro lie lie lie<br><br> Lys<br><br> Ala<br><br> Gly<br><br> Asp<br><br> Trp<br><br> Gin<br><br> Glu<br><br> Phe<br><br> Arg<br><br> Glu<br><br> Lys<br><br> Leu<br><br> Thr<br><br> Phe<br><br> Tyr<br><br> Leu<br><br> Val<br><br> Thr<br><br> Leu<br><br> 20<br><br> Glu<br><br> Gin<br><br> Ala<br><br> Gin<br><br> Glu<br><br> Gin<br><br> Gin<br><br> (SEQ ID<br><br> NO:225) ;<br><br> t<br><br> Ala<br><br> Asn<br><br> Cys<br><br> 3er lie<br><br> Met lie<br><br> Asp<br><br> Glu lie lie<br><br> His<br><br> His<br><br> Leu<br><br> Lys<br><br> 25<br><br> Arg Asp<br><br> Pro Met<br><br> Pro Asp<br><br> Asn lie<br><br> Pro Leu<br><br> Leu Met<br><br> Leu Glu<br><br> Asp Arg<br><br> Pro Asn<br><br> Asn Leu<br><br> Asn Arg<br><br> Leu Thr<br><br> Asn Pro<br><br> Ser Asn<br><br> Glu Leu<br><br> Leu<br><br> Ala<br><br> Phe<br><br> Val<br><br> Arg<br><br> Ala<br><br> Val<br><br> Lys<br><br> His<br><br> Leu<br><br> Glu<br><br> Asn<br><br> Ala<br><br> Ser<br><br> Gly<br><br> 30<br><br> lie<br><br> Glu<br><br> Ala lie<br><br> Leu<br><br> Arg<br><br> Asn<br><br> Leu<br><br> Gin<br><br> Pro<br><br> Cys<br><br> Leu<br><br> Pro<br><br> Ser<br><br> Ala<br><br> Thr<br><br> Ala<br><br> Ala<br><br> Pro<br><br> Ser<br><br> Arg<br><br> His<br><br> Pro lie lie lie<br><br> Lys<br><br> Ala<br><br> Gly<br><br> Asp<br><br> 35<br><br> Trp Glu<br><br> Gin Gin<br><br> Glu Ala<br><br> Phe Gin<br><br> Arg Glu<br><br> Glu Gin<br><br> Lys Gin<br><br> Leu Thr (SEQ ID<br><br> Phe Tyr NO:226)<br><br> Leu<br><br> /<br><br> Val<br><br> Thr<br><br> Leu<br><br> 40<br><br> Ala Val<br><br> Asn Pro<br><br> Cys Pro<br><br> Ser Ala lie Pro<br><br> Met Leu lie Leu<br><br> Asp Asp<br><br> Glu Ser lie Asn lie Asn<br><br> His Leu<br><br> His Asn<br><br> Leu Ser<br><br> Lys Glu<br><br> Asp<br><br> Met<br><br> Asp lie<br><br> Leu<br><br> Met<br><br> Glu<br><br> Arg<br><br> Asn<br><br> Leu<br><br> Arg<br><br> Leu<br><br> Pro<br><br> Asn<br><br> Leu<br><br> 45<br><br> Leu<br><br> Ala<br><br> Phe<br><br> Val<br><br> Arg<br><br> Ala<br><br> Val<br><br> Lys<br><br> Asn<br><br> Leu<br><br> Glu<br><br> Asn<br><br> Ala<br><br> Ser<br><br> Gly<br><br> lie<br><br> Glu<br><br> Ala lie lieu<br><br> Arg<br><br> Asn<br><br> Leu<br><br> Gin<br><br> Pro<br><br> Cys<br><br> Leu<br><br> Pro<br><br> Ser<br><br> Ala<br><br> 50<br><br> Thr Trp<br><br> Ala Gin<br><br> Ala Glu<br><br> Pro Phe<br><br> Ser Arg<br><br> Arg Glu<br><br> His Lys<br><br> Pro Leu lie Thr lie Phe lie Lys Tyr Leu<br><br> Ala Val<br><br> Gly Thr<br><br> Asp Leu<br><br> Glu<br><br> Gin<br><br> Ala<br><br> Gin<br><br> Glu<br><br> Gin<br><br> Gin<br><br> (SEQ ID<br><br> NO:<br><br> 227)<br><br> ; and<br><br> 55<br><br> w tJ w 523<br><br> Asn<br><br> Cys<br><br> Ser lie<br><br> Met lie<br><br> Asp<br><br> Glu lie lie<br><br> His<br><br> His<br><br> Leu<br><br> Lys<br><br> Arg<br><br> Pro<br><br> Pro<br><br> Ala<br><br> Pro<br><br> Leu<br><br> Leu<br><br> Asp<br><br> Pro<br><br> Asn<br><br> Asn<br><br> Leu<br><br> Asn<br><br> Asp<br><br> Glu<br><br> Asp<br><br> Val<br><br> Ser lie<br><br> Leu<br><br> Met<br><br> Asp<br><br> Arg<br><br> Asn<br><br> Leu<br><br> Arg<br><br> Leu<br><br> Pro<br><br> Asn<br><br> Leu<br><br> Glu<br><br> Ser<br><br> Phe<br><br> Val<br><br> Arg<br><br> Ala<br><br> Val<br><br> Lys<br><br> Asn<br><br> Leu<br><br> Glu<br><br> Asn<br><br> Ala<br><br> Ser<br><br> Gly lie<br><br> Glu<br><br> Ala lie<br><br> Leu<br><br> Arg<br><br> Asn<br><br> Leu<br><br> Gin<br><br> Pro<br><br> Cys<br><br> Leu<br><br> Pro<br><br> Ser<br><br> Ala<br><br> Thr<br><br> Ala<br><br> Ala<br><br> Pro<br><br> Ser<br><br> Arg<br><br> His<br><br> Pro lie lie lie<br><br> Lys<br><br> Ala Gly<br><br> Asp<br><br> Trp<br><br> Gin<br><br> Glu<br><br> Phe<br><br> Arg<br><br> Glu<br><br> Lys<br><br> Leu<br><br> Thr<br><br> Phe<br><br> Tyr<br><br> Leu<br><br> Val<br><br> Thr<br><br> Leu<br><br> Glu<br><br> Gin<br><br> Ala<br><br> Gin<br><br> Glu<br><br> Gin<br><br> Gin<br><br> (SEQ ID<br><br> N0:i<br><br> 228)<br><br> 3. A substantially pure hematopoietic protein comprising; an amino acid sequence of the formula:<br><br> RI-L1-R2, R2-L1-R1, R1-R2, or R2-R1<br><br> wherein Ri is a polypeptide comprising; a modified human G-CSF amino acid sequence of the formula:<br><br> 1 10<br><br> Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gin Ser Xaa<br><br> 20<br><br> Leu Leu Xaa Xaa Xaa Glu Gin Val Xaa Lys Xaa Gin Gly Xaa Gly<br><br> 30 40<br><br> Ala Xaa Leu Gin Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa<br><br> 50<br><br> Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly lie Pro Trp 60 70<br><br> INTELLECTUAL PROPERTY OFFICE OF N.Z.<br><br> 2 5 JAN 2001<br><br> I3E6E1VED |<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 524<br><br> Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly<br><br> 80<br><br> Xaa Leu Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu<br><br> 90 100<br><br> Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu<br><br> 110<br><br> Xaa Thr Leu Gin Xaa Asp Val Ala Asp Phe Ala Xaa Thr lie Trp<br><br> 120 130<br><br> Gin Gin Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gin Pro Thr<br><br> 140<br><br> Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gin Xaa Xaa Ala<br><br> 150 160<br><br> Gly Gly Val Leu Val Ala Ser Xaa Leu Gin Xaa Phe Leu Xaa Xaa<br><br> 170<br><br> Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gin Pro (SEQ ID NO:l)<br><br> wherein<br><br> Xaa at position<br><br> 1 is Thr,<br><br> Ser, Arg,<br><br> Tyr or Gly;<br><br> Xaa at position<br><br> 2 is Pro or Leu;<br><br> Xaa at position<br><br> 3 is Leu,<br><br> Arg, Tyr or Ser;<br><br> Xaa at position<br><br> 13<br><br> is<br><br> Phe,<br><br> Ser, His,<br><br> Thr or Pro;<br><br> Xaa at position<br><br> 16<br><br> is<br><br> Lys,<br><br> Pro, Ser,<br><br> Thr or His;<br><br> Xaa at position<br><br> 17<br><br> is<br><br> Cys,<br><br> Ser, Gly,<br><br> Ala, lie, Tyr or Arg<br><br> Xaa at position<br><br> 18<br><br> is<br><br> Leu,<br><br> Thr, Pro,<br><br> His, lie or Cys;<br><br> xaa at position<br><br> 22<br><br> is<br><br> Arg,<br><br> Tyr, Ser,<br><br> Thr or Ala;<br><br> Xaa at position<br><br> 24<br><br> is<br><br> He,<br><br> Pro, Tyr or Leu;<br><br> Xaa at position<br><br> 27<br><br> is<br><br> Asp,<br><br> or Gly;<br><br> Xaa at position<br><br> 30<br><br> is<br><br> Ala,<br><br> lie, Leu or Gly;<br><br> Xaa at position<br><br> 34<br><br> is<br><br> Lys or Ser;<br><br> Xaa at position<br><br> 36<br><br> is<br><br> Cys or Ser;<br><br> Xaa at position<br><br> 42<br><br> is<br><br> Cys or Ser;<br><br> Xaa at position<br><br> 43<br><br> is<br><br> His,<br><br> Thr, Gly.,<br><br> Val, Lys, Trp, Ala,<br><br> Arg, Cys, or<br><br> Leu<br><br> 7<br><br> Xaa at position<br><br> 44<br><br> is<br><br> Pro,<br><br> Gly, Arg,<br><br> Asp, Val, Ala, His,<br><br> Trp, Gin, or '<br><br> Thr<br><br> /<br><br> Xaa at position<br><br> 46<br><br> is<br><br> Glu,<br><br> Arg, Phe,<br><br> Arg, lie or Ala;<br><br> Xaa at position<br><br> 47<br><br> is<br><br> Leu or Thr;<br><br> Xaa at position<br><br> 49<br><br> is<br><br> Leu,<br><br> Phe, Arg or Ser;<br><br> Xaa at position<br><br> 50<br><br> is<br><br> Leu,<br><br> lie, His,<br><br> Pro or Tyr;<br><br> Xaa at position<br><br> 54<br><br> is<br><br> Leu or His;<br><br> Xaa at position<br><br> 64<br><br> is<br><br> Cys or Ser;<br><br> Xaa at position<br><br> 67<br><br> is<br><br> Gin,<br><br> Lys, Leu or Cys;<br><br> Xaa at position<br><br> 70<br><br> is<br><br> Gin,<br><br> Pro, Leu,<br><br> Arg or Ser;<br><br> Xaa at position 74<br><br> is<br><br> Cys or Ser;<br><br> 7<br><br> 525<br><br> Xaa at pos:.~ion<br><br> 104<br><br> is<br><br> Asp,<br><br> Gly or Val;<br><br> Xaa at position<br><br> 108<br><br> is<br><br> Leu,<br><br> Ala, Val, Arg, Trp, Gin or<br><br> Gly;<br><br> Xaa at position<br><br> 115<br><br> is<br><br> Thr,<br><br> His, Leu or Ala;<br><br> Xaa at position<br><br> 120<br><br> is<br><br> Gin,<br><br> Gly, Arg, Lys or His<br><br> Xaa at position<br><br> 123<br><br> is<br><br> Glu,<br><br> Arg, Phe or Thr<br><br> Xaa at position<br><br> 144<br><br> is<br><br> Phe,<br><br> His, Arg, Pro, Leu, Gin or<br><br> Glu;<br><br> Xaa at position<br><br> 146<br><br> is<br><br> Arg or Gin;<br><br> Xaa at position<br><br> 147<br><br> is<br><br> Arg or Gin;<br><br> Xaa at position<br><br> 156<br><br> is<br><br> His,<br><br> Gly or Ser;<br><br> Xaa at position<br><br> 159<br><br> is<br><br> Ser,<br><br> Arg, Thr, Tyr, Val or Gly;<br><br> Xaa at position<br><br> 162<br><br> is<br><br> Glu,<br><br> Leu, Gly or Trp;<br><br> Xaa at position<br><br> 163<br><br> is<br><br> Val,<br><br> Gly, Arg or Ala;<br><br> Xaa at position<br><br> 169<br><br> is<br><br> Arg,<br><br> Ser, Leu, Arg or Cys;<br><br> Xaa at position<br><br> 170<br><br> is<br><br> His,<br><br> Arg or Ser;<br><br> 15<br><br> wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted from said modified human G-CSF amino acid sequence; and<br><br> 20 wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;<br><br> 25<br><br> 38-39<br><br> 62-63<br><br> 123-124<br><br> 39-40<br><br> 63-64<br><br> 124-125<br><br> 40-41<br><br> 64-65<br><br> 125-126<br><br> 41-42<br><br> 65-66<br><br> 126-127<br><br> 42-43<br><br> 66-67<br><br> 128-129<br><br> 30<br><br> 43-44<br><br> 67-68<br><br> 128-129<br><br> 45-46<br><br> 68-69<br><br> 129-130<br><br> 48-49<br><br> 69-70<br><br> 130-131<br><br> 49-50<br><br> 70-71<br><br> 131-132<br><br> 52-53<br><br> 71-72<br><br> 132-133<br><br> 35<br><br> 53-54<br><br> 91-92<br><br> 133-134<br><br> 54-55<br><br> 92-93<br><br> 134-135<br><br> 55-56<br><br> 93-94<br><br> 135-136<br><br> 56-57<br><br> 94-95<br><br> 136-137<br><br> 57-58<br><br> 95-96<br><br> 137-138<br><br> 40<br><br> 58-59<br><br> 96-97<br><br> 138-139<br><br> 59-60<br><br> 97-98<br><br> 139-140<br><br> 60-61<br><br> 98-99<br><br> 140-141<br><br> 61-62<br><br> 99-100<br><br> 141-142 or 142-143<br><br> 45<br><br> respectively;<br><br> 526<br><br> wherein R2 is a polypeptide comprising; a modified human IL-3 amino acid sequence of the formula:<br><br> 5 Ala Pro Met Thr Gin Thr Thr Ser Leu Lys Thr Ser Trp Val Asn<br><br> 1 5 10 15<br><br> Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 20 25 30<br><br> 10<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 35 40 45<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 15 50 55 60<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 65 70 75<br><br> 20 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 80 85 90<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 95 100 105<br><br> 25<br><br> Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 110 115 120<br><br> Xaa Xaa Xaa Gin Gin Thr Thr Leu Ser Leu Ala lie Phe<br><br> 30 , 125 130 (SEQ ID NO:2)<br><br> wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gin, or Arg;<br><br> Xaa at position 18 is Asn, His, Leu, lie, Phe, Arg, or Gin;<br><br> Xaa at position 19 is Met, Phe, lie, Arg, Gly, Ala, or Cys;<br><br> 35 Xaa at position 20 is lie, Cys, Gin, Glu, Arg, Pro, or Ala;<br><br> 527<br><br> Xaa at posit\.jn 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gin, Asn,<br><br> ' Thr, Ser or Val;<br><br> Xaa at position'22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gin, Leu, Val or. Gly.;<br><br> 5<br><br> Xaa at position<br><br> Leu, Ser,<br><br> Xaa at position<br><br> Xaa at position<br><br> Xaa at position<br><br> 10<br><br> Xaa at position<br><br> Xaa at position<br><br> Xaa at position<br><br> Xaa at position<br><br> Xaa at position<br><br> 15<br><br> Xaa at position<br><br> Xaa at position<br><br> Xaa at position<br><br> Arg, Ala,<br><br> Xaa at position<br><br> 20<br><br> Xaa at position<br><br> Xaa at position<br><br> Xaa at position<br><br> Xaa at position<br><br> Xaa at position<br><br> 25<br><br> Xaa at position<br><br> Val, Glu,<br><br> Xaa at position<br><br> Gin, Arg,<br><br> Xaa at position<br><br> 30<br><br> Glu, Asn,<br><br> Xaa at position<br><br> Trp, Asp,<br><br> Xaa at position<br><br> Lys, His,<br><br> 35<br><br> Xaa at position<br><br> 528<br><br> Xaa at position 48 is Leu, Ser, Cys, -Arg, lie, His, Phe, Glu,<br><br> Lys, Thr, Ala, Met, Val or Asn;<br><br> Xaa at position' 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;<br><br> Xaa at position 50 is.Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, 5 Ala, lie, Val, His, Phe, Met or Gin;<br><br> Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;<br><br> Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;<br><br> Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;<br><br> Xaa at position 54 is Arg, Asp, lie, Ser, Val, Thr, Gin, Asn, 10 Lys, His, Ala or Leu;<br><br> Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;<br><br> Xaa at position 56 is Pro, Gly, Cys, Ser, Gin, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;<br><br> Xaa at position<br><br> 57<br><br> is<br><br> Asn or Gly;<br><br> 15<br><br> Xaa at position<br><br> 58<br><br> is<br><br> Leu,<br><br> Ser,<br><br> Asp,<br><br> Arg,<br><br> Gin,<br><br> Val,<br><br> or Cys;<br><br> Xaa at position<br><br> 59<br><br> is<br><br> Glu<br><br> Tyr,<br><br> His, Leu,<br><br> Pro, i or Arg;<br><br> Xaa at position<br><br> 60<br><br> is<br><br> Ala,<br><br> Ser,<br><br> Pro,<br><br> Tyr,<br><br> Asn,<br><br> or Thr;<br><br> Xaa at position<br><br> 61<br><br> is<br><br> Phe,<br><br> Asn,<br><br> Glu,<br><br> Pro,<br><br> Lys,<br><br> Arg,<br><br> or Ser;<br><br> Xaa at position<br><br> 62<br><br> is<br><br> Asn,<br><br> His,<br><br> Val,<br><br> Arg,<br><br> Pro,<br><br> Thr,<br><br> Asp,<br><br> or lie;<br><br> 20<br><br> Xaa at position<br><br> 63<br><br> is<br><br> Arg,<br><br> Tyr,<br><br> Trp,<br><br> Lys,<br><br> Ser,<br><br> His,<br><br> Pro,<br><br> or Val;<br><br> Xaa at position<br><br> 64<br><br> is<br><br> Ala,<br><br> Asn,<br><br> Pro,<br><br> Ser,<br><br> or Lys;<br><br> Xaa at position<br><br> 65<br><br> is<br><br> Val,<br><br> Thr,<br><br> Pro,<br><br> His,<br><br> Leu,<br><br> Phe,<br><br> or Ser;<br><br> Xaa at position<br><br> 66<br><br> is<br><br> Lys,<br><br> He,<br><br> Arg,<br><br> Val,<br><br> Asn,<br><br> Glu,<br><br> or Ser;<br><br> Xaa at position<br><br> 67<br><br> is<br><br> Ser,<br><br> Ala,<br><br> Phe,<br><br> Val,<br><br> Gly,<br><br> Asn,<br><br> lie.<br><br> Pro, or<br><br> His;<br><br> 25<br><br> Xaa at position<br><br> 68<br><br> is<br><br> Leu,<br><br> Val,<br><br> Trp,<br><br> Ser,<br><br> lie,<br><br> Phe,<br><br> Thr,<br><br> or His;<br><br> Xaa at position<br><br> 69<br><br> is<br><br> Gin,<br><br> Ala,<br><br> Pro,<br><br> Thr,<br><br> Glu,<br><br> Arg,<br><br> Trp,<br><br> Gly, or<br><br> Leu;<br><br> Xaa at position<br><br> 70<br><br> is<br><br> Asn,<br><br> Leu,<br><br> Val,<br><br> Trp,<br><br> Pro,<br><br> or Ala;<br><br> Xaa at position<br><br> 71<br><br> is<br><br> Ala,<br><br> Met,<br><br> Leu,<br><br> Pro 1<br><br> Arg,<br><br> Glu,<br><br> Thr,<br><br> Gin,<br><br> Trp, or Asn ;<br><br> 30<br><br> Xaa at position<br><br> 72<br><br> is<br><br> Ser,<br><br> Glu,<br><br> Met,<br><br> Ala,<br><br> His,<br><br> Asn,<br><br> Arg,<br><br> or Asp;<br><br> Xaa at position<br><br> 73<br><br> is<br><br> Ala,<br><br> Glu,<br><br> Asp,<br><br> Leu,<br><br> Ser,<br><br> Gly,<br><br> Thr,<br><br> or Arg;<br><br> Xaa at position 74<br><br> is lie<br><br> ■, Met, Thr,<br><br> Pro<br><br> , Arg<br><br> , Gly<br><br> , Ala;<br><br> Xaa at position 75<br><br> is<br><br> Glu,<br><br> Lys,<br><br> Gly,<br><br> Asp,<br><br> Pro,<br><br> Trp,<br><br> Arg,<br><br> Ser,<br><br> Gin, or Leu;<br><br> 35<br><br> Xaa at position 76<br><br> is<br><br> Ser,<br><br> Val,<br><br> Ala,<br><br> Asn,<br><br> Trp,<br><br> Glu,<br><br> Pro,<br><br> Gly, or<br><br> Asp;<br><br> 529<br><br> Xaa at position 77 is lie, Ser, Arg, Thr, or Leu;<br><br> Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;<br><br> Xaa at position 79 is Lys, Thr, Asn, Met, Arg, lie, Gly, or Asp;<br><br> Xaa a.t position 80 is. Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;<br><br> 5 Xaa at position 81 is Leu, Gin, Gly, Ala, Trp, Arg, Val, or Lys;<br><br> Xaa at position 82 is Leu, Gin, Lys, Trp, Arg, Asp, Glu, Asn,<br><br> His, Thr, Ser, Ala, Tyr, Phe, lie. Met or Val;<br><br> Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;<br><br> Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;<br><br> 10 Xaa at position 85 is Leu, Asn, Val, or Gin;<br><br> Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;<br><br> Xaa at position 87 is Leu, Ser, Trp, or Gly;<br><br> Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;<br><br> Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;<br><br> 15 Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, lie, or Met;<br><br> Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;<br><br> Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, lie or Leu;<br><br> Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;<br><br> 20 Xaa at position 94 is Arg, lie, Ser, Glu, Leu, Val, Gin, Lys, His, Ala, or Pro;<br><br> Xaa at position<br><br> Lys, Ser,<br><br> Xaa at position<br><br> 25<br><br> Xaa at position<br><br> Xaa at position<br><br> Glu, Gin,<br><br> Xaa at position<br><br> Gly, Ser,<br><br> 30<br><br> Xaa at position<br><br> Xaa at position<br><br> Tyr, Glu,<br><br> Xaa at position<br><br> Xaa at position<br><br> 35<br><br> Xaa at position<br><br> 530<br><br> Gin, Lys, Ala, Phe, or Gly;<br><br> Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gin, Tyr,<br><br> Leu, Lys, lie, Asp, or His;<br><br> Xaa at position 106 .is Glu, Ser, Ala, Lys, Thr, lie, Gly, or Pro;<br><br> 5 Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, lie,"Gin, His, Ser, Ala or Pro;<br><br> Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;<br><br> Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gin, His, Glu, Ser, or Trp;<br><br> 10 Xaa at position 111 is Leu, lie, Arg, Asp, or Met;<br><br> Xaa at position 112 is Thr, Val, Gin, Tyr, Glu, His, Ser, or Phe;<br><br> Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp,<br><br> Lys, Leu, lie, Val or Asn;<br><br> Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;<br><br> 15 Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;<br><br> Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu,<br><br> Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gin, or lie;<br><br> Xaa at position 117 is Thr, Ser, Asn, lie, Trp, Lys, or Pro;<br><br> 20 Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;<br><br> Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;<br><br> Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gin;<br><br> Xaa at position 121 is Ala, Ser, lie, Asn, Pro, Lys, Asp, or Gly;<br><br> Xaa at position 122 is Gin, Ser, Met, Trp, Arg, Phe, Pro, His, 25 He, Tyr, or Cys;<br><br> Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;<br><br> wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can 30 optionally be deleted from the C-terminus of said modified human interleukin-3 amino acid sequence; and wherein from 0 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; and<br><br> 35<br><br> wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids; - ■<br><br> 5<br><br> 26-27<br><br> 49-50<br><br> 83-84<br><br> 27-28<br><br> 50-51<br><br> 84-85<br><br> 28-29<br><br> 51-52<br><br> 85-86<br><br> 29-30<br><br> 52-53<br><br> 86-87<br><br> 30-31<br><br> 53-54<br><br> 87-88<br><br> 31-32<br><br> 54-55<br><br> 88-89<br><br> 32-33<br><br> 64-65<br><br> 89-90<br><br> 33-34<br><br> 65-66<br><br> 90-91<br><br> 34-35<br><br> 66-67<br><br> 91-92<br><br> 35-36<br><br> 67-68<br><br> 92-93<br><br> 36-37<br><br> 68-69<br><br> 97-98<br><br> 37-38<br><br> 69-70<br><br> 98-99<br><br> 38-39<br><br> 70-71<br><br> 99-100<br><br> 39-40<br><br> 71-72<br><br> 100-101<br><br> 40-41<br><br> 72-73<br><br> 101-102<br><br> 41-42<br><br> 82-83<br><br> 102-103<br><br> or 103-104 respectively;<br><br> wherein L± is a linker capable of linking Ri to R2; and<br><br> 10 said hematopoietic protein can optionally be immediately preceded by (methionine-1), (alanine-1) or (methionine-^, alanine-1).<br><br> 15<br><br> 4. A substantially pure hematopoietic protein comprising; an amino acid sequence of the formula:<br><br> RI-L1-R2, R2-L1-R1, R1-R2, or R2-R1<br><br> 20<br><br> wherein Ri is a polypeptide comprising; a modified human G-CSF amino acid sequence of the formula:<br><br> 1 10<br><br> Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gin Ser Xaa<br><br> INTELLECTUAL PROPERTY OFFICE OF N.Z.<br><br> 2 5 JAN 2001<br><br> E5EGEJV<br><br> J ^<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 532<br><br> Gin Gly Xaa Gly 40<br><br> Lys Leu Xaa Xaa<br><br> Gly lie Pro Trp 70<br><br> Xaa Leu Ala Gly<br><br> Tyr Gin Gly Leu 100<br><br> Gly Pro Thr Leu<br><br> Xaa Thr lie Trp 130<br><br> Leu Gin Pro Thr<br><br> Gin Xaa Xaa Ala 160<br><br> Phe Leu Xaa Xaa<br><br> (SEQ ID NO:1) wherein<br><br> Xaa at position 1 is Thr, Ser, Arg, Tyr or Gly;<br><br> Xaa at position 2 is Pro or Leu;<br><br> Xaa at position 3 is Leu, Arg, Tyr or Ser;<br><br> Xaa at position 13 is Phe, Ser, His, Thr or Pro;<br><br> Xaa at position 16 is Lys, Pro, Ser, Thr or His;<br><br> Xaa at position 17 is Cys, Ser, Gly, Ala, lie, Tyr or Arg;<br><br> Xaa at position 18 is Leu, Thr, Pro, His, lie or Cys;<br><br> Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala;<br><br> Xaa at position 24 is lie, Pro, Tyr or Leu;<br><br> Xaa at position 27 is Asp, or Gly;<br><br> Xaa at position 30 is Ala, lie. Leu or Gly;<br><br> Xaa at position 34 is Lys or Ser;<br><br> Xaa at position 36 is Cys or Ser;<br><br> Xaa at position 42 is Cys or Ser;<br><br> Xaa at position 43 is His, Thr, Gly, val, Lys, Trp, Ala, Arg, Cys, or Leu;<br><br> 20<br><br> Leu Leu Xaa Xaa Xaa Glu Gin Val Xaa Lys Xaa 30<br><br> Ala Xaa Leu Gin Glu Xaa Leu Xaa Ala Thr Tyr<br><br> 50<br><br> Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa 60<br><br> Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu<br><br> 80<br><br> Xaa Leu Ser Gin Leu His Ser Gly Leu Phe Leu 90<br><br> Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu<br><br> 110<br><br> Xaa Thr Leu Gin Xaa Asp Val Ala Asp Phe Ala 120<br><br> Gin Gin Met Glu Xaa Xaa Gly Met Ala Pro Ala<br><br> 140<br><br> Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa 150<br><br> Gly Gly Val Leu Val Ala Ser Xaa Leu Gin Xaa<br><br> 170<br><br> Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gin Pro<br><br> 533<br><br> Xaa at pos:._.ion<br><br> 44<br><br> is<br><br> Pro, Gly, Arg, Asp, Val, Ala, His,<br><br> Trp, Gin, or Thr;<br><br> Xaa at position<br><br> 46<br><br> is<br><br> Glu, Arg, Phe, Arg, lie or Ala;<br><br> Xaa at position<br><br> 47<br><br> is<br><br> Leu or Thr;<br><br> 5<br><br> Xaa at position<br><br> 49<br><br> is<br><br> Leu, Phe, Arg or Ser;<br><br> Xaa at position<br><br> 50<br><br> is<br><br> Leu, lie. His, Pro or Tyr;<br><br> Xaa at position<br><br> 54<br><br> is<br><br> Leu or His;<br><br> Xaa at position<br><br> 64<br><br> is<br><br> Cys or Ser;<br><br> Xaa at position<br><br> 67<br><br> is<br><br> Gin, Lys, Leu or Cys;<br><br> 10<br><br> xaa at position<br><br> 70<br><br> is<br><br> Gin, Pro, Leu, Arg or Ser;<br><br> xaa at position<br><br> 74<br><br> is<br><br> Cys or Ser;<br><br> Xaa at position<br><br> 104<br><br> is<br><br> Asp, Gly or Val;<br><br> xaa at position<br><br> 108<br><br> is<br><br> Leu, Ala, Val, Arg, Trp, Gin or Gly;<br><br> Xaa at position<br><br> 115<br><br> is<br><br> Thr, His, Leu or Ala;<br><br> 15<br><br> Xaa at position<br><br> 120<br><br> is<br><br> Gin, Gly, Arg, Lys or His<br><br> Xaa at position<br><br> 123<br><br> is<br><br> Glu, Arg, Phe or Thr<br><br> Xaa at position<br><br> 144<br><br> is<br><br> Phe, His, Arg, Pro, Leu, Gin or Glu;<br><br> Xaa at position<br><br> 146<br><br> is<br><br> Arg or Gin;<br><br> Xaa at position<br><br> 147<br><br> is<br><br> Arg or Gin;<br><br> 20<br><br> Xaa at position<br><br> 156<br><br> is<br><br> His, Gly or Ser;<br><br> Xaa at position<br><br> 159<br><br> is<br><br> Ser, Arg, Thr, Tyr, Val or Gly;<br><br> Xaa at position<br><br> 162<br><br> is<br><br> Glu, Leu, Gly or Trp;<br><br> Xaa at position<br><br> 163<br><br> is<br><br> Val, Gly, Arg or Ala;<br><br> Xaa at posxtion<br><br> 169<br><br> is<br><br> Arg, Ser, Leu, Arg or Cys;<br><br> 25<br><br> Xaa at position<br><br> 170<br><br> is<br><br> His, Arg or Ser;<br><br> 30<br><br> 35<br><br> wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted from said modified human G-CSF amino acid sequence; and wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;<br><br> 38-39 62-63 123-124<br><br> 39-40 63-64 124-125<br><br> 40-41 64-65 125-126<br><br> 41-42 65-66 126-127 40 42-43 66-67 128-129<br><br> 43-44 67-68 128-129<br><br> 45-46 \ 68-69 129-130<br><br> 48-49 69-70 130-131<br><br> 49-50 70-71 131-132 45 52-53 71-72 132-133<br><br> 53-54 91-92 133-134<br><br> 54-55 92-93 134-135<br><br> 55-56 93-94 135-136<br><br> 56-57 94-95 136-137<br><br> 534<br><br> 57-58 95-96 137-138<br><br> 58-59 96-97 138-139<br><br> 59-60 97-98 139-140<br><br> 60-61 ' 98-99 140-141<br><br> 61-62 99-100 141-142<br><br> or 142-143 respectively; and<br><br> R2 is a polypeptide comprising; a modified human IL-3 amino acid sequence of the formula:<br><br> Ala Pro Met Thr Gin Thr Thr Ser Leu Lys Thr Ser Trp Val Asn 1 5 10 15<br><br> Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 20 25 30<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 35 40 45<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 50 55 60<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 65 70 75<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 80 85 90<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 95 100 105<br><br> Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 110 115 120<br><br> Xaa Xaa Xaa Gin Gin Thr Thr Leu Ser Leu Ala lie Phe<br><br> 535<br><br> 125 130<br><br> Xaa at position<br><br> 1-8<br><br> is<br><br> Asn,<br><br> His,<br><br> Leu,<br><br> lie,<br><br> Phe,<br><br> Arg,<br><br> or Gin;<br><br> 5<br><br> Xaa at position<br><br> 19<br><br> is<br><br> Met,<br><br> Phe,<br><br> lie.<br><br> Arg,<br><br> Gly,<br><br> Ala,<br><br> or Cys;<br><br> Xaa at position<br><br> 20<br><br> is lie,<br><br> Cys,<br><br> Gin,<br><br> Glu,<br><br> Arg,<br><br> Pro,<br><br> or Ala;<br><br> Xaa at position<br><br> 21<br><br> is<br><br> Asp,<br><br> Phe,<br><br> Lys,<br><br> Arg,<br><br> Ala,<br><br> Gly,<br><br> Glu, Gin, Asn,<br><br> Thr, Ser or Val t<br><br> Xaa at position<br><br> 22<br><br> is<br><br> Glu,<br><br> Trp,<br><br> Pro,<br><br> Ser,<br><br> Ala,<br><br> His,<br><br> Asp, Asn, Gin,<br><br> 10<br><br> Leu, Val or Gly<br><br> Xaa at position<br><br> 23<br><br> is lie.<br><br> Val,<br><br> Ala,<br><br> Gly,<br><br> Trp,<br><br> Lys,<br><br> Phe,<br><br> Leu, Ser,<br><br> or<br><br> Arg;<br><br> Xaa at position<br><br> 24<br><br> is lie,<br><br> Gly,<br><br> Val,<br><br> Arg,<br><br> Ser,<br><br> Phe.<br><br> or Leu;<br><br> Xaa at position<br><br> 25<br><br> is<br><br> Thr,<br><br> His,<br><br> Gly,<br><br> Gin,<br><br> Arg,<br><br> Pro,<br><br> or Ala;<br><br> 15<br><br> Xaa at position<br><br> 26<br><br> is<br><br> His,<br><br> Thr,<br><br> Phe,<br><br> Gly,<br><br> Arg,<br><br> Ala,<br><br> or Trp;<br><br> Xaa at position<br><br> 27<br><br> is<br><br> Leu,<br><br> Gly,<br><br> Arg,<br><br> Thr,<br><br> Ser,<br><br> or Ala;<br><br> Xaa at position<br><br> 28<br><br> is<br><br> Lys,<br><br> Arg,<br><br> Leu,<br><br> Gin,<br><br> Gly,<br><br> Pro,<br><br> Val or Trp;<br><br> Xaa at position<br><br> 29<br><br> is<br><br> Gin,<br><br> Asn,<br><br> Leu,<br><br> Pro,<br><br> Arg,<br><br> or Val;<br><br> Xaa at position<br><br> 30<br><br> is<br><br> Pro,<br><br> His,<br><br> Thr,<br><br> Gly,<br><br> Asp,<br><br> Gin,<br><br> Ser, Leu, or Lys<br><br> 20<br><br> Xaa at position<br><br> 31<br><br> is<br><br> Pro,<br><br> Asp,<br><br> Gly,<br><br> Ala,<br><br> Arg,<br><br> Leu,<br><br> or Gin;<br><br> Xaa at position<br><br> 32<br><br> is<br><br> Leu,<br><br> Val,<br><br> Arg,<br><br> Gin,<br><br> Asn,<br><br> Gly,<br><br> Ala, or Glu;<br><br> Xaa at position<br><br> 33<br><br> is<br><br> Pro,<br><br> Leu,<br><br> Gin,<br><br> Ala,<br><br> Thr,<br><br> or Glu;<br><br> Xaa at position<br><br> 34<br><br> is<br><br> Leu,<br><br> Val,<br><br> Gly,<br><br> Ser,<br><br> Lys,<br><br> Glu,<br><br> Gin, Thr,<br><br> Arg, Ala,<br><br> Phe,<br><br> lie or Met f<br><br> 25<br><br> Xaa at position<br><br> 35<br><br> is<br><br> Leu,<br><br> Ala,<br><br> Gly,<br><br> Asn,<br><br> Pro,<br><br> Gin,<br><br> or Val;<br><br> Xaa at position<br><br> 36<br><br> is<br><br> Asp,<br><br> Leu,<br><br> or Val;<br><br> Xaa at position<br><br> 37<br><br> is<br><br> Phe,<br><br> Ser,<br><br> Pro,<br><br> Trp,<br><br> or lie;<br><br> Xaa at position<br><br> 38<br><br> is<br><br> Asn,<br><br> or Ala;<br><br> Xaa at position<br><br> 40<br><br> is<br><br> Leu,<br><br> Trp,<br><br> or Arg;<br><br> 30<br><br> Xaa at position<br><br> 41<br><br> is<br><br> Asn,<br><br> Cys,<br><br> Arg,<br><br> Leu,<br><br> His,<br><br> Met,<br><br> or Pro;<br><br> Xaa at position<br><br> 42<br><br> is<br><br> Gly,<br><br> Asp,<br><br> Ser,<br><br> Cys,<br><br> Asn,<br><br> Lys,<br><br> Thr, Leu,<br><br> Val, Glu,<br><br> Phe,<br><br> Tyr,<br><br> lie.<br><br> Met or Ala<br><br> /<br><br> Xaa at position<br><br> 43<br><br> is<br><br> Glu,<br><br> Asn,<br><br> Tyr,<br><br> Leu,<br><br> Phe,<br><br> Asp,<br><br> Ala, Cys,<br><br> Gin, Arg,<br><br> Thr,<br><br> Gly or Ser;<br><br> 35<br><br> Xaa at position<br><br> 44<br><br> is<br><br> Asp,<br><br> Ser,<br><br> Leu,<br><br> Arg,<br><br> Lys,<br><br> Thr,<br><br> Met, Trp,<br><br> 536<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> Glu, Asn,<br><br> Gin, Ala or Pro;<br><br> Xaa at position<br><br> 45 is Gin,<br><br> Pro,<br><br> Phe,<br><br> Val,<br><br> Met,<br><br> Leu,<br><br> Thr,<br><br> Lys,<br><br> Trp, Asp",<br><br> Asn, Arg,<br><br> Ser,<br><br> Ala,<br><br> lie, Glu or His<br><br> 7<br><br> Xaa at position<br><br> 46 is Asp,<br><br> Phe,<br><br> Ser,<br><br> Thr,<br><br> Cys,<br><br> Glu,<br><br> Asn,<br><br> Gin,<br><br> Lys, His,<br><br> Ala, Tyr,<br><br> He,<br><br> Val or Gly;<br><br> Xaa at position<br><br> 47 is lie,<br><br> Gly,<br><br> Val,<br><br> Ser,<br><br> Arg,<br><br> Pro,<br><br> or His;<br><br> Xaa at position<br><br> 48 is Leu,<br><br> Ser,<br><br> Cys,<br><br> Arg,<br><br> lie,<br><br> His,<br><br> Phe,<br><br> Glu,<br><br> Lys, Thr,<br><br> Ala, Met,<br><br> Val or Asn<br><br> 7<br><br> Xaa at position<br><br> 49 is Met,<br><br> Arg,<br><br> Ala,<br><br> Gly,<br><br> Pro,<br><br> Asn,<br><br> His,<br><br> or Asp;<br><br> Xaa at position<br><br> 50 is Glu,<br><br> Leu,<br><br> Thr,<br><br> Asp,<br><br> Tyr,<br><br> Lys,<br><br> Asn,<br><br> Ser,<br><br> Ala, lie.<br><br> Val, His,<br><br> Phe,<br><br> Met or Gin;<br><br> Xaa at position<br><br> 51 is Asn,<br><br> Arg,<br><br> Met,<br><br> Pro,<br><br> Ser,<br><br> Thr,<br><br> or His;<br><br> Xaa at position<br><br> 52 is Asn,<br><br> His,<br><br> Arg,<br><br> Leu,<br><br> Gly,<br><br> Ser,<br><br> or Thr;<br><br> Xaa at position<br><br> 53 is Leu,<br><br> Thr,<br><br> Ala,<br><br> Gly,<br><br> Glu,<br><br> Pro,<br><br> Lys,<br><br> Ser, or<br><br> Xaa at position<br><br> 54 is Arg,<br><br> Asp,<br><br> lie.<br><br> Ser,<br><br> Val,<br><br> Thr,<br><br> Gin,<br><br> Asn,<br><br> Lys, His,<br><br> Ala or Leu<br><br> • 7<br><br> Xaa at position<br><br> 55 is Arg,<br><br> Thr,<br><br> Val,<br><br> Ser,<br><br> Leu,<br><br> or Gly;<br><br> Xaa at position<br><br> 56 is Pro,<br><br> Gly,<br><br> Cys,<br><br> Ser,<br><br> Gin,<br><br> Glu,<br><br> Arg,<br><br> His,<br><br> Thr, Ala,<br><br> Tyr, Phe,<br><br> Leu,<br><br> Val or Lys;<br><br> 35<br><br> Xaa at position<br><br> 57<br><br> is<br><br> Asn or Gly;<br><br> Xaa at position<br><br> 58<br><br> is<br><br> Leu,<br><br> Ser,<br><br> Asp,<br><br> Arg,<br><br> Gin,<br><br> Val.<br><br> or Cys;<br><br> Xaa at position<br><br> 59<br><br> is<br><br> Glu<br><br> Tyr,<br><br> His,<br><br> Leu,<br><br> Pro,<br><br> or Arg;<br><br> Xaa at position<br><br> 60<br><br> is<br><br> Ala,<br><br> Ser,<br><br> Pro,<br><br> Tyr,<br><br> Asn,<br><br> or Thr;<br><br> Xaa at position<br><br> 61<br><br> is<br><br> Phe,<br><br> Asn,<br><br> Glu,<br><br> Pro,<br><br> Lys,<br><br> Arg,<br><br> or Ser;<br><br> Xaa at position<br><br> 62<br><br> is<br><br> Asn,<br><br> His,<br><br> Val,<br><br> Arg,<br><br> Pro,<br><br> Thr,<br><br> Asp, or He;<br><br> Xaa at position<br><br> 63<br><br> is<br><br> Arg,<br><br> Tyr,<br><br> Trp,<br><br> Lys,<br><br> Ser,<br><br> His,<br><br> Pro, or Val;<br><br> Xaa at position<br><br> 64<br><br> is<br><br> Ala,<br><br> Asn,<br><br> Pro,<br><br> Ser,<br><br> or Lys;<br><br> Xaa at position<br><br> 65<br><br> is<br><br> Val,<br><br> Thr,<br><br> Pro,<br><br> His,<br><br> Leu,<br><br> Phe,<br><br> or Ser;<br><br> Xaa at position<br><br> 66<br><br> is<br><br> Lys,<br><br> lie.<br><br> Arg,<br><br> Val,<br><br> Asn,<br><br> Glu,<br><br> or Ser;<br><br> Xaa at position<br><br> 67<br><br> is<br><br> Ser,<br><br> Ala,<br><br> Phe,<br><br> Val,<br><br> Gly,<br><br> Asn,<br><br> Ile, Pro, or His;<br><br> Xaa at position<br><br> 68<br><br> is<br><br> Leu,<br><br> Val,<br><br> Trp,<br><br> Ser,<br><br> He,<br><br> Phe,<br><br> Thr, or His;<br><br> Xaa at position<br><br> 69<br><br> is<br><br> Gin,<br><br> Ala,<br><br> Pro,<br><br> Thr,<br><br> Glu,<br><br> Arg,<br><br> Trp, Gly, or Leu;<br><br> Xaa at position<br><br> 70<br><br> is<br><br> Asn,<br><br> Leu,<br><br> Val,<br><br> Trp,<br><br> Pro,<br><br> or Ala;<br><br> Xaa at position 71<br><br> is<br><br> Ala,<br><br> Met,<br><br> Leu,<br><br> Pro,<br><br> Arg,<br><br> Glu,<br><br> Thr, Gin,<br><br> Trp, or Asn;<br><br> 537<br><br> Xaa at position<br><br> 72<br><br> is<br><br> Ser,<br><br> Glu,<br><br> Met,<br><br> Ala,<br><br> His,<br><br> Asn,<br><br> Arg,<br><br> or Asp;<br><br> Xaa at position" 73<br><br> is<br><br> Ala,<br><br> Glu,<br><br> Asp,<br><br> Leu,<br><br> Ser,<br><br> Gly,<br><br> Thr,<br><br> or Arg;<br><br> Xaa at position<br><br> 74<br><br> is lie,<br><br> Met,<br><br> Thr,<br><br> Pro,<br><br> Arg,<br><br> Gly,<br><br> Ala;<br><br> Xaa at position 75<br><br> is<br><br> Glu,<br><br> Lys,<br><br> Gly,<br><br> Asp,<br><br> Pro,<br><br> Trp,<br><br> Arg,<br><br> Ser,<br><br> 5<br><br> Gin, or Leu;<br><br> Xaa at position<br><br> 76<br><br> is<br><br> Ser,<br><br> Val,<br><br> Ala,<br><br> Asn,<br><br> Trp,<br><br> Glu,<br><br> Pro,<br><br> Gly, or &lt;<br><br> Xaa at position<br><br> 77<br><br> is lie.<br><br> Ser,<br><br> Arg,<br><br> Thr,<br><br> or Leu;<br><br> Xaa at position<br><br> 78<br><br> is<br><br> Leu,<br><br> Ala,<br><br> Ser,<br><br> Glu,<br><br> Phe,<br><br> Gly,<br><br> or Arg;<br><br> Xaa at position<br><br> 79<br><br> is<br><br> Lys,<br><br> Thr,<br><br> Asn,<br><br> Met,<br><br> Arg,<br><br> He,<br><br> Gly,<br><br> or Asp;<br><br> 10<br><br> Xaa at position<br><br> 80<br><br> is<br><br> Asn,<br><br> Trp,<br><br> Val,<br><br> Gly,<br><br> Thr,<br><br> Leu,<br><br> Glu,<br><br> or Arg;<br><br> Xaa at position<br><br> 81<br><br> is<br><br> Leu,<br><br> Gin,<br><br> Gly,<br><br> Ala,<br><br> Trp,<br><br> Arg,<br><br> Val,<br><br> or Lys;<br><br> Xaa at position<br><br> 82<br><br> is<br><br> Leu,<br><br> Gin,<br><br> Lys,<br><br> Trp,<br><br> Arg,<br><br> Asp,<br><br> Glu,<br><br> Asn,<br><br> His, Thr,<br><br> Ser, Ala,<br><br> Tyr,<br><br> Phe,<br><br> lie, j<br><br> Met or Val<br><br> /<br><br> Xaa at position<br><br> 83<br><br> is<br><br> Pro,<br><br> Ala,<br><br> Thr,<br><br> Trp,<br><br> Arg,<br><br> or Met;<br><br> 15<br><br> Xaa at position<br><br> 84<br><br> is<br><br> Cys,<br><br> Glu,<br><br> Gly,<br><br> Arg,<br><br> Met,<br><br> or Val;<br><br> Xaa at position<br><br> 85<br><br> is<br><br> Leu,<br><br> Asn,<br><br> Val,<br><br> or Gin;<br><br> Xaa at position<br><br> 86<br><br> is<br><br> Pro,<br><br> Cys,<br><br> Arg,<br><br> Ala,<br><br> or Lys;<br><br> Xaa at position<br><br> 87<br><br> is<br><br> Leu,<br><br> Ser,<br><br> Trp,<br><br> or Gly;<br><br> -<br><br> Xaa at position<br><br> 88<br><br> is<br><br> Ala,<br><br> Lys,<br><br> Arg,<br><br> Val,<br><br> or Trp;<br><br> 20<br><br> Xaa at position<br><br> 89<br><br> is<br><br> Thr,<br><br> Asp,<br><br> Cys,<br><br> Leu,<br><br> Val,<br><br> Glu,<br><br> His,<br><br> Asn, or ;<br><br> Xaa at position<br><br> 90<br><br> is<br><br> Ala,<br><br> Pro,<br><br> Ser,<br><br> Thr,<br><br> Gly,<br><br> Asp,<br><br> lie,<br><br> or Met;<br><br> Xaa at position<br><br> 91<br><br> is<br><br> Ala,<br><br> Pro,<br><br> Ser,<br><br> Thr,<br><br> Phe,<br><br> Leu,<br><br> Asp,<br><br> or His;<br><br> Xaa at position Leu;<br><br> 92<br><br> • is<br><br> Pro,<br><br> Phe,<br><br> Arg,<br><br> Ser,<br><br> Lys,<br><br> His,<br><br> Ala,<br><br> Gly, lie<br><br> 25<br><br> Xaa at position<br><br> 93<br><br> is<br><br> Thr,<br><br> Asp,<br><br> Ser,<br><br> Asn,<br><br> Pro,<br><br> Ala,<br><br> Leu,<br><br> or Arg;<br><br> Xaa at position<br><br> 94<br><br> is<br><br> Arg,<br><br> lie,<br><br> Ser,<br><br> Glu,<br><br> Leu,<br><br> Val,<br><br> Gin,<br><br> Lys, His<br><br> Ala, or Pro;<br><br> Xaa at position 95 is His, Gin, Pro, Arg, Val, Leu, Gly, Thr, Asn,<br><br> Lys, Ser, Ala, Trp, Phe, lie, or Tyr;<br><br> \<br><br> 30 Xaa at position 96 is Pro, Lys, Tyr, Gly, lie, or Thr;<br><br> Xaa at position 97 is1 lie, Val, Lys, Ala, or Asn;<br><br> Xaa at position 98 is His, lie, Asn, Leu, Asp, Ala, Thr,<br><br> Glu, Gin, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro;<br><br> Xaa at position 99 is lie, Leu, Arg, Asp, Val, Pro, Gin, 35 Gly, Ser, Phe, or His;<br><br> 538<br><br> Xaa at position 100 is Lys, Tyr, Leu, His, Arg, lie, Ser, Gin, or Pro;<br><br> Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val,<br><br> -Tyr, Glu, Asn, Ser, Ala, Gly, lie, Leu, or Gin;<br><br> Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;<br><br> 5 Xaa at position 103 is Asp, or Ser;<br><br> Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gin, Lys, Ala, Phe, or Gly;<br><br> Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gin, Tyr, Leu, Lys, lie, Asp, or His;<br><br> 10 Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, lie, Gly, or Pro;<br><br> Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, lie, Gin, His, Ser, Ala or Pro;<br><br> Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;<br><br> Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gin, His, Glu, 15 Ser, or Trp;<br><br> Xaa at position 111 is Leu, lie, Arg, Asp, or Met;<br><br> Xaa at position 112 is Thr, Val, Gin, Tyr, Glu, His, Ser, or Phe;<br><br> Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, lie, Val or Asn;<br><br> 20 Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;<br><br> Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr,<br><br> Trp, or Met ;<br><br> Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gin, or lie;<br><br> 25<br><br> Xaa at position<br><br> 117<br><br> is<br><br> Thr,<br><br> Ser,<br><br> Asn,<br><br> lie,<br><br> Trp,<br><br> Lys,<br><br> or Pro;<br><br> Xaa at position<br><br> 118<br><br> is<br><br> Leu,<br><br> Ser,<br><br> Pro,<br><br> Ala,<br><br> Glu,<br><br> Cys,<br><br> Asp, or Tyr;<br><br> Xaa at position<br><br> 119<br><br> is<br><br> Glu,<br><br> Ser,<br><br> Lys,<br><br> Pro,<br><br> Leu,<br><br> Thr,<br><br> Tyr, or Arg;<br><br> Xaa at position<br><br> 120<br><br> is<br><br> Asn,<br><br> Ala,<br><br> Pro,<br><br> Leu,<br><br> His,<br><br> Val,<br><br> or Gin;<br><br> Xaa at position<br><br> 121<br><br> is<br><br> Ala,<br><br> Ser,<br><br> lie,<br><br> Asn,<br><br> Pro,<br><br> Lys,<br><br> Asp, or Gly;<br><br> 30<br><br> Xaa at position<br><br> 122<br><br> is<br><br> Gin,<br><br> Ser,<br><br> Met,<br><br> Trp,<br><br> Arg,<br><br> Phe,<br><br> Pro, His,<br><br> lie, Tyr, or Cys;<br><br> Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;<br><br> 35<br><br> wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can<br><br> 15<br><br> 20<br><br> 35<br><br> ^ a Q<br><br> 539<br><br> optionally be deleted from the C-terminus; and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; ...<br><br> ■ 5<br><br> wherein Li is a linker capable of linking Ri to R2; and additionally said hematopoietic protein can be immediately preceded by (methionine-1), (alanine-1) or 10 (methionine-^, alanine-1).<br><br> 5. A substantially pure hematopoietic protein comprising; an amino acid sequence of the formula:<br><br> R1-L1-R2, R2-L1-R1, R1-R2, or R2~Rl wherein Ri is a polypeptide comprising; a modified human G-CSF amino acid sequence of the formula:<br><br> 1 10<br><br> Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gin Ser Xaa<br><br> 20<br><br> 25 Leu Leu Xaa Xaa Xaa Glu Gin Val Xaa Lys Xaa Gin Gly Xaa Gly<br><br> 30 40<br><br> Ala Xaa Leu Gin Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa<br><br> 30 50<br><br> Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly lie Pro Trp<br><br> 60 70<br><br> Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly<br><br> 80<br><br> Xaa Leu Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu<br><br> 90 100<br><br> 40 Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu<br><br> 110<br><br> Xaa Thr Leu Gin Xaa Asp Val Ala Asp Phe Ala Xaa Thr lie Trp<br><br> INTELLECTUAL PROPERTY OFFICE OF N.Z.<br><br> 2 5 JAN 2001<br><br> U IE (D E E E 0<br><br> 540<br><br> 120 130<br><br> Gin Gin Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gin Pro Thr<br><br> 5 140<br><br> Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gin Xaa Xaa Ala<br><br> 150 160<br><br> Gly Gly Val Leu Val Ala Ser Xaa Leu Gin Xaa Phe Leu Xaa Xaa<br><br> 10<br><br> 170<br><br> Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gin Pro (SEQ ID NO:l) wherein<br><br> 15<br><br> Xaa at position 1 is Thr, Ser, Arg, Tyr or Gly;<br><br> Xaa at position 2 is Pro or Leu;<br><br> Xaa at position 3 is Leu, Arg, Tyr or Ser;<br><br> Xaa at position 13 is Phe, Ser, His, Thr or Pro; 20 Xaa at position 16 is Lys, Pro, Ser, Thr or His;<br><br> Xaa at position 17 is Cys, Ser, Gly, Ala, lie, Tyr or Arg; Xaa at position 18 is Leu, Thr, Pro, His, lie or Cys;<br><br> Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala;<br><br> Xaa at position 24 is lie. Pro, Tyr or Leu;<br><br> 25 Xaa at position 27 is Asp, or Gly;<br><br> Xaa at position 30 is Ala, lie. Leu or Gly; , ,<br><br> Xaa at position 34 is Lys or Ser;<br><br> Xaa at position 36 is Cys or Ser;<br><br> Xaa at position 42 is Cys or Ser;<br><br> 30 Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala,<br><br> Arg, Cys, or Leu;<br><br> Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His,<br><br> Trp, Gin, or Thr;<br><br> Xaa at position 46 is Glu, Arg, Phe, Arg, lie or Ala; 35 Xaa at position 47 is Leu or Thr;<br><br> Xaa at position 49 is Leu, Phe, Arg or Ser;<br><br> Xaa at position 50 is Leu, lie, His, Pro or Tyr;<br><br> Xaa at position 54 is Leu or His;<br><br> Xaa at position 64 is Cys or Ser;<br><br> 40 Xaa at position 67 is Gin, Lys, Leu or Cys;<br><br> Xaa at position 70 is Gin, Pro, Leu, Arg or Ser;<br><br> Xaa at position 74 is Cys or Ser;<br><br> Xaa at position 104 is Asp, Gly or Val;<br><br> Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gin or Gly; 45 Xaa at position 115 is Thr, His, Leu or Ala;<br><br> Xaa at position 120 is Gin, Gly, Arg, Lys or His Xaa at position 123 is Glu, Arg, Phe or Thr Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gin or Glu; Xaa at position 146 is Arg or Gin;<br><br> 50 Xaa at position 147 is Arg or Gin;<br><br> Xaa at position 156 is His, Gly or Ser;<br><br> Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly;<br><br> 541<br><br> Xaa at position 162 is Glu, Leu, Gly or Trp;<br><br> Xaa at position 163 is Val, Gly, Arg or Ala;<br><br> Xaa at position 169 is Arg, Ser, Leu, Arg or Cys;<br><br> Xaa at position 170 is His, Arg or Ser;<br><br> 5<br><br> wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted from said modified human G-CSr amino acid sequence; and<br><br> 10 wherein the N-terminus is joined to the C-terminus directly<br><br> or through a linker capable of joining the<br><br> N-terminus to the<br><br> C-terminus and having new C- and N-termini at amino acids;<br><br> 15<br><br> 38-39<br><br> 62-63<br><br> 123-124<br><br> 39-40<br><br> 63-64<br><br> 124-125<br><br> 40-41<br><br> 64-65<br><br> 125-126<br><br> 41-42<br><br> 65-66<br><br> 126-127<br><br> 42-43<br><br> 66-67<br><br> 128-129<br><br> 20<br><br> 43-44<br><br> 67-68<br><br> 128-129<br><br> 45-46<br><br> 68-69<br><br> 129-130<br><br> 48-49<br><br> 69-70<br><br> 130-131<br><br> 49-50<br><br> 70-71<br><br> 131-132<br><br> 52-53<br><br> 71-72<br><br> 132-133<br><br> 25<br><br> 53-54<br><br> 91-92<br><br> 133-134<br><br> 54-55<br><br> 92-93<br><br> 134-135<br><br> 55-56<br><br> 93-94<br><br> 135-136<br><br> 56-57<br><br> 94-95<br><br> 136-137<br><br> 57-58<br><br> 95-96<br><br> 137-138<br><br> 30<br><br> 58-59<br><br> 96-97<br><br> 138-139<br><br> 59-60<br><br> 97-98<br><br> 139-140<br><br> 60-61<br><br> 98-99<br><br> 140-141<br><br> 61-62<br><br> 99-100<br><br> 141-142<br><br> or 142-143<br><br> 35<br><br> respectively; and<br><br> R2 is a polypeptide comprising; a modified human c-mpl ligand amino acid sequence of the formula:<br><br> 40 SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer<br><br> 1 5 10 15<br><br> HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 25. 30 35<br><br> 45<br><br> ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55<br><br> 542<br><br> ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 60 65 70 75<br><br> AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGiyGlnLeuSerGly 80 85 90 95<br><br> GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110<br><br> XaaG lyAr gThrThr AlaHisLy s AspProAsnAl a 11 ePheLeuS er PheGlnHi s 115 120 125 130<br><br> LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150<br><br> Arg (SEQ ID NO:256) 153<br><br> wherein;<br><br> Xaa at position 112 is deleted or Leu, Ala, Val, lie, Pro, Phe, Trp, or Met;<br><br> Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, lie, Trp, or Met;<br><br> Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, lie, Trp, or Met;<br><br> Xaa at position 115 is deleted or Gin, Gly, Ser, Thr, Tyr, or Asn; and wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;<br><br> 26-27<br><br> 51-52<br><br> 108-109<br><br> 27-28<br><br> 52-53<br><br> 109-110<br><br> 28-29<br><br> 53-54<br><br> 110-111<br><br> 29-30<br><br> 54-55<br><br> 111-112<br><br> 30-31<br><br> 55-56<br><br> 112-113<br><br> 32-33<br><br> 56-57<br><br> 113-114<br><br> 33-34<br><br> 57-58<br><br> 114-115<br><br> 34-35<br><br> 58-59<br><br> 115-116<br><br> 36-37<br><br> 59-60<br><br> 116-117<br><br> 37-38<br><br> 78-79<br><br> 117-118<br><br> 38-39<br><br> 79-80<br><br> 118-119<br><br> 40-41<br><br> 80-81<br><br> 119-120<br><br> 41-42'<br><br> 81-82<br><br> 120-121<br><br> 42-43<br><br> 82-83<br><br> 121-122<br><br> 43-44<br><br> 83-84<br><br> 122-123<br><br> 44-45<br><br> 84-85<br><br> 123-124<br><br> 46-47<br><br> 85-86<br><br> 124-125<br><br> 47-48<br><br> 86-87<br><br> 125-126<br><br> 48-49<br><br> 87-88<br><br> 126-127<br><br> 50-51<br><br> 88-89<br><br> or 127-128;<br><br> wherein Li is a linker capable of linking Ri to R2; and additionally said hematopoietic protein can be 5 immediately preceded by (methionine-1), (alanine-1) or<br><br> (methionine-^r alanine-1).<br><br> 6. A substantially pure hematopoietic protein comprising; an amino acid sequence of the formula:<br><br> 10<br><br> R1-L1-R2, R2-L1-R1, Rl~R2, or R2~Rl wherein Ri is a polypeptide comprising; a modified human c-mpl ligand amino acid sequence of the formula:<br><br> 15<br><br> SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer 15 10 15<br><br> HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 20 25 30 35<br><br> ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55<br><br> 25 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla<br><br> 60 65 70 75<br><br> AlaArgGlyGlhLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95<br><br> 30<br><br> GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110<br><br> XaaG lyAr gThrThr AlaHisLysAspProAsnAlallePheLeuSerPheGlnHis<br><br> INTELLECTUAL PROPERTY OFFICE OF N.Z.<br><br> 2 5 JAN 2001<br><br> 544<br><br> 115 120 125 130<br><br> LeuLeuArgGZyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150<br><br> Arg (SEQ ID NO:256)<br><br> 153<br><br> wherein;<br><br> Xaa at position 112 is deleted or Leu, Ala, Val, lie, Pro, Phe, Trp, or Met;<br><br> Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, lie, Trp, or Met;<br><br> Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, lie, Trp, or Met;<br><br> Xaa at position 115 is deleted or Gin, Gly, Ser, Thr, Tyr, or Asn,- and wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;<br><br> 26-27 51-52 108-109<br><br> 27-28 52-53 109-110<br><br> 28-29 53-54 110-111<br><br> 29-30 54-55 111-112<br><br> 30-31 55-56 112-113<br><br> 32-33 56-57 113-114<br><br> 33-34 57-58 114-115<br><br> 34-35 58-59 115-116<br><br> 36-37 59-60 116-117<br><br> 37-38 78-79 117-118<br><br> 38-39 ' 79-80 118-119<br><br> 40-41 80-81 119-120<br><br> 41-42 81-82 120-121<br><br> 42-43 82-83 121-122<br><br> 43-44 83-84 122-123<br><br> 44-45 84-85 123-124<br><br> 46-47 85-86 124-125<br><br> 47-48 86-87 125-126<br><br> 48-49 87-88 126-127<br><br> 545<br><br> 50-51 88-89 or 127-128;<br><br> wherein R2 is a polypeptide comprising; a modified human IL-3 amino acid sequence of the formula:<br><br> Ala Pro Met Thr Gin Thr Thr Ser Leu Lys Thr Ser Trp Val Asn 15 10 15<br><br> Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 20 25 30<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 35 40 45<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 50 55 60<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 65 70 75<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 80 85 90<br><br> Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 95 100 105<br><br> Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa<br><br> 110 115 120<br><br> Xaa Xaa Xaa Gin Gin Thr Thr Leu Ser Leu Ala lie Phe<br><br> 125 130<br><br> wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gin, or Arg; Xaa at position 18 is Asn, His, Leu, lie, Phe, Arg, or Gin;<br><br> ft<br><br> ■ -<br><br> 546<br><br> w<br><br> Xaa at position<br><br> 19<br><br> is Met,<br><br> Phe,<br><br> lie.<br><br> Arg,<br><br> Gly,<br><br> Ala,<br><br> or Cys;<br><br> Xaa at position<br><br> 20<br><br> is lie,<br><br> Cys,<br><br> Gin,<br><br> Glu,<br><br> Arg,<br><br> Pro,<br><br> or Ala;<br><br> Xaa at position 21<br><br> is Asp,<br><br> Phe,<br><br> Lys,<br><br> Arg,<br><br> Ala,<br><br> Gly,<br><br> Glu, Gin,<br><br> Asn,<br><br> . Thr, Ser or Val;<br><br> 5<br><br> Xaa at position 22<br><br> is Glu,<br><br> Trp,<br><br> Pro,<br><br> Ser,<br><br> Ala,<br><br> His,<br><br> Asp, Asn,<br><br> Gin,<br><br> Leu, Val or Gly;<br><br> Xaa at position<br><br> 23<br><br> is lie.<br><br> Val,<br><br> Ala,<br><br> Gly,<br><br> Trp,<br><br> Lys,<br><br> Phe,<br><br> Leu, Ser,<br><br> or<br><br> Arg;<br><br> Xaa at position<br><br> 24<br><br> is lie.<br><br> Gly,<br><br> Val,<br><br> Arg,<br><br> Ser,<br><br> Phe,<br><br> or Leu;<br><br> 10<br><br> Xaa at position<br><br> 25<br><br> .is Thr,<br><br> His,<br><br> Gly,<br><br> Gin,<br><br> Arg,<br><br> Pro,<br><br> or Ala;<br><br> Xaa at position<br><br> 26<br><br> is His,<br><br> Thr,<br><br> Phe,<br><br> Gly,<br><br> Arg,<br><br> Ala,<br><br> or Trp;<br><br> Xaa at position<br><br> 27<br><br> is Leu,<br><br> Gly,<br><br> Arg,<br><br> Thr,<br><br> Ser,<br><br> or Ala;<br><br> Xaa at position<br><br> 28<br><br> is Lys,<br><br> Arg,<br><br> Leu,<br><br> Gin,<br><br> Gly,<br><br> Pro,<br><br> Val or Trp<br><br> ;<br><br> Xaa at position<br><br> 29<br><br> is Gin,<br><br> Asn,<br><br> Leu,<br><br> Pro,<br><br> Arg,<br><br> or Val;<br><br> 15<br><br> Xaa at position<br><br> 30<br><br> is Pro,<br><br> His,<br><br> Thr,<br><br> Gly,<br><br> Asp,<br><br> Gin,<br><br> Ser, Leu,<br><br> or Lys;<br><br> Xaa at position<br><br> 31<br><br> is Pro,<br><br> Asp,<br><br> Gly,<br><br> Ala,<br><br> Arg,<br><br> Leu,<br><br> or Gin;<br><br> Xaa at position<br><br> 32<br><br> is Leu,<br><br> Val,<br><br> Arg,<br><br> Gin,<br><br> Asn,<br><br> Gly,<br><br> Ala, or Glu;<br><br> Xaa at position<br><br> 33<br><br> is Pro,<br><br> Leu,<br><br> Gin,<br><br> Ala,<br><br> Thr,<br><br> or Glu;<br><br> Xaa at position<br><br> 34<br><br> is Leu,<br><br> Val,<br><br> Gly,<br><br> Ser,<br><br> Lys,<br><br> Glu,<br><br> Gin, Thr,<br><br> 20<br><br> Arg, Ala,<br><br> Phe, lie or Met<br><br> /<br><br> Xaa at position<br><br> 35<br><br> is Leu,<br><br> Ala,<br><br> Gly,<br><br> Asn,<br><br> Pro,<br><br> Gin,<br><br> or Val;<br><br> Xaa at position<br><br> 36<br><br> is Asp,<br><br> Leu,<br><br> or Val;<br><br> Xaa at position<br><br> 37<br><br> is Phe,<br><br> Ser,<br><br> Pro,<br><br> Trp,<br><br> or lie;<br><br> Xaa at position<br><br> 38<br><br> is Asn,<br><br> or Ala;<br><br> 25<br><br> Xaa at position<br><br> 40<br><br> is Leu,<br><br> Trp,<br><br> or Arg;<br><br> Xaa at position<br><br> 41<br><br> is Asn,<br><br> Cys,<br><br> Arg,<br><br> Leu,<br><br> His,<br><br> Met,<br><br> or Pro;<br><br> Xaa at position<br><br> 42<br><br> is Gly,<br><br> Asp,<br><br> Ser,<br><br> Cys,<br><br> Asn,<br><br> Lys,<br><br> Thr, Leu,<br><br> Val, Glu,<br><br> Phe, Tyr,<br><br> He,<br><br> Met or Ala t<br><br> Xaa at position<br><br> 43<br><br> is Glu,<br><br> Asn,<br><br> Tyr,<br><br> Leu,<br><br> Phe,<br><br> Asp,<br><br> Ala, Cys,<br><br> 30<br><br> Gin, Arg,<br><br> Thr, Gly or Ser<br><br> /<br><br> Xaa at position<br><br> 44<br><br> is Asp,<br><br> Ser,<br><br> Leu,<br><br> Arg,<br><br> Lys,<br><br> Thr,<br><br> Met, Trp,<br><br> Glu, Asn,<br><br> Gin, Ala or Pro<br><br> /<br><br> Xaa at position<br><br> 45<br><br> is Gin,<br><br> Pro,<br><br> Phe,<br><br> Val,<br><br> Met,<br><br> Leu,<br><br> Thr, Lys,<br><br> Trp, Asp,<br><br> Asn, Arg,<br><br> Ser,<br><br> Ala,<br><br> lie.<br><br> Glu or His<br><br> $<br><br> 35<br><br> Xaa at position<br><br> 46<br><br> is Asp,<br><br> Phe,<br><br> Ser,<br><br> Thr,<br><br> Cys,<br><br> Glu,<br><br> Asn, Gin,<br><br> 547<br><br> Lys, His, Ala, Tyr, lie, Val or Gly;<br><br> Xaa at position 47 is lie, Gly, Val, Ser, Arg, Pro, or His;<br><br> Xaa at position'48 is Leu, Ser, Cys, Arg, lie. His, Phe, Glu, .Lys, Thr, Ala, .Met, Val or Asn;<br><br> 5 Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;<br><br> Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser,<br><br> Ala, lie, Val, His, Phe, Met or Gin;<br><br> Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;<br><br> Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; 10 Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;<br><br> Xaa at position 54 is Arg, Asp, lie, Ser, Val, Thr, Gin, Asn,<br><br> Lys, His, Ala or Leu;<br><br> Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;<br><br> Xaa at position 56 is Pro, Gly, Cys, Ser, Gin, Glu, Arg, His, 15 Thr, Ala, Tyr, Phe, Leu, Val or Lys;<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> Xaa at position<br><br> 57<br><br> is<br><br> Asn or Gly;<br><br> Xaa at position<br><br> 58<br><br> is<br><br> Leu,<br><br> Ser,<br><br> Asp,<br><br> Arg,<br><br> Gin,<br><br> Val,<br><br> or Cys;<br><br> Xaa at position<br><br> 59<br><br> is<br><br> Glu<br><br> Tyr,<br><br> His,<br><br> Leu,<br><br> Pro,<br><br> or Arg;<br><br> Xaa at position<br><br> 60<br><br> is<br><br> Ala,<br><br> Ser,<br><br> Pro,<br><br> Tyr,<br><br> Asn,<br><br> or Thr;<br><br> Xaa at position<br><br> 61<br><br> is<br><br> Phe,<br><br> Asn,<br><br> Glu,<br><br> Pro,<br><br> Lys,<br><br> Arg,<br><br> or Ser;<br><br> Xaa at position<br><br> 62<br><br> is<br><br> Asn,<br><br> His,<br><br> Val,<br><br> Arg,<br><br> Pro,<br><br> Thr,<br><br> Asp,<br><br> or He;<br><br> Xaa at position<br><br> 63<br><br> is<br><br> Arg,<br><br> Tyr,<br><br> Trp,<br><br> Lys,<br><br> Ser,<br><br> His,<br><br> Pro,<br><br> or Val;<br><br> Xaa at position<br><br> 64<br><br> is<br><br> Ala,<br><br> Asn,<br><br> Pro,<br><br> Ser,<br><br> or Lys;<br><br> Xaa at position<br><br> 65<br><br> is<br><br> Val,<br><br> Thr,<br><br> Pro,<br><br> His,<br><br> Leu,<br><br> Phe,<br><br> or Ser;<br><br> Xaa at position<br><br> 66<br><br> is<br><br> Lys,<br><br> lie.<br><br> Arg,<br><br> Val,<br><br> Asn,<br><br> Glu,<br><br> or Ser;<br><br> Xaa at position<br><br> 67<br><br> is<br><br> Ser,<br><br> Ala,<br><br> Phe,<br><br> Val,<br><br> Gly,<br><br> Asn,<br><br> lie.<br><br> Pro, or<br><br> Xaa at position<br><br> 68<br><br> is<br><br> Leu,<br><br> Val,<br><br> Trp,<br><br> Ser,<br><br> He,<br><br> Phe,<br><br> Thr,<br><br> or His;<br><br> Xaa at position<br><br> 69<br><br> is<br><br> Gin,<br><br> Ala,<br><br> Pro,<br><br> Thr,<br><br> Glu,<br><br> Arg,<br><br> Trp,<br><br> Gly, or<br><br> Xaa at position 70<br><br> is<br><br> Asn,<br><br> Leu,<br><br> Val,<br><br> Trp,<br><br> Pro,<br><br> or Ala;<br><br> Xaa at position 7^1<br><br> is<br><br> Ala,<br><br> Met,<br><br> Leu,<br><br> Pro,<br><br> Arg,<br><br> Glu,<br><br> Thr,<br><br> Gin,<br><br> Trp, or Asn;<br><br> Xaa at position<br><br> 72<br><br> is<br><br> Ser,<br><br> Glu,<br><br> Met,<br><br> Ala,<br><br> His,<br><br> Asn,<br><br> Arg,<br><br> or Asp;<br><br> Xaa at position 73<br><br> is<br><br> Ala,<br><br> Glu,<br><br> Asp,<br><br> Leu,<br><br> Ser,<br><br> Gly,<br><br> Thr,<br><br> or Arg;<br><br> Xaa at position 74<br><br> is lie,<br><br> Met,<br><br> Thr,<br><br> Pro,<br><br> Arg,<br><br> Gly,<br><br> Ala;<br><br> Xaa at position 75<br><br> is<br><br> Glu,<br><br> Lys,<br><br> Gly,<br><br> Asp,<br><br> Pro,<br><br> Trp,<br><br> Arg,<br><br> Ser,<br><br> 548<br><br> Gin, or Leu;<br><br> Xaa at position<br><br> 76<br><br> is<br><br> Ser,<br><br> Val,<br><br> Ala,<br><br> Asn,<br><br> Trp,<br><br> Glu,<br><br> Pro,<br><br> Gly, or Asp;<br><br> Xaa at position<br><br> 77<br><br> is<br><br> He,<br><br> Ser,<br><br> Arg,<br><br> Thr,<br><br> or Leu;<br><br> Xaa at position<br><br> 7.8<br><br> is.<br><br> Leu,<br><br> Ala,<br><br> Ser,<br><br> Glu,<br><br> Phe,<br><br> Gly,<br><br> or Arg;<br><br> 5<br><br> Xaa at position<br><br> 79<br><br> is<br><br> Lys,<br><br> Thr,<br><br> Asn,<br><br> Met,<br><br> Arg,<br><br> lie.<br><br> Gly,<br><br> or Asp;<br><br> Xaa at position<br><br> 80<br><br> is<br><br> Asn,<br><br> Trp,<br><br> Val,<br><br> Gly,<br><br> Thr,<br><br> Leu,<br><br> Glu,<br><br> or Arg;<br><br> Xaa at position<br><br> 81<br><br> is<br><br> Leu,<br><br> Gin,<br><br> Gly,<br><br> Ala,<br><br> Trp,<br><br> Arg,<br><br> Val,<br><br> or Lys;<br><br> Xaa at position<br><br> 82<br><br> is<br><br> Leu,<br><br> Gin,<br><br> Lys,<br><br> Trp,<br><br> Arg,<br><br> Asp,<br><br> Glu,<br><br> Asn,<br><br> His, Thr,<br><br> Ser, Ala,<br><br> Tyr,<br><br> Phe,<br><br> lie.<br><br> Met or Val t<br><br> 10<br><br> Xaa at position<br><br> 83<br><br> is<br><br> Pro,<br><br> Ala,<br><br> Thr,<br><br> Trp,<br><br> Arg,<br><br> or Met;<br><br> Xaa at position<br><br> 84<br><br> is<br><br> Cys,<br><br> Glu,<br><br> Gly,<br><br> Arg,<br><br> Met,<br><br> or Val;<br><br> Xaa at position<br><br> 85<br><br> is<br><br> Leu,<br><br> Asn,<br><br> Val,<br><br> or Gin;<br><br> Xaa at position<br><br> 86<br><br> is<br><br> Pro,<br><br> Cys,<br><br> Arg,<br><br> Ala,<br><br> or Lys;<br><br> Xaa at position<br><br> 87<br><br> is<br><br> Leu,<br><br> Ser,<br><br> Trp,<br><br> or Gly;<br><br> 15<br><br> Xaa at position<br><br> 88<br><br> is<br><br> Ala,<br><br> Lys,<br><br> Arg,<br><br> Val,<br><br> or Trp;<br><br> Xaa at position<br><br> 89<br><br> is<br><br> Thr,<br><br> Asp,<br><br> Cys,<br><br> Leu,<br><br> Val,<br><br> Glu,<br><br> His,<br><br> Asn, or Ser;<br><br> Xaa at position<br><br> 90<br><br> is<br><br> Ala,<br><br> Pro,<br><br> Ser,<br><br> Thr,<br><br> Gly,<br><br> Asp,<br><br> He,<br><br> or Met;<br><br> Xaa at position<br><br> 91<br><br> is<br><br> Ala,<br><br> Pro,<br><br> Ser,<br><br> Thr,<br><br> Phe,<br><br> Leu,<br><br> Asp,<br><br> or His;<br><br> Xaa at position<br><br> 92<br><br> is<br><br> Pro,<br><br> Phe,<br><br> Arg,<br><br> Ser,<br><br> Lys,<br><br> His,<br><br> Ala,<br><br> Gly, lie or<br><br> 20<br><br> Leu;<br><br> Xaa at position<br><br> 93<br><br> is<br><br> Thr,<br><br> Asp,<br><br> Ser,<br><br> Asn,<br><br> Pro,<br><br> Ala,<br><br> Leu,<br><br> or Arg;<br><br> Xaa at position<br><br> 94<br><br> is<br><br> Arg,<br><br> lie,<br><br> Ser,<br><br> Glu,<br><br> Leu,<br><br> Val,<br><br> Gin,<br><br> Lys, His,<br><br> Ala, or Pro ,-<br><br> Xaa at position 95 is His, Gin, Pro, Arg, Val, Leu, Gly, Thr, Asn, 25 Lys, Ser, Ala, Trp, Phe, lie, or Tyr;<br><br> Xaa at position 96 is Pro, Lys, Tyr, Gly, lie, or Thr;<br><br> Xaa at position 97 is lie, Val, Lys, Ala, or Asn;<br><br> Xaa at position 98 is His, lie, Asn, Leu, Asp, Ala, Thr,<br><br> Glu, Gin, Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro; 30 Xaa at position 99 is lie, Leu, Arg, Asp, Val, Pro, Gin,<br><br> Gly, Ser, Phe, or His;<br><br> Xaa at position 100 is Lys, Tyr, Leu, His, Arg, lie, Ser, Gin, or Pro; Xaa at position 101 is Asp, Pro; Met, Lys, His, Thr, Val,<br><br> Tyr, Glu, Asn, Ser, Ala, Gly, lie. Leu, or Gin;<br><br> 35 Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;<br><br> 549<br><br> Xaa at position 103 is Asp, or Ser;<br><br> Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu,<br><br> Gin, Lys," Ala, Phe, or Gly;<br><br> Xaa a.t position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gin, Tyr, 5 Leu, Lys, lie. Asp, or His;<br><br> Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, lie, Gly, or Pro;<br><br> Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, lie. Gin, His, Ser, Ala or Pro;<br><br> Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;<br><br> 10 Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gin, His, Glu, Ser, or Trp;<br><br> Xaa at position 111 is Leu, lie, Arg, Asp, or Met;<br><br> Xaa at position 112 is Thr, Val, Gin, Tyr, Glu, His, Ser, or Phe;<br><br> Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp,<br><br> 15 Lys, Lea, lie, Val or Asn;<br><br> Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;<br><br> Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr,<br><br> Trp, or Met;<br><br> Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, 20 Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gin, or lie;<br><br> Xaa at position 117 is Thr, Ser, Asn, lie, Trp, Lys, or Pro;<br><br> Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;<br><br> Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;<br><br> Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gin;<br><br> 25 Xaa at position 121 is Ala, Ser, lie, Asn, Pro, Lys, Asp, or Gly;<br><br> Xaa at position 122 is Gin, Ser, Met, Trp, Arg, Phe, Pro, His,<br><br> lie, Tyr, or Cys;<br><br> Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;<br><br> 30 wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human interleukin-3 amino acid sequence; and wherein from 1 to 44 of the amino acids designated by Xaa are different<br><br> 550<br><br> from the corresponding amino acids of native (1-133) human interleukin-3;<br><br> .wherein Li. is.a linker capable of linking Ri to R2; and<br><br> 5<br><br> said hematopoietic protein can optionally be immediately preceded by (methionine-1), (alanine-1) or (methionine-^, alanine-1).<br><br> 10 9. The hematopoeitic protein of claim 6 or 8 wherein R2 is selected from the group consisting of;<br><br> Ala<br><br> Asn<br><br> Cys<br><br> Ser lie<br><br> Met lie<br><br> Asp Glu lie lie<br><br> His<br><br> His<br><br> Leu<br><br> Lys<br><br> 15<br><br> Arg<br><br> Pro<br><br> Pro<br><br> Ala<br><br> Pro<br><br> Leu<br><br> Leu<br><br> Asp<br><br> Pro<br><br> Asn<br><br> Asn<br><br> Leu<br><br> Asn<br><br> Ala<br><br> Glu<br><br> Asp<br><br> Val<br><br> Asp lie<br><br> Leu<br><br> Met<br><br> Glu<br><br> Arg Asn<br><br> Leu<br><br> Arg<br><br> Leu<br><br> Pro<br><br> Asn<br><br> Leu<br><br> 20<br><br> Glu<br><br> Ser<br><br> Phe<br><br> Val<br><br> Arg<br><br> Ala<br><br> Val<br><br> Lys<br><br> Asn<br><br> Leu<br><br> Glu<br><br> Asn<br><br> Ala<br><br> Ser<br><br> Gly<br><br> lie<br><br> Glu<br><br> Ala lie<br><br> Leu<br><br> Arg<br><br> Asn<br><br> Leu<br><br> Gin<br><br> Pro<br><br> Cys<br><br> Leu<br><br> Pro<br><br> Ser<br><br> Ala<br><br> Thr<br><br> Ala<br><br> Ala<br><br> Pro<br><br> Ser<br><br> Arg<br><br> His<br><br> Pro lie lie lie<br><br> Lys<br><br> Ala<br><br> Gly<br><br> Asp<br><br> 25<br><br> Trp<br><br> Gin<br><br> Glu<br><br> Phe<br><br> Arg<br><br> Glu<br><br> Lys<br><br> Leu<br><br> Thr<br><br> Phe<br><br> Tyr<br><br> Leu<br><br> Val<br><br> Thr<br><br> Leu<br><br> Glu<br><br> Gin<br><br> Ala<br><br> Gin<br><br> Glu<br><br> Gin<br><br> Gin<br><br> (SEQ ID<br><br> NO:225)<br><br> 7<br><br> 30<br><br> Ala<br><br> Asn<br><br> Cys<br><br> Ser lie<br><br> Met lie<br><br> Asp<br><br> Glu lie lie<br><br> His<br><br> His<br><br> Leu<br><br> Lys<br><br> Arg<br><br> Pro<br><br> Pro<br><br> Asn<br><br> Pro<br><br> Leu<br><br> Leu<br><br> Asp<br><br> Pro<br><br> Asn<br><br> Asn<br><br> Leu<br><br> Asn<br><br> Ser<br><br> Glu<br><br> 35<br><br> Asp<br><br> Met<br><br> Asp lie<br><br> Leu<br><br> Met<br><br> Glu<br><br> Arg<br><br> Asn<br><br> Leu<br><br> Arg<br><br> Thr<br><br> Pro<br><br> Asn<br><br> Leu<br><br> Leu<br><br> Ala<br><br> Phe<br><br> Val<br><br> Arg<br><br> Ala<br><br> Val<br><br> Lys<br><br> His<br><br> Leu<br><br> Glu<br><br> Asn<br><br> Ala<br><br> Ser<br><br> Gly<br><br> lie<br><br> Glu<br><br> Ala lie<br><br> Leu<br><br> Arg<br><br> Asn<br><br> Leu<br><br> Gin<br><br> Pro<br><br> Cys<br><br> Leu<br><br> Pro<br><br> Ser<br><br> Ala<br><br> 40<br><br> Thr<br><br> Ala<br><br> Ala<br><br> Pro<br><br> Ser<br><br> Arg<br><br> His<br><br> Pro lie lie lie<br><br> Lys<br><br> Ala<br><br> Gly<br><br> Asp<br><br> Trp<br><br> Gin<br><br> Glu<br><br> Phe<br><br> Arg<br><br> Glu<br><br> Lys<br><br> Leu<br><br> Thr<br><br> Phe<br><br> Tyr<br><br> Leu<br><br> Val<br><br> Thr<br><br> Leu<br><br> 45<br><br> Glu<br><br> Gin<br><br> Ala<br><br> Gin<br><br> Glu<br><br> Gin<br><br> Gin<br><br> (SEQ ID<br><br> NO: 2 2 6)<br><br> f<br><br> Ala<br><br> Asn<br><br> Cys<br><br> Ser lie<br><br> Met lie<br><br> Asp<br><br> Glu lie lie<br><br> His<br><br> His<br><br> Leu<br><br> Lys<br><br> Val<br><br> Pro<br><br> Pro<br><br> Ala<br><br> Pro<br><br> Leu<br><br> Leu<br><br> Asp<br><br> Ser<br><br> Asn<br><br> Asn<br><br> Leu<br><br> Asn<br><br> Ser<br><br> Glu<br><br> Asp<br><br> Met<br><br> Asp lie<br><br> Leu<br><br> Met<br><br> Glu<br><br> Arg<br><br> Asn<br><br> Leu<br><br> Arg<br><br> Leu<br><br> Pro<br><br> Asn<br><br> Leu<br><br> Leu<br><br> Ala<br><br> Phe<br><br> Y'il<br><br> Arg<br><br> Ala<br><br> Val<br><br> Lys<br><br> Asn<br><br> Leu<br><br> Glu<br><br> Asn<br><br> Ala<br><br> Ser<br><br> Gly<br><br> 5<br><br> lie<br><br> Glu<br><br> Ala lie<br><br> Leu<br><br> Arg<br><br> Asn<br><br> Leu<br><br> Gin<br><br> Pro<br><br> Cys<br><br> Leu<br><br> Pro<br><br> ■Ser<br><br> Ala<br><br> Thr<br><br> Ala<br><br> Ala<br><br> Pro<br><br> Ser<br><br> Arg<br><br> His<br><br> Pro lie lie lie<br><br> Lys<br><br> Ala<br><br> Gly Asp<br><br> Trp<br><br> Gin<br><br> Glu<br><br> Phe<br><br> Arg<br><br> Glu<br><br> Lys<br><br> Leu<br><br> Thr<br><br> Phe<br><br> Tyr<br><br> Leu<br><br> Val<br><br> Thr<br><br> Leu<br><br> 10<br><br> Glu<br><br> Gin<br><br> Ala<br><br> Gin<br><br> Glu<br><br> Gin<br><br> Gin<br><br> (SEQ ID<br><br> NO:227);<br><br> ; and<br><br> Asn<br><br> Cys<br><br> Ser lie<br><br> Met lie<br><br> Asp<br><br> Glu lie lie<br><br> His<br><br> His<br><br> Leu<br><br> Lys<br><br> Arg<br><br> Pro<br><br> Pro<br><br> Ala<br><br> Pro<br><br> Leu<br><br> Leu<br><br> Asp<br><br> Pro<br><br> Asn<br><br> Asn<br><br> Leu<br><br> Asn<br><br> Asp<br><br> Glu<br><br> Asp<br><br> 15<br><br> Val<br><br> Ser lie<br><br> Leu<br><br> Met<br><br> Asp<br><br> Arg<br><br> Asn<br><br> Leu<br><br> Arg<br><br> Leu<br><br> Pro<br><br> Asn<br><br> Leu<br><br> Glu<br><br> Ser<br><br> Phe<br><br> Val<br><br> Arg<br><br> Ala<br><br> Val<br><br> Lys<br><br> Asn<br><br> Leu<br><br> Glu<br><br> Asn<br><br> Ala<br><br> Ser<br><br> Gly lie<br><br> Glu<br><br> Ala lie<br><br> Leu<br><br> Arg<br><br> Asn<br><br> Leu<br><br> Gin<br><br> Pro<br><br> Cys<br><br> Leu<br><br> Pro<br><br> Ser<br><br> Ala<br><br> Thr<br><br> Ala<br><br> Ala<br><br> Pro<br><br> Ser<br><br> Arg<br><br> His<br><br> Pro lie lie lie<br><br> Lys<br><br> Ala<br><br> Gly<br><br> Asp<br><br> Trp<br><br> Gin<br><br> Glu<br><br> Phe<br><br> Arg<br><br> Glu<br><br> Lys<br><br> Leu<br><br> Thr<br><br> Phe<br><br> Tyr<br><br> Leu<br><br> Val<br><br> Thr<br><br> Leu<br><br> Glu<br><br> 20<br><br> Gin<br><br> Ala<br><br> Gin<br><br> Glu<br><br> Gin<br><br> Gin<br><br> (SEQ ID NO<br><br> :228;<br><br> ) -<br><br> 25<br><br> 30<br><br> 8. A substantially pure hematopoietic protein comprising; an amino acid sequence of the formula:<br><br> R1-L1-R2, R2-L1-R1, R1-R2, R2-R1<br><br> wherein Ri is a polypeptide comprising; a modified human c-mpl ligand amino acid sequence of the formula:<br><br> SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer 15 10 15<br><br> HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 35 20 25 30 35<br><br> ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55<br><br> 40 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla<br><br> 60 65 70 75<br><br> AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95<br><br> INTELLECTUAL PROPERTY OFFICE OF N.Z.<br><br> 2 5 JAN 2001<br><br> U E © IE IV E 0<br><br> 552<br><br> 10<br><br> 15<br><br> GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110<br><br> XaaGlyAr gThrThr AlaHisLysAspProAsnAlallePheLeuSerPheGlnHis 115 ' 120 125 130<br><br> LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150<br><br> Arg (SEQ ID NO:256)<br><br> 153<br><br> wherein,*.;Xaa at position 112 is deleted or Leu, Ala, Val, lie, Pro,;Phe, Trp, or Met;;Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, lie, Trp, or Met;;20 Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, lie, Trp, or Met;;Xaa at position 115 is deleted or Gin, Gly, Ser, Thr, Tyr, or Asn; and;25 wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;;25-27 51-52 108-109;27-28 52-53 109-110;28-29 53-54 110-111;29-30 54-55 111-112;30-31 55-56 112-113;32-33 56-57 113-114;33-34 57-58 114-115;34-35 58-59 115-116;36-37 59-60 116-117;37-38 78-79 117-118;38-39 79-80 118-119;40-41 80-81 119-120;41-42 81-82 120-121;42-43 82-83 121-122;553;43-44 83-84 122-123;44-45 84-85 123-124;46-47 85-86 124-125;47-48 ' 86-87 125-126;48-49 87-88 126-127 50-51' 88-89 or 127-128;respectively;;wherein R2 is G-CSF or G-CSF Ser17;;wherein Li is a linker capable of linking Ri to R2; and;5;said hematopoietic protein can.optionally be immediately preceded by (methionine-1), (alanine-1) or (methionine-2, alanine-1).;10;11. The hematopoietic protein as recited in claim 1, 2, 3, 4, 5, 6, 7, 8, or 10 wherein said linker (L2) is selected from the group consisting of;;GlyGlyGlySer (SEQ ID NO:12); 15 GlyGlyGlySerGlyGlyGlySer (SEQ ID NO:242);;GlyGlyGlySerGlyGlyGlySerGlyGlyGlySer (SEQ ID NO:243); SerGlyGlySerGlyGlySer (SEQ ID NO:244); GluPheGlyAsnMetAla (SEQ ID NO:245); GluPheGlyGlyAsnMetAla (SEQ ID NO:246); 20 GluPheGlyGlyAsnGlyGlyAsnMetAla (SEQ ID NO:247); and;GlyGlySerAspMetAlaGly (SEQ ID NO:248).;12. The hematopoietic protein as recited in claim 9 wherein said linker (L2) is selected from the group;25 consisting of;;GlyGlyGlySer (SEQ ID NO:12);;GlyGlyGlySerGlyGlyGlySer (SEQ ID NO:242); GlyGlyGlySerGlyGlyGlySerGlyG lyGlySer (SEQ ID NO: 243); SerGlyGlySerGlyGlySer (SEQ ID NO:244); 30 GluPheGlyAsnMetAla (SEQ ID NO:245);;G lu PheG ly G lyAsnMe t Al a (SEQ ID NO:246); GluPheGlyGlyAsnGlyGlyAsnMetAla (SEQ ID NO:247); and GlyGlySerAspMetAlaGly (SEQ ID NO: 248).;5 13. The hematopoietic protein as recited in claim 1;wherein said protein is ^elected from the group consisting of;;10;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;15;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Tyr;Val;Glu;Gly;Gly;Gly;Gly;Ser;Pro;Gly;Gly;Gly;Ser;Gly;Gly;Gly;Ser;Asn;Met;Ala;Tyr;Lys;Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly;His;Ser;Leu;Gly lie;Pro;20;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu;Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;Met;Ala;Pro;Ala;Leu;Gin;Pro;25;Thr;Gin;Gly;Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly;Val;Leu;Val;Ala;Ser;His;Leu;Glh;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Ser;Gly Gly;Ser;Gly;Gly;Ser;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin;Gly;Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;30;Ala;Thr;(SEQ ID;NO:166);;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;35;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie;He;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;40;Gin;Ala;Gin;Glu;Gin;Gin;Tyr;Val;Glu;Gly;Gly;Gly;Gly;Ser;Pro;Gly;Glu;Pro;Ser;Gly;Pro lie;Ser;Thr lie;Asn;Pro;Ser;Pro;Pro;Ser;Lys;Glu;Ser;His;Lys;Ser;Pro;Asn;Met;Ala;Tyr;Lys;Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly;His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;45;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu;Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;Met;Ala;Pro;Ala;Leu;Gin;Pro;Thr;Gin;Gly;Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;•;555;Ala;Gly;Gly Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Ser;Gly;Gly;Ser;Gly;Gly;Ser;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie Gin Gly Asp Gly Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;5;Ala;Thr;(SEQ ID;NO:167)j r;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;10;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;15;Gin;Ala;Gin;Glu;Gin;Gin Tyr Val;Glu;Gly;Gly;Gly;Gly;Ser;Pro;Gly;Gly;Gly;Ser Gly;Gly;Gly;Ser;Asn;Met;Ala;Pro;Glu;Leu;Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;Met;Ala;Pro;Ala;Leu;Gin;Pro;Thr;Gin;Gly;Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;20;Arg;Arg;Ala;Gly;Gly;Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Ser;Gly;Gly;Ser;Gly Gly;Ser;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin Gly'Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lys;Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;25;Leu;Gly;His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie Ser (SEQ ID NO:168);;30;Asn;Cys;Sex lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;35;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin Tyr Val;Glu;Gly;Gly;Gly;Gly;Ser;Pro;Gly;Glu;Pro;Ser Gly;Pro lie;Ser;Thr lie;Asn;Pro;Ser;Pro;Pro;40;Ser;Lys;Glu;Ser;His;Lys;Ser;Pro;Asn;Met;Ala;Pro;Glu;Leu;Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;Met;Ala;Pro;Ala;Leu;Gin;Pro;Thr;Gin;Gly;Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly;Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;45;Leu;Glu;Val;Ser;'Tyr;Arg Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Ser;Gly;Gly;Ser;Gly;Gly;Ser;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin Gly Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lys;Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly;His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;50;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin;Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie Ser (SEQ ID NO:169);;5;10;15;20;25;30;35;40;45;50;556;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Tyr;Val;Glu Gly;Gly;Gly;Gly;Ser;Pro;Gly;Gly;Gly;Ser;Gly;Gly;Gly;Ser;Asn;Met;Ala;Met;Ala;Pro;Ala;Leu;Gin;Pro;Thr;Gin;Gly Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Ser;Gly;Gly;Ser Gly;Gly;Ser;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin;Gly;Asp Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lys;Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly;His;Ser;Leu Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin;Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Sej.";Pro;Glu;Leu Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;(SEQ ID;NO:17 0) ;;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Tyr;Val;Glu;Gly;Gly;Gly;Gly;Ser;Pro;Gly;Glu;Pro;Ser;Gly;Pro lie;Ser;Thr lie;Asn;Pro;Ser;Pro;Pro;Ser;Lys;Glu;Ser;His;Lys;Ser;Pro;Asn;Met;Ala;Met;Ala;Pro;Ala;Leu;Gin;Pro;Thr;Gin;Gly Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Ser;Gly;Gly;Ser;Gly;Gly;Ser;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin;Gly;Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lys;Leu;Cys;'His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly;His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin;Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;(SEQ ID;NO:171);;r;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;5;10;15;20;25;30;35;40;45;50;557;Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gl'y Gly Ser Gly Gly Gly Ser Asn Met Ala Thr Gin Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gin Pro Ser Gly Gly Ser Gly Gly Ser Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie Gin Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin Ala Leu Gin Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe Leu Tyr Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gin Pro (SEQ ID NO:172);;Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg;Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp;Val Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu;Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie;Glu Ala lie Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr;Ala Ala Pro Ser Arg His Pro lie lie lie Lys Ala Gly Asp Trp;Gin Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu;Gin Ala Gin Glu Gin Gin Tyr Val Glu Gly Gly Gly Gly Ser Pro;Gly Glu Pro Ser Gly Pro lie Ser Thr lie Asn Pro Ser Pro Pro;Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Thr Gin Gly Ala;Met Pro Ala Phe Ala Ser Ala Phe Gin Arg Arg Ala Gly Gly Val;Leu Val Ala Ser His Leu Gin Ser Phe Leu Glu Val Ser Tyr Arg;Val Leu Arg His Leu Ala Gin Pro Ser Gly Gly Ser Gly Gly Ser;Gin Ser Phe Leu Leu Lys Ser Leu Glu Gin Val Arg Lys lie Gin;Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu Cys Ala Thr Tyr Lys;Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly lie Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gin Ala Leu Gin;Leu Ala Gly Cys Leu Ser Gin Leu His Ser Gly Leu Phe Leu Tyr;Gin Gly Leu Leu Gin Ala Leu Glu Gly lie Ser Pro Glu Leu Gly;Pro Thr Leu Asp Thr Leu Gin Leu Asp Val Ala Asp Phe Ala Thr;Thr lie Trp Gin Gin Met Glu Glu Leu Gly Met Ala Pro Ala Leu;Gin Pro (SEQ ID NO:173);;Asn;Cys;Ser lie;•Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Tyr;Val;Glu;Gly;Gly;Gly;Gly;Ser;Pro;5;10;15;20;25;30;35;40;45;50;558;Gly;Gly Gly;Ser;Gly Gly;Gly;Ser;Asn;Met;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Aid;Gly;Gly Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Ser;Gly;Gly;Ser;Gly;Gly Ser;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie Gin;Gly;Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr Lys;Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly;His;Ser;Leu Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly Leu;Phe;Leu Tyr;Gin;Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu Gly Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;Met;Ala;Pro;Ala Leu;Gin;Pro;Thr;Gin;Gly;Ala;Met;Pro;Ala;Phe;Ala;(SEQ ID;NO: 174:) ;;Asn;Cys;Ser lie;Met;He;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Tyr;Val;Glu;Gly;Gly;Gly;Gly;Ser;Pro;Gly;Glu;Pri';Ser;Gly;Pro lie;Ser;Thr lie;Asn;Pro;Ser;Pro;Pro;Ser;Lys;Glu;Ser;His;Lys;Ser;Pro;Asn;Met;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly;Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Ser;Gly;Gly;Ser;Gly;Gly;Ser;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin;Gly;Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lys;Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly;His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin;Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu;Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;Met;Ala;Pro;Ala;Leu;Gin;Pro;Thr;Gin;Gly;Ala;Met;Pro;Ala;Phe;Ala;(SEQ ID;NO:175);;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu.;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Serv- Arg;His;Pro lie;He lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Tyr;Val;Glu;Gly;Gly;Gly;Gly;Ser;Pro;Gly;Gly;Gly;Ser;Gly;Gly;Gly;Ser;Asn;Met;Ala;Tyr;Lys;Leu;Cys;His;Pro;Glu;Glu;Leu val;Leu;Leu;Gly;His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin;Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu;Gly;Pro;Thr;5;10;15;20;25;30;35;40;45;559;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly Met;Ala;Pro;Ala;Leu;Gin;Pro;Thr;Gin;Gly Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Thr;Pro;Leu;Gly;Pro;Ala;Ser;Ser;Leu;Pro;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin;Gly Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;(SEQ ID;NO:" 176) ;;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe va:;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;"Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Tyr;Val;Glu;Gly;Gly;Gly;Gly;Ser;Pro;Gly;Glu;Pro;Ser;Gly;Pro lie;Ser;Thr lie;Asn;Pro;Ser;Pro;Pro;Ser;Lys;Glu;Ser;His;Lys;Ser;Pro;Asn;Met;Ala;Tyr;Lys;Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly;His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu;Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;Met;Ala;Pro;Ala;Leu;Gin;Pro;Thr;Gin;Gly;Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly;Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Thr;Pro;Leu;Gly;Pro;Ala;Ser;Ser;Leu;Pro;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin;Gly;Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;(SEQ ID;NO:177);;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu.;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Tyr;Val;Glu Gly;Gly;Gly;Gly;Ser;Pro;Gly;Glu;Pro;Ser;Gly;Pro lie;Ser;Thr lie;Asn;Pro;Ser;Pro;Pro;Ser;Lys;Glu;Ser;His;Lys;Ser;Pro;Asn;Met;Ala;Pro;Glu;Leu Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;Met;Ala;Pro;Ala;Leu;Gin;Pro;Thr;Gin;Gly Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Thr;Pro;Leu;Gly;Pro;Ala;Ser;Ser;Leu;Pro;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin;Gly;Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lys;Leu;Cys;His;Pro;Glu;Glu;5;10;15;20;25;30;35;40;45;50;560;Leu;Val;Leu;Leu;Gly;His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser-;Gly;Leu;Phe;Leu;Tyr;Gin;Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly;Ile;Ser;(SEQ ID;NO:179);;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Tyr;Val;Glu;Gly;Gly Gly;Gly;Ser;Pro;Gly;Glu;Pro;Ser;Gly;Pro lie;Ser;Thr lie;Asn;Pro;Ser;Pro;Pro;Ser;Lys;Glu;Ser;His;Lys;Ser;Pro;Asn;Met;Ala;Met;Ala;Pro;Ala;Leu;Gin;Pro;Thr;Gin;Gly;Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly;Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Thr;Pro;Leu;Gly;Pro;Ala;Ser;Ser;Leu;Pro;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin;Gly Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lys;Leu Cys;His;Pro;Glu;Glu;Leu;Va3;Leu;Leu;Gly;His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin;Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu;Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;(SEQ ID;NO:181);;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Tyr;Val;Glu;Gly;Gly;Gly;Gly;Ser;Pro;Gly;Gly;Gly;Ser;Gly;Gly;Gly;Ser;Asn;Met;Ala;Thr;Gin;Gly Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Thr;Pro;Leu;Gly;Pro;Ala;Ser;Ser;Leu;Pro;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin;Gly;Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lyri;Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly;His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin;Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu;Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;Met;Ala;Pro;Ala;Leu;Gin;Pro;(SEQ ID;NO.-:;182);t;5;10;15;20;25;30;35;40;45;50;561;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly;He;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gil1;Glu;Gin;Gin;Tyr;Val;Glu Gly;Gly;Gly;Gly;Ser;Pro;Gly;Glu;Pro;Ser;Gly Pro lie;Ser;Thr lie;Asn;Pro;Ser;Pro;Pro;Ser;Lys;Glu;Ser;His;Lys;Ser;Pro;Asn;Met;Ala;Thr;Gin;Gly;Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly;Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Thr;Pro;Leu;Gly;Pro;Ala;Ser;Ser;Leu;Pro;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin;Gly;Asp Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lys;Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly;His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin;Gly Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu;Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;Met;Ala;Pro;Ala;Leu;Gin;Pro;(SEQ ID;NO:183);;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Tyr;Val;Glu;Gly;Gly;Gly;Gly;Ser;Pro;Gly;Gly;Gly;Ser;Gly Gly;Gly;Ser;Asn;Met;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Thr;Pro;Leu;Gly;Pro;Ala;Ser;Ser;Leu;Pro;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin Gly;Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lys;Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly Leu;Phe;Leu;Tyr;Gin;Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu;Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;, Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly &gt;Met Ala;Pro;Ala;Leu;Gin;Pro;Thr;Gin;Gly;Ala;Met;Pro;Ala;Phe;Ala;(SEQ ID;NO:184);r;MetAlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAla ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer GlylleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro;562;SerArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaTyrLysLeuCysHisProGluGluLeuValLeuLeu 5 GlyHisSerLeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln AlaLeuGluGlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVal AlaAspPheAlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu GlnProThrGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGly 10 ValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHis LeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeu ProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAla AlaLeuGlnGluLysLeuCysAlaThr (SEQ ID NO:194);;15;MetAlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAla ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer GlylleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro 20 SerArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr;PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaProGluLeuGlyProThrLeuAspThrLeuGlnLeu AspValAlaAspPheAlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaPro;2 5 AlaLeuGlnProThxGlnGlyAlaMetProAlaPheAlaSerAlaPheGlnArgArgAla;GlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeu ArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSer SerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAsp GlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeu;3 0 ValLeuLeuGlyHisSerLeuGlylleProTrpAlaProLeuSerSerCysProSerGln;AlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGly LeuLeuGlnAlaLeuGluGlylleSer (SEQ ID NO:195);;35 MetAlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAla;ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsxiLeuGluAsnAlaSer GlylleGliiAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro S er Ar gHi sProIlellell eLy s AlaG lyAspTrpG InG luPheAr gG luLy sL euThr;4 0 PheTy rL euV dlThr L euGluG InAlaG InG luG InG InTy rVa 1G luGly G ly G lyG ly;SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuVal AlaSerHisLeuGlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGln ProGlyGlyGlySerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSer 45 PheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGln;GluLysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHis SerLeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAla GlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeu GluGlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAsp;5 0 pheAlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeuGlnPro;ThrGlnGlyAlaMetProAlaPheAla (SEQ ID NO:196);;5;10;15;20;25;30;35;40;45;50;563;MetAlaAsnCysSerlleMetlleAspGlullelleHisHisLeuLysArgProProAla ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer GlylleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro SerArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGiuProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaMetAlaProAlaLeuGlnProThrGlnGlyAlaMet ProAlaPheAlaSerAlaPheGlnArgArgAlaGlyGlyValLeuValAlaSerHisLeu GlnSerPheLeuGluValSerTyrArgValLeuArgHisLeuAlaGlnProGlyGlyGly SerAspMetAlaThrProLeuGlyProAlaSerSerLeuProGlnSerPheLeuLeuLys SerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCys AlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSerLeuGlylle ProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSer GlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlylleSer ProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPheAlaThrThr IleTrpGlnGlnMetGluGluLeuGly (SEQ ID NO:197);;MetAlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAla ProLeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsn LeuArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSer GlylleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaPro SerArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThr PheTyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer TyrArgValLf.uArgHisLeuAlaGlnProGlyGlyGlySerAspMetAlaThrProLeu GlyProAlaSerSerLeuProGlnSerPheLeuLeuLysSerLeuGluGlnValArgLys IleGlnGlyAspGlyAlaAlaLeuGlnGluLysLeuCysAlaThrTyrLysLeuCysHis ProGluGluLeuValLeuLeuGlyHisSerLeuGlylleProTrpAlaProLeuSerSer CysProSerGlnAlaLeuGlnLeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPhe LeuTyrGlnGlyLeuLeuGlnAlaLeuGluGlylleSerProGluLeuGlyProThrLeu AspThrLeuGlnLeuAspValAlaAspPheAlaThrThrlleTrpGlnGlnMetGluGlu LeuGlyMetAlaProAlaLeuGlnPro (SEQ ID NO:198);;Ala;Asn;Cys;Ser lie;Met lie;Asp Glu lie lie;His;His;Leu Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp Pro;Asn;Asn;Leu;Asn;Asp Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg Asn;Leu;Arg;Leu;Pro;Asn Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys Asn;Leu;Glu Asn Ala Ser Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu Gin;Pro;Cys;Leu;Pro;Ser Ala;Thr;Ala;Ala;Pro;\Ser;Arg;His;Pro lie lie lie;Lys;Ala Gly Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu Thr;Phe;Tyr;Leu;Val;Thr Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Tyr Val;Glu;Gly;Gly;Gly;Ser Pro;Gly;Glu;Pro;Ser;Gly;Pro lie;Ser Thr lie;Asn;Pro;Ser;Pro Pro;Ser;Lys;Glu;Ser;His;Lys;Ser;Pro Asn;Met;Gly;Pro;Thr;Cys Leu;Ser;Ser;Leu;Leu;Gly;Gin;Leu;Ser Gly;Gin;Val;Arg;Leu;Leu Leu;Gly;Ala;Leu;Gin;Ser;Leu;Leu;Gly Thr;Gin;Leu;Pro;Pro;Gin Gly;5;10;15;20;25;30;35;40;45;50;564;Arg;Thr;Thr;Ala;His;Lys;Asp;Pro;Asn;Ala lie Phe;Leu;Ser;Phe;Gin;His;Leu;Leu;Arg;Gly;Lys;Val;Arg;Phe;Leu Met;Leu;Val;Gly;Gly;Ser;Thr;Leu;Cys;Val;Arg;Glu;Phe;Gly;Gly Asn;Met;Ala;Ser;Pro;Ala;Pro;Pr'o;Ala;Cys;Asp;Leu;Arg;Val;Leu Ser;Lys;Leu;Leu;Arg;Asp;Ser;His;Val;Leu;His;Ser;Arg;Leu;Ser Gin;Cys;Pro;Glu;Val;His;Pro;Leu;Pro;Thr;Pro;Val;Leu;Leu;Pro Ala;Val;Asp;Phe;Ser;Leu;Gly;Glu;Trp;Lys;Thr;Gin;Met;Glu;Glu Thr;Lys;Ala;Gin;Asp lie;Leu;Gly Ala;Val;Thr;Leu;Leu;Leu;Glu Gly;Val;Met;Ala;Ala;Arg;Gly;Gin;Leu;(SEQ ID;NO:209);;Ala Asn Cys Ser lie Met lie Asp Glu lie lie His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser lie Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly lie Glu Ala lie Leu Arg Asn Leu Gin Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro lie lie lie Lys Ala Gly Asp Trp Gin Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gin Ala Gin Glu Gin Gin Tyr Val Glu Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro lie Ser Thr lie Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Gly Thr Gin Leu Pro Pro Gin Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala lie Phe Leu Ser Phe Gin His Leu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gin Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gin Met Glu Glu Thr Lys Ala Gin Asp lie Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg Gly Gin Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gin Leu Ser Gly Gin Val Arg Leu Leu Leu Gly Ala Leu Gin Ser Leu Leu (SEQ ID NO:210);;Ala Asn Cys Ser lie Met lie Asp Arg Pro Pro Ala Pro Leu Leu Asp Asp Val Ser lie Leu Met Asp Arg Glu Ser Phe Val Arg Ala Val Lys lie Glu Ala lie Leu Arg Asn Leu Thr Ala Ala Pro Ser Arg His Pro Trp Gin Glu Phe Arg Glu Lys Leu Glu Gin Ala Gin Glu Gin Gin Tyr Gly Glu Pro Ser Gly Pro lie Ser Ser Lys Glu Ser His Lys Ser Pro His Lys Asp Pro Asn Ala lie Phe Arg Gly Lys Val Arg Phe Leu Met Cys Val Arg Glu Phe Gly Gly Asn Ala Cys Asp Leu Arg Val Leu Ser Val Leu His Ser Arg Leu Ser Gin Pro Thr Pro Val Leu Leu Pro Ala Trp Lys Thr Gin Met Glu Glu Thr Ala Val Thr Leu Leu Leu Glu Gly;Glu lie lie;His;His;Leu;Lys;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Asn;Leu;Glu;Asn;Ala;Ser;Gly;Gin;Pro;Cys;Leu;Pro;Ser;Ala lie lie lie;Lys;Ala;Gly;Asp;Thr;•Phe;Tyr;Leu;Val;Thr;Leu;Val;Glu;Gly;Gly;Gly;Ser;Pro;Thr lie;Asn;Pro;Ser;Pro;Pro;Asn;Met;Gly Arg;Thr;Thr;Ala;Leu;Ser;Phe;Gin;His;Leu;Leu;Leu;Val;Gly;Gly;Ser;Thr;Leu;Met;Ala;Ser;Pro;Ala;Pro;Pro;Lys;Leu;Leu;Arg;Asp;Ser;His;Cys;Pro;Glu;Val;His;Pro;Leu;Val;Asp;Phe;Ser;Leu;Gly;Glu;Lys;Ala;Gin;Asp lie;Leu;Gly;Val;Met;Ala;Ala;Arg;Gly;Gin;5;10;15;20;25;30;35;40;45;50;565;Leu;Gly;Pro;Thr;Cys;Leu;Ser;Ser;Leu;Leu;Gly;Gin;Leu;Ser;Gly;Gin;Val;Arg;Leu;Leu;Leu;Gly;Ala;Leu;Gin;Ser;Leu;Leu;Gly;Thr;Gin;Leu;Pro;Pro;Gin;(SEQ ID;NO:211) ;;r;Ala;Asn;Cy;:;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Tyr;Val;Glu;Gly;Gly;Gly;Ser;Pro;Gly;Glu;Pro;Ser;Gly;Pro lie;Ser;Thr lie;Asn;Pro;Ser;Pro;Pro;Ser;Lys;Glu;Ser;His;Lys;Ser;Pro;Asn;Met;Ala;His;Lys;Asp;Pro;Asn;Ala lie;Phe;Leu;Ser;Phe;Gin;His;Leu;Leu;Arg;Gly;Lys;Val;Arg;Phe;Leu;Met;Leu;Val;Gly;Gly;Ser;Thr;Leu;Cys;Val;Arg;Glu;Phe;Gly;Gly Asn Met;Ala;Ser;Pro;Ala;Pro;Pro;Ala;Cys;Asp;Leu;Arg;Val;Leu;Ser;Lys;Leu;Leu;Arg;Asp;Ser;His;Val;Leu;His;Ser;Arg;Leu;Ser;Gin;Cys;Pro;Glu;Val;His;Pro;Leu;Pro;Thr;Pro;Val;Leu;Leu;Pro;Ala;Val;Asp;Phe;Ser;Leu;Gly;Glu;Trp;Lys;Thr;Gin;Met;Glu;Glu;Thr;Lys;Ala;Gin;Asp lie;Leu;Gly;Ala;Val;Thr;Leu;Leu;Leu;Glu Gly Val Met;Ala;Ala;Arg;Gly;Gin;Leu;Gly;Pro.;Thr;Cys;Leu;Ser;Ser;Leu;Leu;Gly;Gin;Leu;Ser;Gly;Gin;Val;Arg;Leu;Leu;Leu;Gly Ala Leu Gin;Ser;Leu;Leu;Gly;Thr;Gin;Leu;Pro;Pro;Gin;Gly;Arg;Thr;Thr;(SEQ ID;NO:212);;t;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Gly;Gly Gly;Ser;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Tyr;Val;Glu;Gly Gly;Gly;Gly;Ser;Pro;Gly Glu;Pro;Ser;Gly;Pro lie;Ser;Thr lie;Asn;Pro;Ser;Pro;Pro;Ser;Lys;Glu;Ser;His;Lys;Ser;Pro;Asn;Met;Ala;Thr;Gin;Gly Ala Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Ser;Gly Gly;Ser;Gly;Gly;Ser;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie Gin Gly Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lys; Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly;His;Ser;Leu Gly;1 lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser Gly;Leu;Phe;Leu Tyr;Gin Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly Met;Ala;Pro;Ala;Leu;Gin;Pro;(SEQ ID;NO-.:;L86);t;5;10;15;20;25;30;35;40;45;50;566;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Gly;Gly;Gly;Ser;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Tyr;Val;Glu;Gly Gly;Gly;Gly;Ser;Pro;Gly Glu;Pro;Ser;Gly;Pro lie;Ser;Thr lie;Asn;Pro;Ser;Pro;Pro;Ser;Lys;Glu;Ser;His;Lys;Ser;Pro;Asn;Met;Ala;Thr;Gin;Gly;Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly;Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Ser;Gly Gly;Ser;Gly;Gly;Ser;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin Gly Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lys;Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly;His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu;Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly Met;Ala;Pro;Ala;Leu;Gin;Pro;(SEQ ID;NO:187);;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin Gin Gly;Gly;Gly;Ser;Asn;Cys;Ser lie;Met lie;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly;He;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Tyr;Val;Glu;Gly;Gly;Gly;Gly;Ser;Pro;Gly;Glu;Pro;Ser;Gly;Pro lie;Ser;Thr lie;Asn;Pro;Ser;Pro;Pro;Ser;Lys;Glu;Ser;His;Lys;Ser;Pro;Asn;Met;Ala;Thr;Gin;Gly;Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly;Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu val;Ser;Tyr;Arg;Val;Leu;Arg;His;Leu;Ala;Gin;Pro;Ser;Gly;Gly;Ser;Gly;Gly;Ser;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin;Gly Asp;Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lys;Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;Leu Gly;His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala;Gly;Cys;Leu;Ser;Gin;Leu;His;Ser Gly;Leu;Phe;Leu;Tyr;Gin Gly;Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu;Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly Met;Ala;Pro;Ala;Leu;Gin;Pro;(SEQ ID;NO:189),;r;Leu;Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp;Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val;Lys;Asn;Leu;Glu;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro;Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;5;10;15;20;25;30;35;40;45;50;567;His;Pro lie lie lie;Lys;Ala;Gly;Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe;Tyr;Leu;Val;Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Gly;Gly;Gly;Ser;Gly;Gly;Gly;Ser;Gly;Gly;Gly;Ser;Asn;Cys;Ser lie;Met;He;Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Tyr;Val;Glu;Gly;Gly;Gly;Gly;Ser;Pro;Gly;Glu;Pro;Ser;Gly;Pro lie;Ser;Thr lie;Asn;Pro;Ser;Pro;Pro;Ser;Lys;Glu;Ser;His;Lys;Ser;Pro;Asn;Met;Ala;Thr;Gin;Gly;Ala;Met;Pro;Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly;Val;Leu;Val;Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu Arg;His;Leu;Ala;Gin;Pro;Ser;Gly;Gly;Ser;Gly;Gly;Ser;Gin;Ser;Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin;Gly;Asp Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lys;Leu;Cys;His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly;His;Ser;Leu;Gly lie;Pro;Trp;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin;Gly Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu;Gly;Pro;Thr;Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie;Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;Met;Ala;Pro;Ala;Leu;Gin;Pro;(SEQ;ID NO:190);;Asn;Ala;Ser;Gly lie;Glu;Ala lie;Leu;Arg;Asn;Leu;Gin;Pro Cys;Leu;Pro;Ser;Ala;Thr;Ala;Ala;Pro;Ser;Arg;His;Pro lie lie lie;Lys;Ala;Gly Asp;Trp;Gin;Glu;Phe;Arg;Glu;Lys;Leu;Thr;Phe Tyr;Leu;Val;.Thr;Leu;Glu;Gin;Ala;Gin;Glu;Gin;Gin;Gly;Gly;Gly Ser;Gly;Gly;Gil;Ser;Gly;Gly;Gly;Ser;Asn;Cys;Ser lie;Met lie Asp;Glu lie lie;His;His;Leu;Lys;Arg;Pro;Pro;Ala;Pro;Leu;Leu Asp;Pro;Asn;Asn;Leu;Asn;Asp;Glu;Asp;Val;Ser lie;Leu;Met;Asp Arg;Asn;Leu;Arg;Leu;Pro;Asn;Leu;Glu;Ser;Phe;Val;Arg;Ala;Val Lys;Asn;Leu;Glu;Tyr;Val;Glu;Gly;Gly;Gly;Gly;Ser;Pro;Gly;Glu Pro;Ser;Gly;Pro lie;Ser;Thr lie;Asn;Pro;Ser;Pro;Pro;Ser;Lys Glu;Ser;His;Lys;Ser;Pro;Asn;Met;Ala;Thr;Gin;Gly;Ala;Met;Pro Ala;Phe;Ala;Ser;Ala;Phe;Gin;Arg;Arg;Ala;Gly;Gly;Val;Leu;Val Ala;Ser;His;Leu;Gin;Ser;Phe;Leu;Glu;Val;Ser;Tyr;Arg;Val;Leu Arg;His;Leu;Ala;Gin;Pro;Ser;Gly;Gly;Ser;Gly;Gly;Ser;Gin;Ser Phe;Leu;Leu;Lys;Ser;Leu;Glu;Gin;Val;Arg;Lys lie;Gin;Gly;Asp Gly;Ala;Ala;Leu;Gin;Glu;Lys;Leu;Cys;Ala;Thr;Tyr;Lys;Leu;Cys His;Pro;Glu;Glu;Leu;Val;Leu;Leu;Gly;His;Ser;Leu;Gly;He;Pro Tip;Ala;Pro;Leu;Ser;Ser;Cys;Pro;Ser;Gin;Ala;Leu;Gin;Leu;Ala Gly;Cys;Leu;Ser;Gin;Leu;His;Ser;Gly;Leu;Phe;Leu;Tyr;Gin;Gly Leu;Leu;Gin;Ala;Leu;Glu;Gly lie;Ser;Pro;Glu;Leu;Gly;Pro;Thr Leu;Asp;Thr;Leu;Gin;Leu;Asp;Val;Ala;Asp;Phe;Ala;Thr;Thr lie Trp;Gin;Gin;Met;Glu;Glu;Leu;Gly;Met;Ala;Pro;Ala;Leu;Gin;Pro;;(SEQ ID;NO:191);MetAlaAsnCysSerAsnMetlleAspGlullelleThrHisLeuLysGlnProProLeu ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsn LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer AlalleGluSerlleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro ThrArgHisProIleHisIleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThr PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly;5;10;15;20;25;30;35;40;45;50;568;SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu;SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe;GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer;TyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPhe;LeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAlaLeuGlnGlu;LysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSer;LeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly;CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGlu;GlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPhe;AlaThrThr11eTrpGInGInMe t G luGluLeuGlyMe tAlaProAlaLeuG1nPro;;(SEQ ID NO:199);MetAlaAsnCysSerAsnMetlleAspGluIlelleThrHisLeuLysGlnProProLeu ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetGluAsnAsn LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer AlalleGluSerlleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro ThrArgHi s Pro Ilellell eAr gAspG lyAspTrpAsnG luPheAr gAr gLy sL euThr PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu S erHi sLys S erProAsnMetAlaThrGInGlyAlaMetProAlaPheAlaS erAlaPhe GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer TyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuPro GlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla LeuGlnGluiysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeu GlyHisSerLeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln AlaL euGluGly11eS erProGluLeuGlyProThrLeuAspThrLeuGInLeuAspVa1 AlaAspPheAlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu GlnPro (SEQ ID NO:200);;MetAlaAsnCysSerAsnMetlleAspGluIlelleThrHisLeuLysGlnProProLeu Pr oLeuL euAspPheAsnAsnLeuAsnG lyG luAspGlnAspIl eLeuMe tGluAsnAsn LeuArgArgProAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer AlalleGluSerlleLeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro ThrArgHisProIlellelleArgAspGlyAspTrpAsnGluPheArgArgLysLeuThr PheTyrLeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly SerProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGlu SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer TyrArgValLeuArgHisLeuAlaGlnProSerGlyGlySerGlyGlySerGlnSerPhe L euL piit.y s S erLeuG luG InVal Ar gLy s 11 eG 1 nG ly As pG lyAl aAl aL euG InG lu LysLeuCysAlaThrTyrLysLeuCysHisProGluGluLeuValLeuLeuGlyHisSer LeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGlnLeuAlaGly CysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaLeuGlu GlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspValAlaAspPhe AlaThrThr11eTrpGInGInMetGluGluLeuGlyMetAlaProAlaLeuGInPro ;;(SEQ ID NO:201);MetAlaAsnCysSerAsnMetlleAspGluIlelleThrHisLeuLysGlnProProLeu;4;5;10;15;20;25;30;35;40;45;50;569;ProLeuLeuAspPheAsnAsnLeuAsnGlyGluAspGlnAspIleLeuMetAspAsnAsn LeuArgArgP-noAsnLeuGluAlaPheAsnArgAlaValLysSerLeuGlnAsnAlaSer AlalleGluSerll^LeuLysAsnLeuLeuProCysLeuProLeuAlaThrAlaAlaPro ThrArgHisProIleHislleLysAspGlyAspTrpAsnGluPheArgArgLysLeuThr PheTyr.LeuLysThrLeuGluAsnAlaGlnAlaGlnGlnTyrValGluGlyGlyGlyGly S erPr oGlyG luProS erGly Prol 1 eS erThr II eAsnPr oS erPr oProSerLy sG lu SerHisLysSerProAsnMetAlaThrGlnGlyAlaMetProAlaPheAlaSerAlaPhe GlnArgArgAlaGlyGlyValLeuValAlaSerHisLeuGlnSerPheLeuGluValSer TyrArgValLeuArgHisLeuAlaGlnProThrProLeuGlyProAlaSerSerLeuPro GlnSerPheLeuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAlaAla LeuG InG ltiLy sLeuCy sAlaThrTyrLy sLeuCy sHi s Pr oG luGluLeuVa IL euLeu GlyHisSerLeuGlylleProTrpAlaProLeuSerSerCysProSerGlnAlaLeuGln LeuAlaGlyCysLeuSerGlnLeuHisSerGlyLeuPheLeuTyrGlnGlyLeuLeuGln AlaLeuGluGlylleSerProGluLeuGlyProThrLeuAspThrLeuGlnLeuAspVal AlaAspPheAlaThrThrlleTrpGlnGlnMetGluGluLeuGlyMetAlaProAlaLeu GlnPro (SEQ ID NQ:202);;AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaS erGly 11 eGluAlal 1 eLeuAr gAsnLeuGlnProCy sLeuPr oS erAlaThrAlaAl aPr oS er ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluP?. oSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly G InValArgL euLeuLeuG lyAlaLeuG InSerLeuLeuGlyThrG InLeuPr oPr oGln Gly Ar gThrThr AlaHisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeu ArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu ArgAspS erHi sValL euHis S erArgLeuS erGlnCy s Pr oGluValHi s Pr oLeuPr o ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla AlaArgGlyGlnLeu (SEQ ID NO:221);;AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro L euLeuAspPr oAsnAsnLeuAsnAspG luAspVa 1S er 11 eLeuMe t AspAr gAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaS erGly 11 eG luAl a 11 eL euAr gAsnL euGlnPr oCy sLeuPr oS er Al aThr Al aAl aPr oS er ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyArgThrThrAlaHisLys AspProAsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheLeu MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyAsnMetAlaSerProAla ProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHis S er ArgLeuS er GlnCy s ProG luValHis Pr oLeuPr oThrProVa lLeuLeuProAl a ValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLysAlaGlnAspIle LeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyPro ThrCy sLeuS er S erL euLeuG ly GlnLeuS er G lyG InVa lAr gLeuLeuLeuGlyAl a LeuGlnSerLeuLeu (SEQ ID NO:222);;570;AlaAsnCysSerlleMetlleAspGlullelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu 5 ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly 11eGluAlalleLeuArgAsnLeuGInProCysL euProS e rAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer 10 HisLysSerP^oAsnMetGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGln GlyAr gThrThrAlaHisLysAspProAsnAlallePheLeuSerPheGlnHisLeuLeu ArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPhe GlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeu 15 SerLysLeuLeuArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluVal HisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLys ThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGlu GlyValMetAlaAlaArgGlyGlnLeu (SEQ ID NO:223;;20;AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer 25 ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe;TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetGlyThrGlnLeuProProGlnGlyAr gThrThrAlaHisLys AspProAsnAlallePheLeuSerPheGlnHisLeuLeuArg'-"lyLysValArgPheLeu 3 0 MetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMet AlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrProVal LeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGluThrLys AlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAlaAlaArgGly 3 5 GlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGlnValArgLeu LeuLeuGlyAlaLeuGlnSerLeuLeu (SEQ ID NO:234);;AlaAsnCys S er11eMe11leAspGluIlelleHi sHi sLeuLysArgProProAlaPro 4 0 LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLe'uMetAspArgAsnLeu;ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer 4 5 ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer;HisLysSerProAsnMetGlyArgThrThrAlaHisLysAspProAsnAlallePheLeu SerPheGlnHisLeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThr LeuCysValArgGluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProProAla CysAspLeuArgValLeuSerLysLeuLeuArgAspSerHisValLeuHisSerArgLeu 50 S erGInCys ProGluValHi s ProLeuProThrProValLeuL euProAlaVa1AspPhe;S erL euGlyGluTrpLysThrGInMetGluGluThrLysAlaGInAsp11eLeuGlyAla ValThrLeuLeuLeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeu;*<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 571<br><br> Ser S erL euL euGlyGInLeuS erGlyGInValArgLeuLeuLeuGlyAlaLeuGInSer LeuLeuGlyThrGlnLeuProProGln (SEQ ID NO:235);<br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAlaHisLysAspProAsnAlallePheLeuSerPheGlnHis LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArg GluPheGlyGlyAsnGlyGlyAsnMetAlaSerProAlaProVroAlaCysAspLeuArg ValLeuSerLysLeuLeiiArgAspSerHisValLeuHisSerArgLeuSerGlnCysPro GluValHisProLeuProThrProValLeuLeuProAlaValAspPheSerLeuGlyGlu TrpLysThrGlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeu LeuGluGlyValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeu GlyGlnLeuSerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThr GlnLeuProProGlnGlyArgThrThr (SEQ ID NO:236);<br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLetiArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArg GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly GlyAsnGlyGlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSer LysLeuLe-uArgAspSerHisValLeuHisSerArgLeuSerGlnCysProGluValHis ProLeuProThxProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThr GlnMetGluGluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGly ValMetAlaAlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeu SerGlyGlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuPro ProGlnGlyArgThrThrAlaHisLys (SEQ ID NO:237);<br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuL euAspProAsnAsnLeuAsnAspGluAspValSerll eLeuMe t AspAr gAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysVal ArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGlyGlyAsnGly GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu ArgAspSerHisValLeiiHisSerArgLeuSerGlnCysProGluValHisProLeuPro ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlxiMetGlu<br><br> 572<br><br> GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln ValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnLeuProProGlnGly ArgThrThrAlaHisLysAspProAsn (SEQ ID NO:238); and<br><br> 5 • . • ■<br><br> AlaAsnCysSerlleMetlleAspGluIlelleHisHisLeuLysArgProProAlaPro LeuLeuAspProAsnAsnLeuAsnAspGluAspValSerlleLeuMetAspArgAsnLeu ArgLeuProAsnLeuGluSerPheValArgAlaValLysAsnLeuGluAsnAlaSerGly 10 IleGluAlalleLeuArgAsnLeuGlnProCysLeuProSerAlaThrAlaAlaProSer ArgHisProIlellelleLysAlaGlyAspTrpGlnGluPheArgGluLysLeuThrPhe TyrLeuValThrLeuGluGlnAlaGlnGluGlnGlnTyrValGluGlyGlyGlyGlySer ProGlyGluProSerGlyProIleSerThrlleAsnProSerProProSerLysGluSer HisLysSerProAsnMetAspProAsnAlallePheLeuSerPheGlnHisLeuLeuArg 15 GlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysValArgGluPheGly<br><br> GlyAsnMetAlaSerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeu ArgAspSerHisValLeuHisSer ArgLeuS erGlnCysProGluValHisProLeuPro ThrProValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGlu GluThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 2 0 AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGlyGln<br><br> Val Ar gLeuL euL euG lyAlaL euG InS erLeuL euG lyThrG InG lyAr gThrThr Al a HisLys (SEQ ID NO:239).<br><br> 12- The hematopoietic protein of claim 1, 2, 3, 4, 5, 6, 7, 25 8, 10 or 11 wherein said colony stimulating factor is selected from the group consisting of GM-CSF, G-CSF, G-CSF Ser17, c-mpl ligand (TPO), M-CSF, erythropoietin (EPO), IL-1, IL-4, IL-2, IL-3, IL-5, IL 6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-15, LIF, flt3/flk2 ligand, human growth hormone, B-cell growth factor, 30 B-cell differentiation factor, eosinophil differentiation factor and stem cell factor (SCF).<br><br> 13 . The hematopoietic protein of claim 14 wherein said colony stimulating factor is selected from the group 35 consisting of G-CSF, G-CSF Ser17 and c-mpl ligand (TPO).<br><br> 14'. A nucleic acid molecule encoding said hematopoietic protein of claim 1.<br><br> 40<br><br> 573<br><br> 15 . A nucleic acid molecule encoding said hematopoietic protein of claim 2.<br><br> 16 . A nucleic acid molecule encoding said hematopoietic protein of claim 3.<br><br> 10 17 . A nucleic acid molecule encoding said hematopoietic protein of claim 4.<br><br> 18 . A nucleic acid molecule encoding said hematopoietic protein of claim5 .<br><br> 15<br><br> 19 . A nucleic acid molecule encoding said hematopoietic protein of claim 6.<br><br> 20 . A nucleic acid molecule encoding said hematopoietic<br><br> 20 protein of claim 7.<br><br> 21. A nucleic acid molecule encoding said hematopoietic protein of claim 8 .<br><br> 25 22. A nucleic acid molecule encoding said hematopoietic protein of claim 9 .<br><br> 23. A nucleic acid molecule encoding said hematopoietic protein of claim 10.<br><br> 30 v<br><br> 24. A nucleic acid molecule encoding said hematopoietic protein of claim 11.<br><br> 25. A nucleic acid molecule encoding said hematopoietic<br><br> 35 protein of claim 12 .<br><br> «<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 574<br><br> 26.• A nueleic acid molecule encoding said hematopoietic protein of claim 13.<br><br> 27. The nucleic acid molecule according to claim 23 selected from group consisting of;<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 3Q1 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT<br><br> 401 ACAAGCTGTG CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC<br><br> 451 ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC<br><br> 501 AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC<br><br> 551 TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA<br><br> 601 CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA<br><br> 651 AGAACTGGGA ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG<br><br> 701 CCTTCGCCTC TGCTTTCCAG CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC<br><br> 751 CATCTGCAGA GCTTCCTGGA GGTGTCGTAC CGCGTTCTAC GCCACCTTGC<br><br> 801 GCAGCCCTCT GGCGGCTCTG GCGGCTCTCA GAGCTTCCTG CTCAAGTCTT<br><br> 851 TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG<br><br> 901 CTGTGTGCCA CCTAATAA {SEQ ID NO:94);<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTACAAG<br><br> 451 CTGTGCCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC<br><br> 501 CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT<br><br> 551 GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG<br><br> 601 GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA<br><br> 651 GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC<br><br> 701 TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GCCGGCCTTC<br><br> 751 GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT<br><br> 801 GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC<br><br> 851 CCTCTGGCGG CTCTGGCGGC TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG<br><br> 901 CAAGTGAGAA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG<br><br> 951 TGCCACCTAA TAA (SEQ ID NO:95);<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 575<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC<br><br> 401 CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT<br><br> 451 GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT<br><br> 501 GCAGCCCACC CAGGGTGCCA TGCCGGCCTT CGCCTCTGCT TTCCAGCGCC<br><br> 551 GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT CCTGGAGGTG<br><br> 601 TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCTCTGGCG GCTCTGGCGG<br><br> 651 CTCTCAGAGC TTCCTGCTCA AGTCTTTAGA GCAAGTGAGA AAGATCCAGG<br><br> 701 GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CAAGCTGTGC<br><br> 751 CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC<br><br> 801 TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA<br><br> 851 GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG<br><br> 901 GAAGGGATAT CCTAATAA (SEQ ID NO:96);<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCCCGAG<br><br> 451 TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC<br><br> 501 CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC<br><br> 551' CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA<br><br> 601 GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA<br><br> 651 CCGCGTTCTA CGCCACCTTG CGCAGCCCTC TGGCGGCTCT GGCGGCTCTC<br><br> 701 AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG TGAGAAAGAT CCAGGGCGAT<br><br> 751 GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC<br><br> 801 CGAGGAGCTG GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC<br><br> 851 TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA<br><br> 901 CTCCATAGCG GCCTTTTCCT CTACCAGGGG CTCCTGCAGG CCCTGGAAGG<br><br> 951 GATATCCTAA TAA (SEQ ID NO:97);<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 576<br><br> 401 TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC CTTCGCCTCT<br><br> 451 GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC ATCTGCAGAG<br><br> 501 CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG CAGCCCTCTG<br><br> 551 GCGGCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTG<br><br> 601 AGAAAGATCC AGGGCGATGG CGCAGCGCTC CAGGAGAAGC TGTGTGCCAC<br><br> 651 CTACAAGCTG TGCCACCCCG AGGAGCTGGT GCTGCTCGGA CACTCTCTGG<br><br> 701 GCATCCCCTG GGCTCCCCTG AGCTCCTGCC CCAGCCAGGC CCTGCAGCTG<br><br> 751 GCAGGCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT ACCAGGGGCT<br><br> 801 CCTGCAGGCC CTGGAAGGGA TATCCCCCGA GTTGGGTCCC ACCTTGGACA<br><br> 851 CACTGCAGCT GGACGTCGCC GACTTTGCCA CCACCATCTG GCAGCAGATG<br><br> 901 GAAGAACTGG GATAATAA (SEQ ID NO:98);<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTATGGCC<br><br> 451 CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT<br><br> 501 CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC<br><br> 551 TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CTCTGGCGGC<br><br> 601 TCTGGCGGCT CTCAGAGCTT CCTGCTCAAG TCTTTAGAGC AAGTGAGAAA<br><br> 651 GATCCAGGGC GATGGCGCAG CGCTCCAGGA GAAGCTGTGT GCCACCTACA<br><br> 701 AGCTGVGCCA CCCCGAGGAG CTGGTGCTGC TCGGACACTC TCTGGGCATC<br><br> 751 CCCTGGGCTC CCCTGAGCTC CTGCCCCAGC CAGGCCCTGC AGCTGGCAGG<br><br> 801 CTGCTTGAGC CAACTCCATA GCGGCCTTTT CCTCTACCAG GGGCTCCTGC<br><br> 851 AGGCCCTGGA AGGGATATCC CCCGAGTTGG GTCCCACCTT GGACACACTG<br><br> 901 CAGCTGGACG TCGCCGACTT TGCCACCACC ATCTGGCAGC AGATGGAAGA<br><br> 951 ACTGGGATAA TAA (SEQ ID NO:99);<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA<br><br> 401 CCCAGGGTGC CATGCCGGCC TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA<br><br> 451 GGGGTCCTGG TTGCTAGCCA TCTGCAGAGC TTCCTGGAGG TGTCGTACCG<br><br> 501 CGTTCTACGC CACCTTGCGC AGCCCTCTGG CGGCTCTGGC GGCTCTCAGA<br><br> 551 GCTTCCTGCT CAAGTCTTTA GAGCAAGTGA GAAAGATCCA GGGCGATGGC<br><br> 601 GCAGCGCTCC AGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA<br><br> 651 GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA<br><br> 701 GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC 751 . CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT<br><br> 801 ATCCCCCGAG TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 577<br><br> 851 ACTTTGCCAC CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT 901 GCCCTGCAGC CCTAATAA (SEQ ID NO:100);<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG<br><br> 451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT<br><br> 501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC<br><br> 551 TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC<br><br> 601 CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC<br><br> 651 GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC<br><br> 701 TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC<br><br> 751 TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG<br><br> 801 CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC<br><br> 851 CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT<br><br> 901 GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT<br><br> 951 GCAGCCCTAA TAA (SEQ ID NO:101);<br><br> 1 ATGGCTAACT GCTCTATAAT<br><br> 51 ACCACCTGCA CCTTTGCTGG<br><br> 101 CTATCCTGAT GGACCGAAAC<br><br> 151 AGGGCTGTCA AGAACTTAGA<br><br> 201 TAATCTCCAA CCATGTCTGC<br><br> 251 CAATCATCAT CAAGGCAGGT<br><br> 301 TTCTATCTGG TTACCCTTGA<br><br> 351 CGGTGGAGGC TCCCCGGGTG<br><br> 401 CTGCTTTCCA GCGCCGGGCA<br><br> 451 AGCTTCCTGG AGGTGTCGTA<br><br> 501 TGGCGGCTCT GGCGGCTCTC<br><br> 551 TGAGAAAGAT CCAGGGCGAT<br><br> 601 ACCTACAAGC TGTGCCACCC<br><br> 651 GGGCATCCCC TGGGCTCCCC<br><br> 701 TGGCAGGCTG CTTGAGCCAA<br><br> 751 CTCCTGCAGG CCCTGGAAGG<br><br> 801 CACACTGCAG CTGGACGTCG<br><br> 851 TGGAAGAACT GGGAATGGCC<br><br> 901 CCGGCCTTCG CCTAATAA 0<br><br> GATCGATGAA ATTATACATC ACTTAAAGAG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTTCGACTTC CAAACCTGGA GAGCTTCGTA AAATGCATCA GGTATTGAGG CAATTCTTCG CCTCTGCCAC GGCCGCACCC TCTCGACATC GACTGGCAAG AATTCCGGGA AAAACTGACG GCAAGCGCAG GAACAACAGT ACGTAGAGGG GTGGTTCTGG CGGCGGCTCC AACATGGCTT GGAGGGGTCC TGGTTGCTAG CCATCTGCAG CCGCGTTCTA CGCCACCTTG CGCAGCCCTC AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC CGAGGAGCTG GTGCTGCTCG GACACTCTCT TGAGCTCCTG CCCCAGCCAG GCCCTGCAGC CTCCATAGCG GCCTTTTCCT CTACCAGGGG GATATCCCCC GAGTTGGGTC CCACCTTGGA CCGACTTTGC CACCACCATC TGGCAGCAGA CCTGCCCTGC AGCCCACCCA GGGTGCCATG EQ ID NO:102);<br><br> PMON25191<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 578<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTCCCGAG<br><br> 451 TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC<br><br> 501 CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC<br><br> 551 CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA<br><br> 601 GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA<br><br> 651 CCGCGTTCTA CGCCACCTTG CGCAGCCCAC ACCATTGGGC CCTGCCAGCT<br><br> 701 CCCTGCCCCA GAGCTTCCTG CTCAAGTCTT TAGAGCAAGT GAGAAAGATC<br><br> 751 CAGGGCGATG GCGCAGCGCT CCAGGAGAAG CTGTGTGCCA CCTACAAGCT<br><br> 801 GTGCCACCCC GAGGAGCTGG TGCTGCTCGG ACACTCTCTG GGCATCCCCT<br><br> 851 GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG CCCTGCAGCT GGCAGGCTGC<br><br> 901 TTGAGCCAAC TCCATAGCGG CCTTTTCCTC TACCAGGGGC TCCTGCAGGC<br><br> 951 CCTGGAAGGG ATATCCTAAT AA (SEQ ID NO:107);<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTCTGCT<br><br> 451 TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT<br><br> 501 CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCTCTGGCG<br><br> 551 GCTCTGGCGG CTCTCAGAGC TTCCTGCTCA AGTCTTTAGA GCAAGTGAGA<br><br> 601 AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGT GTGCCACCTA<br><br> 651 CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACAC TCTCTGGGCA<br><br> 701 TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA<br><br> 751 GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT<br><br> 801 GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC<br><br> 851 TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCA GCAGATGGAA<br><br> 901 GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGC<br><br> 951 CTTCGCCTAA TAA (SEQ ID NO: 103);<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT<br><br> 401 ACAAGCTGTG CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC<br><br> 451 ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC<br><br> 501 AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC<br><br> I<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 579<br><br> 551 TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA<br><br> 601 CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA<br><br> 651 AGAACTGGGA ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG<br><br> 701 CCTTCGCCTC TGCTTTCCAG CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC<br><br> 751 CATCTGCAGA .GC.TTCCTGGA GGTGTCGTAC CGCGTTCTAC GCCACCTTGC<br><br> 801 GCAGCCCACA CCATTGGGCC CTGCCAGCTC CCTGCCCCAG AGCTTCCTGC<br><br> 851 TCAAGTCTTT AGAGCAAGTG AGAAAGATCC AGGGCGATGG CGCAGCGCTC<br><br> 901 CAGGAGAAGC TGTGTGCCAC CTAATAA (SEQ ID NO:104);<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTTACAAG<br><br> 451 CTGTGCCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC<br><br> 501 CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT<br><br> 551 GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG<br><br> 601 GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA<br><br> 651 GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC<br><br> 701 TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GCCGGCCTTC<br><br> 751 GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT<br><br> 801 GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC<br><br> 851 CCACACCATT GGGCCCTGCC AGCTCCCTGC CCCAGAGCTT CCTGCTCAAG<br><br> 901 TCTTTAGAGC AAGTGAGAAA GATCCAGGGC GATGGCGCAG CGCTCCAGGA<br><br> 951 GAAGCTGTGT GCCACCTAAT AA (SEQ ID NO:105);<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTATGGCC<br><br> 451 CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT<br><br> 501 CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC<br><br> 551 TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CACACCATTG<br><br> 601 GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA<br><br> 651 AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG<br><br> 701 CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CGGACACTCT<br><br> 751 CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA<br><br> 801 GCTGGCAGGC TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG<br><br> 851 GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TCCCACCTTG<br><br> 901 GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA<br><br> 951 GATGGAAGAA CTGGGATAAT AA (SEQ ID NO:109);<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 580<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 .CTATCCTGAT. GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA<br><br> 401 CCCAGGGTGC CATGCCGGCC TTCGCCTCTG CTTTCCAGCG CCGGGCAGGA<br><br> 451 GGGGTCCTGG TTGCTAGCCA TCTGCAGAGC TTCCTGGAGG TGTCGTACCG<br><br> 501 CGTTCTACGC CACCTTGCGC AGCCCACACC ATTGGGCCCT GCCAGCTCCC<br><br> 551 TGCCCCAGAG CTTCCTGCTC AAGTCTTTAG AGCAAGTGAG AAAGATCCAG<br><br> 601 GGCGATGGCG CAGCGCTCCA GGAGAAGCTG TGTGCCACCT ACAAGCTGTG<br><br> 651 CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG<br><br> 701 CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG<br><br> 751 AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC TGCAGGCCCT<br><br> 801 GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA CTGCAGCTGG<br><br> 851 ACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AGAACTGGGA<br><br> 901 ATGGCCCCTG CCCTGCAGCC CTAATAA (SEQ ID NO:110);<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG<br><br> 451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT<br><br> 501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC<br><br> 551 TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC<br><br> 601 CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA<br><br> 651 TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC<br><br> 701 CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC CTGGGCTCCC<br><br> 751 CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA<br><br> 801 ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG<br><br> 851 GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC<br><br> 901 GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC<br><br> 951 CCCTGCCCTG CAGCCCTAAT AA (SEQ ID NO:111);<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 581<br><br> 351 CGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTT<br><br> 401 CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG<br><br> 451 AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCAC<br><br> 501 ACCATTGGGC CCTGCCAGCT CCCTGCCCCA GAGCTTCCTG CTCAAGTCTT 551 . TAGAGCAAGT GAGAAAGATC CAGGGCGATG GCGCAGCGCT CCAGGAGAAG<br><br> 601 CTGTGTGCCA CCTACAAGCT GTGCCACCCC GAGGAGCTGG TGCTGCTCGG<br><br> 651 ACACTCTCTG GGCATCCCCT GGGCTCCCCT GAGCTCCTGC CCCAGCCAGG<br><br> 701 CCCTGCAGCT GGCAGGCTGC TTGAGCCAAC TCCATAGCGG CCTTTTCCTC<br><br> 751 TACCAGGGGC TCCTGCAGGC CCTGGAAGGG ATATCCCCCG AGTTGGGTCC<br><br> 801 CACCTTGGAC ACACTGCAGC TGGACGTCGC CGACTTTGCC ACCACCATCT<br><br> 851 GGCAGCAGAT GGAAGAACTG GGAATGGCCC CTGCCCTGCA GCCCACCCAG<br><br> 901 GGTGCCATGC CGGCCTTCGC CTAATAA (SEQ ID NO:112);<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGATCGAAAC CTTCGACTTC- CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTTACAAG<br><br> 451 CTGTGCCACC CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC<br><br> 501 CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT<br><br> 551 GCTTGAGCCA ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG<br><br> 601 GCCCTGGAAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA<br><br> 651 GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC<br><br> 701 TGGGAATGGC CCCTGCCCTG CAGCCCACCC AGGGTGCCAT GCCGGCCTTC<br><br> 751 GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT<br><br> 801 GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC<br><br> 851 CCGGCGGCGG CTCTGACATG GCTACACCAT TAGGCCCTGC CAGCTCCCTG<br><br> 901 CCCCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGGA AGATCCAGGG<br><br> 951 CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAA TAA (SEQ ID NO:155);<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTCCCGAG<br><br> 451 TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC<br><br> 501 CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC<br><br> 551 CCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA<br><br> 601 GGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTA<br><br> 651 CCGCGTTCTA CGCCACCTTG CGCAGCCCGG CGGCGGCTCT GACATGGCTA<br><br> 701 CACCATTAGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT<br><br> 4<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 3-5<br><br> 40<br><br> 45<br><br> 50<br><br> 582<br><br> 751 TTAGAGCAAG TGAGGAAGAT CCAGGGCGA' 801 GCTGTGTGCC ACCTACAAGC TGTGCCACCC 851 GACACTCTCT GGGCATCCCC TGGGCTCCC(fc 901 GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA 951 CTACCAGGGG CTCCTGCAGG CCCTGGAAGG NO:156);<br><br> GGCGCAGCGC TCCAGGAGAA CGAGGAGCTG GTGCTGCTCG TGAGCTCCTG CCCCAGCCAG CTCCATAGCG GCCTTTTCCT GATATCCTAA TAA (SEQ ID<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTTCTGCT<br><br> 451 TTCCAGCGCC GGGCAGGAGG GGTCCTGGTT GCTAGCCATC TGCAGAGCTT<br><br> 501 CCTGGAGGTG TCGTACCGCG TTCTACGCCA CCTTGCGCAG CCCGGCGGCG<br><br> 551 GCTCTGACAT GGCTACACCA TTAGGCCCTG CCAGCTCCCT GCCCCAGAGC<br><br> 601 TTCCTGCTCA AGTCTTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC<br><br> 651 AGCGCTCCAG GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG<br><br> 701 AGCTGGTGCT GCTCGGACAC TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC<br><br> 751 TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA GGCTGCTTGA GCCAACTCCA<br><br> 801 TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG GAAGGGATAT<br><br> 851 CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CGTCGCCGAC<br><br> 901 TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC<br><br> 951 CCTGCAGCCC ACCCAGGGTG CCATGCCGGC C/TTCGCCTAA TAA; (SEQ ID NO:157)<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA/ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA/CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGATCGAAAC CTTCGACTTC) CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA\GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC ^GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTATGGCC<br><br> 451 CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT<br><br> 501 CCAGCGCCGG GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC<br><br> 551 TGGAGGTGTC GTACCGCGTT CTACGCCACC TTGCGCAGCC CGGCGGCGGC<br><br> 6,01 TCTGACATGG CTACACCATT AGGCCCTGCC AGCTCCCTGC CCCAGAGCTT<br><br> 651 CCTGCTCAAG TCTTTAGAGC AAGTGAGGAA GATCCAGGGC GATGGCGCAG<br><br> 701 CGCTCCAGGA GAAGCTGTGT GCCACCTACA AGCTGTGCCA CCCCGAGGAG<br><br> 751 CTGGTGCTGC TCGGACACTC TCTGGGCATC CCCTGGGCTC CCCTGAGCTC<br><br> 801 CTGCCCCAGC CAGGCCCTGC AGCTGGCAGG CTGCTTGAGC CAACTCCATA<br><br> 851 GCGGCCTTTT CCTCTACCAG GGGCTCCTGC AGGCCCTGGA AGGGATATCC<br><br> 901 CCCGAGTTGG GTCCCACCTT GGACACACTG CAGCTGGACG TCGCCGACTT<br><br> 951 TGCCACCACC ATCTGGCAGC AGATGGAAGA ACTGGGATAA TAA; (SEQ ID NO:158)<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 583<br><br> 1 ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG<br><br> 51 ACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT<br><br> 101 CTATCCTGAT GGATCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA<br><br> 151 AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG<br><br> 201 TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC<br><br> 251 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG<br><br> 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GTCTACCCAG<br><br> 451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT<br><br> 501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC<br><br> 551 TACGCCACCT TGCGCAGCCC GGCGGCGGCT CTGACATGGC TACACCATTA<br><br> 601 GGCCCTGCCA GCTCCCTGCC CCAGAGCTTC CTGCTCAAGT CTTTAGAGCA<br><br> 651 AGTGAGGAAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAG AAGCTGTGTG<br><br> 701 CCACCTACAA GCTGTGCCAC CCCGAGGAGC TGGTGCTGCT CGGACACTCT<br><br> 751 CTGGGCATCC CCTGGGCTCC CCTGAGCTCC TGCCCCAGCC AGGCCCTGCA<br><br> 801 GCTGGCAGGC TGCTTGAGCC AACTCCATAG CGGCCTTTTC CTCTACCAGG<br><br> 851 GGCTCCTGCA GGCCCTGGAA GGGATATCCC CCGAGTTGGG TCCCACCTTG<br><br> 901 GACACACTGC AGCTGGACGT CGCCGACTTT GCCACCACCA TCTGGCAGCA<br><br> 951 GATGGAAGAA CTGGGAATGG CCCCTGCCCT GCAGCCCTAA TAA; (SEQ ID NO:159)<br><br> gctaactgctctataatgatcgatgaaattatacatcacttaaagagaccacctgcacct ttgctggacccgaacaacctcaatgacgaagacgtctctatcctgatggaccgaaacctt cgacttccaaacctggagagcttcgtaagggctgtcaagaacttagaaaatgcatcaggt attgaggcaattcttcgtaatctccaaccatgtctgccctctgccacggccgcaccctct cgacatccaatcatcatcaaggcaggtgactggcaagaattccgggaaaaactgacgttc tatctggttai 1ccttgagcaagcgcaggaacaacagtacgtagagggcggtggaggctcc ccgggtgaaccgtctggtccaatctctactatcaacccgtctcctccgtctaaagaatct cataaatctc caaacatgggacccacttgcctctcatccctcctggggcagctttctgga caggtccgtctcctccttggggccctgcagagcctccttggaacccagcttcctccacag ggcaggaccacagctcacaaggatcccaatgccatcttcctgagcttccaacacctgctc cgaggaaaggtgcgtttcctgatgcttgtaggagggtccaccctctgcgtcagggaattc ggcggcaacatggcgtctccggcgccgcctgcttgtgacctccgagtcctcagtaaactg cttcgtgactcccatgtccttcacagcagactgagccagtgcccagaggttcaccctttg cctacacctgtcctgctgcctgctgtggactttagcttgggagaatggaaaacccagatg gaggagaccaaggcacaggacattctgggagcagtgacccttctgctggagggagtgatg gcagcacggggacaactg (SEQ id NO:124); '<br><br> gctaactgctctataatgatcgatgaaattatacatcacttaaagagaccacctgcacct ttgctggacccgaacAacctcaatgacgaagacgtctctatcctgatggaccgaaacctt cgacttccaaacctggagagcttcgtaagggctgtcaagaacttagaaaatgcatcaggt attgaggcaattcttcgtaatctccaaccatgtctgccctctgccacggccgcaccctct cgacatccaatcatcatcaaggcaggtgactggcaagaattccgggaaaaactgacgttc tatctggttacccttgagcaagcgcaggaacaacagtacgtagagggcggtggaggctcc ccgggtgaaccgtctggtccaatctctactatcaacccgtctcctccgtctaaagaatct cataaatctccaaacatgggaacccagcttcctccacagggcaggaccacagctcacaag gatcccaatgccatcttcctgagcttccaacacctgctccgaggaaaggtgcgtttcctg<br><br> 584<br><br> ATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCG GCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTT CACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCT GCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGAC ATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGA CCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGG GCCCTGCAGAGCCTCCTT (SEQ ID NO:125);<br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTG AGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACC CTCTGCGTCAGGGAATTCGGCGGCAACATGGCGTCTCCGGCGCCGCCTGCTTGTGACCTC CGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGC CCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGA GAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTT CTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTC CTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGA ACCCAGCTTCCTCCACAG (SEQ ID NO:126);<br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACAC CTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG GAATTCGGCGGCAACATGGCGTCTCCGGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGT AAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCAC CCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACC CAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGA GTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTT TCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCT CCACAGGGCAGGACCACA (SEQ ID NO: 127);<br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT<br><br> #<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 585<br><br> CATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA GGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC GGCAACATGGCGTCTCCGGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTT CGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCT ACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAG GAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCA GCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAG GTCCGTCTCCr|,CCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGC AGGACCACAGCTCACAAG (SEQ ID NO:128);<br><br> 1 ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA<br><br> 51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG<br><br> 101 ATATCCTAAT. GGACAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC<br><br> 151 CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA<br><br> 201 AAATCTCCTG CCATGTCTGC CGCTAGCCAC GGCCGCACCC ACGCGACATC<br><br> 251 CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC<br><br> 301 TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG<br><br> 451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT<br><br> 501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC<br><br> 551 TACGCCACCT TGCGCAGCCC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC<br><br> 601 CTGCTCAAGT CTTTAGAGCA AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC<br><br> 651 GCTCCAGGAG AAGCTGTGTG CCACCTACAA GCTGTGCCAC CCCGAGGAGC<br><br> 701 TGGTGCTGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCTGAGCTCC<br><br> 751 TGCCCCAGCC AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC AACTCCATAG<br><br> 801 CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGGAA GGGATATCCC<br><br> 851 CCGAGTTGGG TCCCACCTTG GACACACTGC AGCTGGACGT CGCCGACTTT<br><br> 901 GCCACCACCA TCTGGCAGCA GATGGAAGAA CTGGGAATGG CCCCTGCCCT<br><br> 951 GCAGCCCTAA TAA (SEQ ID NO:114);<br><br> 1 ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA<br><br> 51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG<br><br> 101 ATATCCTGAT GGAAAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC<br><br> 151 CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA<br><br> 201 AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC ACGCGACATC<br><br> 251 CAATCATCAT CCGTGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC<br><br> 301 TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG<br><br> 451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT<br><br> 501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC<br><br> 551 TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC<br><br> 601 CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA<br><br> 651 TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC<br><br> 701 CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC CTGGGCTCCC<br><br> 751 CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA<br><br> 8.01 ACTCCATAGC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG<br><br> 851 GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 586<br><br> 901 GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC 951 CCCTGCCCTG CAGCCCTAAT AA (SEQ ID NO:115);<br><br> 1 ' ATGGCTAACT GCTCTAACAT<br><br> 51 GCCACCGCTG CCGCTGCTGG<br><br> 101 ATATCCTGAT GGAAAATAAC<br><br> 151 CGTGCTGTCA AGTCTCTGCA<br><br> 201 AAATCTCCTG CCATGTCTGC<br><br> 251 CAATCATCAT CCGTGACGGT<br><br> 301 TTCTATCTGA AAACCTTGGA<br><br> 351 CGGTGGAGGC TCCCCGGGTG<br><br> 401 CGTCTCCTCC GTCTAAAGAA<br><br> 451 GGTGCCATGC CGGCCTTCGC<br><br> 501 CCTGGTTGCT AGCCATCTGC<br><br> 551 TACGCCACCT TGCGCAGCCC<br><br> 601 CTGCTCAAGT CTTTAGAGCA<br><br> 651 GCTCCAGGAG AAGCTGTGTG<br><br> 701 TGGTGCTGCT CGGACACTCT<br><br> 751 TGCCCCAGCC AGGCCCTGCA<br><br> 801 CGGCCTTTTC CTCTACCAGG<br><br> 851 CCGAGTTGGG TCCCACCTTG<br><br> 901 GCCACCACCA TCTGGCAGCA<br><br> 951 GCAGCCCTAA TAA (SEQ II<br><br> GATCGATGAA ATCATCACCC ACCTGAAGCA ACTTCAACAA CCTCAATGGT GAAGACCAAG CTTCGTCGTC CAAACCTCGA GGCATTCAAC GAATGCATCA GCAATTGAGA GCATTCTTAA CCCTGGCCAC GGCCGCACCC ACGCGACATC GACTGGAATG AATTCCGTCG TAAACTGACC GAACGCGCAG GCTCAACAGT ACGTAGAGGG AACCGTCTGG TCCAATCTCT ACTATCAACC TCTCATAAAT CTCCAAACAT GGCTACCCAG CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT AGAGCTTCCT GGAGGTGTCG TACCGCGTTC TCTGGCGGCT CTGGCGGCTC TCAGAGCTTC AGTGAGAAAG ATCCAGGGCG ATGGCGCAGC CCACCTACAA GCTGTGCCAC CCCGAGGAGC CTGGGCATCC CCTGGGCTCC CCTGAGCTCC GCTGGCAGGC TGCTTGAGCC AACTCCATAG GGCTCCTGCA GGCCCTGGAA GGGATATCCC GACACACTGC AGCTGGACGT CGCCGACTTT GATGGAAGAA CTGGGAATGG CCCCTGCCCT i NO:116);<br><br> 1 ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA<br><br> 51 GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG<br><br> 101 ATATCCTAAT GGACAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC<br><br> 151 CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA<br><br> 201 AAATCTCCTG CCATGTCTGC CGCTAGCCAC GGCCGCACCC ACGCGACATC<br><br> 251 CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC<br><br> 301 TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT ACGTAGAGGG<br><br> 351 CGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC<br><br> 401 CGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACCCAG<br><br> 451 GGTGCCATGC CGGCCTTCGC CTCTGCTTTC CAGCGCCGGG CAGGAGGGGT<br><br> 501 CCTGGTTGCT AGCCATCTGC AGAGCTTCCT GGAGGTGTCG TACCGCGTTC<br><br> 551 TACGCCACCT TGCGCAGCCC ACACCATTGG GCCCTGCCAG CTCCCTGCCC<br><br> 601 CAGAGCTTCC TGCTCAAGTC TTTAGAGCAA GTGAGAAAGA TCCAGGGCGA<br><br> 651 TGGCGCAGCG CTCCAGGAGA AGCTGTGTGC CACCTACAAG CTGTGCCACC<br><br> 701 CCGAGGAGCT GGTGCTGCTC GGACACTCTC TGGGCATCCC CTGGGCTCCC<br><br> 751 CTGAGCTCCT GCCCCAGCCA GGCCCTGCAG CTGGCAGGCT GCTTGAGCCA<br><br> 801 ACTCCATAGrC GGCCTTTTCC TCTACCAGGG GCTCCTGCAG GCCCTGGAAG<br><br> 851 GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTGCA GCTGGACGTC<br><br> 901 GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC TGGGAATGGC<br><br> 951 CCCTGCCCTG CAGCCCTAAT AA (SEQ ID NO:117);<br><br> 1 ATGGCTCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT 51 GGACCGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA<br><br> 587<br><br> 101 AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCG TAATCTCCAA<br><br> 151 CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC CAATCATCAT<br><br> 201 CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG TTCTATCTGG<br><br> 251 TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TAACTGCTCT<br><br> 5 301 ATAATGATCG ATGAAATTAT ACATCACTTA AAGAGACCAC CTGCACCTTT<br><br> 351 ' GTACGTAGAG GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT<br><br> 401 CTACTATCAA CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC<br><br> 451 ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG<br><br> 501 GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT<br><br> 10 551 CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC<br><br> 601 TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG<br><br> 651 CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC<br><br> 701 ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT<br><br> 751 CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG<br><br> 15 801 CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG<br><br> 851 AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC<br><br> 901 GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT<br><br> 951 GGCCCCTGCC CTGCAGCCCT AATAA (SEQ ID NO:86);<br><br> 20<br><br> 1 ATGGCTAATG CATCAGGTAT TGAGGCAATT CTTCGTAATC TCCAACCATG<br><br> 51 TCTGCCCTCT GCCACGGCCG CACCCTCTCG ACATCCAATC ATCATCAAGG<br><br> 101 CAGGTGACTG GCAAGAATTC CGGGAAAAAC TGACGTTCTA TCTGGTTACC<br><br> 151 CTTGAGCAAG CGCAGGAACA ACAGGGTGGT GGCTCTAACT GCTCTATAAT<br><br> 25 201 GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA CCTTTGCTGG<br><br> 251 ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC<br><br> 301 CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA<br><br> .351 ATACGTAGAG GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT<br><br> 401 CTACTATCAA CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC<br><br> 30 451 ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG<br><br> 501 GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT<br><br> 551 CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC<br><br> 601 TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG<br><br> 651 CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC<br><br> 35 701 ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT<br><br> 751 CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG<br><br> 801 CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG<br><br> 851 AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC<br><br> 901 GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT<br><br> 40 951 GGCCCCTGCC CTGCAGCCCT AATAA (SEQ ID NO:87);<br><br> 1 ATGGCTGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAG GTGACTGGCA<br><br> 51 AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTT GAGCAAGCGC<br><br> 45 101 AGGAACAACA GGGTGGTGGC TCTAACTGCT CTATAATGAT CGATGAAATT<br><br> 151 ATACATCACT TAAAGAGACC ACCTGCACCT TTGCTGGACC CGAACAACCT<br><br> 201 CAATGACGAA GACGTCTCTA TCCTGATGGA CCGAAACCTT CGACTTCCAA<br><br> 251 ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAA TGCATCAGGT<br><br> 301 ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCT CTGCCACGGC<br><br> 50 351 CTACGTAGAG GGCGGTGGAG GCTCCCCGGG TGAACCGTCT GGTCCAATCT<br><br> 401 CTACTATCAA CCCGTCTCCT CCGTCTAAAG AATCTCATAA ATCTCCAAAC<br><br> 451 ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 588<br><br> 501 GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAGGTGT<br><br> 551 CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC<br><br> 601 TCTCAGAGCT TCCTGCTCAA GTCTTTAGAG CAAGTGAGAA AGATCCAGGG<br><br> 651 CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAC AAGCTGTGCC<br><br> 701 ACCCCGAGGA GCTGGTGCTG CTCGGACACT CTCTGGGCAT CCCCTGGGCT<br><br> 751 CCCCTGAGCT CCTGCCCCAG CCAGGCCCTG CAGCTGGCAG GCTGCTTGAG<br><br> 801 CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGGGCTCCTG CAGGCCCTGG<br><br> 851 AAGGGATATC CCCCGAGTTG GGTCCCACCT TGGACACACT GCAGCTGGAC<br><br> 901 GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT<br><br> 951 GGCCCCTGCC CTGCAGCCCT AATAA (SEQ ID NO:88);<br><br> 1 atggctctgg acccgaacaa<br><br> 51 ggaccgaaac cttcgacttc<br><br> 101 agaacttaga aaatgcatca<br><br> 151 ccatgtctgc cctctgccac<br><br> 201 caaggcaggt gactggcaag<br><br> 251 ttacccttga gcaagcgcag<br><br> 301 agcggcggcg gttctaactg<br><br> 351 cttaaagaga ccacctgcac<br><br> 401 cgggtgaacc gtctggtcca<br><br> 451 aaagaatctc ataaatctcc<br><br> 501 cttcgcctct gctttccagc<br><br> 551 atctgcagag cttcctggag<br><br> 601 cagccctctg gcggctctgg<br><br> 651 agagcaagtg agaaagatcc<br><br> 701 tgtgtgccac ctacaagctg<br><br> 751 cactctctgg gcatcccctg<br><br> 801 cctgcagctg gcaggctgct<br><br> 851 accaggggct cctgcaggcc<br><br> 901 accttggaca cactgcagct<br><br> 951 gcagcagatg gaagaactgg<br><br> (SEQ ID NO:90);<br><br> cctcaatgac gaagacgtct ctatcctgat caaacctgga gagcttcgta agggctgtca ggtattgagg caattcttcg taatctccaa ggccgcaccc tctcgacatc caatcatcat aattccggga aaaactgacg ttctatctgg gaacaacagg gtggtggctc tggcggtggc ctctataatg atcgatgaaa ttatacatca ctttgtacgt agagggcggt ggaggctccc atctctacta tcaacccgtc tcctccgtct aaacatggct acccagggtg ccatgccggc gccgggcagg aggggtcctg gttgctagcc gtgtcgtacc gcgttctacg ccaccttgcg cggctctcag agcttcctgc tcaagtcttt agggcgatgg cgcagcgctc caggagaagc tgccaccccg aggagctggt gctgctcgga ggctcccctg agctcctgcc ccagccaggc tgagccaact ccatagcggc cttttcctct ctggaaggga tatcccccga gttgggtccc ggacgtcgcc gactttgcca ccaccatctg gaatggcccc tgccctgcag CCCTAATAA<br><br> 1 ATGGCTAATG CATCAGGTAT<br><br> 51 TCTGCCCTCT GCCACGGCCG<br><br> 101 CAGGTGACTG GCAAGAATTC<br><br> 151 CTTGAGCAAG CGCAGGAACA<br><br> 201 CGGCGGTTCT AACTGCTCTA<br><br> 251 AGAGACCACC TGCACCTTTG<br><br> 301 GTCTCTATCC TGATGGACCG<br><br> 351 CGTAAGGGCT GTCAAGAACT<br><br> 401 CGGGTGAACC GTCTGGTCCA<br><br> 451 AAAGAATCTC ATAAATCTCC<br><br> 501 CTTCGCCTCT GCTTTCCAGC<br><br> 551 ATCTGCAGAG CTTCCTGGAG<br><br> 601 CAGCCCTCTG GCGGCTCTGG<br><br> 651 AGAGCAAGTG AGAAAGATCC<br><br> 701 TGTGTGCCAC CTACAAGCTG<br><br> 751 CACTCTCTGG GCATCCCCTG<br><br> 801 CCTGCAGCTG GCAGGCTGCT<br><br> tgaggcaatt cttcgtaatc tccaaccatg caccctctcg acatccaatc. atcatcaagg cgggaaaaac tgacgttcta tctggttacc acagggtggt ggctctggcg gtggcagcgg taatgatcga tgaaattata catcacttaa ctggacccga acaacctcaa tgacgaagac aaaccttcga cttccaaacc tggagagctt tagaatacgt agagggcggt ggaggctccc atctctacta tcaacccgtc tcctccgtct aaacatggct acccagggtg ccatgccggc gccgggcagg aggggtcctg gttgctagcc gtgtcgtacc gcgttctacg ccaccttgcg cggctctcag agcttcctgc tcaagtcttt agggcgatgg cgcagcgctc caggagaagc tgccaccccg aggagctggt gctgctcgga ggctcccctg agctcctgcc ccagccaggc tgagccaact ccatagcggc cttttcctct<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 589<br><br> 851 accaggggct cctgcaggcc ctggaaggga tatcccccga gttgggtccc 901 accttggaca cactgcagct ggacgtcgcc gactttgcca ccaccatctg 951 gcagcagatg gaagaactgg gaatggcccc tgccctgcag ccctaataa (seq id no:91);<br><br> gctaactgctctataatgatcgatgaaattatacatcacttaaagagaccacctgcacct ttgctggacccgaacaacctcaatgacgaagacgtctctatcctgatggaccgaaacctt cgacttccaaacctggagagcttcgtaagggctgtcaagaacttagaaaatgcatcaggt attgaggcaattcttcgtaatctccaaccatgtctgccctctgccacggccgcaccctct cgacatccaatcatcatcaaggcaggtgactggcaagaattccgggaaaaactgacgttc tatctggttacccttgagcaagcgcaggaacaacagtacgtagagggcggtggaggctcc ccgggtgaaccgtctggtccaatctctactatcaacccgtctcctccgtctaaagaatct cataaatctccaaacatgggacccacttgcctctcatccctcctggggcagctttctgga caggtccgtctcctccttggggccctgcagagcctccttggaacccagcttcctccacag ggcaggaccacagctcacaaggatcccaatgccatcttcctgagcttccaacacctgctc cgaggaaaggtgcgtttcctgatgcttgtaggagggtccaccctctgcgtcagggaattc ggcaacatggcgtctcccgctccgcctgcttgtgacctccgagtcctcagtaaactgctt cgtgactcccatgtccttcacagcagactgagccagtgcccagaggttcaccctttgcct acacctgtcctgctgcctgctgtggactttagcttgggagaatggaaaacccagatggag gagaccaaggcacaggacattctgggagcagtgacccttctgctggagggagtgatggca gcacggggacaactg (seq id no:136);<br><br> gctaactgctctataatgatcgatgaaattatacatcacttaaagagaccacctgcacct ttgctggacc^gaacaacctcaatgacgaagacgtctctatcctgatggaccgaaacctt cgacttccaaacctggagagcttcgtaagggctgtcaagaacttagaaaatgcatcaggt attgaggcaattcttcgtaatctccaaccatgtctgccctctgccacggccgcaccctct cgacatccaatcatcatcaaggcaggtgactggcaagaattccgggaaaaactgacgttc tatctggttacccttgagcaagcgcaggaacaacagtacgtagagggcggtggaggctcc ccgggtgaaccgtctggtccaatctctactatcaacccgtctcctccgtctaaagaatct cataaatctccaaacatgggaacccagcttcctccacagggcaggaccacagctcacaag gatcccaatgccatcttcctgagcttccaacacctgctccgaggaaaggtgcgtttcctg atgcttgtaggagggtccaccctctgcgtcagggaattcggcaacatggcgtctcccgct ccgcctgcttgtgacctccgagtcctcagtaaactgcttcgtgactcccatgtccttcac agcagactgagccagtgcccagaggttcaccctttgcctacacctgtcctgctgcctgct gtggactttagcttgggagaatggaaaacccagatggaggagaccaaggcacaggacatt ctgggagcagtgacccttctgctggagggagtgatggcagcacggggacaactgggaccc acttgcctctcatccctcctggggcagctttctggacaggtccgtctcctccttggggcc ctgcagagcctcctt (seq ID NO:137);<br><br> gctaactgctctataatgatcgatgaaattatacatcacttaaagagaccacctgcacct ttgctggacccgaacaacctcaatgacgaagacgtctctatcctgatggaccgaaacctt cgacttccaaacctggagagcttcgtaagggctgtcaagaacttagaaaatgcatcaggt attgaggcaattcttcgtaatctccaaccatgtctgccctctgccacggccgcaccctct cgacatccaatcatcatcaaggcaggtgactggcaagaattccgggaaaaactgacgttc tatctggttacccttgagcaagcgcaggaacaacagtacgtagagggcggtggaggctcc ccgggtgaaccgtctggtccaatctctactatcaacccgtctcctccgtctaaagaatct cataaatctccaaacatgggacccacttgcctctcatccctcctggggcagctttctgga caggtccgtctcctccttggggccctgcagagcctccttggaacccagcttcctccacag ggcaggaccacagctcacaaggatcccaatgccatcttcctgagcttccaacacctgctc cgaggaaaggtgcgtttcctgatgcttgtaggagggtccaccctctgcgtcagggaattc<br><br> 5S0<br><br> GGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTC AGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTT CACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAA ACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAG GGAGTGATGGCAGCACGGGGACAACTG (SEQ ID NO:148);<br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCGTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCACAAG GATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTG ATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATG GCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCC CATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTC CTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAG GCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGA CAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTC CTCCTTGGGGCCCTGCAGAGCCTCCTT (SEQ ID NO:149);<br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGGCAGGACCACAGCTCACAAGGATCCCAATGCCATCTTCCTG AGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACC CTCTGCGTCAGGGAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCT TGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTG AGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTT AGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCA GTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTC TCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGC CTCCTTGGAACCCAGCTTCCTCCACAG (SEQ ID NO:150);<br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTC CAAACATGGCTCACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACAC CTGCTCCGAGGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGG<br><br> i<br><br> 5<br><br> 10<br><br> 15<br><br> 20<br><br> 25<br><br> 30<br><br> 35<br><br> 40<br><br> 45<br><br> 50<br><br> 591<br><br> GAATTCGGCGGCAACGGCGGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGA GTCCTCAGTAAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCA GAGGTTCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAA TGGAAAACCCAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTG CTGGAGGGAGTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTG GGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACC CAGCTTCCTCCACAGGGCAGGACCACA (SEQ ID NO:151);<br><br> GCTAACTGCTCTATAATGATCGAT.GAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA GGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC GGCAACGGCGRCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGT AAACTGCTTCGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCAC CCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACC CAGATGGAGGAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGA GTGATGGCAGCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTT TCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCT CCACAGGGCAGGACCACAGCTCACAAG (SEQ ID.NO:152);<br><br> GCTAACTGCTCT AT AATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT CATAAATCTCCAAACATGGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTG CGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACGGC GGCAACATGGCGTCCCCAGCGCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTT CGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCT ACACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAG GAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCA GCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAG GTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGC AGGACCACAGCTCACAAGGATCCCAAT (SEQ ID NO:153); and<br><br> GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTAAAGAGACCACCTGCACCT TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGAACTTAGAAAATGCATCAGGT ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAATTCCGGGAAAAACTGACGTTC TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC CCGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT<br><br> 10<br><br> CATAAATCTCCAAACATGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGA GGAAAGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGC GGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTT CGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCT ACACCTGTCC-'GCTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAG GAGACCAAGGCACAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCA GCACGGGGACAACTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAG GTCCGTCTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGGAACCCAGGGCAGGACCACAGCT CACAAG (SEQ ID NO:154).<br><br> 23. A method of producing a hematopoietic protein comprising: growing under suitable nutrient conditions, a host cell transformed or transfected with a replicable vector comprising a nucleic acid molecule of claim 15, 15 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 in a manner allowing expression of said hematopoietic protein and recovering said hematopoietic protein.<br><br> 2g . A pharmaceutical composition comprising; the 20 hematopoietic protein according to claim 1, 2, 3, 4, 5, 6,<br><br> 8, 9, 10, 11 or 12 an(j a pharmaceutical ly acceptable carrier.<br><br> 25 30. The use, in the manufacture of a medicament, of the hematopoietic protein as recited in claim 1, 2, 3, 4, 5, 6, 8, 9, 10, 11 or 12 in a composition for stimulating the production of hematopoietic cells in a patient in admixture with an inert carrier.<br><br> 30 31. The use, in the manufacture of a medicament, of the hematopoietic protein as recited in claim 7 in a composition for stimulating the production of hematopoietic cells in a patient in admixture with an inert carrier.<br><br> 35 32. A method for selective ex vivo expansion of stem cells,<br><br> comprising the steps of;<br><br> (a) separating stem cells from other cells;<br><br> INTELLECTUAL PROPERTY OFFICE OF N.Z.<br><br> 1 5 FEB 2001<br><br> RECEIVED<br><br> (b) culturing said separated stem cells with a selected culture medium comprising; the hematopoietic protein of claim 1, 2, 3, 4, 5, 6, 8, 9, 10, 11 or 12 ■ and<br><br> (c) harvesting" said cultured cells.<br><br> 33. A method for selective ex vivo expansion of stem cells, comprising the steps of;<br><br> (a) separating stem cells from other cells;<br><br> (b) culturing said separated stem cells with a selected culture medium comprising; the hematopoietic protein of claim 7 ; and<br><br> (c) harvesting said cultured cells.<br><br> 34. The use, in the manufacture of a medicament, of the hematopoietic protein of claim 1, 2, 3, 4, 5, 6, 8, 9, 10, 11 or 12 in a composition for treatment of a patient having a hematopoietic disorder in admixture with an inert carrier, the treatment comprising the steps of;<br><br> (a) removing stem cells;<br><br> (b) separating stem cells from other cells;<br><br> (c) culturing said separated stem cells with a selected culture medium;<br><br> (d) harvesting said cultured cells; and<br><br> (e) transplanting said cultured cells into said patient.<br><br> 35. The use, in the manufacture of a medicament, of the hematopoietic protein of claim 7 in a composition for treatment of a patient having a hematopoietic disorder in admixture with an inert carrier, the treatment comprising the steps of;<br><br> (a) removing stem cells;<br><br> (b) separating stem cells from other cells;<br><br> (c) culturing said separated stem cells with a selected culture medium;<br><br> (d) harvesting said cultured cells; and<br><br> (e) transplanting said cultured cells into said patient.<br><br> INTELLECTUAL PROPERTY OFFICE OF N.Z.<br><br> 1 5 FEB 2001 RECEIVED<br><br> 594<br><br> 36. The use, in the manufacture of a medicament, of the hematopoietic protein of claim 1, 2, 3, 4, 5, 6, 8, 9, 10, 11 or 12 in a composition for human gene therapy in admixture with an inert carrier, the treatment comprising the steps of;<br><br> (a) removing stem cells from a patient;<br><br> (b) separating said stem cells from other cells;<br><br> (c) culturing said separated stem cells with a selected culture medium;<br><br> (d) introducing DNA into said cultured cells;<br><br> (e) harvesting said transduced cells; and<br><br> (f) transplanting said transduced cells into said patient.<br><br> 37. The use, in the manufacture of a medicament, of the hematopoietic protein of claim 9 in a composition for human gene therapy in admixture with an inert carrier, the treatment comprising the steps of;<br><br> (a) removing stem cells from a patient;<br><br> (b) separating said stem cells from other cells;<br><br> (c) culturing said separated stem cells with a selected culture medium;<br><br> (d) introducing DNA into said cultured cells;<br><br> (e) harvesting said transduced cells; and<br><br> (f) transplanting said transduced cells into said patient.<br><br> 38. A substantially pure hematopoietic protein substantially as herein described with reference to the accompanying Examples.<br><br> 39. A substantially pure nucleic acid molecule encoding the hematopoietic protein of claim 38.<br><br> 40. A method of producing a hematopoietic protein substantially as herein described with reference to the accompanying Examples.<br><br> INTELLECTUAL PROPERTY OFFICE OF N.Z.<br><br> 1 5 FEB 2001 RECEIVED<br><br> </p> </div>
NZ320978A 1995-10-05 1996-10-04 Hematopoietic proteins and nucleic acid sequences encoding them NZ320978A (en)

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Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5581476A (en) 1993-01-28 1996-12-03 Amgen Inc. Computer-based methods and articles of manufacture for preparing G-CSF analogs
US5969105A (en) * 1996-10-25 1999-10-19 Feng; Yiqing Stem cell factor receptor agonists
US6967092B1 (en) 1996-10-25 2005-11-22 Mc Kearn John P Multi-functional chimeric hematopoietic receptor agonists
US6660257B1 (en) 1996-10-25 2003-12-09 Pharmacia Corporation Circular permuteins of flt3 ligand
US6242570B1 (en) 1997-07-10 2001-06-05 Beth Israel Deaconess Medical Center Production and use of recombinant protein multimers with increased biological activity
US6165476A (en) * 1997-07-10 2000-12-26 Beth Israel Deaconess Medical Center Fusion proteins with an immunoglobulin hinge region linker
US6187564B1 (en) 1997-07-10 2001-02-13 Beth Israel Deaconess Medical Center DNA encoding erythropoietin multimers having modified 5′ and 3′ sequences and its use to prepare EPO therapeutics
AU7825500A (en) * 1999-10-07 2001-04-23 Pharmacia Corporation Inhibition enzyme linked immunosorbent assay (iELISA) for the detection and quantification of antibodies in biological samples
AU2002325819B2 (en) 2001-07-11 2008-06-19 Maxygen, Inc. G-CSF Conjugates
KR20080027291A (en) 2005-06-01 2008-03-26 맥시겐 홀딩스 엘티디 Pegylated g-csf polypeptides and methods of producing same
WO2007075899A2 (en) * 2005-12-21 2007-07-05 Maxygen, Inc. Dual agonist compounds and uses thereof
CN102675472B (en) * 2012-05-07 2014-07-30 北京诺派生物科技有限公司 Kit for detecting pig suffering from porcine reproductive and respiratory syndrome
ES2896354T3 (en) * 2012-12-21 2022-02-24 Astellas Inst For Regenerative Medicine Methods for the production of platelets from pluripotent stem cells
LT6161B (en) 2013-09-27 2015-06-25 Uab Profarma Fused proteins of granulocyte colony-stimulating factor with other partners of growh factor, preferably with stem cell factor, and method of preparation thereof

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU5355790A (en) * 1989-04-19 1990-11-16 Cetus Corporation Multifunctional m-csf proteins and genes encoding therefor
US6057133A (en) * 1992-11-24 2000-05-02 G. D. Searle Multivariant human IL-3 fusion proteins and their recombinant production
US5738849A (en) * 1992-11-24 1998-04-14 G. D. Searle & Co. Interleukin-3 (IL-3) variant fusion proteins, their recombinant production, and therapeutic compositions comprising them
US5635599A (en) * 1994-04-08 1997-06-03 The United States Of America As Represented By The Department Of Health And Human Services Fusion proteins comprising circularly permuted ligands

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NO981500D0 (en) 1998-04-02
AU7384496A (en) 1997-04-28
BRPI9610977A2 (en) 2019-09-17
KR100456212B1 (en) 2005-01-15
WO1997012985A2 (en) 1997-04-10
JPH11510062A (en) 1999-09-07
MX9802730A (en) 1998-09-30
WO1997012985A3 (en) 1997-08-07
CZ96598A3 (en) 1998-09-16
NO981500L (en) 1998-05-20
PL184424B1 (en) 2002-10-31
CZ295518B6 (en) 2005-08-17
CN1124348C (en) 2003-10-15
IL123832A0 (en) 1998-10-30
CN1590407A (en) 2005-03-09
AU705083B2 (en) 1999-05-13
CN1204369A (en) 1999-01-06
CA2234061A1 (en) 1997-04-10
PL326072A1 (en) 1998-08-17
EP0854928A2 (en) 1998-07-29

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