PL184424B1 - Agonists of haemopoietic multifunctional receptors - Google Patents

Abstract

Disclosed are novel multi-functional hematopoietic receptor agonist proteins, DNAs which encode the multi-functional hematopoietic receptor agonists proteins, methods of making the multi-functional hematopoietic receptor agonists proteins and methods of using the multi-functional hematopoietic receptor agonists proteins.

Description

The invention relates to a hematopoietic protein selected from: SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID MR215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ Π0 HR218, SEQ ID

NO: 219, SEQ ID NO: 220, SEQ ID NO: ^^ l, SEQ ID NO: 222, SEQ ID NO: 223, SEQ UD

NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ D NO: 228, SEQ ID NO:

NO: 229, SEQ ID SEQ ID SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID

NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238 and SEQ ID NO: 239.

The invention also relates to a nucleic acid molecule encoding a hematopoietic protein selected from SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: NO: 209, SEQ ID JNR: 210, SEQ ID

NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ TO SEQ ID

NO: 216, SEQ ID NO: 27, SEQ ID SEQ ID NO: 219, SEQ D NO: 220. SEQ ID

NO: 221, SEQ ID NO; 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ TO NO: 225, SEQ ID NO:

NO: 226, SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO:

NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ TO NO: 235, SEQ ID NO:

NO: 236, SEQ ID NO: 237, SEQ ID NO: 238, and SEQ ID NO: 239.

Preferably, the nucleic acid molecule according to the invention is characterized in that it is selected from SEQ ID NO: 118, SEQ D NO: 119, SEQ ID NO: O, SEQ U) NO: 121, SEQ ID NO: 122, SEQ ID NO: 122 , SEQ ID NO: 124, SEQ D! ^ ^ ^ ^: 2 ^ 5, SEQ ID NO

NO: 126, SEQ ID NO: 127, SEQ ID SEQ ID NO: 129, aSQ D, SEQ ID

NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID

NO: 136, SEQ ID NO: 137, SEQ ID NO: B8, SEQ ID NO: 139, SEQ D NR1140, SEQ ID

NO: 141, SEQ ID NO: 142, SEQ ID NO: M3, SEQ ID NO: 144, SEQ ID ERLU, SEQ ID

NO: 146, SEQ ID NO-.147, SEQ ID NO-.148, aSE ID SEQ ID NO-. 150, SEQ ID

NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, aSQ ID NO: 154, and sequences equivalent to these sequences resulting from the degeneracy of the genetic code.

The invention also relates to a method for producing a hematopoietic protein, characterized in that it comprises: culturing, under appropriate nutritional conditions, host cells transformed or transfected with a replication vector containing a nucleic acid molecule encoding a hematopoietic protein in a manner allowing expression of said hematopoietic protein, and recovering said hematopoietic protein, where the nucleic acid molecule encodes a hematopoietic protein selected from SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO ^, SEQID ΠR: 209, SEQro NO: 210, S1Q ID NO. 1, SEQ ID NO

NO: 212, aSQ ID NRN13, SEQ H) DRS1 !, SEQID NO: 2H, S1Q EQ NO ^ I ^ REQ ID

NO: 217, SEQ ID NO! ^, DR :: 19, SEQID NO: 22 (), SEQ IU NO. ^ H REe ID

NS: 222, SEQ ID NO: 2R3, 3EQ Π) DR ^ ,, SEQro NO: 22N, S2Q ID NO ^^ REp ID

184 424

NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238 and SEQ ID NO: 239.

Preferably the method according to the invention is characterized in that the nucleic acid molecule is selected from SEQ ID NO: 118e SEQ ID NO: 119, SEQ ED KRAO. SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126e SEQ ID NO: 127, SEQ ID NO: 128e SEQ ID NO: 129, SEQ ID NO: BO, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID

NO: 136e SEQ iD) NO: 137e SEQ ED NO: 138, SEQ ID NO: B9, SEQ ID MRMO, SEQ ID

NO: 141, SEQ ID NO: 142, SEQED NRA43, SEQ ID NRA44, SEQ ID NO: ^, SEQ ID

NO: 146i SEQ ID NO: 147e SEQ ED NO: 148, SEQ ID NRE49, SEQ ID INRHO, SEQ ID

NO: 151e, SEQ ID NO: 152, SEQ D NR-.U3, EEQnD NO: 154, and sequences equivalent to these sequences resulting from the degeneracy of the genetic code.

The invention also relates to a pharmaceutical composition, characterized in that it comprises a hematopoietic protein selected from: SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 207 : 208, SEQ ID NO: 209, SEQ ID NO: 210, ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQED NO: 217, SEQ IID NO: 228, SEQ ID NO: 229, SEQ ID

NO: 220, SEQ ID NO: 221, SFJE ED NO: 222, SEQ ED NO: 223, SEQ ED NO: 224, SEQ ID

NO: 225, SEQ ID NO: 226, SEQED NO: 227, SEQ ED NO: 228, SEQ IID NO: 229, SEQ ID

NO: 230, SEQ ID NO. ^ H, SEQED NO: 232, SEQ ID NO: 233, SEQ ED NO: 234, SEQ ID

NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238 and SEQ ID NO: 239 and a pharmaceutically acceptable carrier.

Preferably, the pharmaceutical composition according to the invention is characterized in that it additionally comprises at least one colony stimulating factor, cytokine, lymphokine, interleuein, hematopoietic factor selected from the group consisting of: GM-CSF, G-CSF, c-mpl ligand (TPO), 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-B, 1L-15, LIF, flt3 ligand, stem cell factor (SCF).

The invention also relates to the use of a hematopoietic protein selected from: SEQ ID NO: 203, SEQ ED NO: 204, SEQ ID NO: 205, SEQ ED NO: 206, SEQ ID NO:

NO: 207, SEQ ID NO: 208, SFQ ED NO: 209, SEQ IID NO: 210, SEQ IID NO: 211, SEQ ID

No. 1B, SEQ ID NO: 2B, SEQ ED NO: 214, SEQ ID MR2B, IID NIMB. SEQ ID

NO: 217, SEQ ID NO: 218, SEQ ED MR219, S ^ Q ID NO222, SEQ ID NO ^ h SEQ ID

NO ^, SEQ ID NO: 233, SEQ ED TNR: 224, SEQ IID NO: ^ 22, SEQ ID NO ^, SEQ ID

NO: 227, SEQ ID NO: 1, SEQED NO: 229, SEQ ID NO: 0, SEQ ID NO: 1, SEQ UD

NO ^ H, SEQ ID NO ^ U, SEQED NO: 234, SEQ ED NO ^ H, SEQ ID NO: 226, SEQ ID

NO 257, SEQ ID NO: 238 and SEQ ID NO: 0 for the manufacture of a drug for stimulating the production of hematopoietic cells in a patient.

The invention also relates to an agent for stimulating the production of hematopoietic cells in a patient comprising an active agent and a pharmaceutically acceptable carrier, characterized in that the active agent comprises a hematopoietic protein selected from: SEQ ID NO: 203, SEQ ID NO: 203, SEQ ID NO: 305 , SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 2B, SEQ SEQ ID NO. ^ M, SEQ ID NO. ^ H, SEQ ID NO. ^, SEQ ID NO. ^, SEQ ID NO: 218, SEQ ID NO: 219, SEQED MR220, SEQ IID No. ^ E SEQ ID IN ^: ^ 22, SEQ ID

NO ^, SEQ ID NO ^, SEQ ED NO: 225, SEQ IID NO: ^ 22i, SEQ IID NR227, SEQ ID

NO: 228, SEQ ID NO: 229, SEQ ED NO: 230, SEQ ID NO / BR SEQ ID NRBU, SEQ ID

NO: 233, SEQ ID NO: 234, SEQED NO: 235, SEQ IID MMH, SEQ IID NO: 235, SEQ ED

NO: 238 and SEQ ID NO: 239.

The invention also relates to a method for the selective ex vivo expansion of hematopoietic cells, characterized in that it comprises the steps of: (a) culturing the separated hematopoietic cells in a culture medium containing a hematopoietic protein selected from: SEQ ID NO: 305, SEQ ID NO: 204, SEQ ID NO: : 205, SEQ ID NO: 206, SEQ ID NO

184 424

NO: 207, SEQ ID NO: 208, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO

NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO:

NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ UD

NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO:

NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO:

NO: 237, SEQ ID NO: 238 and SEQ ID NO: 239; and (b) harvesting the cultured cells.

The invention also relates to a method for the selective ex vivo expansion of stem cells, characterized in that it comprises the steps of: (a) separating the stem cells from other cells, (b) culturing the separated hematopoietic cells in a culture medium containing a hematopoietic protein selected from: SEQ ID NO: 203 , SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 2B, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO

NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO:

NO: 219, SEQ ID NO: 220, SEQ D NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO:

NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO:

NO: 229, SEQ ID NO: 230, SEQ ID NO: 23,, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO:

NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238 and SEQ ID NO: 239; and (c) harvesting the cultured cells.

Figure 1 illustrates schematically a protein sequence rearrangement. The N (N) terminus and the C (C) terminus of the native protein are linked via a linker or directly connected. The protein opens at the breakpoint, creating a new N-terminus (new N) and a new C-terminus (new C), resulting in a new linear amino acid sequence. The rebuilt molecule can be synthesized from scratch as a linear molecule and not go through the steps of combining the original N-terminus and C-terminus and opening the protein at the breakpoint.

Figure 2 shows a schematic of the Method for creating new proteins in which the original N-terminus and the C-terminus of the native protein are joined by a linker and another N-terminus and C-terminus of the protein are formed. In the example, the sequence rearrangement shown results in a new gene encoding a protein with a new N-terminus formed at amino acid 97 of the original protein, the original C-terminus (amino acid 174) joined to amino acid 11 (amino acids 1-10 removed) via the linker region, and a new terminus C formed at amino acid 96 of the original sequence.

Figure 3 shows a diagram of method II, creating new proteins, in which the original N-terminus and C-terminus of the native protein are joined without a linker, and a different N-terminus and C-terminus of the protein are formed. In the example, the sequence rearrangement shown results in a new gene encoding a protein with a new N-terminus formed at amino acid 97 of the original protein, the original C-terminus (amino acid 174) fused to the original N-terminus, and a new C-terminus formed at amino acid 96 of the original sequence.

Figure 4 shows a diagram of method II for creating new proteins, in which the original N-terminus and C-terminus of the native protein are joined by a linker and a different N-terminus and C-terminus of the protein are formed. In the example, the sequence rearrangement shown results in a new gene encoding a protein with a new N-terminus formed at amino acid 97 of the original protein, the original C-terminus (amino acid 174) joined to the amino acid and through the linker region, and a new C-terminus formed at amino acid 96 of the original sequence.

The present invention encompasses multi-functional hematopoietic receptor agonists made of covalently linked polypeptides, each of which may interact through a different and specific cell receptor to initiate complementary biological activity. Hematopoiesis requires a complex series of cellular events in which stem cells continuously produce 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 only stimulate one type or another of colony formation in vitro, the exact pattern of colony formation stimulated by each regulator is quite, different. There are no two regulators that stimulate the exact same colony formation pattern as assessed34

The number of colonies or, more importantly, the line and maturation pattern of the cells that make up the developing colonies, was 184,424. The proliferative response is most readily analyzed in simplified in vitro culture systems. Three completely different parameters can be distinguished: change in colony size, change in colony number, and cell lineage. Two or more factors may act on the parent cell to induce the production of more offspring, thereby increasing the size of the colony. Two or more factors may allow more parental cells to proliferate, either because there are different subsets of parental cells that respond to only one factor or because some parental cells require stimulation with two or more factors before they are able to respond. Activation of additional receptors on the cell by the use of two or more agents is likely to enhance mitotncann signal due to the coalescence of initially different signaling pathways into a common terminal pathway reaching the nucleus (Metcalf, Nature 339: 27, 19S9). The other mechanisms could be explained by synergy. For example, if one signaling pathway is constrained by indirect activation of an additional signaling pathway caused by the second factor, this may result in a hyperadditive response. In some cases, activation of one type of receptor can induce enhanced expression of other receptors (Metcalf, Blood S2: 3313-S32S, 1993). Two or more factors may result in a different cell line pattern than with a single factor. The use of agonists for multiplication receptors covenanting may have the potential clinical benefit of a proliferative response that is not possible with any single factor.

Hematopoietic and other growth factor receptors can be grouped into two different families of related proteins: (1) tumor kinase receptors, including those for epidermal growth factor, M-CSF (SCcto, Blood, 3: 1, 1990) and SCF (Yarden et al. , EMBO J.6: 3341, 1987): and (2) hematopoietic receptors which do not contain a tyrosine kinase domain but show clear homology in their extracheal domain (Bazan, PNAS USA 87: 6934-6938, 1.0). The latter group includes erythropoietin (EPO) (DAndrea et al. Cell 37: 277, 1989), GM-CSF (Gearing et al., EMBO J. S: 3667, 1989), IL-3 (Kitamura et al., Cell 66: 1163, 1991), G-CSF (Fukunaga et al., J.Btol.Chem. 263: 14008-13, 190), IL-4 (Harada et al., PNAS USA 87: 837, 1990), IL-3 (Takaki et al., EMBO J, 9: 4367, 1990), IL-6 (Yamasaki et al., Science 241: 823, 1988), IL-7 (Goodwin et al., Cell, 60: 941 -31,1990), LIF (Gearing et al., EMBO J, 10: 2839, 1991) and IL-2 (Cosm ^ et al., Mol-Immuzl. 23: 933-94, 1986). Most of the latter group of receptors exist in high affinity form as heterodimers. After ligand binding, specific? Chains bind to at least one other receptor chain (β chain, y chain). Many of these factors share a common receptor subunit. A-chains for GM-CSF, IL-3 and IL-3 share the same β chain (Kimurura et al., Cell 66: 1163, 1991), Takaki et al., EMBO J. 10: 28833-8, 1991). and the receptor complexes for IL-6, LIF and IL-11 share a common p chain (gp130) (Taga et al., Cell 38: 373-81, 1989; Gearing et al., Science 233: 1434-7, 1992). The IL-2 receptor, IL-4, IL-7, IL-9 and IL-13 complexes share a common γ chain (Kondo et al., Science 262: 1874, 1993; Russell et al., Science 262:

1993; Giri et al., EMBO J. 13: 282 ^^^ 2 ^ 230 1994).

The use of a multiply acting hematopoietic factor may also have the potential benefit of reducing the demands placed on the factor producing cells and their induction systems. If there are limitations to the cell's ability to produce the factor, then by lowering the required concentrations of each factor and using them in combination, it can usefully reduce the requirement of the cells that produce the factor. The use of a multifunctional hematopoietic factor may reduce the number of factors needed, possibly reducing the possibility of undesirable side effects.

The novel compounds of this invention are represented by a formula selected from the group consisting of:

R: -L, -R2, R2-L1-R1 and R2-R:

where R: and R2 are as defined above.

184 424

R? is preferably a colony stimulating factor with a different but complementary activity than R1. By complementary activity is meant an activity that enhances or modifies a response to another cellular modulator. The R1 polypeptide is linked either directly or via a linker segment to the R2 polypeptide. The term "directly" denotes a multi-functional hematopoietic receptor agonist in which the polypeptides associate without the peptide linker. Thus, L1 represents a chemical bond or polypeptide segment to which both R1 and R2 are attached in frame, with L1 being most often a linear peptide to which R1 and R2 are joined by amide bonds connecting the carboxyl terminus of R1 to the amino terminus of L1 and the carboxy terminus of L1 with the amino terminus of R2. By "appended in frame" it is meant that there is no translation termination or interruption between reading frames of the DNA encoding R1 and R2.

A non-exclusive list of other growth factors, i.e., colony stimulating factors (CSFs), which are cytokines, lymphokines, interleukes, hematopoietic growth factors, which can be combined with (I), (II) and (III) include GM-CSF, G- CSF, ligand, c-mpl (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, flt3 / flk2 ligand, human growth hormone, B-cell growth factor, cell differentiation factor B, eosinophilic cell differentiation factor, and stem cell factor (SCF) also known as steel factor or c-kit ligand. Additionally, this invention encompasses the use of modified R1 or R2 molecules, or mutated or modified DNA sequences that encode these R1 or R2 molecules. The present invention also includes agonists of multi-functional hematopoietic receptors in which R1 or R2 is hIL-3 variant, c-mpl variant ligand or variant G-CSF. A "hIL-3 variant" is defined as an hIL-3 molecule that has amino acid substitutions and / or deletions of hIL-3 portions as disclosed in WO 94/12638, WO 94/12639 and WO 95/00646, as well as other known variations. in the field. A "c-mpl ligand variant" is defined as a c-mpl ligand molecule that has the amino acid substitutions and / or deletions of a portion of the c-mpl molecule disclosed in US Application Serial Number 08/383 035, as well as other variants known therein. field. A "G-CSF variant" is defined as a G-CSF molecule that has amino acid substitutions and / or deletions of portions of the G-CSF molecule as disclosed herein, as well as other variants known in the art.

The L1 binding group is generally a polypeptide with a length of 1-500 amino acids. Linkers linking two molecules are preferably designed to (1) allow the two molecules to fold and act independently of each other, (2) have no tendency to develop an ordered secondary structure which would interfere with the functional domains of the two proteins, (3) have minimal hydrophobic characteristics, which would interact with the functional domains of the proteins and (4) ensure the spatial separation of R1 and R2 so that R1 and R2 could interact simultaneously with their respective receptors on a single cell. Typically, surface amino acids in the flexible regions of the protein include Gly, Asn, and Ser. Indeed, any permutation of amino acid sequences containing Gly, Asn and Ser is expected to meet the above criteria for a linker sequence. Other neutral amino acids, such as Thr and Ala, can also be used in the linker sequence. Additional amino acids can also be taken into the linkers as the addition of unique restriction sites in the linker sequence will facilitate the construction of multi-functional hematopoietic receptor agonists.

Preferred L1 linkers according to the present invention are sequences selected from the group with the formulas:

(Gly ³ Ser) n (SEQ ID NO: 4), (Gly ⁴ Ser / (SEQ ID NO: 5), (Gly ⁵ Se · / (SEQ ID NO: 6), (GlynSer) (SEQ ID NO: 7 ) or (AlaGlySer) '(SEQ ID NO: 8).

An example of a highly flexible linker is the glycine-serine-rich separation region present inside the pIII protein of filamentous bacteriophages, e.g. M13 or FD bacteriophages (Schaller et al. "PNAS USA 72: 737-741, 1975).

This region provides a long flexible interface between the two domains of the pIII surface protein. The spacer consists of the amino acid sequence:

184 424

GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGluGlyGlyGlySerGluGlyGlyGlySerGluGlyGlyGly SerGluGlyGlyGlySerGlyGlyGlySer (SEQ ID NO: 9).

The present invention also includes linkers wherein the endopeptidase recognition sequence is included. Such a cleavage site may be of value in separating the individual components of the multi-functional hematopoietic receptor agonists, determining whether they are properly assembled and active in vitro. Examples of various endopeptidases include, but are limited to, plasmin, enterokinase, kallikrein, urokinase, tissue plasminogen activator, clostripain, chymosin, collagenase, Russell's viper protease, postproline cleavage enzyme, V8 protease, thrombin, and factor Xa.

Peptide linker segments from the IgG, IgA, IgM, IgD, or IgE heavy chain hinge region provide an angular relationship between the linked polypeptides. Especially useful are those hinge regions where cysteines are converted to serines. Preferred linkers according to the present invention are sequences derived from the mouse IgG gamma 2b hinge region in which cysteines have been converted to serines. These linkers may also include an endopeptide cleavage site and are: Examples of such linkers are the following sequences:

IleSerGluProSerGlyProIleSerThrlleAsrProSerProProSerLysGlu

SerHisLysSerPro (SeQ ID NO: 10) and

IleGluGlyArgIleSerGluProSerGlyProIleSerTh ^ IleAsnProSerPro

ProSerLysGluSerHisLysSerPro (SEQ ID NO: 11).

However, the present invention is not limited by the form, size, or number of linker sequences used, and the only requirement for the linker is that it does not functionally interfere with the folding and function of individual multi-functional hematopoietic receptor agonist molecules.

Linker L2 term.

The length of the amino acid sequence of the L2 linker used in IR and R2 may be selected empirically or by guidance of structural information, or by using a combination of the two approaches.

In the absence of structural information, small series of linkers for testing can be produced using a pattern whose length varies to extend the range from 0 to 50 A, and whose sequence is selected to agree with surface exposure (hydrophilicity, Hopp and Woods, Mol. Immunol. 20: 483-489,1983), Kyte and Doolittle, J. Mol. Biol. 157: 105-132; surface area exposed to solvent, Lee and Richards, J.Mol.Biol. 55: 379-400, 1971) and the ability to adapt the necessary conformation without disturbing the R1 or R2 conformation (conformationally flexible; Karplus and Schulz, Naturwissenschafen 72: 212-213, 1985). Assuming an average translation of 2.0-3.8 for the remainder, this would mean the length to be tested would be between 0-30 residues, with a recommended range of 0-15 residues. An example of such empirical series would be the assembly of linkers using a cassette sequence such as Gly-Gly-Gly-Ser (SEq ID NO: 12) repeated n times, where n is 1, 2, 3 or 4. Those skilled in the art will recognize that there are many such sequences which are of variable length or composition which may serve as linkers with the main note that they cannot be excessively long or short (compare Sandhu, Critical Rev. Biotech. 12: 437-462, 1992); if they are too long, the entropy effect is likely to destabilize the three-dimensional assembly and can also make folding kinetically impractical, and if they are too short, they are likely to destabilize the molecule due to torsional or spatial distortion. Those skilled in the art of analyzing protein structural information will recognize that the use of chain end spacing, referred to as c-alpha carbon distance, can be used to determine the length of the sequence used, or at least to limit the number of possibilities that must be tested in empirical selection of linkers. They will also learn that it will sometimes happen that the end positions of a polypeptide chain are undefined in structural models derived from X-ray diffraction or nuclear magnetic resonance spectroscopy data, and that when this is true, this situation will need to be taken into account to correctly estimate the required linker length. From those residues whose positions are well defined, two residues are selected that are in sequence

184,424 are near the ends of the chain, and the distance between their c-alpha carbons is used to calculate the approximate length of the linker between them. Using the approximate length as a guide, linkers ranging in number of residues (calculated using 2 to 3.8 a remainder) are then selected. These linkers may consist of the original sequence, truncated or lengthened as needed, and when lengthened, additional residues may be selected as flexible and hydrophilic as described above; or alternatively, the original sequence can be substituted for the use of a series of linkers, one example being the Gly-GlyGly-Ser cassette (SEQ ID 10: 12) mentioned above; or, alternatively, a combination of the original sequence and a new sequence having the appropriate overall length can be used.

Determination of the amino and carboxyl terminus of R1 and R2.

The R, and R2 sequences, which allow the folding of biologically active states, can be generated by appropriately selecting the starting (amino-terminus) and terminating (carboxy-terminus) positions within the original polypeptide chain, using the L2 linker sequence as described above. The amino and carboxyl termini are selected from within the common sequence region referred to as the breakpoint region, using the lines of procedure described above. In this way, a new amino acid sequence is created by selecting the amino and carboxyl terminals from within the same breakpoint region. In many cases, the selection of new ends will be such that the original carboxyl terminal position immediately precedes the amino terminus. However, those skilled in the art will recognize that selecting the ends anywhere within the region can work and that this will effectively lead to either deletion or addition to the amino or carboxyl portions of the new sequence.

The general principle of molecular biology is that the β-cross-border amino acid sequence of a protein imposes folding into the three-dimensional structure necessary for the expression of its biological function. Those skilled in the art are familiar with methods of obtaining and interpreting information about the three-dimensional structure using X-ray diffraction of single protein crystals, or nuclear magnetic resonance spectroscopy of protein solutions. Examples of structure information that is necessary to identify breakpoint regions include the location and type of protein secondary structure (alpha and 3-10 helices, parallel and antiparallel beta planes, and chain inversions and twists and loops; Kabsch and Sander, Biopolymers 22: 2377-2637, 1983), the degree of solvent exposure of amino acid residues, the extent and type of interaction of the residues with others (Chothia, Ann. Rev. Biochem. 33: 337-372, 1984), and the static and dynamic distribution of conformations along the polypeptide chain (Alber and Mathews, Methods Enzymmi. 134: 311-333, 1987). In some cases, additional information is known about exposure of the residues to the solvent; an example is the site of post-translational attachment of the hydrocarbon which is necessarily on the surface of the protein. When experimental structure information is unavailable or not obtainable, methods for primary amino acid sequence analysis are also available to make assumptions about the tertiary and secondary structure of a protein, solvent availability, and the occurrence of twists and loops. Sometimes, empirical methods to determine surface exposure are also used when direct structural methods are not feasible; for example, using limited proteolysis chain cleavage identification to infer surface exposure (Gentile and Sa ^ atere, Qur. J. BiocCem. 218: 603-621, 1993). Thus, using either experimental or predictive methods (e.g., Srinivisan and Rose, Proteins: Struci., Funct. & Genetics, 22: 81-99, 1993), the primary amino acid sequence is examined to classify the regions according to whether or not they are or are not integral to the maintenance of the secondary and tertiary structure. Occurrence of sequences within regions known to be associated with periodic secondary structure (alpha and 3-10 helices, parallel and inadvertent beta planes) are regions; which should be avoided. Likewise, the regions of the .alpha.'s sequence where low solvent exposure is observed or predicted to occur are more likely part of the so-called hydrophobic nucleus of the protein and should also be avoided when selecting the amino and carboxyl terminus. On the contrary, those regions known or predicted to be

They are in surface twists or loops, and especially those regions known not to be required for biological activity are the preferred sites for placing the ends of the polypeptide chain. The continuous extent of the amino acid sequence that is recommended based on the above criteria is referred to as the breakpoint region.

Non-circulating multifunctional hematopoietic growth factors.

An alternative method of combining two hematopoietic growth factors is an eicovalent interaction. Such complexed proteins can be described by one of the formulas:

R1-C1 + R2-C2; or C1-R1 + C2-R2; C1-R1 + R2-C2; or Ca-IR + R2-C2.

R1 and R2 are as defined above. The C1 C2 domains are either identical or not identical chemical structures, usually proteinaceous, that can form specific non-covalent linkages. The complexes between C1 and C2 result in a one to one stoichiometric ratio between IR and R2 for each complex. Examples of domains that associate are the "leucine zipper" domains of traescription factors, dimerization domains of bacterial transcriptional repressors, and immunoglobulin constant domains. Covalent bonds connect R1 and C and R2 and C2, respectively. As indicated in the formula, the C1 and C2 domains may be present either at the N-terminus or at the C-terminus of their corresponding hematopoietic growth factor (R). These multimerization domains (C1 and C2) include those derived from the bZIP 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 = 651, 1988), as well as the multimerization domains of the helix-loop-loop family of proteins (Abel et al., Nature 341: 24-25, -484 ; Murre et al., Cell 56: 777-783, 1989; Tapscott et al., Science 242: 405-4111 Fisher et al., Genes & Dev. 5: 2342-2552, ^ O.

Preferred agonists for the multifunctional hematopoietic receptors of the present invention are colony stimulating factors dimerized by their incorporation properties as translational multifunctional agonists with the dimerization domains of the leucine zipper proteins of the Fos and Jun family of bZIP proteins. The Jun leucine zipper domain is capable of interacting with identical domains. On the other hand, the Fos leucine zipper domain interacts with the Jun leucine zipper domain, but does not interact with the Fos leucine zipper domains. Mixtures of Fos and Jun primarily result in the formation of Fos-Jun heterodimers. Thus, when combined with colony stimulating factors, the Jun domain can be used to drive the formation of either homo- or heterodimers. The favorable formation of heterodimers can be achieved if one of the colony stimulating factor partners is engineered to have a Jun leucine zipper domain while the other is constructed to have a Fos zipper.

Additional peptide sequences may also be added to facilitate purification or identification of multi-functional (e.g. poly-His) hematopoietic receptor agonists. A highly antimicrobial peptide could also be added which would be capable of the rapid determination and easy purification of the multi-functional hematopoietic receptor agonist with a specific monoclonal antibody.

"Mutant amino acid sequence", "mutant protein", "altered protein", "mutein", or "mutant polypeptide" refer to a polypeptide having an amino acid sequence that changes from the parent sequence, due to amino acid deletions, substitutions, or one and the other the second, or is encoded by a nucleotide sequence that is intended to be a variation from the native sequence. "Native sequence" refers to an amino acid or nucleic acid sequence that is identical to the wild-type or native form of a gene or protein. Hematopoietic growth factors can be characterized by their ability to stimulate colony formation by human hematopoietic parent cells. The colonies formed include erythroids, granulocytes, megakaryocytes, granulocytic macrophages, and mixtures thereof. Many of the hematopoietic growth factors have shown the ability to restore bone marrow function and the cell population in peripheral blood to therapeutically beneficial levels in studies conducted initially in primates and then in humans. Many or all of these biological activities of hematopoietic growth factors include signal transduction and receptor binding

184,424 with high affinity. The multi-functional hematopoietic receptor agonists of the present invention may exhibit useful properties such as having a similar or greater biological activity as compared to a single agent, or having an improved half-life, or less undesirable side effects, or a combination of these properties.

Multi-functional hematopoietic receptor agonists having little or no U agonist activity may be useful as antagonists, as antigens in the production of antibodies for use in immunology or immunotherapy, as genetic probes, or as intermediates used to construct other useful h.IL-3 muteins.

The biological activity of the multifunctional hematopoietic receptor agonist proteins of the present invention can be determined by DNA synthesis in factor dependent cell lines or by counting colony forming units in an in vitro bone marrow assay.

The multi-functional hematopoietic receptor agonists of the present invention may have an improved therapeutic profile compared to single acting hematopoietic agonists. For example, some of the multifunctional hematopoietic receptor agonists of the present invention may possess a like or stronger growth factor activity relative to other hematopoietic agonists without having similar or correspondingly greater side effects.

The present invention also includes DNA sequences that encode multifunctional hematopoietic receptor agonist proteins, DNA sequences that are substantially similar and perform essentially the same function, and DNA sequences that differ from the DNAs encoding the multi-functional hematopoietic receptor agonists of the invention only due to degeneration of the genetic code. . The RinieUpzy invention also includes oligonucleatides intermediates used to construct mutant DNAs and polypeptides encoded by these oligonucleatides.

Genetic engineering techniques currently standard in the art (US Patent 4,935,233 and Sambrook et al., "Molecular Cloning a Laboratory Manual" Cold Spring Harbor Laboratory, 1989) can be used in constructing the DNA sequences of the present invention. One such method is the mutagenesis cassette (Wells et al., Gene 34: 315-329, 1985), in which part of the coding sequence in the plasmid is replaced with a synthetic oligonucleotide that codes for the desired amino-wapow substitutions in the part of the gene between two restriction sites.

Pairs of complementary synthetic oligonucleotides encoding the desired gene can be generated and hybridized to one another. The DNA sequence of the oligonucleotide will encode the amino acid sequence of the desired gene with the exception of those substituted and / or deleted from the sequence.

The plasmid DNA can be treated with a selected restriction endanuclease, then ligated with hybridized oligonucleotides. The combined mixture can be used to transform JM101 competent cells for resistance to the appropriate antibiotic. Single colonies can be picked and plasmids examined by restriction analysis and / or DNA sequencing to identify plasmids with the desired genes.

The cloning of the DNA sequences of the novel multifunctional hematopoietic receptor agonists, with at least one of the DNA sequences of a different colony stimulating factor, may be achieved by using indirect vectors. Alternatively, one gene can be cloned directly into a vector containing another gene. Linkers and adapters can be used to join DNA sequences, as well as to replace lost sequences where the restriction site was internal to the region of interest. In this way, the genetic material (DNA) encoding one polypeptide, peptide linker, and another polypeptide intrudes into an appropriate expression vector that is designed to transform bacterial, yeast, insect, or mammalian cells. The transformed organism is cultivated and the protein is isolated by standard techniques. The product obtained is thus a novel protein which has a colony stimulating factor linked via a linker region to a second colony stimulating factor.

184 424

Another aspect of the present invention relates to DNA plasmid 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 for the novel polypeptides of the invention. Suitable vectors which can transform microorganisms which enable expression of multifunctional hematopoietic receptor agonists include expression vectors containing nucleotide sequences encoding multifunctional hematopoietic receptor agonists linked to transcriptional or translational regulatory sequences which are selected according to the host cells used.

Vectors comprising modified sequences as described above fall within the scope of the present invention and are useful in the production of multi-functional hematopoietic receptor agonist polypeptides. The vector used in the method also contains selected regulatory sequences in operative relationship with the sequences encoding the DNA of the invention and which allow directing their replication and expression in selected host cells.

As another aspect of the present invention, there is provided a method of producing novel multi-functional hematopoietic receptor agonists. The method of the present invention comprises culturing suitable cells or a cell line that has been transformed with a vector containing a coding sequence to express a novel multi-functional hematopoietic receptor agonist. Suitable cells or cell lines may be bacterial cells. For example, various strains of E. coli are well known as host cells in the field of biotechnology. Examples of such strains include E. coli JM101 strains (Yanisch-Perron et al., Gene 33: 103-119, 1985) and MON105 Obukowicz et al., Applied Environmental Microbiology 58: 151101523, 192). The present invention also encompasses multifunctional hematopoietic receptor agonist proteins using a chromosomal expression vector for E. coli based on the Mu bacteriophage (Wemberg et al., Gene 126: 25-33, 1993). Various strains of B.subtilis can also be used in this method. Many strains of yeast cells known to those skilled in the art are also available as host cells for the expression of the polypeptides of the present invention. When the expression is in the cytoplasm of E. coli, a gene encoding multi-functional hematopoietic receptor agonists can also be constructed such that codons encoding Met'2-Ala'1- or Met- are added to the N-terminus of the protein at the 5 'end of the gene. The N-terminus of proteins produced in the E. coli cytoplasm is influenced by post-translational treatment with methionine aminopeptidase (Ben Bassat et al., J.Bac. 169: 751-757, 1987) and possibly other peptidases such that the methion is severed from the end during expression N. The multifunctional hematopoietic receptor agonists of the present invention can include multifunctional hematopoietic agonist polypeptides having Met'1 Ala 'or Met'2-Ala'1 at the N-terminus. Expression of these mutant multifunctional hematopoietic receptor agonists can also occur in E. coli by linking the secretion signal peptide to the N-terminus. This signal peptide is cleaved from the polypeptide as part of the secretion process.

Mammalian cells, such as Chinese hamster ovary (CHO) cells, are also suitable for use in the present invention. General methods for the expression of foreign genes in mammalian cells are provided by R.J. Kaufman, 1987, Genetic Engineering, Principles and Methods, Vol. 9, J.K.Setlow, editor, Plenum Press, New York. An expression vector is assembled in which a strong primer capable of acting in mammalian cells directs the transcription of a eukaryotic secretion signal peptide coding region that is translationally linked to the multi-functional hematopoietic receptor agonist coding region. For example, plasmids such as pcDNA I / Neo, pRc / RSV, and pRc / CMV (obtained from Invitrogen Corp. San Diego, California) can be used. The eukaryotic coding region for a secretion signal peptide may be from the gene itself or from another secreted mammalian protein (M.L.Bayne, Proc. Natl. Acad. Sci. USA 84: 2638-2642, 1987). After the vector containing the gene is assembled, the vector DNA is transfected into mammalian cells. Such cells can be, for example, COS7, HeLA, BHK, CHO or mouse L lines. Cells can be grown, for example, in DMEM media (JRH Scentific). The polypeptide secreted into the media can be recovered by standard methods after transient expression for 24-72 hours after cell transfection or after establishing stable cell lines after selection for antibiotic resistance. Selection of suitable mammalian host cells and methods for transformation, culture, amplification, screening and product preparation 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., US Patent No. 4,419,446. Another and suitable mammalian cell line is the monkey COS-1 cell line. A similarly useful mammalian cell line is the CV-1 cell line.

If desired, insect cells may be used as host cells in the method of the present invention. See, e.g., Miller et al., Genetic Engineering, 8: 277-298 (Plenum Press 1986) and references cited herein. Additionally, general methods of expression of foreign genes in insect cells using Bakulovirus vectors are described in M.D.Summers and G.E. Smith, 1987) - a Manual of methods gor Baculovirus vectors and insects cell culture procedures. Texas Agricultural Experiment Station Bulletin No. 1555. An expression vector is constructed containing a baculovirus transfer vector in which a strong baculovirus primer (such as a polyhedral primer) drives the transcription of a eukaryotic secretion signal peptide coding region that is translationally linked to the polypeptide coding region of the hematopoietic agonist polypeptide coding region . For example, plasmid pVL1392 (obtained from Invitrogen Corp., San Diego, California) can be used. After the vector carrying the gene encoding the multifunctional hematopoietic receptor agonist polypeptide has been assembled, two micrograms of this DNA with one microgram of baculovirus DNA (see Summers and Smith, 1987) are co-transfected into insect cells, strain SF9. Pure recombinant baculovirus, harboring a multi-functional hematopoietic receptor agonist, is used to infect cultured cells, e.g. in Excell 401 serum free medium (JHR Biosciences, Lenexa, Kansas). The multi-functional hematopoietic receptor agonist secreted into the medium can be recovered by standard biochemical methods. Supernatants from mammalian or insect cells expressing a multifunctional hematopoietic receptor agonist protein can first be concentrated using any of a variety of commercial devices.

The multi-functional hematopoietic receptor agonists of the present invention may be useful in the treatment of diseases characterized by depleted levels of myeloid, erythroid, lymphoid or megakaryocyte cells of the hematopoietic system, or combinations thereof. Additionally, they can be used to activate mature myeloid and / or lymphoid cells. Among the disease states amenable to treatment with the polypeptides of the present invention is leukopenia, a decrease in the number of circulating leukocytes (white blood cells) in the peripheral blood. Leukopenia can be caused by exposure to certain viruses or radiation. It is often a side effect of various forms of cancer therapy, such as exposure to chemotherapy drugs, radiation, and infections and hemorrhages. Therapeutic treatment of leukopenia with these multi-functional hematopoietic receptor agonists of the present invention can help avoid the undesirable side effects caused by currently available drugs.

The multi-functional hematopoietic receptor agonists of the present invention may be useful in the treatment of neutropenia and, for example, in the treatment of conditions such as aplastic anemia, periodic neutropenia, idiopathic neutropenia, Chediak-Higashi syndrome, systemic lupus erythematosus (SLE), leukemia, myelodysplastic syndrome, and .

The multi-functional hematopoietic receptor agonist of the present invention may be useful in the treatment or prevention of thrombocytopenia. Currently, the only treatment for thrombocytopenia is platelet transfusion, which is expensive and carries a significant risk of infection (HIV, HBV), and alloimmunization). A multi-functional hematopoietic receptor agonist may meet or reduce the need for platelet transfusions. Serious thrombocytopenia can result from genetic defects such as Fancome's, Wiscott-Aldrich's or May Hegglin's syndromes. Acquired thrombocytopenia can result from self or foreign antibodies, such as immune thrombocytopenic purpura, systemic

184,424 lupus erythematosus, hemolytic anemia, or mother-fetal incompatibility. In addition, spleen enlargement, disseminated intravascular thrombus, Moschowitz disease, infection, or prosthetic heart valve can all cause thrombocytopenia. Serious thrombocytopenia can also result from chemotherapy and / or radiation therapy or cancer. Thrombocytopenia can also result from bone marrow invasion by cancer, lymphoma, leukemia, or fibrosis.

The multi-functional hematopoietic receptor agonists of the present invention may be useful in the mobilization of hematopoietic parental cells and stem cells in the peripheral blood. Peripheral blood parental cells have been found to be effective in restoring patients in consolidating autologous bone marrow transplant. Hematopoietic growth factors, including G-CSF and GM-CSF, have been shown to increase the number of circulating parental cells and stem cells in the peripheral blood. This simplified the procedure of collecting peripheral blood stem cells and dramatically reduced the cost of the procedure by reducing the amount of fluid required (pheresis). A multi-functional hematopoietic receptor agonist may be useful in mobilizing stem cells and further enhancing the effectiveness of peripheral stem cell transplantation.

The multi-functional hematopoietic receptor agonists of the present invention may also be useful in the ex vivo expansion of hematopoietic parental cells and stem cells. Colony stimulating factors (CSFs) such as hIL-3 have been administered alone, given concurrently with other CSFs, or in combination with bone marrow transplants following high-dose chemotherapy to treat the neutropenia and thrombocytopenia that often result from such treatments. However, the period of severe neutropenia and thrombocytopenia may not be completely eliminated. The myeloid strain, consisting of monocytes (macrophages), granulocytes (including neutrophils) and megakaryocytes, is critical in preventing infection and bleeding, which could save lives. Neutropenia and thrombocytopenia can also result from disease, genetic disorder, drugs, toxins, radiation, and a variety of medical treatments such as conventional cancer therapy.

Bone marrow transplantation has been used to treat this patient population. However, many problems relate to using bone marrow to restore an impaired hematopoietic system, including the following: I) the number of stem cells in the bone marrow, spleen or peripheral blood is limited, 2) host rejection disease, 3) transplant rejection, and 4) possible tumor cell contamination. Stem cells make up a very small percentage of the nucleated cells in the bone marrow, spleen and peripheral blood. It is clear that there is a dose response so that more stem cells will enhance recovery of hematopoiesis. Thus, in vitro expansion of the stem cells should aid in recovery of hematopoiesis and patient survival. Bone marrow from an allogeneic donor was used to provide the bone marrow for transplant. However, graft rejection disease by the host and graft rejection limit bone marrow transplantation even in sibling recipients with an HLA-matched system. Aetological transplants are alternative to allogeneic bone marrow transplants. In autologous bone marrow transplantation, some patients' own bone marrow is harvested prior to marrow disrupting therapy, such as high-dose chemotherapy, and transplanted back into the patient. Autologous transplants eliminate the risk of disease host rejection and transplant rejection. However, autologous bone marrow transplants continue to suffer from a limited number of stem cells in the marrow and possible contamination with tumor cells. A limited number of stem cells can be overcome by ex vivo expansion of the stem cells. In addition, stem cells can be specifically isolated on the basis of the presence of specific surface antigens, such as CD34 +, to reduce contamination with bone marrow transplant tumor cells.

The following patents provide additional details regarding the separation of stem cells, CD34 + cells, culture of cells with hematopoietic factors,

The use of cells for the treatment of patients with hematopoietic diseases and the use of hematopoietic factors in cell expansion and gene therapy.

199 620 relates to compositions containing human hematopoietic stem cells provided by separating the stem cells from dedicated cells.

199,942 describes a method for autologous hematopoietic cell transplantation, comprising: (1) obtaining hematopoietic parental 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 fused protein, GM-CSF / IL-3 and combinations thereof ; (3) administering the cell preparation to the patient.

240 836 relates to a cell separator that includes an apparatus for automatically controlling the cell separation process.

WO 91/16116 describes devices and methods for the selective isolation and separation of target cells from a cell mixture.

WO 91/18972 describes in vitro methods for culturing bone marrow by incubating a suspension of bone marrow cells using a hollow fiber binactor.

WO 92/18613 relates to the process of maintaining and spreading bone marrow cells in culture containing specific mixtures of cytokines for use in transplants.

WO 93/08268 describes a method for selectively expanding stem cells, comprising the steps of (a) separating CD34 + stem cells from other cells and (b) incubating the separated cells in a selective medium such that the stem cells are selectively expanded.

WO 93/18136 describes the in vitro process of utranium ⁱⁿ mammalian cells derived from peripheral blood.

WO 93/18648 relates to a composition comprising human neutrophil precursor cells with high myeloblast and promyelocyte content for the treatment of genetic and acquired neutropenia.

WO 94/08039 describes a method of enriching human hematopoietic stem cells by selecting for cells that express the c-kit protein.

WO 94/11493 describes a population of stem cells that are CD34 + and small in size, which were isolated using a flow-through elutriation method.

WO 94/27698 relates to a method of combining immunoaffinity separation and continuous flow centrifugal separation for the selective separation of a heterogeneous nucleated cell population from a mixture of heterogeneous cells.

WO 94/23848 describes a cell separator for harvesting and manipulating target cells.

Long-term culture, very rich in CD34 + caffeine-forming precursors of parental cells from human bone marrow in cultures containing IL-1a, IL-3, IL-6 or GM-CSF is discussed in Brandt et al., J.Clin. Invest. 86: 932-941, (1990).

One aspect of the present invention relates to a method for the selective expansion of stem cells. The term "stem cell" refers to hematopoietic stem cells capable of multidirectional differentiation as well as early precursors and parental cells that can be isolated from bone marrow, spleen or peripheral blood. The term "expansion" refers to the differentiation and proliferation of cells. The present invention provides a method for the selective ex-vivo expansion of stem cells, comprising the steps of: (a) separating the stem cells from other cells, (b) culturing said separated stem cells with selective media that contains the protein (a) multi-functional hematopoietic receptor agonists and ( c) harvesting said stem cells. Stem cells, as well as the involved parental cells, which will be neutrophils, erythrocytes, platelets, etc., can be distinguished from most other cells by the presence or absence of particular parent marker antigens, such as CD34, which are present on the surface of these cells and / or by characteristics morphological. The phenotype for the highly enriched fraction of human stem cells is termed CD34 +, Thy-1 and lin- but it should be understood that the present invention is not limited to the expansion of this stem cell population. Embrace44

The CD34 + fraction of human stem cells can be separated by a number of methods described, including affinity columns or beads, magnetic beads, or flow cytometry using antibodies to surface antigens such as CD34 +. Further, physical separation methods such as flow-meter elutriation can be used to enrich hematopoietic parental cells. Parental CD34 + cells are heterogeneous and can be divided into several sub-populations, characterized by the presence or absence of co-expression of different lineages associated with molecules associated with the cell surface. Most of the immature parental cells do not express any known strain-related markers such as HLA-DR or CD38, but may express CD90 (thy-1). Other surface antigens such as CD33, cD38, CD41, CD71, HLA-DR or c-kit can also be used for the selective isolation of hematopoietic parental cells. The separated cells can be incubated in a selective medium, culture flask, sterile bag, or empty fibers. Various colony stimulating factors can be used for the selective expansion of cells. Representative factors that have been used for ex-vivo bone marrow expansion are c-kit ligand, IL-3, G-CSF, GM-CSF, IL-1, IL-6, IL-11, flt-3 ligand or combinations thereof. Stem cell proliferation can be monitored by counting the number of stem cells and other cells by standard techniques (e.g., hemacytometer, CFU, LTCIC) or by flow cytometry before and after incubation.

Several methods for ex-vivo expansion of stem cells have been reported, employing multiple selection and expansion methods using colony stimulating factors, including the c-kit ligand (Brandt et al., Blood 83: 1507-1514 [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], IL-1 (Muench et al., Blood 81: 34633473 [1993], IL-6 (Sato et al., Blood 82: 3600-3609 [1993], IL- 11 (Lemoli et al., Exp. Hem. 21: 1668-1672 [193], Sato et al., Blood 82: 3600-3609 [1993], flt-3 (McKenna et al., Blood 86: 3413-3420 [1995], and / or combinations thereof (Brandt et al., Blood 83: 1507-1514 [1994], Haylock et al., Blood 80: 1405-1412 [1992], Koller et al., Biotechnology 11: 358- 363 [1993], (Lemoli et al., Exp. Hem. 21: 1668-1672 [193], McKenna et al., Blood 86: 3413-3420 [1995], Muench et al., Blood 81: 3463-3473 [1993], Patchen et al., Biotherapy 7: 13-26 [1994], Sato et al., Blood 82: 3600-3609 [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 was found to be one of the most potent expansion of CD34 + cells in peripheral blood (Sato et al., Blood 82: 3600-3609 [1993], Kobayashi et al., Blood 73: 1836-). 1841 [1989] However, no single growth factor has been shown to be as effective as a combination of multiple factors The present invention provides an ex vivo expansion method that employs multi-functional hematopoietic receptor agonists more effective than the single factor.

Another aspect of the invention provides a method of supporting and / or expanding hematopoietic precursor cells that includes inoculating cells into a culture vessel containing a culture medium conditioned by exposure to a stroma cell line such as HS-5 (WO 96/02662, Rocklein and Torok-Strob , Blood 85: 9971105, 1995), supplemented with the multi-functional hematopoietic receptor agonist of the present invention.

Another projected clinical application of growth factors was the in vitro activation of hematopoietic parental cells and stem cells for gene therapy. Due to the long duration of hematopoietic parental cells and the breakdown of their daughter cells throughout the body, hematopoietic parental cells are good candidates for ex vivo gene transfection. In order to have an interesting gene integrated into the genome of a hematopoietic parent cell or stem cell, cell division and DNA replication must be stimulated. The hematopoietic stem cell cycle has a very low frequency, meaning that growth factors can be useful in stimulating gene transduction, thereby enhancing the clinical outlook for gene therapy. Potential applications of gene therapy (Crystal, Science 270: 404-410 [1995] include: 1) the treatment of many

184,424 congenital metabolic diseases and immune deficiencies (Kay and Woo Trends Genet. 10: 253-257, [1994], 2) neurological diseases (Friedmann, Trends Genet. 10: 210-214 [1994], 3) cancer (Culver Trends Genet. 10: 174-178 [1994] and 4) infectious diseases (Gilboa and Smith Trends Genet. 10: 139-144 [1994]).

There are many methods known to those skilled in the art for introducing genetic material into a host cell. Many vectors, both viral and non-viral, have been used to transfer therapeutic genes into primary cells. Virus-based vectors include 1) Replication-deficient recombinant reterovtrus (Tcoris-Lawrie and Temin, Curz.Opin.Gbnet.Dev. 3: 102-109 [1993], Boris-Lawrie and Temin, Annal. New York Acad. Sci. 716: 59-71 [1994], Miller, Current Top. Microbiol. Immunol. 158: 1-24 [1992]) and the non-replication recombinant Adbnovisus (Berkner BioTbchniqubs 6: 616-629 [1988], Berkner, Current Top. Microbiol. Immunol. 158: 39-66 [1992]). Non-viral vectors include protein / DNA complexes (Cristiano et al., PNAS USA 90: 2122-2126 [1993], Curiel et al., PNAS uSa 88: 8850-8854 [1991], Curiel et al., Annal. New York Acad. .Sci.716: 36-58 [1994], electroporation and liposome-mediated delivery such as cationic liposomes (Farhood et al., Annal. New York Acad. Sci.716: 23-35 [1994]).

The present invention relates to an improvement of existing methods of hematopoietic cell expansion that introduces new genetic material, wherein methods are provided that employ multi-functional hematopoietic receptor agonist proteins to improve biological activity, including activity not visualized by a single colony stimulating factor.

Many drugs can cause bone marrow suppression or hematopoietic deficiencies. Examples of such drugs are AZT, DDI, alkalizing agents and antimetabolites used in chemotherapy, antibiotics such as chloramphenicol, penicillin, ganciclovirin, daunomycin and sulfa drugs, phenothiazones, sedatives such as mbprobamate, analgesics, and dipyronopyrins such as anticonvulsants such as phenytoin or carbamazepine, anti-thyroid agents such as pesopylthiouoacil and methimazole, and diuretics. The multi-functional hematopoietic receptor agonists of the present invention may be useful in the prevention or treatment of bone marrow suppression or hematopoietic deficiencies which are common in patients treated with these drugs.

Hematopoietic deficiencies can also occur as a result of viral, microbial or parasitic infections and as a result of treatment of kidney disease or renal failure, e.g. dialysis. The multi-functional hematopoietic receptor agonists of the present invention may be useful in the treatment of such hematopoietic deficiencies.

Treatment of a hematopoietic deficiency may involve administering to the patient a pharmaceutical composition comprising the multi-functional hematopoietic receptor agonists. The multi-functional hematopoietic receptor agonists of the present invention may also be useful for the activation and support of hematopoietic precursor cells by treating these cells in vitro with the multi-functional hematopoietic receptor agonist proteins of the present invention, prior to injecting the cells into a patient.

Treatment with the multi-functional hematopoietic receptor agonists of the present invention may also have a beneficial effect on various immunodeficiencies, e.g., T and / or B lymphocytes, or immune disorders, e.g. rheumatoid arthritis. Immunodeficiencies can be the result of viral infections, eg HTLVI, HTLVI, HTLVIII, severe radiation exposure, cancer therapy, or other medical treatment. The multi-functional hematopoietic receptor agonists of the present invention can also be used, alone or in combination with other colony stimulating factors, to treat other blood cell deficiencies including thrombocytopenia (platelet deficiency) or anemia. Another application of these new polypeptides is the in vivo and ex vivo treatment of bone marrow transplant patients and in the development of monoclonal and polyclonal antibodies produced by standard methods for diagnostic or therapeutic use.

Other aspects of the present invention are therapeutic methods and compositions

Treatment of the disease states noted above. Such compositions comprise a therapeutically effective amount of one or more multi-functional hematopoietic receptor agonists of the present invention in admixture with a pharmaceutically acceptable carrier. These compositions can be administered parenterally, intravenously or subcutaneously. When administered, the therapeutic composition for use in this invention is preferably in the form of a pyrogen-free parenterally acceptable aqueous solution. The preparation of such a parenterally acceptable protein solution, which is isotonic, stable, etc. depending on the pH, is known to those skilled in the art.

The dosage regimen used in the method of treating the above-described conditions will be determined by the treating physician considering various factors that modify the action of the drug, e.g., the condition, body weight, sex and diet of the patient, the severity of each infection, the timing of administration, and other clinical factors. In general, the daily regimen may vary from 0.2-150 pg / kg multifunctional hematopoietic receptor agonist protein per kilogram body weight. The dosage will be adjusted according to the activity of the given multifunctional hematopoietic receptor agonist protein, and it will not be unreasonable to note that dosage regimes may be very low, such as 0.1 microgram, and very high, such as 1 milligram per kilogram of body weight per day. In addition, there may be specific circumstances in which dosages of the multifunctional hematopoietic agonist will be set higher or lower than the range of 0.2-150 micrograms per kilogram body weight. This includes the co-administration of other colony stimulating factors or IL-3 variants or growth factors; simultaneous administration of chemotherapeutic drugs and / or irradiation; the use of glycosylated proteins of multifunctional hematopoietic receptor agonists; and the various patient related matters mentioned earlier in this section. As indicated above, the treatment method and compositions may also include co-administration with other human agents. A non-exclusive list of other suitable colony stimulating factors (CSFs), cytokines, 11, seals, hematopoietic growth factors and ietcrleukie for simultaneous and sequential administration with the polypeptides of the present invention 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, IL-16, LIF, flt3 / flk2 ligand, B cell growth factor, B cell differentiation factor and eosinophilic cell differentiation factor, and stem cell factor (SCF) also known as steel factor or c-kit ligand, or combinations thereof. The dosage recited above will be adjusted to compensate for such additional ingredients in the therapeutic composition. The progress of the treated patient can be monitored by periodic evaluation of the hematological profile, e.g., differential cell counts and the like.

Materials and methods

Unless otherwise noted, all chemicals were obtained from Sigma Co (St. Louis, MO). Restriction endonuclease and T4 DNA ligase were obtained from New England Biolabs (Beverly, MA) or Boehringer Munich, (Indianapolis, IN).

Transformation of E. coli strains

E. coli strains such as DH5a ™ (Life Technologies, Gaithersburg, MD) and TG1 (Amersham Corp., Arlington Heights, IL) are used to transform the ligation reaction and are a source of plasmid DNA for the transcection of mammalian cells. E. coli strains such as JM101 (Yanisch-Perroe et al., Gene 33: -03-19, 1985) and MON105 (Obukowicz et al., Appl.Envir.Micr., 58: 1511-1523, -442 ), can be used to express the multi-functional hematopoietic receptor agonists of the present invention in the cytoplasmic or periplasmic space.

MON105 ATCC # 55204: F-, lambda-, IN (rrnD, rrE) L rpoD +, rpoH358

DH5a ™: Fi, phi80dlacZdeltaM15, deltaOazZYAargFjUUR deoR, recAL EndA1, hsdR17 (rk-, mk +), phoA, supE44lambda-, thi-1, gyrA96, relA1,

TG1: delta (lac-pro), supE, thi-1, hsdD5 / F '(traD36, proA + B, lacIq, lacZdeltaM15)

JM101 ATCC # 33876: delta (por lac), supE thi, F '(traD36, proA + B +, lacIq, lacZdeltaM15)

184 424

Cells for efficient DH5a ™ subcloning are purchased as competent cells and are ready for transformation using the manufacturer's protocol, while both E. coli TG1 and MON105 strains are made competent for DNA uptake using the CaCl method. Typically, 20-50 ml of cells are grown in LB medium (1% bacto-tryptone, 0.5% bacto-yeast extract, 150 mM NaCl), to a density of about 1.0 optical density unit at 600 nanometers (OD600) as measured Spectronic Baush and Lomba spectrophotometer (Rochester, NY). Cells are harvested by centrifugation and resuspended in one fifth of the culture volume with CaCl solution (50 mM CaCl2, 10 mM Tris-Cl, pH 7.4) and kept at 4 ° C for 30 minutes. Cells are harvested again by centrifugation and resuspended in a tenth volume of culture with CaCl solution. Pooled DNA is added to 0.2 ml of these cells and samples are kept at 4 ° C for 30-60 minutes. The temperature of the samples is changed to 42 ° C for 2 minutes and 1.0 ml of LB is added before the samples are shaken at 37 ° C for one hour. Cells from these samples are scattered on plates (LB medium plus 1.5% bacto-agar) containing either ampicillin (100 micrograms / ml) for selection for ampicillin resistant transformants, or spectinomycin (75 pg / ml) for selection for spectinomycin resistant transformants. Plates were ineubated overnight at 37 ° C.

Colonies are harvested, inoculated into LB plus an appropriate antibiotic (100 (µg / ml ampicillin or 75 µg / ml spectinomycin) and grown at 37 ° C with shaking.

Ways of making genes with a new N-terminus / C-terminus

Method I. Generation of genes with a new N-terminus / C-terminus that contain a linker (L2) region.

Genes with a novel N-terminus / C-terminus that contain a linker (L2) region separating the original C-terminus and N-terminus can be made essentially according to the method described by L.S. Mullins et al., J.Am.Chem.Soc. 116: 5529-5533,1994). Multiple amplification steps in the polymerase chain reaction (PCR) are used to rearrange the DNA sequence that encodes the original amino acid sequence of a protein. The steps are illustrated in Fig. 2.

In the first step, the first primer set ("new start" and "start linker") is used to generate and amplify, from the original geographic sequence, a DNA fragment ("Fragment Start") which contains the sequence encoding the new N-terminal part. the new protein, followed by a linker (L1) that joins the C-terminal and N-terminal ends of the original protein. In the second step, a second set of primers ("new stop" and "stop linker") is used to create and duplicate, from the original gene sequence, a DNA fragment ("Fragment Stop") that codes for the same linker as used above, and then a new C-terminal part of a new protein. The "new start" and "new stop" primers are designed to include appropriate restriction sites that allow the new gene to be cloned into expression plasmids. Typical PCR conditions are one melt cycle at 95 ° C for 2 minutes; 25 cycles of denatured at 94 ° C for one minute, hybridization at 50 ° C for one minute, and extension at 72 ° C for one minute; plus one 72 ° C extension cycle for seven minutes. The Perkin Elmer GeneAmp PCR Core Reagents kit is used. 100 µl of reaction contains 100 pmol of each primer and one µg of template DNA; and 1x PCR buffer, 200 pM dGTP, 200 pM dATP, 200 pM dTTP, 200 pM dCTP, 2.5 units AmpliTaq Dna polymerase and 2 mM MgCl2. PCR reactions are performed on a Model 480 DNA thermal cycler (Perkin Elmer Corporation, Norwalk, CT).

"Start Fragment" and "Stop Fragment", which have a complementary sequence in the linker region and a coding sequence for the two aminoews on either side of the linker, are joined together in a third PCR step to generate a full-length gene encoding the new protein. The DNA fragments "Fragment Start" and "Fragment Stop" are dissolved on a 1% TAE gel, stained with Etidium Bromide and isolated using the Qiaex Gel Sχjraction kit (Qiagen). These fragments are pooled in equimolar amounts, heated at 70 ° C for ten minutes, and slowly cooled to allow their split sequence to hybridize into "linker start" and "linker stop". In the third PCR step, the "new start" and "new stop" primers are added to the braided fragments to generate and amplify a full-length gene with a new N-terminus / C-terminus. Typical PCR conditions are one melting cycle at 95 ° C by

184,424 mmuty; 55 coI-1 and Seaaeurcuji wtemseraeuese 44 ° C for eedna 1 ™yszne ^, hbbjydya.auia at 60 ° C for one minute and extension at 72 ° C for one minute; plus one elongation cycle at 72 ° C for seven minutes. The Perkin Elmer GeneAmp PCR Core Reagents kit is used. 100 µg of reaction mix contains 100 pmol of each primer and approximately 0.5 µg of DNA; and 1x PCR buffer, 200 µM dGTP, 200 µM dATP, 200 µM dTTP, 200 µM dCTP, 2.5 units of palimeraec DNA AmpliTaq and 2 mM MgCA. PCR reaction media is purified using the Wizard PCR Preps kit (Promega).

Method II. Generation of genes with a new N-terminus / C-terminus without the linOer region.

Genes of genes with a new N-terminus / C-terminus without a linker joining the original N-terminus and C-terminus can be made using D-w (5 (^^^ eeps of amplification of PCR and open-end ligation. The steps are illustrated in Figure 3.) in the first step, a set of primers ("new start" and "P-bl star") are used to generate and amplify, from the original gene sequence, a DNA fragment ("Fragment Start") which contains the sequence encoding the new N-terminal part of the new In the second step, a second set of primers ("new stop" and "p-bl stop") are used to generate a DNA fragment ("Fragment Stop") that contains the sequence encoding the new C-terminal part of the new protein. new start "and" new stop "are designed to contain appropriate restriction sites that allow the new gene to be cloned into expression vectors. Typical PCR conditions are: one melting cycle at 95 ° C for two minutes; 25 cycles of denaturation at temperature 94 ° C for one minute, hecrimination at 50 ° C for 45 seconds and an extension at 72 ° C for 45 seconds. To eliminate the occurrence of overhangs, Deep Vent polymerase (New England Biolabs) is used under the conditions recommended by the manufacturer. The primers "P-bl start" and "P-bl stop" t <o ^] ^ f ^ ar ^^ ι ^ e ^ siię at the 5 'end to assist in ligating and open end of "Fragment Start" and "Fragment Stop" " between each other. 100 µl of the reaction mixture contained 150 pmol of each primer and one µg of template DNA; and 1x Vent Buffer (New England Biolabs), 300 µM dGTP, 300 µM dATP, 300 µM dTTP, 300 µM dCTP and 1 palimcraey Deep Vent. PCR reactions are performed in a Model 80 DNA thermal cylinder (Perkin Elmer Corporation, Norwalk, CT). PCR reaction products are purified using the Wizard PCR Preps kit (Promega).

The primers were designed to contain appropriate restriction sites that would allow the new gene to be cloned into expression vectors. Typically, a "Fragment Start" is designed to create an NcoI restriction site and a "Fragment Stop" is designed to create a HindIII restriction site. The restriction digestion reaction environments are cleaned using the Magic DNA Clean-up System (Promega). The Start and Stop fragments are dissolved in a 1% TAE gel, stained with etidium bromide and isolated using the Qiaex Gel Extraction kit (Qiagen). These fragments were ligated and hybridized to the ~ 3800 bp of RcoI / HindIII vector fragment pMOR9934 by heating at 50 ° C for ten minutes and allowed to cool slowly. The three fragments are ligated using T4 DNA ligase (Boehringer Munich). The result is a plasmid containing the gene with the new N-terminus / C-terminus. Part of the ligation reaction is used to transfer cells of the E. coli DH5a strain (Life Technologies, Gaitherpbergh, MD). Plasmid DNA is purified and sequences confirmed as follows.

Method III. Generation of a gene with a new N-terminus / C-terminus by tandem duplication.

Genes with a new N-terminus / C-terminus can be generated based on the method described in R.A. HorlicOA et al., Protein Eng. 5: 457-431, (1992). Polymerase chain reaction (PCR) amplification of genes with a new N-terminus / C-terminus is performed using a tandem duplicated DNA template. The steps are illustrated in Fig. 3.

The tandem duplicated DNA template is produced by cloning and contains a DNA sequence split gene encoding a linker joining the original C and N-terminus of the two gene copies. A specific set of primers is used to generate and amplify a full-length gene with a new N-terminus / C-terminus from tandem duplicate DNA templates. These primers were designed to contain appropriate reptraction sites that would allow a non-novel gene to be cloned into expression vectors. Typical PCR conditions are one cycle of melting at 95 ° C for two minutes; 25 cycles of denaturation at 94 ° C for one minute, hybridization at 50 ° C for one minute, and extension at 7.0 ° C for one minute; plus one 72 ° C extension cycle for seven minutes. The Perkin Elmer GeneAmp PCR Core Reagents kit (Perkin Elemr Corporation, Norwalk, CT) is used. 100 µl of reaction mixture contains 100 pmol of each primer and one µg of template DNA; and 1x PCR buffer, 200 pM dGTP, 200 pM dATP, 200 pM dTTP, 200 pM dCTP, 2.5 units AmpliTaq DNA polymerase and 2 mM MgCl. PCR reactions are performed on a Model 480 DNA thermal cycler (Perkin Elmer Corporation, Norwalk, CT). PCR reaction mixtures are purified using the Wizard PCR Preps kit (Promega).

Cloning of genes with a new N-terminus / C-terminus into multifunctional hematopoietic receptor agonist expression vectors.

A gene with a new N-terminus / C-terminus is digested with restriction endonucleases to generate ends compatible with the insertion into the expression vector containing the colony stimulating factor gene. This expression vector is similarly digested with restriction endonucleases to create compatible ends. After purification, the gene and vector DNA are ligated and ligated using T4 DNA ligase. Part of the ligation reaction is used to transform E. coli. Plasmid DNA is purified and quenched to confirm correct insert. Correct clones are grown for protein expression.

DNA isolation and characterization

Plasmid DNA can be isolated by a variety of methods and using commercially available kits known to those skilled in the art. Several such methods are presented here. Plasmid DNA is isolated using the Promega Wizard ™ Miniprep kit (Madison, WI), Qiagen QIAwell Plasmid isolation kits (Chatsworth, CA), or the Qiagen Plasmid kit. These kits follow the same general procedure for isolating plasmid DNA. Briefly, cells are pelleted by centrifugation (5000 x g), plasmid DNA released by sequential NAOH / acid treatment, and cell debris removed by centrifugation (10000 x g). The supernatant (containing the plasmid DNA) is applied to the column containing the DNA binding resins, the column is washed, and the plasmid DNA of the TE is eluted. After screening for colonies with the plasmid of interest, E. coli cells are inoculated into 50-100 ml LB plus an appropriate antibiotic for cultivation overnight at 37 ° C in an aeration-shaking incubator. Purified plasmid DNA is used for DNA sequencing, further restriction digest, additional subcloning, and transfection into mammalian, E. coli, or other cells.

Confirmation of the sequence

The purified plasmid DNA is resuspended in dH, O and quantified by measuring absorbance at 260/280 nm on a Spectronic 601 UV Bausch and Lomba spectrometer. The DNA samples are sequenced using ABI PRISM ™ DyeDnoxy ™ terminator sequencing chemistry kits (Applied Biosystems Division of Perkin Elmer Corporation, Lincoln City, CA) (lot number 401388 or 402078) according to a protocol suggested by the manufacturers, usually modified by adding 5% DMSO to the sequencing mixture. The sequencing reactions are performed on a Model 480 DNA thermal cycler (Perkin Elmer Corporation, Norwalk, CT) following the recommended conditions. Samples are purified to remove excess dye terminators using Centri-Sep ™ spinning columns (Princeton Separation, Adelphia, NJ) and lyophilized. The sequencing reaction media labeled with a fluorescent dye are resuspended in deionized formamide and sequentially over 4.75% polyacrylamide denaturing urea gels using an ABI Model 373A automated DNA sequencer. Overlapping DNA sequence fragments are analyzed and assembled into major adjacent DNAs using Snqunncher v2.1 analysis computer software (Gene Codes Corporation, Ann Arbor, MI).

Expression of multi-functional hematopoietic receptor agonists in mammalian cells

184 424

Mammalian cell transfection / production of conditioned media

The BHK-21 cell line can be obtained from ATCC (Rockville, MD). Cells are grown in Dulbecco's Modified Eagl's Medium (DMEM / glucose-enriched), supplemented with 2 mM (m) L-glutamine and 10% Fetal Bovine Serum (FBS). This preparation is labeled as BHK growth medium. Selective medium is BHK growth medium supplemented with 453 units / ml Hygromycin B (Calbiochem, San Diego, CA). The BHK-21 cell line was previously stably transfected with the HSV VP16 transactivation protein, which transactivates the IE110 primer found in the pMON3359 plasmid (see Hippenmeyer et al., Bio / Technology, pp. 1037-1041, 1993). The VP16 protein drives the expression of the inserted genes in addition to the IE 110 primer. BHK-21 cells expressing the transactivating VP16 protein were designated BHK-YP16. The plasmid pMON1118 (see Highkin et al., Poultry Sci. 70: 970-981, 1991) expresses the hygromycin resistance gene from the SV40 primer. A similar plasmid, pSV2-hph, is available from ATCC.

BHK-VP16 cells are seeded in a 60 millimeter (mm) tissue culture plate at 3 x 10 ⁵ cells per plate, 24 hours prior to transfection. Cells are transfected for 16 hours in 3 ml of "OPTIMEM" ™ (Gibco-BRL, Gaithersburg, MD) containing 10 µg of plasmid DNA with the gene of interest, 3 µg of hygromycin resistance plasmid, pMON1118, and 80 µg of "LIPOFECTaMiNE" ™ from Gibco -BRL, to the board. The medium is then aspirated and replaced with 3 ml of growth medium. 48 hours after transfection, media from each plate is harvested and assayed for activity (conditioned medium). Cells are removed from the plate with trypsin-EDTA diluted 1:10 and transferred to 100 mm tissue culture plates containing 10 ml of selective medium. After about 7 days, resistant cells grow into colonies several millimeters in diameter. Colonies are removed from the plate 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 containing 1 ml of selective medium. After clones are grown and confluent, the conditioned media * is retested and positive clones are dispersed in the growth medium.

Expression of multi-functional hematopoietic receptor agonists in E. coli

The E. coli MON105 or JM101 strain containing the plasmid of interest is grown at 37 ° C in M9 plus amino acid medium by shaking in a Model G25 air incubator from New Brunswick Scentific (Edison, Ne Jersey). Growth is monitored at OD 600 until a value of 1.0 is reached, at which point nalidixic acid (10 milligrams / ml) in 0.1 N NaOH is added to a final concentration of 50 µg / ml. The cultures are then shaken at 37 ° C for three to four additional hours. A high degree of aeration is maintained throughout the cultivation period in order to obtain the maximum production of the desired gene product. Cells are examined under light microscopy for the presence of inclusion bodies (IB). Equal amounts of one ml of cultures are removed for protein content analysis, by boiling the granulated cells, treating them with reducing buffer and electrophoresis by SDS-PAGE (see Maniatis et al., Molecular Cloning: a Laboratory Manual, 1982). The culture is centrifuged (5000 x g) to / granulate the cells.

Inclusion body fabrication, extraction, refolding, dialysis, DEAE chromatography, and characterization of multi-functional hematopoietic receptor agonists that accumulate inclusion bodies in E. coli.

Isolation of inclusion bodies:

The cell pellet from 330 ml of E. coli culture is resuspended in 15 ml of sonication buffer (10 mM 2-amino-2- (hydroxymethyl) -1.3-propanediol hydrochloride (Tris-HCl), pH 8.0 + 1 mM ethylenediaminetetraacetic acid (EDTA) These suspended cells are sonicated using a Sonicator Cell Disruptor microcap probe (Model W-375, Heat Systems-Ultrasonics, Inc., Farmingdale, New York). Three cycles of sound treatment in treatment buffer are used. sounds, then centrifugation to destroy cells, and washing of the inclusion bodies (IB).

The sound is 3 minutes of bursting followed by 1 minute of bursting, and the final two cycles of sound treatments are 1 minute each.

Protein extraction and refolding from clumps of inclusion bodies:

After the final centrifugation step, the IB pellet is resuspended in 10 ml 50 mM Tris-HCl, pH 9.5, 8 M urea and 5 mM dithiothreitol (DTT) and stirred at room temperature for approximately 45 minutes to allow the proteins to denature from expression.

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 gently shake exposed to air at 4 ° C for 18-48 hours, allowing the proteins to refold. Folding is monitored by analysis on a C18 column of reversed phase high pressure liquid chromatography (RP-HPLC) Vydac (Hesperia, Ca) (0.46 x 25 cm). A linear gradient of 40% to 65% acetonitrile containing 0.1% trifluoroacetic acid (TFA) is used to monitor folding. The gradient is developed for 30 minutes at a flow rate of 1.5 ml per minute. Generally, the denatured proteins elute later in the gradient than the refolded proteins.

Cleansing:

After refolding, E. coli contaminated proteins are removed by acid precipitation. The pH of the refolding solution is titrated to a pH of between 5.0-5.2 with 15% (v / v) acetic acid (HOAc). This solution is stirred at 4 ° C for hours and then centrifuged for 20 minutes at 12,000 x g to granulate the insoluble protein.

The supernatant from the acid precipitation step is dialyzed using a Spectra / Por 3 membrane with a molecular weight cut-off (MWCO) of 3500 Daltons. Dialysis is performed against 2 shifts of 4 liters (50 fold excess) of 10 mM Tris-HCl, pH 8.0 for a total period of 18 hours. Dialysis lowers the conductivity of the sample and removes urea prior to DEAE chromatography. The sample is then centrifuged (20 minutes at 12,000 x g) to granulate all the undissolved protein after dialysis.

A Bio-Rad Bio-Scale DEAE2 column (7 x 52 mm) is used for ion exchange chromatography. The column is equilibrated in a buffer containing 10 mM Tris-HCl, pH 8.0, and a 0-500 mM sodium chloride gradient in the equilibration buffer is applied over 45 column volumes to elute the protein. The run uses a flow rate of 1.0 mL per minute. Column fractions (2.0 ml per fraction) are collected by gradient and analyzed by RP HPLC on a Vydac C18 column (Hesperia, Ca.) (0.46 x 25 cm). A linear gradient of 4 -% - 65% acetonitrile containing 0.1% trifluoroacetic acid (TFA) is used. The gradient is developed for 30 minutes at a flow rate of 1.5 ml per minute. The pooled fractions are then dialyzed against a change of 4 liters (50,500 fold excess) of 10 mM ammonium acetate (NHAc), pH 4.0 for a total period of 18 hours. Dialysis is performed using Spectra / Por 3 membrane with a MWCO of 3,500 Daltons. Finally, the sample is sterile filtered using a 0.22 µm syringe filter (pStar LB syringe filter, Costar, Cambridge, Ma.) And stored at 4 ° C.

In some cases, the folded proteins can be affinity purified using affinity reagents such as mAbs or receptor subunits linked to an appropriate base. Alternatively (or additionally), purification may be achieved using any of a variety of chromatographic methods such as ion exchange, gel filtration or hydrophobic chromatography or reverse phase HPLC.

These and other methods of protein purification are described in detail in Methods in Enzymology, Vol. 182 "Guide to Protein Puritication" edited by Murray Deutscher, Academic Press, San Diego, CA, (1990).

Protein Characterization:

The purified protein is analyzed by RP-HPLC, electron spray mass spectrometry, and SDS-PAGE. Protein quantification is done by amino acid composition, RP-HPLC and determination of Bradford proteins. In some cases, tryptic mapping of amino acids in conjunction with spray mass spectrometry is performed.

184,424 electrons (electrospray) to confirm protein identity.

AML proliferation assay for bioactive human interlueCny-3

Factor-dependent cell line AML 193 was obtained from the American Standard Cultures Collection (ATCC, Rockville, MD). This cell line, established from an acute myeloid leukemia patient, is an agent-dependent cell line that has shown enhanced growth in GM-CSF supplemented medium (B. Lange et al., Blood 70: 192, 1987; M. Ualtieri et al. , J. Immunol. 138: 4042, 1987). The ability of AML 193 cells to proliferate in the presence of human 1L - 3 has also been documented. (D. Santoli et al., J. Immunol. 139: 348, 1987). A variant cell line, AML 193 3.5, was used, which was adapted to long-term culture of wIL-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 replicated at 1x10 [mu] l cells / well in a 24-well plate in medium containing 100 units / ml of IL-3. The rapid growth of wIL-3 cells lasted for about 2 months. These cells were maintained as AML 193 1.3, after which the tissue culture medium (see below) was supplemented with human IL-3.

AML 193 1.3 cells are washed 6 times in Hanks' balanced salt solution (HBSS, Gibco, Grand Island, NY) by centrifuging the cell suspensions at 250 x g for 10 minutes followed by superantant decanting. Granulated cells are resuspended in HBSS and the procedure repeated until six washing cycles are complete. Cells washed six times in this procedure are resuspended in tissue culture medium at a density ranging from 2 x 10 to 5 x 10 "viable cells / ml." This medium is prepared by supplementing Iscove's Modified Dulbecco's Medium (IMDM, Hazelton, Lenexa, KS) with albumin, transferrin, lipids and 2-mereaptoethanol. Bovine albumin (Boehringer-Munich, Indianapolis, IN) is added at 500 pg / ml; human transferrin (Boehringer-Munich, Indianapolis, IN) at 100 pg / ml; Soybean lipids (BoehringerMonachium, Indianapolis, IN) at 50 pg / ml and 2-mereαptoethanol (Sigma, St. Louis, MO) are added at 5 x 10, M.

Serial dilutions of human interleukin-5 or multifunctional hematopoietic receptor agonist proteins are made in triplicate lots in tissue culture medium supplemented as above in Costar 3596 96 well tissue culture plates. Each plate contained 50 µl of medium containing a single dilution made or multifunctional hematopoietic receptor agonist proteins. The control wells contained tissue culture medium only (negative control). The AML 193 1.3 cell suspensions prepared as above were added to each well by pipetting 50 µl (2.5 x 10 ⁴ cells) into each well. Tissue culture plates are incubated at 37 ° C with 5% CO2 in humidified air for 3 days. On the third day, 0.5 µCi-thymidine (2 Ci / mM, New England Nuclear, Boston, MA) is added in 50 µl tissue culture medium. The culture is incubated at 37 ° C with 5% CO2 in humidified air for 18-24 hours. Cellular DNA is harvested onto glass filter mats (Pharmacia LKB, Gaithersburg, MD) using a TOMTEC cell harvester (TOMTEC, Orange, CT) which used a water wash cycle followed by a 70% ethanol wash cycle. The filter mats are allowed to air dry and the ίe is then placed in sample bags to which βογηΙγΜαλΑηγ fluid (Scintwerse II, Fisher Scientific, St. Louis, MO or BetaPlate Scintillation Fluid, Pharmacia LKB, Gaithersburg, MD) is added. Emissions of beta samples from individual culture wells are counted in a LKB BetaPlate model 1205 scintillation counter (Pharmacia LKB, Gaithersburg, MD) and data are expressed as counts per minute of β-thymidine incorporated into cells from each tissue culture well. The activity of each human interleukin-3 preparation or multifunctional hematopoietic receptor agonist protein preparation is quantified by measuring cell proliferation (inclusion of β-thymidine) induced by graded concentrations of interleuein-3 or multifunctional hematopoietic receptor agonist. Typically, these assays quantify a concentration range of 0.05 µM-10, µM. Activity is determined by measuring the dose of Interleukin-5, or a multifunctional hematopoietic receptor agonist protein, that protects 50% of proliferation

184,424 maximum (EC50 = 0.5 x (maximum mean counts per minute of SH-yimidine incorporated per well of the triplicate cultures at all concentrations of interleukin3 tested - background proliferation is measured by the inclusion of SH-yimidine observed in triple cultures without injerleukin-S). This EC 50 value is also equal to 1 bioactivity unit.

Each determination is performed with native. interleukin-3 as a standard reference so that an activity level can be determined.

Typically, multifunctional hematopoietic receptor agonist proteins were tested in a concentration range of 2000 pM to 0.06 pM by titration in a series of 9-fold dilutions.

The activity of each sample was determined by the concentration that produced 50% of the maximal response, by fitting to the data of a four-parameter logistic model. It was observed that the upper plateau (maximum response) for the sample and the standard with which it was compared did not differ. Thus, the calculation of the relative potency for each sample was determined from the sample and standard EC50 estimates as indicated above. AML cells 193.1.3. proliferation in response to hIL-3, hGM-CSF and hG-CSF. Thus, the following additional assays were performed for some samples to demonstrate that the G-CSF agonist portion of the multifunctional hematopoietic receptor agonist proteins was active. A proliferation assay was performed with a combinist of the multifunctional hematopoietic receptors plus and minus monoclonal antibodies neutralizing the hIL-3 receptor agonist portion. In addition, the molecule linked to the factor Xa cleavage site was cleaved, then purified, and half the molecule was assayed for proliferative activity. These experiments indicated that both components of the multifunctional hematopoietic receptor agonist proteins are active.

Assay for c-mpl ligand dependent proliferation of TF1

The proliferative activity of the c-mpl ligand was determined using a subclone of the human TF1 cell line with multidirectional differentiation capacity (Kitamura et al., J. Cell Physiol. 140: 323-334, [1989]). TF1 cells are maintained with wh-IL3 (100 units / ml). To establish a subclone responsive to the c-mpl ligand, cells are maintained in passage medium containing 10% supernatant from ligand transfected BHK cells (pMON26448). Most cells die, but a subset of cells survives. After dilution cloning, a clone responsive to the c-mpl ligand is selected and these cells are divided into passage medium to a density of 0.3 x 10 ⁶ cells / ml the day before setting the assay. Passage medium for these cells is as follows: RPMI 1640 (Gibco), 10% FBS (Harlan, lot # 91206), 10% ligand supernatant c = mpl from transfected BHK cells, 1 mM sodium pyruvate (Gibco). The next day, cells are harvested and washed twice in RPMI or IMDM medium with a final wash in ATL or assay medium. The ATL medium is as follows: IMDM (Gibco), 500 pg / ml bovine serum albumin, 100 pg / ml human transferrin, 50 pg / ml soybean lipids, x 10 ', M beta-mercaptoethanol and 2 ml A9909 (Sigma, antibiotic solution) per 1000 ml ATL. Cells are diluted in assay media to a final density of 0.25 x 106 cells / ml in a 96-µm low evaporation pin plate (Costar) with a final volume of 50 µl. Short term supernatants (conditioned media) from transfected clones are added as duplicate samples at 50% final concentration and 3-fold diluted to a final dilution of 1.8%. Triplicate samples with the IL-3 variant pMON2S2S8 dose curve starting at 1 ng / ml and diluted with triplicate dilutions to 0.0014 ng / ml are included as a positive control. The plates are incubated at 5% CO2 and 37 ° C. On day six of culture, the plates are pulsed with 0.5 Ci SH / well (NEN) in a volume of 20 µl / well and allowed to incubate at 5% CO and 37 ° C for four hours. Plates are collected and counted on a Betaplate counter.

Other in vitro cell assays based on proliferation

Other in vitro cell-based assays known to those skilled in the art may also be useful in determining the activity of multi-functional hematopoietic receptor agonists depending on the factors that involve the molecule in a manner similar to

184 424 described in the AML cell proliferation assay 193.1.3. The following are examples of other useful markings.

TF1 proliferation assay: TF1 is a human cell line with multidirectional differentiation capacity (Kitamura et al., J. Cell PhysioL 140: 323-334. [1994]) that responds to hIL-3.

32D Proliferation Assay: 32D is a murine IL-3 dependent cell line that does not respond to human IL-3 but responds to human G-CSF that is not limited to species.

Baf73 proliferation assay: Baf / 3 is a murine human IL-3 dependent cell line that does not respond to human IL-3 or human c-mpl ligand but responds to human G-CSF, which is not limited to species.

T1163 Proliferation Assay: T1163 cells are a murine IL-6 dependent cell line (Ndan et al., 1986) that responds to IL-6 and IL-11.

Human plasma coagulation meg-CSF assay: used to determine the colony-forming activity of megacroiocnts (Mazur et al., 1981).

Transfection cell lines:

Cell lines, such as the murine Baf / 3 cell line, can be transfected with a colony stimulating factor receptor such as the human G-CSF receptor or the human c-mpl receptor, which the cell lines lack. These transfected cell lines can be used to determine the activity of a ligand for which the receptor circulates into the cell line.

One such transfected Baf / 3 cell line was generated by cloning a cDNA encoding c-mpl from a library made from a cell line responding to c-mpl and cloned into the pcDNA3 plasmid multiple cloning site (Invitrogen, San Diego, CA). Baf / 3 cells were transfected with plasmid by electroporation. Cells were cultured with G418 selection in the presence of murine IL-3 in Wehi eonditioning medium. Clones were established by limited dilution.

In a similar manner, the human G-CSF receptor can be transfected into the Baf / 3 cell line and used to determine the bioactivity of multi-functional hematopoietic receptor agonists.

Analysis of the proliferative activity of the c-mpl ligand

Methods

1. Determination of bone marrow proliferation

a. Purification of the CD34 + cell

Bone marrow aspirates (13-20 ml) were obtained from normal aHogenicanegn bone marrow donors with informed consent. Cells were diluted 1: 3 in phosphate buffered saline (PBS, Gibco-BRL), 30 ml spilled over 13 ml Histopaque-1077 (Sigma) and centrifuged for 30 minutes at 300 RCF. The mononuclear boundary layer was collected and washed in PBS. CD34 + cells were enriched from the mononuclear cell preparation using the affinity column according to the manufacturer's instructions (Cell. Pro, Inc, Bothell WA). After enrichment, the purity of CD34 + cells averaged 70% as determined by cytometric flow analysis using fluorescein-conjugated anti-CD38 monoclosive antibody conjugated with phytoerythrin (Becton Diykiżson, Walkersville, MD) and 1 ml was coated in 12-well plates. for tissue culture (Costar). RWL-3 growth factor at 100 ng / ml (pMON3873) was added to some wells. The hIL3 variant was used at 10ng / ml to 100ng / ml. Conditioned medium of BHK cells transfected with a plasmid, encoding the c-mpl ligand or multi-functional hematopoietic receptor agonists, was tested by adding 100 µl of supernatant added to 1 ml of culture (approximately 10% dilution). The cells were boiled at 37 ° C for 8-14 days in a humidified incubator with 3% CO2 at 37 ° C.

b. Cell collection and analysis:

At the end of the culture period, the total number of cells was obtained for each condition. For fluorescence analysis and ploidy determination, cells were washed in megrricrioyite buffer (MK buffer, 13.6 mM sodium citrate, 1 mM theophylline, 2.2 µM PGE1, 11 mM glucose,

184 424

3% w / v BSA in PBS, pH 7.4) (Tomer et al., Blood 70: -735-1742, 1987) was resuspended in 500 µl MK buffer containing the anti-CD41a FITC antibody (1: 200, AMAC , Westbrook, ME) and washed in MK buffer. For DNA analysis, cells were permeated in Mk buffer containing 0.5% Tween 20 (Fisher, Fair Lawn NJ) for 20 minutes on ice, followed by fixation in 0.5% Tween-20 and 1% paraformaldehyde (Fisher Chemical) with 30 minutes followed by incubation in propidium iodide (Calbiochem, La Jolla Ca) (50 pg / ml) with RNAase (400 units / ml) in 55% vol MK buffer (200 mOsm) for 1-2 hours on ice. Cells were analyzed on a FACScan or a Vantage flow cytometer (Becton Dickinson, San Jose, CA). Green fluorescence (CD41aFITC) was collected according to linear and log red fluorescence (PI) signals to determine DNA ploidy. All cells were harvested to determine the percentage of cells that were CD41 +. Data analysis was performed using the LYSIS computer program (Becton Dickinson, San Jose, CA). The percentage of cells expressing CD41 antigen was obtained by cytometric flow analysis (Percent). The absolute (Abs) number of CD41 + cells / ml was calculated by: (Abs) = (cell count) * (percent) / 100.

2. Determination of the megakaryocyte fibrin clot

The CD34 + enriched population was isolated as described above. Cells were resuspended at 25,000 cells / ml with or without cytokine (s) in medium consisting of Iscove's basal IMDM medium suspended with 0.3% BSA, 0.4 mg / ml apotrain, 6.67 pM FeCl2, 25 pg / ml CaCLm 25 pg / ml L-asparagine, 500 pg / ml ε-amino-n-caproic acid and penicillin / streptomycin. Before coating the 35 mm plate, thrombin (0.25 units / ml) was added to initiate clot formation. Cells were incubated at 37 ° C for 13 days with 5% CO 2 in a humidified 37 ° C incubator.

At the end of the incubation period, the plates were fixed with the mixture. methanolacetone (1: 3), air dried and stored at -200 ° C until staining. An immunocytochemical peroxidase staining procedure (Zymed, Histostain-SP, San Francisco, CA) was used with the primary monoclonal antibody mixture consisting of anti-CD41, CD42 and CD61. Colonies were counted after staining and classified as negative, CFU-MK (small colonies, 1-2 focal, and less than about 25 cells), BFU-MK (large multifocal colonies> 25 cells), or mixed colonies (mixture of cells of both positive and negative.

Determination of methylcellulose

This assay reflects the ability of colony stimulating factors to stimulate normal bone marrow cells to produce various types of hematopoietic colonies in vitro (Bradley et al., Aust. Exp. Biol. Sci. 44: 287-300, 1966), Pluznik et al., J . Cell Physio 66: 3-4-324, 1965).

Methods

Approximately 30 ml of an aspirate of fresh normal healthy bone marrow is obtained from the people after informed consent. Under sterile conditions, samples are diluted 1: 5 with 1x PBS (# 14040.059 Life Technologies, Gaithersburg, Corning MD). Fikol (Histopaque 1077 Sigma H-8889) is watered under the diluted sample and centrifuged, 300 x g for 30 minutes. The mononuclear cell band is removed and washed twice in 1x PBS and once with 1% BSA PBS (Cell Pro Co., Bothel, WA). Mononuclear cells are counted and CD34 + cells are selected using a Ceprate LC (CD34) Kit column (CellPro Co., Bothel, WA). This fractionation is done because all the stem and parental cells in the bone marrow imitate the CD34 surface antigen.

The cultures are set up in triplicate with a final volume of 1.0 ml in a petri dish 35 x 10 mm (Nunc # 174926). Growth medium is purchased from Terry Fox Labs. HCC-4230 medium (Terry Fox Labs, Vancouver, B.C. Canada) and erythropoietin (Amgen, Thousand Oaks, CA) are added to the culture medium. 3,000-10,000 CD34 + cells are added per plate. Recombinant IL-3, purified from mammalian or E. coli cells, and multifunctional hematopoietic receptor agonist proteins are added in conditioned medium from transfected mammalian cells or purified from conditioned medium from transfected mammalian or E. coli cells to the final

184,424 concentrations ranging from 0.01 nM to 10 nM. It is supplemented with recombinant hIL-3, GM-CSF, c-mpl ligand and multi-functional hematopoietic receptor agonist. G-CSF (Neupogen) is from Amgen (Thousand Oaks, California). The cultures are resuspended using a 3 cm ³ syringe and 1.0 ml is dispensed per plate. Control cultures (baseline response) received no colony stimulating factors. Positive control cultures received conditioned media (human PHA stimulated cells: Terry Fox Lab. H2400). Cultures are incubated at 37 ° C, 5% CO2 in humidified air. Hematopoietic colonies that are determined to be greater than 50 cells are counted on the day of peak response (days 10-11) using a Nikon reverse phase microscope with a 40x combination of objectives. Cell groups of less than 50 cells are cited as nests. Alternatively, colonies can be identified by colonizing a slide and staining, or they can be harvested, suspended, and spun on cell spin slides for staining.

Cord blood test for human hematopoietic growth factor

Bone marrow cells have traditionally been used for the in vitro determination of hematopoietic colony stimulating factors (CSf). However, human bone marrow is not always available and there is substantial variability between donors. Umbilical cord blood is comparable to bone marrow as a source of hematopoietic stem and parental cells (Broxmeyer et al., PNAS USA 89: 4109-113, 1992; Mayani et al., Blood 81: 3252-3258, 1993). Unlike bone marrow, cord blood is easier to come by on a normal basis. It is also possible to reduce the variability of the assay by pooling cells obtained from several donors, or creating a frozen cell bank for this purpose. By modifying the culture conditions and / or analyzing for strain-specific markers, it is possible to assay granulocyte / macrophage colony specific (CFU-GM), for CSF mpgakaryocyte activity, or for high proliferative activity of potential colony forming cells (HPP-CFC).

Methods

Mononuclear cells (MNCs) are isolated from cord blood by 24-hour harvesting using a standard density gradient (Histopaque 1.077 g / ml). MNC cord blood was further enriched in stem and parental cells by several procedures, including immunomagnetic selection for CD14-, CD34 + cells; rinsing for SBA-, CD34 + fraction using coated beakers from Applied Immune Science (Santa Clara, CA); and CD34 + selection using a CellPro avidin column (Bothell, WA). Either freshly isolated or frozen fractions enriched in CD34 + cells are used for the assay. Prepared double cultures for each serial dilution of sample (concentration range from 1 pM to 1204 pM) with 1x10 ^'L cells in 1 ml of 0.9% medium containing methylcellulose, without additional growth factors (Methocult H4230 from Stem Cell Technologies, Vancouver, BC). In some experiments, Methcult H4330, containing Erythropoietin (EPO), was used instead of Methocult H4230, or Stem Cell Factor (SCF), 50 ng / ml (Biosurce International, Camarillo, CA) was added. After culturing for 7-9 days, colonies containing> 30 cells are counted. In order to rule out subjective trends in the counts, the determinations were made blindly.

Additional details on recombinant DNA methods that can be used to generate variants, express them in bacteria, mammalian cells or insect cells, purify and refold the desired proteins, and assays for determining the bioactivity of proteins can be found in the co-pending WO 95/006646 applications. 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 their entirety.

Further details known to those skilled in the art can be found in T. Manatis et al., Molecular Cloning, a Laboratory Manual, Cold Spring Harbor Laboratory, 1982, and in the references cited herein, incorporated herein by reference; and in J. Sambrook et al., Molecular Cloning, a Laboratory Manual, Second Edition, Cold Spring Harbor Laboratory, 1989) and the references cited herein, incorporated herein by reference.

184 424

Table 1

C-mpINcoI oligonucleotides

GCGTCCAhGGCNh ^, CNCCNlCNCCNCCTGCTTGhGCACTCCGAGh ^, C (SEQ ID No .: 13) N = A, C, G or T

Ecompl ATGCACGGGhΓTCCCTGACGCGCAGl3GTGGA (SEQ ID No .: 14) c-molHindIII hGACGAGChACCTGAClCAGAGGGhGGACCCT (SEQ ID No .: 15) 4L-5 ' GGhTCGGCGG (SEQ ID No: 16) 4L-3 ' CATlTTGCCG (SEQ ID NO: 17) 5L-5 ' AATTCGGCGGCAA (SEQ ID No: 18) 5L-3 ' CATlTTlCCGCCG (SEQ ID NO: 29) 8L-5 ' GAhTCGGCGGCAAClGCGGCGG (SEQ ID No: 20) 8L-3 ' CAhGhTGCCGCClhhGCClCCG (SEQ ID No. ^ l) 31-5 ' CGhTCGAlGGAGhTTGACCTThGGChD (SEG IG No .: 22) 31-3 ' G7hTCrrl3C ^, h: rhTGGGC7VCTGGCTC7lh'ΓCT (SEQ ID N:, 2)) 35-5 ' C (GhTACATGTTGChTACACCTGTCCTG (SEQ ID No. ^)) 35-3 ' GATCmGCTTmGGGTGmCCTCTGGGCA (SEQ ID IT:, 2)) 39-5 ' CG7hTCC7hlGGTCCTGCTGCCTGCTGTG (SEQ ID 39-3 ' GrhΓC7Al3CTTmGGTGTAGGC7ArYGGGTG (SEQ ID N:, 2)) 43-5 ' CGAT 43-3 ' (SEQ ID No .: 28) rhTrAAGTTrδAGGrΛGrGlGArGlhlTI (EE G I G 0: 229) 45-5 ' CGATCCATGGACTTTAGCTTGGGAGm (SEQ ID O: .0)) 45-3 ' GATCAAGhhGAACGAGGlGGCAGCAGGAG (SEQ ID O:, 3)) 49-5 ' CGATCCATGGGAAAATGGAAAACCCAG (^! QQ ID N:, D) 4 9-3 ' GATCAAGChGAGAAGCTAAAGTCCACAGC (SEQ ID No., 3))

184 444

82-5 '

82-3 '

109-5 '

109-3 '

116-5 '

116-3 '

120-5 '

120-3 '

123-5 '

123-3 '

126-5 '

126-3 'synnoxa1.req

SYNNOKA2.REQ

L1yyn.for

L ^ ci.rev

L3syn.for

L3yyIl. oiv

CGATCCATUGACCCTYCTTGCCTCTCA (SEQ ID No: 84) (ATΓCAAiGCTTΆCAGTTGTCCCCGT (dTΓGC (SEQ ID No: 55)

CA ^^ T ^ C ^ CA ^ T ^ G ^ i ^ C ^ C ^ CA ^^^^^^ C ^ C ^^^ C ^ C ^ A (SEQ ID No .: 365)

GATCAAGGCTTAAAGGAGGCTCTGCAGGGC (SEQ ID No. ^) dATCCATTGGGCAGGACCACAGCTCAC (SEQ ID No. 58)

GATCAAGCTTACTGTGGAGGAAlGCT <llTTT (SEQ ID No: 35)

C ^ GA ^^^ C ^ CA ^ A ^ d ^ C ^^^ CA ^ CAA ^^^ C ^ C ^ C ^ AA ^ T ^ i ^ C ^ C (SEQ ID No. o -15) (ΆTCAAGCTTATGTdTCCTGCCCTGT ( l0 (SEQ ID No: 45)

C ^ <3A ^ T ^ C ^ CA ^^^^ AT ^ C ^ C ^ (AA ^ T ^ C ^ (^ C ^ A ^^ C ^^^ C ^ C ^ 5 ^ G (SEQ ID No: 45)

GATCAAGGCTTACTTGTGAGCTGTGGTCCT (SEQ ID No .: 45)

CiATCCATdCCATCTTCCTGAdTTCCAAO (SEQ ID No .: 44) (SEQ ID Νο: 455

AATTCCGTCG TAAAYCTGACCC T ^ 5 ^^ 5 ^ A ^ 5T ^ 5T (A0 AAACCTTGGA

GAACGdCAG GCTCAACAGT AdTAGAGd dGTGGAGGC

TCC (SEQ ID Νο: 465

CCddAdC TCCAdGdC TCTACGTACT lTTGAlCCTl

CGCGTTCTCC AAGGTTTTCA GATAGAAGGT CAGTTTACGA

CGG (SEQ ID 10: 475

GTTACCCTTG AGCAAGCGCA dAA ^ GAA ^ CA ^ G GGTGGTGGCT

CTAACTGCTC TATAATGAT (SEQ ID Νο: 485

CGATCATTAT AGAGCAGTTA GHGCC1CCCACC CCTGTTGTTC

CTGdCTTGC TCAAGG (SEQ ID No .: 49}

GTTACCCTTG AGCAAGdCA G ^ (^ AA ^^ AA ^^ AG0 GGTGGTGGCT

CTdCdTGG CAGCHCGGC GGTTCTAACT GCTCTATAAT

GAT (SEQ ID Νο: 505

CGATCATTAT AGAGCAGTTA GAACCGCCGC CGCTGCCACC

GCCAGAGCCA CCACCCTGTT GTTCCTGCGC TTGCTCAAGG

184 424

35start.seq

34rev.seq

70start.seq

69oiv.seq

91.start.seq

90rev.ieq

101start.seq

100oev.seq

L-Hstart. seq

L-Hstop.s ^

P-blstaot.seq

P-bnstop.seq

39start.seq

38etop.eeg

97start.seq (SEQ ID NO: 51)

GAhCGACCAh GGChChGGAC CCGAACAACC TC (SEQ ID No: 52)

CCCGACCACG TACSSAGGTG CAGGCTGGT (SEQ ID No: 53)

GATCGACCAT GGCTAATGCA AG (SEQ ID No: 54)

CTCGACCACG TATTCTSSGGT TCTTGACA (SEQ ID No: 55)

GATCGACCAT GGChGCACCC TCTCGACATC CA (SEQ ID No: 56)

CTCGACCACG TAGGCCGTGG CAGAGGGC (SEQ ID No: 57)

GATCGACCAT GGChGCAGGT GACCGGCAAG AA (SEQ ID NO: 58)

ChCGATTACC AACTTGATGA TSATTGSA (SEQ ID No: 59)

GCTCTGAGAG CCGCCAGAGC CGCCAGAGGG

ChGCGCSAGG CGGCGTAGAA CGCG (SEQ ID No: 60)

CAGCCCTCTG GCGGCTChGG CGGCTCTCAG

AGCThCChGC CCSAGTChhT AGAG (SEQ ID No: 61)

GGGCTGCGCA AGGhGGCG (SEQ ID No: 52)

ACACCAhhGG GCCCTGCCAG i (SEQ Ii No .: O3)

GATCGACCAT GGCT TACAAAG CTGTGCCACC CC (SEQ ID No: 64)

CGATCGAAGC TTATTAGGTG TCTCCT (SEQ ID No: 65)

GATCGACCAT GGChCCCGAG CCGGGTCCCA CC

184 424 ft Seq

126start.seq

225stop.Seq

133start.seq

132stop.seq

142start.seq

141stop.Seq

GLYXA1

GLYXA2 lGGGS for lGGGSrev

Synnoxal.req

Synnoxa2.req (SEQ ID No: 66)

CGATCGAAGC TTATTAGGAT ATCCCTTCCA GGGCCT (SEQ ID No .: 67)

GATCGACCAT GGCTATGGCC CCTGCCCTGC AG (SEQ ID No .: 68)

CGATCGAAGC TTATTATCCC AGTTCTTCCA TCTGCT (SEQ ID No .: 69)

GATCGACCAT GGCTACCCAG GGTGCCATGC CG (SEQ ID No .: 70)

CGATCGAAGC TTATTAGGGC TGCAGGGCAG GGGCCA (SEQ ID No .: 71)

GATCGACCAT GGCTTCTGCT TTCCAGCGCC GG (SEQ ID No .: 72)

CGATCGAAGC TTATTAGGCG AAGGCCGGCA TGGCAC (SEQ ID No: 73)

GTAGAGCGCG GTGGAGGCTC C (SEQ ID No.; 74)

CCGGGGAGCC TCCACCGCCC TCTAC (SEQ ID No: 75)

TTCTACGCCA CCTTGCGCAG CCCGGCGGCC GCTCTGACAT

GTCTACACCA TTG (SEQ ID No: 76)

CAATGGTGTA GACATGTCAG AGCCGCCGCC GGGCTGCGCA

AGGTGGCGTA GAA (SEQ ID No: 77)

AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA

GAACGCGCAG GCTCAACAGT ACGTAGAGGG CGGTGGAGGC

TCC (SEQ ID No .: 240)

CCGGGGAGCC TCCACCGCCC TCTACGTACT GTTGAGCCTG

CGCGTTCTCC AAGGTTTTCA GATAGAAGGT CAGTTTACGA

CGG (SEQ ID No.: 241)

184 424

Table 2

Gene sequences of pMON30304

GCTAACTGCTCTATAATGATCGATGAAATTATACATCACTTTAAA3AGACCACCTGCACCT

TTGCTGGACCCGAACAACCTCAATGACGAAGACGTCTCTATCCTGATGGACCGAAACCTT

CGACTTCCAAACCTGGAGAGCTTCGTAAGGGCTGTCAAGTAACTTAGTAAAATGCATCAGGT

ATTGAGGCAATTCTTCGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCCGCACCCTCT

CGACATCCAATCATCATCAAGGCAGGTGACTGGCAAGAArrCCGGGAAAAACTGACGTTC

TATCTGGTTACCCTTGAGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTCC irGGGTGAACCGTCTGGTCCAATCTCTACTATCAACCCGTCTCCTCCGTCTAAAGAATCT

CATAAATCTCCAAACATGT (SEQ ID No: 78)

SMON26458

7CCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGT7AAA: CCCTT TGCTTCGTGACTCCCAT GTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCA ^ ^ T ^ C ^ C ^ C ^ T ^ A ^ C ^ A ^ (^ (^ 'rTTCCTG CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCA TAGGACATTTCGGGAGCAGTGACCCTTCTGCTG <C GGGAGTGATGGCAGCACGGGGATAA CCGGGATCCATCCGTTTTCTATTCTCCTTGGGGTAGTTCCCCGGATAGGCTTGCTCTCTC TTTGGGGTTCTGCAGAGCTCCCCTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGTT TACAAGGATTTTAATGTCATTTCTTTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGcGT CCTTTGATGTCTGTAGGAGGGTTTATTTTCTGCGCTAGGGAATTT (SEQ ID NO: 79) pMON28548

CCCTCAGCCTCACTCGTTCGTGACCTCCGAGTCCTCAG ^Γ CAAACTGCTTCGTGACTTTTAC GTCCTTTATAGTAGATTGAGTCAGTGCCCAGAGGTTCACCCTTTGCCTACATTCGTCTTG TCGTCTGTTGTGGACTTTAGCTTGGGAGAATGGA? AAACCCAGATGGAGGAGATCAAGGTA TAGGACATTCTGGGAGTAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAA CCGGGATCTACCCGTCCTCTACCCTTCCTGGGGCAGCT'CCCTGGACAGGTTTGTTCTTTC TTCGGGGTCCTGTAGAGTCCCTTTGGAACCCAGCTTCCTCCACAGGGCAGGATTATAGCT TATAAGGACTTTAACGTCACCCTCTTGAGCTTC (TAACACCTGCTCCGAGGAAAGGCGCGT CTCTTGATGCTTGTAGGAGGGCTCACCCTCTGCGTCAGGG7AATTCGGCGGCAATACGGTG TCTTTTGTTCTGCTCGCTTGTGACTTCCGAGTCCTCAGTAACTGCTTCGTGATCTTTAT GTCCTCTATAGTAGACCGAGTCAGCGCCCAGAGGTTCACCCTTTGCCTACACTCGCTCTG ^{TCGTCCGTTGTGGAC,} CTCAGCTTGGGA <CAATGGCAAAACCCAGATGGAGGAGACTAAGGCA TAGGATATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGAC-AA. CTGGGATTTATTTGCTTCCTATTTTTTCTGGGGCAGCTTTCTGGACAGGTCTGTTCTTTT TCTGGGGTTTTGTAGAGTTTCCTCGGAACCCAGGGCAGGACCACAGCTCACAAGGACCCτ AATGCTATCTTCCTGAGCCTCCAACACCTGCTCCGAGG2AAACGTGCGTTTCCTGACGTCC GTAGGAGGGTCTATTCCTTGTGCCAGG (SEQ ID NO: 80)

SMON28500

TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTTAAAtTGCTTCGTGACTCCCAT

GTCCTTCACAGCAGACTG ^ GC ^. ^ (^ ^, ^ (^ (^ (^ (^ C ^ <^ G ^^^ l ^ T ^ C ^ i ^ C ^ C ^ C ^ TT ^ T ^ (^ (^ (^ (^ 2 ^ (^. ^^ CTGTCCI ^ G

CTGCCTGCTGTGGACTTTAGCTTGGGAGAATGGAAAACCCAGATGGAGGAGACCAAGGCA

184 424

CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAA CTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC CTTGGGGCCCTGCAGAGCCTCCTTGGGAKCCCAGCTTCCTCCACAGGGCAGGACCACAGCT CACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGT TTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCAACATGGCGTCT CCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCATGTC CTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTG CCTGCTGTGGACTTTAGCTTGGGAGGAATGGTAAAACCCAGATGGAGGAGACCAAGGCACAG GACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAACTG GGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTCCTT GGGGCCCTGCAGAGCCTCCTTGGAACCCAGCTTCCTCCACAGGGCAGGACCACAGCTCAC AAGGATCCCAATGCCATC CTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGTTTC CTGATGCTTGTAGGAGGGTCCACGCTCTGCGTCAGG TTC (SEQ ID NO: 81)

DMON28501

TCCCCAGCTCCACCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT GTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTG CTGCCTGCTGTGGACTTTAGCTTGGGAGGAArGGAAAACCCAGATGGAGGAGACCAAGGCA CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAA CTGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC CTTGGGGCCCTGCAGAGCCTCCTTGGTAAZCCAGCTTCCTCCACAGGGCAGGACCACAGCT CACAAGGATCCCAATGCCATCTTCCTGAGCTTCCAACACCTGCTCCGAGGAAAGGTGCGT TTCCTGATGCTTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGCAACATGGCG TCTCCCGCTCCGCCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGTGACTCCCAT GTCCTTCACAGCAGACT (3j ^ (^ (^ (^ J ^ (^ ^r ^ <G (^ (^ C ^ C ^ (^. A <GGTTCACCCTTTGCCTACACCTGTCCTG CTGCCTGCTGTGGACTTTAGCTTGGGAGGAATGGAAAACCCAGATGGAGGAGACCAAGGCA CAGGACATTCTGGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGACAA CTGGGACCCAGTTGCCTCTCAATCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTC CTTGGGGCCCTGCAGAGCCTCCTTGGGA.CCCAGCTTCCTCCACAGGGCAGGACCACAGCT τATAAGGATTCCAATGCC ATCTTCCTGAGCTTCCAACACTCGCTCCGΛGGAAAGGGGCGC CTTTCGACGTTCGTAGGAGGGTCCACCCTCTGCGGTAGG (SEQ ID NO: 82) pMON28 502

TτTTCAGCGTCGTCTGCTTGTGACCTCCGAGTCCTCAGTAAACTGCTTCGGGACGCCTAC

GTTTTGTACAGTAGACTGAGCCAGTGCCCAGAGGTGTACTTTTTGTCTATATTGGGTCCG τCGTCGGTGGCGGACT ^ G? AGCTTGGGAG, AAGGGAAAATTTAGATGGAGGAGATTAAGGTA

CAGGACAGTTTGGGAGCAGTGACCCTTCTGCTGGAGGGAGCGATGGCAGCATGGGGATAA

TCGGGATTCACCCGCCTCTCATCCCTCCTGGGGCAGCGTGTCGGACAGGGTTGGTTCTTT τTCGGGGCTCTGCAGAGCCTCC ^Γ GΓGGjACCCAGCTTTTGTTACAGGGCAGGATCACAGCC

CATAAGGACCCTAATGCCATCTTCCTGAGCTTCCAATATCTGTCTCGAGGAAAGGTGTGC

TTTTGGAGGCTCGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGCGGTAACGGTGGC

AATAGGGTGCTTTCAGCGCCGCCTGCTTGTGACCTCCGAGTTCCCAGTAAACGGTTCTGC

GATCTCTATGCTCTTCACAGCAGACTGAGCCAGTGCCTAGAGGTTCACCTGGGGCTTATA

CTCGGTTTGCTGTTTGCTGTGGACTTTAGCTTGGGAGAAGGGAAAACTCAGAGGGAGGAG

ATCAAGGTATAGGACATTCTGGGAGCAGTGACCCTTCGGTCGGAGGGAGGGAGGGCAGTA

TGGGGATAACTGGGAeCCACTTGCCTCTCATeCCTCTGGGGGCAGCTTGTGGGACAGGCT

CGTTGTTTTCCCGGGGCCCTGCAGAGCCTCCTTGGAATTTAGTTTTCTTTATAGGGTAGG

ATTATAGCGCATAAGGATCCC7AAΓGCCATCTTCCTGAGTCTCCAACACCGGCGTTGAGGA

AAGGGGTGTTCTCTGATGCTTGTAGGAGGGTCTACCCGTTGCGCCAGG (SEQ ID Nh: 83)

184 424

Syncanl

CATGGCTCACT GCTCTATAA TGATCGATGA 2ATTATACAT 51 GACCAGCTGC ATTTGTGCGC ATCGGCTTA TCGGCGATCA T 101 TCT ATC CTGAT GCATTTATT T CCTCGCCTG CG7TT.CCTAC 151 AAGO5CAGTC AACAACTCAC 7TTTTCGATC TTCCATGGCT 201 GT7CTTCTCCAATTATAAAGC T CCTCCGCCC CTCCGTCATG 251 CC7ATΓCATCAT AATTGGATG GATTGCCTA 7ATTΓTCCGGG T 3 01 G GTTCTATCTG AAACCCTGC CGCTCT3CTCAGGCACTCC; AG 351 σΤ / T ΓΟΤΟετε ATATTAATC T ATG7TTTAA TATATCAttT 401 CCTC-CACCTT T ACAAGACGC TCACGCCCTC TTTTGACG; CG 451 CCTGACGGAC C CATTTCTGC TATCTCCCTA TGTGGAGAGC 501 CTGTCAAGTCT CCAATGTTTTC TTTGAGGCT

551 CTCCGGTTCAT G GGCAGTCCC TGGGACCGCC GGACGGTCTC 501 CATCATC7ATTGCATGGAATG T GCGTTGTTTrT CCGGG7CA7TT

651 ATCTGGTTAC C TTTACTCCT T CGCAGTTG7C TACTTTAC (SEQ ID No: 84)

Syntan3

CATTCGGCAC TACCACATAT TGGTCTGTAG CTTCATAT-GT 51 GACCATCTTG ATCCAAACGC TACCCG7T / CA ACCTCAATGA 101 TCTATCGTGA T AGATTTATT T CTTCGACTT C (AACACCTGG 151 AAGTGGGTTC 7CTTATTAGAT TkAAATGCATC AGGTA ATTGAG 201 GT / GTTCTCCA ATCATGGGTC T CCTCTGCCA iC <G <^ CCGCACC 251 CC7ATΓCATCA. T AATTGGATC T GACTGGC7AG G7TTTTCCGGG 3 01 GTTCCAATAGG GAATCTTGC TGCTtAGCGCA GG7TACAACAG 3 51 CT7A7GCCG7A7GATCAGGACG TGTTCTAACC GCTCTATAAT 401 ATTATAGATC ATTAGTT.TGT CCCACeTGCACCTT TGCTGG 451 CCTC7CTΓGAC G ATTATTTCC TTATCCTGAT GGAC CGAAGC 501 C7TTCCTGGAG ATGAAGTCA CGGGCTGTCAAG7TCTTTAGA 551 GGTATTGAGG AATAAAA C ^ CG T 7> LATCTCC7AA CCATGTCTGC 601 GGCCCG7 ^ 7 \ 7 ^ C ^^ T ATCTATATC T AATCATCAT C.AAG GCAGGT 651 7tATTCCGGGA77TTTCAAATC TTCTATCTGG TTAC CCTTGA

701 G / ATCTACAGT AT (SEE TD Tr: 8d pMON31104

ATGGCTCTGG cACC'CG.TTC7TT CGGGATTCGT CGATACGTCT 51 GGACCG / GCC CTTCG-TCGTC CTTT.TCCGGG GAGCTGCGTA 101 AGTCTCTTAGA TTTATGCATCA GCGATGGGTG C7TTTCTTCG 151 CCAGTGGAGC CCTCTGCCAC GGGCCGATGC TCTGGACATC 201 C7 ^ <GT ^ 7 ^ 7 ^ (^ G7? GACTGGCTTG iTTTCGGGCA 7TTT1CTGACG

51 TTACCCTTC-AGC7TTGCGCAG GAACTTTCAGC GTGGTGGCTC

01 ATTGATGATCG ATGTTTTTTAT TCTTCACTTT TCGAGACCAC

51 GTACGTAGAG GGCGGTGCAG GCTCCCCGGC TG7CCCGTCT

01 CTACTATC7A CCCGTCTCCT CCGTCT7CAC TCTCTCATGC 451 ATGCCCAGTC AGGGTGCCAT GCCGGCCTTC GCGGCTGCTT

CACTTAAAGA

CG7CGACGTT

AGAGCTTCGT

GCTTCrTCTTC

CTCTCGATTG

7TTTTτCTGTC

GGTGGTGGTG

7CTTGAGATCT

ACGTCTCeTG

TTCGTTAC-CC

TCTTCGATTG

GTCATTATTA

CTGACAAACA

CACTTAAAGA

CAATAATTAT

AGATCTATAG

GTAAATTAAG

TTCTCTACAT

AACTTTTTAG

CTCAGAACAC

TTAGTAAGTA

AGGTTAACTT

TTTCAATATC

AATTTTAAAT

GCTTAATGAC

GAGATAAAAT

GGTATTTCAC

CTATATAATA

TCCGTAGATT

ATTTAATTTT

CAATCTATTG

AACTAAAAGG

TTTCTAcATG

CTGCATCAAA

GGTcTTTACA

ATCTCTTTTT

TCTAATAAAG

184 424

501 GGCAGGAGGGGTCCTGGTTG TCAlCTAGCG aGAUCmU CCGGAGGTGT 551 CGTACCGCGTTCTACGCCAC ClTlClCAlC ^ ΤΚ ^ Ο ^ CTCTGGCGGC 601 TCTCAGAGCTTCCTGCTCCAG lGCGTTAlAl CAlTllllAA AGATCCAGGG 651 CGATGGCGCAGCGCTGCAGG 11AA1CG1G1 TGClACllCO TAGCTGTGCC 701 GCTGGTGCTG TCTllAClCG CTClllGlAO CCCCTGGGCT 751 CCCCTGAGCTCCTGCCCCAG CCAllCCCll GAdUCH, GCTGCTTGAG 801 CCAACTCCAT AGCGGCCTTT TCCTCTACCA GGlCGCTClO CAGGCCCTGG 851 AAGGGATATC lllCCCACCl TG1A1C1C1O GCAGCTGGAC 901 GTCGCCGACT TTGCCACCAC CAlClGlCAl CAATlllAlO JUCTGGGAAT 951 GGCCCCTGCC CTGCAGCCCT AHAA (SEQ ID No: 87) pMON31105

AT1T11TG111T1GT111G1 TGAGGCAATT CTTCGTAATC TGCTAACTGT 51 TCTCGlCTTG ClCTlTllCC CACCCTCTCG ACATCCAAIC AlGTSTTAGl 101 CAClGlGlSC llCASlAlTC CGGGAAAAAC TGACGTTdA TTTGlGGASC 151 CTCTGlSlCA 1G1A1G1A1 A ACAGGGTGGT OSCTCTAACG GlTTCASGAT 2 01 GAllGATlClASGGlAlTl'C OlΊΊΊAAlAG ACCACCTGCA CCTGGTlTTG

51 AClCGSACSSc lCTGTlATGAl OlAGlCGGCT CGAGCCGGAG GGlCCGlAAC

01 CTCCGAHTC CTlA-lTCGlG OGS1CGGC1A AGGGCTCTCA AHAATTAGA

51 AGAClClClllllGllGGAG OlTCCCCCll ΤαΛΑ ^ σΤ ^ GllGCTATCT

01 CTAOGAGdC. lCCGGTTCCG OCTGTTCAAG AAGCGTAGAA AGGGCCTSSlC 51 4 AT ^^ T ^ l ^ l ^^ Cί ^ (l ^ (T ^ Γ OlCTllCTGC GCCGTGGCTT TCCAGCGCCG 501 GGlAClAGllllGCCGGTTG TGAlTTATTG GCAGAGCTTC 551 CCGlAGGTGT CGCACCGdC GCTASClCAl TTGlTlTAlC CTCTTGCGGC CCTCTGGCGG 601 TCGCAGAGSTGCCTGCTC <lCTTTGAlAl CAAGTGAGAA AA AC CC GA AGCG 651 CGT ^^ C ^ <^^ <3 ¢ ^ AC ^ C ^ GC ^ T ^ l ^ C2T ^ C ^ C3 AlAAlCGlGl TGCCACCTAC / AillTGTGCC 7 01 ACCCCGAGGAllTGGTGCTG OTTGGACACT CTCGllGClT CCCCTGGGGCAGT 7 51 CCCACTCCAT ΑσοασΟΟΤΤΤ TTTTCGACCA CGSGGTTCCTG CAGGCCCTGG 851 .AAC3l ^ C ^ ^ l ^^ lΓC ΓCCC CCCGl ^ C ^ ^ C ^ ^r Γ7Γ (J llGTTCACTG TGGACACACT GGAGCTGGAC 901 GTCGCCGACT TTGCCACCAC TATCGllTAG CACAUGU 7S \ CTGGGlllT GGUCCTGCC 951 CTGCAGCCCT Ahaa (SEQ I, No, 87 ) pMON31106

ATlGllCClC TTTGCTTGA T ACC.CAlGTl? T ATCAAGGCAC- GTGACTGGCA 51 AGAlGlGCCC lGlAAAATGl OTlTTCGlTT GGTTACCCTT GAGCAAGCGC 101 ΛGGl! Llac llllGllGll OCTGAlTTlT CTATAATGAT CGATGAAATT 151 ATACAClGCl GGAAlAlllC AlCCGlTlCT TTGCTGGACC CGAACA-ACCT 201 CATllGllTllllClGCTCG AGCCTlSTll CCGAAACCT? CGACTTCCAA 251 AClTTGllAl lCTGCGGAll OlTGGTTAll ACIM AGAWA. TGCATCAGlG 301 ATlGGllllTlTGCTTClTA ACTCCTAl CA TGTCTGCCCT CTGCCACGGC 351 CTTGlCGTlllllCllTllG AlCCCTCCll TGmCCGTCT GGTCCAATTG 401 AATCTCATAA ATCTCCAAAC CTTGGTGlATlCCTGGTCCC OTTlGTGAAG 451 ATGTllTClT TSlllClCTl OlTcllCCGC GCCTCTGCCT TCCAGClCCl 501 GGllClllllllGCCTllTC OCGllCTlGT CTGGAllTlT GCAGAGCTTC 551 CGT1G1CC1CTTTG1T1CA1 OCGTlClTll CTCTGlCllC CCTCTGGCGG 601 TCGCGCAlllGTCCGlTCTAc OlGCGGGllG CAAGTGAGAA AGATCCAGU 651 CGTlGTllTlllClTTCAll AlGAllCGlT TGCCACCTAC AllGCTlTlCC

184 424

701 ACCCCGAGGAGlCTllGCTG ChCGlGCGCh ChChlllCAh CCCCTGGGCT 751 CCCCTGAGCTCCCTlCCCAG CCGllCCChl CGlCTGlCAG GCTCCTTlAl 801 CCTGGTCCATAGCGGCCTTT hCThTTGTTG llllCTCCTG GAGC 851 Cm ^ AAGGlATATCCCCCGAGTTG llhTTTGTTh TGGACACACT GCAGChlC-GT 901 GTCGCCGACTTTGCCACCAC CGTCTAACGA CAlATGGm AACTlllArh 951 ggccccagcccagcagccca MAA (SEQ ID y 8)) pMON3 1107

GhAAThACGA AhAGCTAACG G1GGTTTC11 AGATATTTAT T1TTThGhCT 51 11TTGTCChh inCmClC GAAGGCATCG 111T11hl1T TTGGGTTATh 101 CTGhArh1Gh TAGGAGGGGT GGGTGTTGTh TGTGAGAGCT GCCGATGTTT 151 ThAThAAGTT TAGTTGTCCG CGGGAGTAGG AGTATChTTT GCCGAATAAG 201 CTAATGCTGh TAGTTTCCGG GCTh11G1G1 ChhC1hGG11 1Ch1hTGG1G 251 GCTGGGATTA h1TGhCG11T GGTAGAACGA hhTTTC1hGG TTTCTGGTTG 301 T1TTT1CCCh TTACCGCAAT CATGTCThTh CAGCGTTTGG GCGGCGTCGG 351 AhGTATGAGA AACGAGAAGA ATTCTCCAAA T1ArTC1TTh AAGCTTAGCG 401 ChGChGGCGG TTC1TChCCT CTATCTGGGA GGTTTCGhGT GhCTCTGGGT 451 GhAAChGCCC G111h1CCGT ACTAATTTTC 1TTTCh1CTh hTCG1C1TT1 501 GlCnimi ATTCTAGGTA CTGATTTTCT ATGAGAThhT CTG1G11T1T 551 CAhGTCACAT hChGC1CCGC CTTATATGAT CThCT11T11 CTCh11T11T 601 TTTTGAGACT hCTh1ChCAG GhThThGGG1 CGTATAGAGT GAGGCCGGAA 651 CAGhAACACG 1T1CTCCGG1 G1GG1Th1h1 TACCGCThGT GG1CT1hGCC 701 GCTTTAGAAG 1Th1GhGTh1 ThT11GTGTh CTCGAAACAh TTCCT11GTT 751 CTCTGAGACh TCT1TCCCG1 TTG11TTThG CGATTAATGA 1Th1CThGG1 801 CTGrCTCTGT GATAACCGGG GCChCTGCTG AAAACGTTTA CGAGTTCGAA 851 TGAA AGGGGT TTTC1G1Th1 AAGTCCGCTT T11GCGTGCh ATGAChGAGT 901 AhCACCAGCh hT1CCGCCGC CGTCTAACGA CGAGGAAATA TATGAAAGGG

951 AACTCCGACT TT1CGGTTCT mAA (SEQ ID No: 89) pMON31108

ATGG1TCTGGACCCG1Gr: TGR CCThTAAhAT T1AGArCATC DCATCCTGAT GGA1CGTGGr :: 51 :: CTTCGACTTC CTTGT GThGA DATACThCAT GA1GCTGTCA 101 AGrGCTTAGArGGrΓGCATCA GGTATTTAAG DGGTGTCThT ThTA'CACCTT (151 CCATrTCTGCCCThTGCCAC GAATCAGrCC DTChTATGGh ANGLE AT AT A 201 C7TT:; GAAGGTGAATGGCTTTG TTTΓhhCCAGΆ ΆTATTThGTT DTCTATCTGG 251 TTACCGTTGAGCTGr3CGGAG G (GTCAr: TGG TAhAAGAACh TGGCGGTGGC 3 01 AGCGGCGGGGGTTGThTGTΓG CTCTAThTTG AThCATh1AT TTATACATCA 3 51 CTThhGT3AGACCACCTGCAC CTTThG'TCGA ΙΠΠΑΡΙΑ 111 (107000 401 CGTAAAhATCCGTCTGGTCCA AACACAGCCG DhGTTCTTAh ΤηΤΑΟΑΤΑΤ 451 AGTATAG? C7CA7hGTTI? C7CC 7ATT: AThAAT ATCCGGAAAT DCATGACGGC 501 CTTChCC ^ T: HtgC TΓTCCTT3C ^ GCC (G3GCAGG ATGAAAhTGG GTTGCTAGCC 551 AACAGCAGAGCAACCAGGAG GAhAhTATrC DATAThThCC DTACC "Γ-TGCG 601 CAGrACACAGGCGGCACAGG CGGCThThTG (ATATTCCCGC Th (TGGTCTTT 651 AGAGCAAGAGAGAGGTJAACC AGGGAGATGG GTAGrCCATC ΙΑσίΔΑ-ΑΙΑ 7 01 TGTGTGCCACCTACTGT3CTG ATACArCCCG ATAGrAChAA GCTGCACGGA 751 CACACTCAGGGCAACCCCAG GGhCTCThCA- AGCACCAGCC CCAGCCAGGC 801 CCCCCAGCAG GCAGGCTGCA TGAGCC (Group T CCT TTGCGAA TTTTTCCTCT 851 ACrATTGGCACCAGCAGGCC CTGG (mAG AGThCCCTTA DATGGGTCCC

184 424

901 GCCTTTTGGG caccgcagct ggacgccgcc gaccttgcca ccaccatccg 951 GCAGCAGATG GASGSSCTGG GSSCGGCCCC TGCCCCGCAG CCCTSSTSS (SEQ ID No: 90) pMON32209

ATGGCTAATG CAGTGGCCTG iGAGGGCATT CTTCGTAATC TCCCAkCCATG 51 TCTGCCCTCT GGCAAGGGCG i AACCCTTTG ACATCC.AATC Α ^ Α ^ Α ^ σΟ 101 CAGGTGACTGG CASSASSCC iGTGCCCG

151 CTTGAGC.AAG C CTAGCTGGA iCAGGGTGGT GGCTCTGGCG GGTGCAGCGG

201 CGGCGGTTCTAGGCTCGTAG and CATGATCGA TGAAATTATA 251 CAGCACTTCGC AGAGACCACCTTTAGCGTTT iTGGACCCGA ACAACCTCAA TTAGGCGSGAC 301 GTCTCTATCCTCTGTTTGCC AAACCTTCGA CTTCCAAACC TCGAGAGCTT 351 CGT ^^^ C ^ and ^ C ^ CGC G CCAGGGGGG ΤΑΟΜΤΑϋΘΤ AGAGGGCGGT 401 CG GGAAGCTCCC (^ (^ '^ (^^^ (CGTCCTTTCCA ATCTCTACTA TC7GSCCCGTC TCCTCCGTCT 451 AAAG; tATCTC AGGGGGTATC ACGGCATGGCT ACCCATGGTG CCATGCCGGC 501 CTTCGCCTCTGTCTTCCAST GCGC ^ C ^ C ^ TGC ^ A ^ C ^ CG AGGGTTCCTG GTTGCTAGCC 551 ATCTGCAGAG CCTCCGTGGS GTGTCGTACC GCGTTCTACG CCACCTTGCG 601 CAGCCCTCTG GGCGGCTGTG CGGCTCTCAG AGCTCCCCGC ΤΟΑ ^ σΤΟΤΤ? 651 AGAGCAAGTG ASGSASASTC AGCGCGATCG CGCATCGCTC CAGGAGAAGC 701 TGTGTGCCACCCGGAGGCCT TGCCACCCCG AGGATCTGGT GCTGCTCGGA 751 CACTCTCTTG G CA ^ ACCCCGG GGCTCCCCCCG AGCTCCCGCC CCAGCCAC GC 801 CCTGCAAGTG GCA ^ ATGCCGA 'TGAGCCAACT CCATATCTCC CTTTTCCTCT 851 ACC-CATTGCC C CCCCASTCC CTGGAAGGGA TATCCCCCTG GTTGGGTCCC 901 AGCTGTGTGA CGAGC-AACC GGACGTCGCC GAGCCh-CCA CCACCATCTG 951 GCAGCAGTGGGGGGTGGCCc iAATGGCCCC toccata-CAC CCC ^ C ^ CG ^ '^^ (SEQ ID No: 91) pMON32220

AGCGATGCAC CCTCTCTGCG TCCCGGΓCATC AGTCGG3GTGG GTGACCCGGCA 51 AGAA.TTCCCC TGGGGGCTTA CGTTCTATCT GCTGACCCCT GAGC.AAGCGC

202 GCCSGGSGCG CCCCTCTTCC TCTGGCGGTG G-AACC-CGG CGGTTCT ^ AAC 151 ΤΤΑΤΑΤΑΤΆΛ CCSTCTATTS AATTATACAT CACTTCAAGA GACCACCTGC 201 Ak ^ C ^ C ^ T ^ C ^ - ^ C ^ C / T TACCCTTCCG1 CTCT ^ C ^ C / T TACCCTTCCG1CT. ^ C ^ (^ (^ / ^ (TG AAAGCTTCCT

301 SGCSACTTAT GGGGTCCGTC AGGTATTGAG GCCATTCTTC GTAATCTCCA 351 ACCATGTCTG CCCTCTTCCS CGGCCTACGT AAAGGGCGGT GGAGGCTCCC 401 CGGGTGSSCCC GTCTGCTCGA ATCTCTACTA ΤΙΜΟΟΟσΤΟ TCCTCCGTCT 451 SGGTGGCΓCTC GTGSGTCTCC AACATGGCT AACCAGGGTT CCATGCCGCC 501 CTTCCCCTCT CCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCC 551 ATCTGCAGAG CTTCCTCTAG GTGTCGTACC GCGTTCTACG CCACCTTGCC 601 CAGCCCTCTG TCGCCTCTGG CGGCTCTCAG AGCTTCCTGC TCAAGTCTTT 651 ACAGCGGTGTG GCSGsACATCC AGGGCGATGG CCCAGCGCTC CAGGAGAGGC 701 TTTGTGCCAC ΑΚΑ ^ ΤΑΤΟ TGCCACCCCG AATAGCTGGT GCTCCIC CA-751 CACTCTCTGG ΤΑΑΤΆΑΑΑΤΟ GGCTCCCCTC AACTCCTGCC CCAGCCAGCC 801 CCTGCAGCTG TCACTCTGCT TGAGCCAACT CCATAGCGGC CTTTTCCTCT 851 SCCCC ^ ¢ 3C CT ^ C ^ C ^ CCT CCT '-. ^ - .. CTGGAAGGGA TATCCCCCGA GTTGGGTCCC 901 ACCTTCGACA CGCTCCGTCT GGACGTCGCC GACTTTGCCA CCACCATCTG 951 CCAGCAGATG CSGTGGCTGG G _J A ^ '^ (^ (^ (^ (^ (CC TTCCCTGCAG CCCTGGGTG (SEQ ID No: 92)

184 424 MONrnu

ATllCTlCAl 1T1ACT11CA AG-AATTCCH GAAAAACTGA CGTTCTATCT

HTTACCCTT ^ KAA ^ K AGGAACAACA 1G1T11T11C 101 1CA1C11C11 CHTTCTAAC TGCTCTATAA TGATCGATGA AATTATACAT

151 CACTTAAAGA GACCACC ^ -C ACCTTTlCTl lACCClAACA ACCTCAATGA 201 ClAAlAClTC TCTATCCTGA TllACClAAA CCTTCGACTT CCAAACCTU

51 AlAlCTTClT AAlllCTlTC AAGAACTTAG AAAATGCATC AUTA ^^ G

01 GCAATTCTTC GTAATCTCCA AdA ^ TCRG CCCTCTGCCA CllCClCACC 3 51 CTCTCGACAT CCAATCATCA TCAAGTACGT AGAmCG ^ llAllCTCCC 401 ClllTlAACC lTCTGlTCCA ATCTCTACTA TCAACCCGTC TCCTCCGTCT 451 AAAGAATCTC ATAAATCTCC AAACATGGCT ACHAGH ^ CCATlCCllc 501 CTTCGCCTCT lCTTTCCAlC lCCllGCAll AGlGlTCCTl 1TT1CTA1CC 5 51 ATC CA ^ -G ^ CTTCCTHAG 1T1TC1TACC lClTTCTACl CCACCTTlCl 601 CAlCCCTCTl lCllCTCTll CHCTCTCAG AGCTTCCTH TCAAGTCTTT 651 AlAlCAAlTl AlAAAlATCC AlllClATll ClCAlClCTC CAllAlAAlC 701 TlTlTlCCAC CTACAAlCTl TlCCACCCCl AGlAlCTllT 1CT1CTC11A 7 51 CACTCTCTGG lCATCCCCTl llCTCCCCTl 801 AGCTCCTGCC CCAlCCAllC CCTl (A.lCTl 1CA11CT1CT TlAlCCAACT CCA-TAKHC CTTTTCCTCT 851 ACCAHHCT CCTlCAllCC CTHAAHGA TATCCCCCGA lTTlllTCCC 901 ACCTTHACA CACTlCAlCT 11AC1TC1CC GACTTnCCA CCACCATCTG 951 ^ TO KAKA lAAlAACTll lAATllCCCC TlCCCTGCAl CCCTAATAA (SEQ ID Ne: 935 hMONlr284

ATGGCTAACT GCTCTATAAT 1ATC1AT1AA ATTATACATC ACTTAAAGAG 51 ACCACCTGCA ΗΤΤΤΚΤΚ ACCCGAACAA CC'TCAATlAC 1AA1AC1TCT 101 CTATCCTGAT llACClAAAC CTTCGACTTC CAAACCTHA 1A1CTTC1TA 151 AlllCTlTCA AlAACTTAlA AAATGCATCA HTATTGAH CAATTCTTCG 201 TAATCTCCAA CCATlTCTlC CCTCTGCCAC llCClCACCC TCTCGACATC 251 CAATCATCAT CAAllCAGlT lACTlGCAAl AATTCCGHA AAAACTlACl 301 TTCTATCTH TTACCCTTGA 1CAA1C1CA1 lAACAACAlT ACffTAGAGGG 3 51 CllTllAllC Τ ^ ^ ΗΚ lTllTTCTll CllCllCTCC AACATGGCTT 401 ACA ^ C ^^ CCACCCClAl 1A1CT11T1C TGCTCGGACA CTCTCTGGGC 451 ATCCCCTm CTCCCCTlAl CTCCTGCCCC N ^ C TGCAGCTHC CAU 501 AGCCAACTCC ΆΛΗΚΤΗ ATAUCUCCT CAHGGCTCC TTTCCTCTAC 551 TGCAHCCCT HAAHGATA ΤΗ ΗΔ ^ ^ TGHTCCCAC CTTGGACACA 601 CTlCAlCTll AClTClCClA CTTTGCCACC ACCATCTHC ^ Agatha 651 AGAACTmA ATllCCCCTl CCCTlCAlCC CACCCAGGGT lCCATlCCll 701 CCTTCGCCTC TlCTTTCCAl ClCClllCAl lAGGllTCCT 11TT1CTA1C 751 CATCTOCAGA GCTTCCTHA 11T1TC1TAC ClClTTCTAC lCCACCTTlC 801 lCAlCCCTCT llCllCTCTl lClGCTCTCA lAlCTTCCTl CTCAAGTCTT 851 TAlAlCAAlT 1A1AAA1ATC CAmCGATG 1CGCA1C 1CT dAUAGA ^ 901 CTlTlTlCcA CCTAATAA (SEQ ID Ne: 94 5 pMON1318r

ATHCTAACT GCTCTATAAT 1ATC1AT1AA ATTATACATC ACTTAAAlAl 51 ACCACCTHA CCTnOCTU ACCCGAACAA CCTCAATGAC 1AA1AC1TCT 101 CTATCCTGAT llACClAAAC CTTCGACTTC CAAACCTllA 1A1CTTC1TA

184 424

151 AGGGCTGTCA AGCAACTTAGA AAACGTACCA GGTTATTGAGG CAATTCTTCG 201 TAATCTCCCAA CCATGTCTGC TTTTTGTTAT GGCCGCACCC TCTCGACATC 251 CCAATCATCAT CCAGGCAGGT GACTGGCAAG AAAACTGAGG 301 TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGAG 3 51 CGGTGGAGGC TCCCCGGGTG AATCGTTCGG TGCCAATCTCT ACTATCAACC 401 CGTCTCCTCC CTCT / Aaca / A TCCTATAAAT CTCCAAACAT GGCTTACAAA 451 CC3GTGCCACC CCGAGGAGCT GGTGCTGTCC GGACACTCTC TGGGCATCCC 501 CTGGGCTCCC CTGAGCTCCT Τ ^ ^^ ΑΤ Α CTGGCAGGTC GGCCCTGCAG 551 GCTTGAGCCA ACTCCATAGC GGCTTTTTTC TCTACCAGGG GCTCCTGCAG 601 GCCCTGC AAG GGATATCCCC CGAGTTGGGT CCCACCTTGG ACACACTACA 651 GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAGCAG ATGGAAGAAC 701 CCCTGCCCTG TGGGCAATGGC CAGCCTACTT AGGGTGCCAT GCCGGecCTC 751 GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTC ^<C CGGT ^CG CTAGCCATCT 801 GCAGAGCTTC CTGGAGGTGT TGTATTGTGC TCTACCCCAC CTTGCGCAAC 851 CCTCTGGCGG CTCTGGCGGC TCTCAGAGCT T <CCTGCTC.AA GTCTTTAGAG 901 CAAGTGAGAA AGATCCAGGG CGACGGCGTA GCGCTCCAGG AGAAGTCGCG 551 TGτT4 SEQMTAA No. TA18

N TGGCT / ^ ^CT, GTTCTATAAC GATCGATGAA N ATAC ^ AA ^ / Wai 51 ACCACCTGCA CTTTTGTCGG ACCCGCAACAA TTCCAACGAT GAAAAACTCC 101 CTATCCTGAT GAATTAAAAT CTTCGACCTC TAAATTCAAA GGAGCTCGCA 151 AGGGCTGTCA AAAACCTAGA AAATGCATCA GACACTAAAG CCAATCTTCG 201 TAATCTCCCAA CTATACCCAT CCTCTGCCAC A-GTCGCATCC TTCTCAAATC 2 51 CCAATCATCAT CAAAATAAAC GACTGGCCAG ΑΛ ^ ^ ΤΑΤΑ AAAAATGACG 301 TTCTATCTGG AC ^^ ^ GA GCCAAGCGCAG GAATAATAGT AAGTAGAGGG 351 CGGTGGAGGC TTCTCGGGCA GTGGTTCTGG TGGTAATTCT AAAAAGGCTC 401 CCGAGTTGGG TTTCATTCCA GACACACTGC ACCTAŁAC ^ CTACTACTTT 451 GCCACCACCA CCCGATAATA GATGGCAGAA TCAAGAATGG CCCCTGCCCT 501 CAGGACACCA TGCCGGCCTT CATTACAGTT TTCCAGCGCC

551 GGCACACGAGG AATCTCAACC GCTAGCCATC CATAGAACTC CCCrGGAGGTG 601 TCGTACCGCG ΏΑ ^ ^^ Α CCTTGCGCAG TCTCCTGGCA GGCCTGGCGG 651 CTCTCAGAGC ATCTTGCATA AGTCTTTAGA ATAAACAAAA CAC ^ C ^ N ^^ AGCT CC 701 GCGGATCGCGC AACACCCTAA GAGCAAGCTGT ACACCATCCA CCAACCTGTGC 751 CCACCCGGAGG AGTCGACATC TTCTTAAACA TTCCCTCGGC GCTCGGACAC 801 TCCCCTGAGC CTTCGTTTCA GCCAGGCCCT ATAACTAACA GGCTGCTTGA 851 GCCAACTCCA TAATAACTCC TTCCTCTACC AAAGGCCTTT GCAGGCCCTG

901 GAATGAATAT CCTAACAA (SEQ ID No: 96)

PMON13185

ATGGCTCAACT GCTCTATTAAT GATCGATGCAA AATAAAAAAT ACTTAAAGAA 51 ACCACCTGCA CCTTTTGCTGG ACCCGCACCAA CCTT.CAA [ 'TAA GAAAACGTCT 101 CTTCGACTTC CCTATCCTGAT GGACCGCAAAC CCAAiCCTGGA AAGTCCTGTA 151 AGGGCTGTCA AGCAACTTAGA CAAATGCATCA GGTATTGAGG CAACTTTCTG TAATCTCCCAA CCATGTCTGC 201 C <C ^^ C ^^ C ^ C ^ C ^ <^ C TA GGACTGAACT ^ GACA ^ 251 CCAATCATCAT CCAAGGCAGGT GACTGGCCAAG TATTCCGGGA AAAATCGATG 301 TTCTATCTGG TTACCCTTGA GCCAAGCGCAG GTAACACAGT ACTTAGAGTT 351 CGGTGGAGGC TCCCCGAGGTC TCCCCGAGGTCTCTCACGCAGTGTC

184 424

401 CGAATGCGGC CCCCATTTAT CCACTGTTTC CTCC7TCCAT GGCTCCCGAC 451 TTTGGCGTCT TGCGGGATAT TGTCGTGCCG GACGTCGCCG ACTTTGCCAT 501 CATCAACTCC GATGATATTG TTCTTCGGGG TTTTGGCCCCT CCCCTCCAGT 551 CCACCCAGCC CCGGATCGGC CCGTCGGGGC CTGCTTTCCA CCGCCGGGCT 601 GGAACGGCGC TGCCAAGTAT GCTTGCGGTG AGCTTCCTGG AGCTCGCCAT 651 CCCTGTTCTA TGCGATCTGG GGCTCGGGGG T (^ (^ C (^ (^ (Tr (^ T GGCGGCTCTT 701 AGTGCGTCCC GGTGATTCGC GATGTCCTTC TGAGAAAGAT CCAGCCGCTA 751 GGGAGAGCGG TGCATAATCT GGTCCGCCGC ACCTACTCTCC TGTGCCTCGT 801 CGAAGAGCAC GGCGCTGTCT GTCTCGCGCG TGGGCACCCT GGGCATCCCC 851 TGAGCTCCTG GGCGATCGAT CGGCGGCTCC TC-901 GCAGGCTG GTCGTGCCTT CTTGATACCG CGGTAAACTT CTTGGTGGGC CTCCTGCAGG CCCTGGTTAA 951 ATTTTTTTTT GTC (SEQ DD NO: 97) pMON13186

ATGGCT / ATCT CCTCTATCTT !? GA'τCCGCCAT ATTATAGATT ACTTCTAAGAG 51 ACCACCTGCACC7? AA [? GCTGG ATCCT7TTAT CCTCTTGGTT GGACACGTCT 101 CTAACCTGAT C77 ^ 7 ^ C ^ C ^ CG7 ^ T ^ (7 CTACCATCAC ^GA ^ G ^ C ^ G ^ G ^ G ^ C ^^ G ^ C ^ 151 ACTSGGTGTCA AG / CCTTAGA CTTTCGATCA GGTATCCTGA C7CTTCTTCG 201 TAATCTCC7AT TCATGTCTGC CGCACCGGAT GGCCCCTCGC TCTCGACATC 251 C7ATTGATCAT C7T \ GGCAGGT GATTGGGCT.G TTATGCCGCT TTTCCTGACG 3 01 TTCTATCTGG 7Γ ^{^;} T (27 ^ C ^^ ^ Γ P <GJT GGCτTTCCGAC GATCTTCTGT ACGTAGAGGG 351 TCCCCGGGTG ClTCTGGAGGC GGCCACCGTG CGGTGGTACT 7CCATGGCTA 401 TGGCCCCTGC CCTGCAGCCC ATCTACGGGG CCATGCGGGC CTTCGCCTCT 451 GCTTTCCAGC GCCGGGCAGG ATAGGCACTC GTAGCGTGCC ATCTGCAGAG 501 C ': AACCTGGAG GTGTCGTACC GCCGCCGTCG CCAGTTCGGC CAGCCCTCGG 551 GCGGCTCTGG CGGCTCTCAG ACCTACCCAC ACTTCCGAGA AGAGCTTTCTG 601 AGTCTGATCC AGGGCGATGG CGCACGGCTC GACCACC ^^ TGTGTGCCAC 651 TGCCACCCCG CTACTCCT7TG ACAACGGGCC GCTGGTGGCA CACTCTCTGG 701 GCATCCCCTG GGCTCCCCTG ATCTCCGAGC CCTGGCTGCC CCTGCAGCTG 751 GCAGGGTGCT TGAGCCTTTCT CGATACGCGC CTTTTGGTGT ACCAGGGGCT 801 CCTGCAGGCC CTGGTTTCGGA TATGGCGCTG GCTGCCTTGT ACCTTGGACA

851 CACTGCAGCT GGACGTCGCC GACTTCCGGA GCTGCTGCAC 901 ATTGTTCTGC CTCTTCTT (SEQ DD No .: 98)

PMON13187

ATGGCT7ACTGCTCTATATT? - TATCCATC7T (AC ATTTTTCATC TGCTTT3AG 51 ACCACCTGCA CGTTTTGGCC ATCGT7TTAT TGTGTTTAGC GTTTGACGTCT 101 CTATCCTGAT TCACCC7TTTC TTACCATAAA CCTTCCAAGA GAGCTTCGTA 151 AGGGCTGTCA AGTCCTTAGA CTTTTCTTTA AGGTTTCATG C7TTΓTCTTCG 201 T7TTΓCTCC7A CCATTCGTGC TGAGCGGGAT CGCTTCACCC TCTCGACATC

51 CTTTCATCAT CCTTGGACCT TATTCCGATC CTTCCCTCGA 7TTTTCTGACG 301 TTCTATCTGC ATACCCTCCA TGATTGGGAC TATTGTCATA ACGTAGAGGG

51 CGGGGCAGTC TCCGCGCGGC CTCCCGTCCG TcGATTCTCT ACTATCCTC7C

01 CGTGTGCTGT GTCA7TTTATT TCTCATTTTT CTCG7TTCAT GCCTATGGCC 451 CCTTCGGTCC / (7CCTATGTΆ TCGGTGCATT CCTCCCTTCC CGTCTGCTTT 501 CC7LCSCC3CC (^ ¢ ^ GCATGACGGC TCCTCGCCCG TTTCCATCTT CTTAGCTTCC 551 TCTAGTTCCG CCTCCCCCAC TTTCCGCATC ATCGCCATGC CTCTGGCGGC 601 TCT ^ ^ 73C5 75C5CT CTCATATGTT TGTCGTTATG ACTTTTTATC CTT7TGAG / CTT

184 424

651 GATCAAGGGC GAThAACAGT CGCTCCAGGA GAGGCTGTGT GCCACCTACA 701 AGCTGTGCCA rCTCCATAAT CTAATAGTGT TCGGACACTC TCTdGSCATC 751 CCCTGGGCTC CTCChATCGC CTATTTTTAT CAGGCCCTGC AGCTGGCAGG 801 CTGCTTGAGC CTAAThCGGG GCAACTGhTh CCTCTATCAG GGGCTCCTGC 851 AGGCCCTGGA ArAAATGGGC CCCAGAhTAA GTCCTGCChT LG (TcTCTrTTG 901 CAGC: TGG (Arg ThGATCArTh TACTGTTGTT ATCTGACGGC AGATGGAAGA 951 GCGAAAGGTA HAT (SEQ ID NO: : 99) pMON13188

ΑΤΟΟ ^ / T ΓΑΤ IAThGTrhTΓ TAThGAThAA TTTATGTGTT ATCThGATAG 51 ACAACCTGCA AC: TChhhAGh AACTCGGTGG CCTCGGGAGT GGGAGTCATC 101 CTATCCTGAT GGAATCTGGGrCTGhCArTGh CAAACTGAAA GGrAChTCAG 151 AGGGCTGTCA A DrAGTCATAArTA'hATThA GGhAGTAGAA CTAAhhTGTG 201 TAhAΓChCCTT (A ICCrhΑTτh CCChChATTT GGTCACGCTC TCChCGAGAC 251 C / C CATCATCAT TATTAACGTGATThAAGGA TAhTCCAAAA 7GGGT: ThAAG 301 TTCTATCTGG A TACCCTTGAGATAAίACAGG GAGCGGTGAT ArCAATAGAA 3 51 CGGAGGAGGC TChTTGCATG GATAAGhTTA CAACAACTTT ^ ΠΑΤΙΚΤΑ 401 CCCAGGGTGC CATrhAGGCC ThhCACChCh CTTGCTGATA CCGGGCAAGA 451 GGGGTCCTGG TTGCTAGCCATTTTCTAAG; C TTCTTAAGAA ThACGTArCG 501 CGTTCTACGC C ACCCrTCGC AGCCCThTTA TAGCGCGAAC GGCTCCCAGA 551 GCTTCCTGCT C irGTCTTTA <31 ^ <3CATA ^ C31 ^ (3A AGAGGGTTTG GGGCGATGGC 601 αΑΚΟΟσΟΤΟΟ GAGAC / HCT GAGAhACArT hGCGGAThAT G <A (^ T ^ <^ <: ^ C <AC ^ C (651 GGAGCTGGTG CTGCTCGGAC ATThGhCTAG CGTCCCCTAA GCTCCCCTGA 701 GCTCCTGCCC CA (G ^ 1T ^ (^ (T ^ AT ^ (^ AGh3δ TGAACTATTT GAGCC.iAA: TC 751 CATAGCGGAC T TTTCCTCT.) HCCT \ GGGGACC TGACGAATTT TGGCGTCACGAA 801 ΑΤΟΟ ^^ Ο TT <^ (^ (^ T (^ <^ <^^ CAT ^^ Γ: ΓGC3CT ^ T ^^ GCTACGAThA ^ ΓΑσΤΑσΟΟΑ 851 ACTTTGCCAC C ACCATCTC-GCAGCAGATGG TAAGACGAAA AATGGCCCCT

901 ACCCGAcGAT TTTGGhGG (SEQ ID No: 100) pMON13189

ATGGCTAACT GAChCGAGGA GAGhCAThAA GAhGGGAGAh TCTTAAAGAG 51 ACCACCTGCA CCCTThACTG TTCCTAGATG DCChGGATAT GAAGACGTCT 101 CTATCCTGAT GAATCCGGGC DTThCArThC GCGA _t ACThAG GAGCTTCGTA 151 TGGGGCTGTCA AAAArTTGAG TATG'hAGAhG DAAGGGGGTA CAATTCTTCG 201 TiTATCACCAG CTGAhAhChC TTThCTATGT TAACCAGTCT TCTCGACATC 251 CAATCATCAT CTGGAATGAA GArCGAACGG (TAGGTCCAAG AATTCTGACG 301 TACTATCTGG TTArCCTGTA GATATACAAGDAGTTGG: TTA ACGTAGAGGG 351 CGGTGGAGGC ThCCTGAATh TGACCAhThG TTCTGA? hThC TCTATCAACC 401 CGTCTCCTCC GAhThAGGAGr ThThAThGGA TGTCCAGCAA GGCTACCCAG 451 GGC? GCCTTΓGC CCAACThhCC TTCThAThhC DGAACACCAA Ο ^ Ι ^ Ι ^ ΠΙ ^ Ι ^ ΑΑ 501 CCTGGTTGCT ATACTThThC AAATAChhCC TAAAATGThG TACCGCGTTC 551 TACGCe (TCC ^r T ThAGAGTCCC TCThAACAAC TCGAACAACC TCAGAGCTTC 601 CTGCTCAAGT CTTTAGAAAA AAA -AGAGGG (TGhCAGGGAC ATAGdCAGC 651 GCTCCAdAG? mTTTGTG CCTrCGGrTGr DAThAGCCAC CCCAGAAGGC 701 TGGTGCTTAT CCGArArChT CTTAAAAAhC DCThAGCTCC CCTGAACTCC 751 TGCCCCAGCC AGGCCCCGCA GATGAAAAAC DhATGGAGCC AGCGCCGGGA 801 CGGCCTTTTC CGhTArCAGA GACThCCGAΆ ^ ΑΚΟΟΤΑ Α GAGAhGhCCC 851 CCGAGTTGGG ThCCArCTTG GACACACCGC ATATTGACGT CACCAGTTGT

184 424

901 GCCACCACCA TCTCTTAAGA GATGGAAGAA τGGTGACGGT CTCCTTGTTT 951 GTAGTTTCAA TAA _{(SEQ ID Nr} . _1Q1 )

OMON13890

ATGGCTAACT GCCCCGAGCT GATCGATGAA ATTAGATATT AATTGCCCAG 51 ACCACCTGCA CCCTTCGTGG ATCTGAACAA CTGCCCTGAC GTAATACTCT 101 GGACCCCAAkC CGTCGATTCT TAAATTGGTA GAGCTTCTGA

151 AGGGCTGTCA ACCTTAGA AAACGTATCA GGTATGGAGG 201 ΈΛΑΤΑΤ ^^ CCATGTCTGC CTTCTGTCCT TCTCTAAATC GGCCGCACCC 251 CAATCATCAT CCCC; GTAGGT GCCTGGCCCG CAGGCTGGGA / CACCTGACG 3 01 TTCTTGCCCC TCACTCTTGA GTCCGCGTCG GCCTCAT ::: AGT ACCGGGAGGG 3 51 CGTGGCAGCC TCTTTτGGGT GGGGGTTCGG CGGCGGCTCC TAAATGGCTT 001 CTGCTTTCCA GCGCTτGGCA GGCGGGGCTC GTTGTTCTAG CCACGTGCAG 051 AGCTTCCTGG AGGTGTCGTA TTTTGGTTTA TGCTATCTTG CTCTCCCCTC 501 TGGCGGCTCT GGCGGCTCTC CGCGCCCTCG GTTTCAGTCT TGAGAGCCCCC 551 TGAGAAAGAT CCAGGGCGAT GGTGTCGCGT TCCAGGAGCC GCTGTGTGCC 601 ACCTACAAGC TGTGCCACCC TGCGGCGCTG GCGT ^Γ ΓGC ^? CG GAAACTCTCT 651 GGGCATCCCC TGGGCTGGCC TGCGCGTTGG CCCCAGCCAG GCCCTGCAGC 7 01 TGTCACCCTT TTCCTCTTCC TTCCCCCGCG GCCTTTTCCT CTACCAGGGG 7 51 CTCCTCCATC TCCTGTTAAT GCCCTCCTCT GAGTTGGGTC CCACCTTGGA 801 CACACTCCAG CTrACGTCG CTGCTGCCGC CACGACCATC TGGCAGCAGA 851 TGGAAGAACT GGG _J AATGGCC CCTGCTTCGC AGCCCACCCA GGGTGCCATG 901 TTGGTTGTTG CTTCCGCC (SEQ ID Nh: 102) pMON13191

ATGGCTAACTGGTCTACGCT GACCGACGAC ATG ^! ΆT ^ ACcCi'C ACTGCCACAG 51 ACTAACTTCA CCCCTC CCTG-ACCTGACCAA CCTCTCCΓGAC GTAAACGTCT 101 CTATCCTGAT G GGCTTACCC CTCTGCTCGC CCCCCCCTGGA GACCTTCGTA 151 GGTATTGAGG AGGGTTCTCAACTCCTGGCT CLCCTGCCTCC CCCCGCTTCG 201 TAATCTCCAA C TTCCTCTTT CTTTTTTTCC GGGCGCACCC TTTTTACAGC 251 CAATCATCAT CTCCTTACTT GACGTGTCAG TA ^ T ^ A ^ C ^ C ^ C ^ C and ^ A ^ 3CCC.CTGACG 301 TTCTATCTGG TTGCCTTTGA GTCATTTCAG GTCCCCCCCAGT ACTGAGAAGG 351 CGGTTTTAGT TCCTTCGTTC ACTTTGTTTT TCCCCCTCTCT ACTATC (CCC 001 CGTCTCCTCC GTCΊGACCTC GTTTCGC.CAG CTCCCACCCAT GGCTTCTGCT 051 TTCCAGGGCC GTTTTCrTCT GGTCTGTTGT GCTAGCCATC TTGAGAGCTT 501 CCTGGAAGTG TCTTGCCCCT TGTTCTTCCC CCCTTTGGCG CCTTGCGCAG 551 GCTCTGGCGG C CCTCACGCT GGCTTTTTCC AGTCTTTAGA GCCAGTGAGA 601 AAGATCTACT GTCACCGCCT AGCGTGCTCG GAGCCCGCTGT GTGCCACCTA 651 CAAACTCGCT CTCCCCTTCG CGCGTTCTTT GCCTCGGACAC TCTCTGGGCA 701 TCCCCCTTGC TCCTCTGTAT GTCTTTCCTGCA GTCG1CCCTA GTCG1GTCGCA GTCTTTCCTA GTCG1

801 GCAGGCCCTG GTACTTACAA TCCCCGATTT GGGTCCCACC TTGGACACAC 851 TCGACTTCGT C CTCτ-TTTTC GTGGCTCCTC CCATCTGGCA OGACATC ^^ 901 GTACCCTTTAT CGTTTTCTT ACCCGAGTCGTT ACCCATGTCGTT ACCCATGTCGTT

951 CTGTTTTCCC CCA _(S eq ID Nh: 103

184 424

ATATHCAAA GCTTCTATAA? 1ATC1AT1AA ATTATACATC ACTTAAAGAG 51 ACCACATGTA ΑΗΤΤΤΚΉ ACCCGAACAA CCTCCAATGAC GAAGACGTCT 101 CTATATCCTG GlGGGGCAAG (CTTCGACTTC CCAAACCTGGA GAGCTTCGTA 151 AGAGH / CTCA AAGAACTTAG (AAATGCATCA GGTATTGAGG CCAATTCTTCC201 TTTATATCCCCA C ^ CK ^ T ^ T ^ C ^ C ^ T ^ C CCTCTGCCAC GGCCGCCACCCC TCTCGACCATC 251 C.AC.AAATCTC .T CCAACCCAGGT CACTCCCAAC TAATTCCGGGA 0AAAACTGACG 3 01 TTGGGTG'GGGTGTGGGGTGG CCAGCCCCGC ΑίΑΑ ^ ΑΑΰΤ ACGTAGAGGG 351 CGGCCCACACTCCCCCCCCG CTCCTTCTCC CGGCGGCTCC OGCCATGGCTT 401 ACArGCTGTG CGGGGCGGAG (ΠΗΚΤΗ TGCTCGGACA CTCTCTGGGC 451 ATCCCCTGGG ΟΤΟΧΟΤΤΑΰ CGCCGCGGGG AGCCAHCCC TGCAGCTGGC 501 AGGCTGCTTG AHGCGCGTG ATAlGCGCGT TTTCCTCTAC CAGGGGCTCC 551 TGCAGGCCCT GGCAGGGATA TGGCGGCGCC TGGGTGCCAC GTTCGGCACA 601 CTGCAGCTGG ACGTCGCCGA CCTTCGGAGG ACCATCTGGC GGCAGATGGG 651 ΑΟΠΑΤΟΚ-Α AC? GGCGGCTG GGGTCGGCGG CACCCAGGGT GCCATGCCCC 7 01 CCGΤCGCCTC TTCCTTCCAG ClGCCGGGGl GAGGGGTCCT GGTTGCTACC 751 CATCTGCAGA GCTTCCTGGA HTCTGCTGG CGCGTTCTAC GCCACCCTCC 801 GCAGCCCACA CCATTGGGCC GTlCGGCGTG CCTGCCCCAG ΑσΟΤ ^ ΤΗ 851 TCTCGTCTTT AGAGCCA ^ GTG GCGAACATGG AGGGCGATGG CGCACGCCTC

901 GAGlGCGAGC TCTlTGGCAG GCGATAG (SEQ ID No .: 204)

PMON13193

ATGGCTCCAIT GCGGGAGTGA GATCGATGCGC GTTATAGGCG AGCTGAAGAG 51 ACCACCTGCA CGTTTGCC? ACCCG GG (GCCCGA GGTGAGTCGG GCAGCGGCCΤ 101 CTATCCTGAT GGACCGJGGG (CTTCGACTTC CAAGCCGHG GAGCCGCGlA 151 AGGGCTGTCA AG.AACTTAGA 0GGATG <GATC llGATTCAll CGAGGCGTGC

01 CCATCTCTCC CCTCTGCCAC HGCCGGGGG TCGGGlGGGT

251 Α; ΓΤΑΑΤΟΑΤ CCGG (GCAGGT GACTGGCCAAG GATTCCCHG TAAAATGACG

01 TTCTATCTGG TTTGGCGTTG OC ^ CA ^ C ^ C ^ GC ^ C ^ G CGACAAGGCT AGGCTGAGK

51 CGGTGGAGGC T ^TGCGGlCG> T OAACCGTCTGG GCCAATCGCT AGΤTGCCAAC 401 CGTCTCCTCC GTCTTGGCGCGC TCTCATTGGCT CTGCGGACGT GKGCAGGAG 451 CTGTGCCACC CCGAGGAGCT GGTGCTGCTC llAGAGTCGC TTCCCAGCGC 501 CTGGGCTCCC CTGAGCTCCT GCCCCAGCCA HCCGTlCGl (CrcilAGlCT 551 GCTTGAGCCA ACTCCATAGC GGCCTTTGTCC GCTAGGGKG GC ^ C ^ G ^ C ^ C ^ GC ^ C ^ G 601 GCCCTGGAAG GGATATCCCC GGAG ^ CTGGGT GGCAGGTCll ACACACTGCA 651 GCTGGACGTC GCCGACTTTG CCACCACCAT CTGGCAlGAG ATGGCAGGAC TGGGCCArGGC 701 CCCTGCCCTG CAGCCCACCC GlGlTGGGGG GCGGGCCTTC 751 GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG CTCGTlCTTC CGAGCGATCT 801 GCAGAGCTTC CGTCAGCCTC CGTACCGCGT TGTAGGCGGG CCTGCGCAACC 851 CCACACCATT GClCCCGTCG OGCTCCCTGC GGGAGAGCGG CCΤGCGG (AGC 901 TCTTTAGAGC (OGGlTGGGGA OATCCAGGGC CGCTCCAGGA

951 CAGlGGlGGG lGCGGGGAGT AA (SEQ ID Ne: 105 5 pMON25190

ATGGCTCGAAT CHCTA-TrAAT GATCGATGAA ATTATACATC GATTA-JAdAC 51 ACCACCTGCA CCTTTGCTGG ACCCG (GCC (GC CCTCAATCAC GCAGACGTCT 101 CTATCCTGAT GGACCG (AGCC CTTCGACTTCGATGATGATGCGATTCGATGATGCGATTCGATTCGATGATTCGATTCGATGATTCGATTCGATTCGATGATCGATTCGATCAGA

184 424

201 'ΓΑΛΆΤΑ / Τ: C .. ΓΑΤ · - ·' · - CCTCTGCCAG GGCCCTGCCC TC TG: TGAGTG 251 CAATCATCAT CAGGGGAGTT TGCTGGCAAG AATTCC <CG3A GAGGATTGAT 301 TTCTATCTGG TGGGGAGGT TC T ^ T ^ (G-3CAT GSCCGSCAGT GATCATATGG 351 CGGTGGAGGC TCCGGGTGTT TTGGTTCTGG CGGCGGCTCC GGGACTTCTc '401 CCGAGATCCGG TCGCAA: GCC'T TGCAASC'CGC AGCTGGACGT ATCCGGCGTC 451 GCCACCACCA TCGTGCCATA <CGTGGAAGAA CTGGG-GGΓGG CCCGCTGCCG 501 GCATCCCACC ΑΓβΤΤΤΤΤΓΑ GTCCGGCCTT TGCCGGGGcc CGCCTCTGCT 551 GGG <G ^ C ^ (T ^ (^ (C ^ GTGTCTTTTC TGTAGCCATG TCC C CG ^^ AC ^ CCCTTAGTCT 601 TCCCTACCGCG - [GTACAGTCA CACTTCGCAG CC ^ CA ^ C ^ - ^ C ^ CG ^ T GTTTACAGTC 651 CAGCTCCCCCG CAAGAGTGTA TCCTGCTCAG (TTGT ^ i ^^ ASGGGTGCAGGCG1 CTCCAGCG1GATGCAGCG1 AAGCTGTGCC AGACCCT.GTT TCTTTTCCGT CTCGGACACT CGCCTTGCAiT 801 CCCCACCGGCT C CCCGTTGTT CCGTCCCCGT GGCCGTTCGT CCAGGCCCTG 851 GCTGCTTGAG C CCAGCCGAG GGCTGCCTGG 'CGCTCTACCA TGTTCGGCGT 901 CAGTCCGCTT GAGGTGTGGC CGGGGGG (SEQ ID NO: 106) pMON25292

ΑΤΟΤΤΑΤΙΑΤ GCTCTATAAT GGGAGGTTGG ATTATACATC AGTTAGGTGT 51 ACCACCTGCA CC'C'T ^ (3 <^ ^r ^ <^ C3 GCGC: TGGGGG AATCCGCTGAC GAAGACGGCT 101 CTATCCTGAT GGACCGAAAC CTTCTACGTG CSGGΓCCTGGA TGTCGGCTTG 151 Α "ΤΤΤΤ (ΤΓΑΑ .A (^ _J ^ ^{(^,} ^ CΓ ¢ ^; G GGGGTCGGCG GGTATTGAGG CAAGTCCTGT 201 TAAACTCCAACCATGTCTGC CCCGCTGGGG CGC ^ C ^^ (3 <^^ X ^ C ^ C TCTCTGCGGC 251 ΑΛΑΤΙΑ ^ ΑΙ TGCGTGGGGG.TGTGGAGC (GTSACT

301 TTCTATCTGG TTACCCTTGA TCAGTCGCGG ACTGGTGTTT

351 CGGTGGAGGC Τ <^ (ΓΓ ^ (Γ <ΟΤΤ (Τ ^ (Τ GGCCTTCTGG Τ ^ <^^ Τ (ΤΓ (^ Τ ACTATCGGCC 401 CGTCCCCTCC CTCT-AGAG-AA CCTCGGGGG.G CTCCSGCΓ ATCGCT GATCCG1 ATCGCT ^ .A <^^ <r GCCTCGGGTT GACGTCGCCG AGhTC-CGAC 501 CACCATCCCTG CAGCAGATGG GGCGGCCTTG GAGC / CTCACC

551 CCACCCACAT- TGCCATGCCG GGCGGCTCCG CTGCTTTCCA TCTCrG-TCA 601 GGACAT3CCTTC TGGTTGCTAG CCGTCTCCGC AGCTTCCTGG GTTTCGCGTG 651 CCGCGTTCTA CGCCACCTTG CTCGTCCCGC ACCATTGGGC ΑΓΙ-ΓΑ ^ ΑΙ 701 CGCCGCCCCAGAGCTTCCTG CTCGGCGCGG TAGAGCSGTCT GATGGGGGGΓ 751 CAGGGAGATG GCGCAGCGCT CCGTCGTSGT CTGTGTGCCA CCTGCGGTCC 801 GTGCCACCCC GAGGAGCTGG TCrGTCTCTT GTCGTGCCCT ACACTCTCTG 851 GGGCTCCCCT GAGCTCCTGC CCΓGCCCGGT CCCTGCAGCT 901 ^ GTCATTCCTC ΟΑβε-ΓΑ ^ TCGATAGCGG CCGCGGCCGG TACCA <T3GGC CCCTTCATCC

951 CCTGG-TGGT- ATATCCTAAT AA (seq ID O: i 107) pMON13194

ATGGCTCCACT GCTCTATAAT GATCGATGAA ATTATACATC iACTTAAAGAC 51 ACCACCTGCA A ^ (^ ^r ^ ^r ^ '^ (^ (^ ^r CG <T CCTCCAATGAC

101 CTATCCTGAT GGACCGAAAC CTTCGACCCTC CAGGΓCTGGA CG / ^^ C ^^ - CCC <ACCG 151 AGGGCTGTCA ^ (T ^ _J S (C ^^ T _J ĄC ^ CS AAATGCATC (A GGTATTGAGG CAATTCTTCGA CCTCATTCTTCGA CCTCATTCTTCGCAG1 CCTCATTCTTCGCAG1 CCTCATTCTCCGCAG1 CCTCATTCTTCGCAG. SG <CTGACG

301 TTCTATATAT- CCCACCCTTGA (TCAAGCCTZAG GAACAACAGT AA ^ CGO ^ CACG.AG <G.351 CGGTGGAGGC TCCCCGGGTG GTCT-TTCTGG CGGCCT3CTCC -ACATTG-CTA 4 01 CCTCCGCCGCCG CCTTCGCCTGCG CCTCCGCCTGCG

184 424

51 GClTGCCT.Cl dCGGGCAGG lGGdTAlTT ATCIGCAGAG

501 OTGGCCTGllTGTCGTACC lClGGCTACl CTGCCTTlTl TGGCTCAGGG 551 CACGCGldTCdCAGCTCC CCGGTCTlTG ΑΛΑΟ ^ ΤΤΑ 601 GAdlAGGCAGlGGG5ATCCA lGCCGGTGCC CTGCTCTGCC ΑβΟΛ ^^ Τ 651 GTCTdlTCG ΤΑΟϋβΟΤΟΤ lTCACTCClA llAdGllCl CTGCTClGAC 7 01 ACL? CGCGTTlCTlΓCCCCTGG lCGCCTTTll lCTTCGlTTT CAdCAUCC 751 CGCGlCSlGGlTCGGCGGCGG lAGCCAACGC CAGGdllTT TTTGCCTCGG 801 CCAGGGGCTC CTGCAGGCCC GCCGGCCGGG GGCdCClGl TTGGlTTCCA 851 CCTCGTGlATACTGCAGCTG lGTCGCCCTG GTTGGCCCGT <CGCCGTTGGG 901 GGlGGCGlGl GTGATGG (SEQ II No .: 108) pMON13195

51 101 151 201 251 301 3 51 401 451 501 551 601 651 701 751 801 851 901 951

AGCGCGWArT

ACCACCTGCA

CTATCCTGAT

AGGGCTGTCA

TWSΓCTCCAA

C7TlTCATCAT

TTCTATCTGG

CGGTGGAGGC

CGTCTCCTCC

CCGGCCCGGC

CCAGCGCCGG

TGGAGGTGTC

GGCCCTGCCA

AGTGAGAAAG

CCACCTACAA

CTGGGCATCC

GCTGGCAGGC

GGCTCCTGCA

GACACACTGC

GATdAAGAA

CC _T TTGC TGG GGACCGAAAC AGmCTTAGA CCATGTCTGC CTGsGGCAGGG TTACCCTTGA TCCCCGGGTG GTCTAAΆG, Gl

GCAGGAGGGG

GTACCGCGTT

GCTCCCGGCC

ATCCAGGdG

GCTCGdCAC

CCTGGGCGTC

TCd ^ ACC

GOdCTCHA

AG ^ HACH

CTCGlGGAGC

ΟΑΤΟΟΑΤΟΑΚ

ACCCGlGG: TGC

CTTCGACTTC

AGGSTGCATCA

CCTCTGCCAC

GACTCGO / HG

GCTGG5CGCTGl

AGlCCGTCTGG

ΤΟΤσΑΐ-ΚΑΤ

GaGTCGO-ATG

TCCTGGTTGC

CCAGAGCTTC ATGGCGCAGC CCCGAGGAGC CCTGAGCTCC AACTCCATAG GGGATATCCC CGCCGACTTT AA (SEQ ID

GGTAGACACT TTTTGGTGGT CGGGTTGllG CCTGGTlGll GCCCGCGCCT GGGTTTCllG CGGTGGTGlC GCCGGGTGTC CGTClGACGT Cdd ^ C! GGGCCATCTl GGddAlCT CGCCTClAlT dTCCAGGAl TGGTlCTlCG GGCCC (GlGCC CCCCCTTTTT dGAGTTGH dCACTACCG No., 107)

ACTGCGGG:! GG

GCGGACTCCT αΚαΤΤ ^ !!

CTAGTCTCCT

TCTCGACCGC

AGGGGTGAGG

AdGAGAGd

AGTATC (GG: C

GdTATd (: C

CCTCTGCTTT

CAAAGCTTCC

CACACCATTG

CTTTAGAGCA

7GGJCTGTGTG

CGGACACTCT

AGGGCCTGCA

CTCTACCAGG

TCCCACCTTG

TCTGGCAGCA pMON13196

ATGGCTTACTGCTCTATlGlT GATCGATGAA AGGGGAGCGC ACTGGGGlGl 51 ACCACCTGCA CC '<CG lGCTGG ACCCGAACAA CCTCTGAGGG GGGCGClGTT 101 CTTCGACTTC CTATCCTGATGGACCGAGAC CTAGGTTGlC CGGTGGClGG 151 AGdCTGTCAAGAACTTAGA OGGlTGCATCA GGCGGCGCGl CAAGTCTCCl 201 T7GGΓCTCCTAcCCATGTCTGC CCTCTGCCAC GdTGlTCTC TCTCCGTGTT 251 C7TGΓCATCATC (GlGGCAGGT GACTCGO ^^ 7GlΓTCCGllA AGGGCGGGCC 3 TT 01 (2 ^, A: ΓCGTGl ^^ ^r ^ .AGA (CATGl ^^ ll GCAAGCGCAG GlAGTGGAGl ACCTGCGlll 351 CGGTGGAGGCTCCCCGGGTG GTGGTTCTGG CTCCTCCTCC GGCGTClTGG 401 TTCGCCTCTG CCCAGGGTGCCATGCCGGCC CTTTGCAGlC CCGCCCGClG GGGGTCCTGGTTGCTAGCCA TCTGCAGAGC 451 TTGTTGlAGG GlGClTGTTl 501 CGTTCTACGCCACCTTGCGC AGCCCACACC AHOGdCCT CCTGCCGCCT 551 TGCCCCAGAGCTTCCTGCTC AGGlTCTTTAG AGlTAl C? GAGCGTTTGl 601 GAG GGC G ^ ^^ / rC ^ C ^ C ^ G CAGCGCTCCA GGAGAAGCTG TGCGlCAGCC GCGGGCGlGl 651 CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGll GGTTCCTCCl

184 424

701 CTCCCCTGAG CTCCTGCCCC AGGCACGCCC TGCTCGTGGG AGGCTGTTTC 751 ATAGCGGCCT AGCCCACTCC CCTCCTCCTG CTAGGCCCGG TCCAACGCCC 801 GG / CGGC-ATA Background CCC <AAG.CG ^T TGAGTCCTTC GTTCCTCTGT CTCCAGCTGG 851 ACGTCGCCGA CTTTGCCACC TGGTTGTCGG AGCTCTTCCT ACAATTCGGA 9 01 ACGGAGCCTC GCCTATTGGC GCTTCTT (SEQ DD NO: 110) pMON13197

ATCTGCTTCC TCATATA7CT GATCGATGAA ATτΆΊ'AGACG ACTęATT.GAG 51 ACCAGCTGCA CCACCTGTCG ACCCGAACAA CCTCTCTGAC GCTlGACGTCT 101 CT ^ C ^ CCCTT TGATCTGAAC CTTCGACTGC CTTCCCTGGA GAGCTTCGTA 151 AGTCGGCTGT ATATCATATA TAGTZGT C ^ G ^ A5AT CCATTCTTCG 201 GGTATTGAGG TATTTCCC7A TCATCATACC CCCCTCCTAG GGCCGCACCC TCTCGACATC 251 CAAATTACTT CAAAGGAGGG CACTCGCAAG TACTTCCGGGA CAACCTGACG 301 TTTTATCTCT CTTCCTATCA GCTAACGCTC TT C T ^^^ ^ C ^^ T ACGTAGAGGG 3 51 CGGCCCACTG CCGGCAGCGC ATGCCTCTGC TCCTTATCTCT ACTACCAACC 401 CGTGCCCTCT GGCTTAAG7T TCTAATTTTT ΓC 7 ^ ^r ^^ (^. ^ T ^ A7 ¢ GGAT GGCTACCCAG 451 GGGCTGATTT GAACAATCGG CTCTACTTTC CAGCGCCGGG CAGGAGGGGT 501 CCTGCGGCTG TTGTATTTCC TCTACTTCTT GGAGGTGTCG TACCGCGTTC 551 TACTGGAGCT TTGACATCCG ACATTATTAG GCCCTGCCAG CTCCCTGCCC 601 CACAGTGTCC TTGAC / CGTC TCCTATGCT.T GTGAGAAAGA TCCAGGGCGA 651 TGTGGCAGCG CACCAGGAGA TCCTGTCTGC 7G ^ </ <^ ^r ^ T ACτ _J HH CTGTGCCACC 7 01 CCC ^ T ^ C ^^ T ^ C ^ T ^ I 'CACTGTGCTC CGTTTCTTTC TGGGCATCCC CTGGGCTCCC 751 CTGTGCAGCT CGCCGAGCCA CCGCGTGTAC CTGGCAGGCT GCTTGAGCCA 801 ACTGTAAAC C CAGTCTTTCC TGTACTAAGG GCTCCTGCAG GCCCTGGAAG 851 GGAGTTCCAC GGAGTTGGGT CGCTCCTTCG ACACACTGCA GCTGGACGTC 901 GCCGACTTCG GTACGACCAT CCGGTTGCTC ATGCGATAC TGG

951 CCCTGCCCTG C7C7CCCTTTTT TT (SEQ DD No. (111) pMON13198

ATGGCTCCCT GC ^ TA ^Γ ^ .T ^r ^ TT ^ 'Γ GATAGATGAA ATTATACACC AGATA-TACAC 51 ACCACCTGCAGCTTTGCTGG TGTCGTTTTT CCTCATTCAT GAAGATGTAT 101 CTATCCTGAT GGACCGAAAC ^ T ^ C ^< S GATGCGAAAC ^ T CATGC <AA ^ C <S <S .TGTG.TCC CCTTTTCTTGC

201 TAATCTCCCCT CCATGTCTGC CCTATCCTTT GGCCCCACCC TCTCGATATA 251 CTcClTCATCAT CCATGGCAGGT CATTCGTAAG AATTGCGGGA TTTTTTGTGG 301 TTCTATCTGG C ^ ^r ^ .A ¢ A <C (^ TT <Ξ. ^ CGTTGCGCTA GAACATCAGT ACGTAGAGCG 351 CGGTGGAGGC TCCCCGGGTG CCGCTTCTGC CGGCGGTTGG ATCATGGTCT 401 CTGCTTTCCA GCGCCGGGCA CGAGGGGTCG TGGTTCTTAG CCATCTGTTG 451 AGCTTCCTGG AGGTGTCGTA CGGCCTTTTA CGTCACCCTC CGCAGCCTTC 501 ACCATTGGGC CCTGCCAGCT CGATGCCATA GAATTTAATG CTCAAGTCTC 551 TAGAGCAAGT GAGAAAGATC TTGCGGCATG GCGGTCTGTT CCAGGAGAAG 601 CTGTGTGCCACCTACAAGCT GTGGTAGCTC GTGGTGCTGC TGGTGCTCCC 651 ACACTCTCTG GGCATCCCCT GGCCCGCATT GTGCTTCTGG CACAGcCACC 701 CCCTGCAGCT GGCAGGCTGC TCGACGCTAT TGTACAGCGC CCTTTTCTTG 751 TACCAGGGGC TCCTGCAGGC CTTGGTAGGG ATATCCACTC TGTTGGGTGC 801 CACCTTGGAC ACACTGCACC CCGTCCTTGC CGACTTTCCG TTTACTATTT 851 GGCAGCAGAT GGAAGAATCG GCTTTGCCCT GTGGGCTGCA GGGCAGTCAG

901 GGTCGCATCA CCGCCTTGGG ATAATAA ( _qpQ dd No .: 112)

184 424 pMON32399

ΆTGGAA1CTC AChTATGGG TGTCCGCCAG AACCGCCGCC AAGTCGAGAG

ACCACCTGCA A TCThTAGGA GTTTCGGGCG. GTGCCCACAT A1AACCACT 101 CTATCCGGAG T AGTTTAAGT T CCCCGTGCC DCmCH TGTACTCGTA 151 AGGGCTGTCA CTATC'TTACG GGGTTATGGT GAAGTCCGTA Τΐη !! 201 THICIA TGACACGCA T CChChGTGA TAACCAGrCC GCTCGACATC 251 CHATCAC CTGAAAGCAA TGTTTAAΆAG HICIG 1AAATGACG 301 TTC-TCΓCTGGACCTTCTCCG T ATGGACAGG A1CTCCGAA ACGTAGAG! 3 51 CGGIGAGIC CCCTGAAAC ACCCCACGCG TCTTGG? ACTATCTrCC CTCT 401 CGTCT'CCTCC TACCCAGCAA TCTCGTGAAC TCCCTAGAAT AACTTCTGCT 451 HAGCIC GAAATGGACA TAACTCCAAT TATGTACACC T1AGAGCTT 501 CCIGAGU- ACCACTCTAC TCCCCCCAGT TCTTGCGAAG TCCACACCAT 551 ^<ΓCGGCCCTGC TTAATCCCTC TCCCGCAGGT TCCTGCTCTT (601 ΙΑΙΤΑΟΑσ C1GTGAG1 ATATCTGTGG DCHHA 1GCTCCAGG AGAmil 651 TGCCACCTAC1GCTGTGCC ACCCCCAGAA 11GTGCTG CTCGGACACT 701 CTCTGGGCAT TCCCCCAACT TCTTTCACGT CCTGCCCCAG CCAGGCCCTG 751 CAGCTGGCAG TATGACCCAG CCTCCCCTAT AGCGGCCTAT TCCTCTACCA 801 GGGGCTCCTG TGCAACCGGG 1TAAGCGGC CCCCGAGATG GGTCCCACCT 851 TGGACACACT lAlClAC GACCATGGCT TTGCCACCAC CAGCTGGCAG 901 CAGATGG1G 1CCCAA1GT GAACCCCCAC CTGCAGCCCA CCCAGGGTGC 951 CATGCCGGCC ΤΙΟΑσπΤ AA ĄSSQ ID NO: 11 3) pMON33332

ATGGCTAACT GCTCTAACAT GAlGAmi ATCATCACCC ACCTACCGCA

GCCACCGCTG CCGCTGATGG AdClACA CCTC1TGGT GAAGACCAAG 101 ATATCCTAT GGAC1T1C CTCCCACGTC CA1CCTCGA GGCATTCAAC 151 CGTGCTGTCA AGTCTCCGCA G1TGCAACA GC1TTGAGA GCOTTCTTAA 201 1AA11CTG CCATGTCTGC CCATGGATAC GGCCGCACCC ACGCGACATC 251 CUCATAT COOGGOAGGT GACTGG1TG .AATTCCGTCG TAAACTGACC TTCTATCTGA 3 01 aAOCCTTGGA G1CGCGCAG GCTC1CAGT ACGTAACGGG 351 CGGTGGAGGC TCCCCGGGTG ACCGICGG TCC1TCTCT ACTA111 401 cgtctcctcc GτcτhCGCccAτ 1,100,110 ctccaicot ^ σΐΈΛίο 451 GGTGCCATGC CGGCCTTCGC CTCTGCTChΓC CAGCGCCGGG CAGAmi 501 CCTGGTTGCT AGCCATCTGC AGAGCTTIT GGAGGTGTCG TAICHC 551 TACGCCACCT TGCGCAGCCC TCTGGCCGCT CTGGCGGCTC lAGAm 601 CTGCTCAAGT CTTTAGAGCA AdAGim ATCCAGGGCG ATCHCAl 651 GCTCCAAGAG 1GCTGTGTG CCACCTAd GCTGTGCCAC CCCGAAACAC 701 TGGT1TGCT CGGACACTCT CTGGGCATCC CCTGGGCTCC CCCAGACCCC 751 ΤΟϋΠΑΟ AGGCCCTGCA GCTGGCAGGC TGCTTGAGCC CCCCTCGCGA 801 CGGCCTTTTC CTCTACCAGG GGCTCCTGCA GGCCCTGG1 GAGGCGCCTC 851 CCGAATCAGG TCCCACCTTG GACACACTGC AGCTGGACGT TACTAGCCCC 901 GCCACCACCA TCTGGCAGCA GAlCm CTGGGAATGG CCCCCACTCC 951 ACGACTTCCA CGA (SEQ ID NO: 114) pMo ^ m

ΑTGGCCCCCT GCTCT1CAT GA1GATG.AA ATCATCACCC GCCCACAACA

ICAm CCGCTGCTGG ACTTC1CAA CCTC1T1T AAAACTCACA

184 424

ATATCCTGAT GCA (AACG (A PTCCTTCCAC '((((<:( "((PGGATTC <AAC CGTGCTGTCA CCTCCCTCCA PAACCTTCCC PCTACCCGCG GCATTCTTTGA AJAATCTCCTG PTTTCCTCCT PCCCGACATC CAATCATCAT GΊΊACACCAA PACCCTAACC PA (TCCCACΊ PAAACCTGACC TTCTATCTGA (AAAΊTTGAA PAACCTTTTC PATCΊAATGA PCCAAACAGGG CGGTGGAGGCΊCΊΊCCACΤG ACCTTGCTCT PCΊΊAGGΊCΊ PGTATC (A (CC CGTCGCCTCC GAC (TGAAAGA PCTCTCACAC PCCTTAACCC PTCTACCCAG GGTGCCATGC TTTTCTCCCC PTCTTTCCTC PTCCCTCTTT PAGGAGGGGT CCTGGTTGCT AGCΊTGGTCC PCACTCCCCC PCACTTCTCT PCCCGCGTTC TACGCCACCT TGCΊCAGCΊC PCTCTCCTCG PCCCCCCCTC PTCCCTGCCC CAGAGCTTCC TCCCCTACGC PCCACGCTTA TCCCCGGGCGA TGGCGCAGCG CC ^ G ^ C ^ C ^ C ^ C ^ C ^ C ^ CC ACTTCTCGTT PTCCCACTAC PCGTGCCACC CCGAGGAGCT <3C ^ C? ^ C ^ 7PC ^ C? 0 ^ C PCGCTCTCCC PCGCCACCCC PTGGGCTCCC CTGAGCTCCT GCCCCAGCCA PCCTTTCCTC PTCCCACCCT GCTTGAGCCA AC ^ (CCC ^: PC ^ <3CC GCCTTTTTCC TGΊGCCTAGCGAT ((GCCTCCTAGCGAT (( GCCGACTTTG G (^ (^ (: cTG GAT CΊGACTCAC.C ΑΑΆΑ ((Α3 (ΑΑ TGGGTACTGGC CCCTCCCCTCCAGACCTTGAT TA. (SEE, D No .: U5)

1114

ATGGCTAACT GCTCTTGCCAT ΡΑΟΆΤΑ-ΟΆΤΑν AACATCACCC ACCTGAAGCA GCCACCGCTGCCCCTGCTGG ACCACTACTAc CCTCCACTGGT GCAACACCAAG ΑΤΑΤΡΡΤΟΑΤΟΤΤΑΑΑΑΆΑΑ: CTCCCCCCAC CTAAKCCTCGA GGCATTCAAC CGTGCTGTCAAGTCTCTGCA GAAGTCTGTA GCCACTTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCCTCCCTC GGCCGCACCC ACGCGACATC CAATCATCAT CCGTGACGGT ΟΑΑΊΆΤΑΑΑΌ PCCI? TCCGTCG TTAAACTGACC TTCTATCTGACAGCCCTTGGA GCACTCCCTC GCTCCACCAGT ACGTAGAGGG CGC ^ t ^ iT ^ i ^ and ^ C ^ CC TCCCCGGGTG PAACTGCTAT TCCTACTCTCT ACTATCAACC CGTCTCCTCC <CTC ^ <^^ JAA <CJC? A TCTCTCAAAT CTCCCACATAT GGCTACCCAG GGTGCCATGC CGGCCTTCGC CTCCCCCTAC CAGCGCCGGG CAGGAGGGGT CCTGGTTGCT AGCTATCTGC ΑΑΑΑΤΤΊΆΤΤ GGAGGTGTCG TACCGCGTTC TACGCCACCT TGCGCAGCCC TCTCA; CCAGC CTGGCGGCTC TCAGAGCTTC CTGCTCAAGT CTTTAGAGCA AAATAGCGAG ATCCAGGGCG ATGGCGCAGC GCTCCAGGAGCAA3CTGTGTG CCACCCACTAA GATGTGCCAC CCCGAGGAGC TGGTGCTGCTCGGACACTCT ΑΊΌΑΑΤΊΑΆΊ CCTGGGCTCC CCTGAGCTCT TGC ^ C ^^. CGCC <^ <3G <T (^ <^ C ^ <^ <C ^ GCTTT ^ TGGC TGCTTGAGCC -AACirCATAG CC-GCCTTTTC CTCTACCAGG σΤΑΊΆΊΊΆΤΑ GGCCCTGGJAC GGGATATTCT -CCGAGTTGGG TCCCACCTTG TCTGCTC AGCTGGACGT CGCCGACTCC GCCACCACCATCTGGCAGCA GCG3AcaCCAa (CTGGGCGATGG CCCCTGCCCT CTACTTCTAA TAG (SEQ ID No.: 116)

1115

ΟΤΊΆΊΆΑΑΑΑΤ GAGTCAGCAA PGCATCACCC ACCTGAAGCA GCCACCGCTG CTCATGCTGG AACCGT (ATA GJAACACCAAG

ATATCCTAAT GCAAAAAAA: PΊCCΊAGΊAC CTAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA ^Gaag, CCTGCT GCCACTTGAGA GCATTCTTAA TAAATCTCCTG CΊTGCACTGC PΊ (CAC (CTC, (^ (^ (^ (^ (^ (^ (^ (^ (: ACGCGACATC CrAATCCATAT CTACAACGGT GACΊCAAAGT TTAA-N-t ^ and ^^ l ^ and ^ C

TTCTATCTGA, ((^ (^ (: (^ (1 (3 (^ ((GAGCCCTCAG PCTCΊA (CAGT ACGTAGAACGG

184 424

51 CGTTGGAGGC TCCCCTGGTT CCTτTCTGTT GCTCCGCTTC ACTATCAACC 001 CGTTGCCTCC GTCTAAA.CCCA TTGCCCCCAc ccτcCccTCC GGCTACCCAG 051 GGTTCGATGCCCTTCTGCTT CGCGTTCTCT TATTGTTGTT CAGCGAGGGGT 501 CCTGGTTGCTACTCACGC GT :( ATCGCCCCTC TGCTGTTCCT TACCGCGTTC 551 TATGCCACCT TCTCGACCCC ATCTTCCGTT TTTTTTTTCT CTCCCTGCCC 601 CACAGCTTCC TCTTCTCATC TGGCTCTTCC TGTCTCACTA GCCAGGGCGA 651 TGTGGCAGCGCCCCAAGAGA CGTCTTTGGT TATTTATCCT CTGTGCCACC 701 CCTAGGAGCTGTTCTTTGTC GTCCCTTCCT GTTGCAGTTT CTGGGCTCCC 751 GCCCCACCCA GTCCTTGCCT TGTTCATTCT GCTTGAGTTC 801 ACTCCATAGCGTGCTTGG [ 'CC CCTCCCCGTT TTTTCGGCCT GCCCTGTCAG 851 GGATATCCCC CGACTGGGGT CTCCCTGTTT ACCCCTGGTA GCTGGACGCT 901 GCCGACTTTG CCACCTCCCAT CGGTCCGCCT AGTGCCTCCT TGGGAATTTT 951 CCCTGCCCTG CACCCCTGCCT AA (SEQ ID Nh: 117) pMON28505

TTCCCTCTTTCGCCCCTTCCTTAGGCCCTGCCCTCGTCCGGCCATCTCTCATTCGCCCτT CCGCTTTACCTGAATAACTCCAAGTATTCAGC.CTGCCCCAGTTTTACTTCTTTCCACCCC TTCCGTTCACACCTTTCGCTCTGCGGCCGTGCTTCTCCGAATGTATCCCC.CTCCGCCTTC CCCTCTTCCATGTTGCGCCCTCTCCCCTTCGTGTTGTTCTCCGCTCTTTTTTTCCCCCTT CTATAGTTCCGTCTCAGTCCTGTCTTGTATGTTCACGCCGGTTTTTCCCCCCTGCTTGTC CATTTTTTTCTTCCGGCTTAATTTTCGTACCCC.CCTCCCTGATCGGGCTTTTTCGGTGTT CTGTGTTCCTTTGTGTTGCCCAGTGCGATGAGTCCTCTTGTGTTGTTGTCCCCCGACGCC TACCCCGCGCCCCCTATTTCGGGTCATTCGGTGTCTCTACCTTTTCTTCCTTTTTTTTTT TCCCTTCTCGGGGTCTCATTGCACCCCCCTATGTCTTCGCTCCCGTTCCCGTCTCGCCTT TTCTTCGTTATTCTTTTTTCTGCTTTAGGTCTTTCCGTACGTTGATACCCGGGCCTTCTC TTTTTCGCCTTCCTCTGGTTTCCTTGGTCGTTACATTCTCTTCGTCCTTCCTTTGCTTCT TCTCTTTTTCGGTTCACTCCGCTTCTTCCACATTTCCTGATCCCATCGTCTCCTGATCTT CCCTTCATTGTTCTTAGCCCTCACTCCCTTTTCTGCTTCAAGGGGTTTCTCTCTATTTTC TCCGTCGGTTTCCCCCGTCTCGGCATTGCCTTCGTCTTTCACCGGTCTGCTTCTGTCCTG TTTGTGCGTGACTTCTGATCTCTCCTTCCCCGTCTTTTTTACTTTTCTTTCTCCCCCCτT CTCCTGATTCCGTTCCTC (SEQ ID Nh: 118) pMON28506

GTGCACGGTGTGATCCGTCTTGAGTACAGGCGACAGCATTGCCCTCGCCTCTCGGTCTCC CCTCTGGCTCTTCCTCCTCCCCATGACTCCGCCTGTTTTCGCCTTC.TGGACTTCCCCTTC CTCTTTTTACCTCGGTCTATCCGCGTCCTTTCGTGCCCGCCCGGCGAACCGTTATCAGTT CTTGCGGCACGGCTTTGGACGCGTCCACTACGTTTTCTTTTTTCTACTTTCTTCTTTCCT CGCTCGTTCCGTCGTCGCACTTTATTGGATGGGCCCG.CCTGTTTGTCCCCCTTTCTGGTC GCTCTTGGGATTTTGTCGTCCGTTCCTGCCTACCCTGCTGGATCTTTCGGGTTAGGTGTC TCTTTTTCACTGGCTTTTTTCATTTTCCTTCGTCCCTTGCCTCCTTCTTCTACCTACGTC CCTCCAGTGCTAACTCGGGGTTTGATCCTGTGCCCGTTTCTGTTGTGTGCCCGGCGCTGT TTCTCATTGCA.CCCTCAGCTGTCTGCTCCTCAGGTATCGTACCGGTGTTTCTCCTGTCCC CGTCTGCGTTATTGCTGTCGTTCCGTCTTTTTCCCCCTTTTATTCCTGGGCTGTTTAGCT TGCCTGGTTCAGCGGGCGTTCCATGGTCGGTGCCGTCTGTTTTTTTGGCCGCGTTGCTTG GTCCCCCCGTGGTCTTCCCCGTTTCGTCTTATCTTGTCCCCTTCGCCCCCTTTTCGTGGT TTTCTCCTCCCCTCTCGTTCTTGCTTCCATGTTCTGCTTTTGAGTTGTTTCTTCGTTCτC CTTCTTGTTTGCCGGTCAGTCTTTGTCCCCAGTTCTCCGTTTTTGCCTCCTGCGGGGGAC TCCCGAGTTTGCAGGCACTTGTGGTTTGCTGTTCCGTGTTGGTCTCTCCGACTGATCTCG CTTCCCTAGGGTTCTCCC (SEQ ID NO: 119)

184 424 pMON28507

1GTGAGG1GTGGGGGAG1GTGCGGCAAGC? TGTGGGTGGGTTAGA1G1GGGGGGGCGGGGT TG1GTCCGGGG1GAGGACGTGGAG1GG1GG1AG1CGGGTGTGCT1GG1CGGGCCAAGGGT G1GCG-GGCGGAGCT11AGG1GGTG ((TGA111GG1TGAA1GACTTACCGGAGCGGTGG11G GGTCGCCGAGGGGGGGlGGAGGGGGGAGCATlTGTCGGGCGGCGGGGlCGGCGGGGGTCG ClGGGTGGGAGGATCAGCCAGlGGllTGGCG (ΠGGAGCGTTCCllCCGGGAGTlGGCGTC TGTGGCCTGGGGGTGlGlCGACGlGGllGAGCGGGlTAGlTGlGllCGllTCCGllGTGC GCG11T1AGCC1GCG11TCGAGT'GGGTAGTATGCGGCC1TCGCCTGC1GGGCGA1GATCG CGGAGG.TGGGGAAAGATGlGCGTCGGlGGTlGGCCllAGCGTG (CCGTCllGCGAGCCGGG GGCGG1AGCCA11G1GCGCGCC1GGGG11GGGGGGC11CAC (GA1T1GGGGTGGTCGT1CG1 11G1T1GT11GA1CGG1GG1AGCAGT111ACGCACGTGGGGCTGATGCCGGCG ((CCGGA1 CGGGGC · llAGGllTCGCGCTCGGGGGTlllCCGGGCGGCGCGCGCGGTlCCGGGGGlGTT ^{CCTGGG.GG111CA1GACGAGGCGGGGCGGG1AGGCCGGG,} 1GCAGCTTGGT1G1CTGGGGA CGCCT1GTGG1A11GGGG1G1GCTTTCCTGATGGGTGGA1GGGG1TGGGCGGTGTCC1GC G11CGAGTGC1C11GGA.CGG1CG1GGTGGG1GGGGCGGT1GTT1GCGGGTGG1GCTGGTG GCTGGGGTlGGCGlTlACTGGGGTlCCGTGGACGCGGC; GGGCGCGGGCGlGGGGCGlcGG GGCGGCTGlGCGGGACCT (SEQ ID Ne : 220) pMON28508

1GTGGGTCGGCTGGGAT1AGGCGTCCGGTT? GTAGGTGAGTGGGA1G1GGGGGGTCGGGGT ^{GTCGTCCGGGC1GACGACCTCAGT,} 1GC1AG1GG1GGTGTGTGGT1GT11GGGCGAGGGGG GCAGTGGGGAGGGT11G1G1GGCG1CGA1G1CTCGGGACCA.GTTA1GAGGT1GGGGG1CG GGG1GC1GGGTTGGGC1GAATGGGGCA.GGGG1GGG1GCGGGTCGGGGC1GGCGGGGGGGG ClACGTGGGATCAGCATGCGC3lGGllGlGCTGGGGAGGAGGCGCGGAAGGACGlGGCGGC TGGGGC-CTGAGGCGTlGlCCGCGlGGlCGGC: CGGGlGGGCTGlGGCCGllGCCGlCGTGG CGllCTlAGCGlGGGGlTCGGATGTGGACGAGCCGGGGlCGGGCTGGCTGGGGACGATGT GAGAGGGGGGGGAGCGGllGGlCCCGCGGGAlCTGlllGCGGTCCGAAAGGGGlGGlCGl 1ACGGGAGC1GAGA11GCAGTGGC1CG1CA1G1GGCCGGGT1GT11GCCCGCTCGG11GG 1GGGC111GGGAGT111AGCGGGTG1CCGGGCAGGGCGGGT1111GG1CGGGGGC1GGGC 1TGGCGGGGCTCGGG111 ((CGGTCGGGA1CCTCGTTG1GAGGGGCGGGCGGGGGGGCCCG AC1GCGGGG1GTGAGGAG1AGGGGGAT1CGATCGTGCGCGCGGTGGAGGGGGT1GGGGCG G1GGA1CT1C1GGGCGG1AGCGTTCCA11G1G1GGGAGGGTGG1GCTGA11CCA.TGGC1G 11GAGGGTCCG1TGTCCG1CTGGCCGGCGGG1T1GGCGGGCG1TGGGGGCTAAAGG1GTT G1G1GGTGGCAG1TGCTCCAGG1GACACG1A1CCGCGC (GGGG1G1CGTGGGGGTCG1GGG AGACGTlTGGTlGGlCGT (SEQ ID Ne: 141) pMON28509 lGGGGGTlGTGTGGAATGAGGlGTCGA AGTGGAGGGGAGTGAGGCGCGGGGGGGlGGGGT

GT1GT1CGGGG1AAGGACGTGGATCGC1AG1AGCTCG.CGGTGGGCGTC1GGGCGGAGGGT

CCGGTTGGAGGCGTllGGG ((GGTGlGGGCllGTlGGGGCGAGTGGCGCAAT'CGGTGGCCT

GTT1GC1GGGTTGGGC1GGGGGTGGGAGGGG1GGCCCCGCGG1GGGG11GGCGGGGGTGT

GCAGGTGGAGTCGGGATCCAlCGGlCGlGGTllGGGCCAT'TGClllGCGAGGTCGGCTTG

GATGGCcGGGGGCTGlGGGGACGCGGlCGGGAGGGCTGGCTGlGCCCGCCTClGllGTGG

CGCClCCGAGGCTCGlCGCCGGGGGGGGGGGGCCGCCClCGGGGGGGCTGCGGAlGATGG

CGGGAGGGTGGGAACATG1AGGTTG1GGT111A1GGTΊCCGAGGGGGCGTCCG1CGCGCG

AG11GGGGC1GGGGGGT11CG1GGCGCGCGCTGGGCGG11G111G1G1GGC1GG1GGGCC

GCGCAGGTCC1GGCCACGG1GGTGGGGTGCCTCGGCG1CGA1GTGTGG11GGGC1GGC1T

GTGGTGGTTllCCCCGTlCGlGCGGGCCGTCCGGGGGGlGGGGGTGGGGACClGAClGGG

184 424

AGAGGCAACCTAGGATCCCATTGCCATCTTCCTGAGCTTCC7TACACCTGCTGGGACGAAAG GTGTGCCCCCTGATGAΓTGTAGGAGGGTCCACCCTCTGCGTCAGGGAATTCGGTGGGAAA ATCGGCTGTCCCGCTCCGCC'TGCTTGCGACCTCCGAGTCCTCΆGTAΆACTCGTTGCCAAC TCGCACGCCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTAGACCT CTGCCGACGACTGTTCTG (SEQ DD NO: 122) pMON28510

GCTTAGCGCTCTATAATGATCGATGATATTATACATCAC7CΓTTTAGAGAAAATTTGCAAAT TTCGCGGTeCCGAAC.ATCCTCCTATGACG7AT3ACGTCTCTATCCTGΆTGGATGGAAACTTT AGAATTCCCAAC7CTGGAGAGCTTCGTAAGGGCTGTCCTA: 77AC: CTTAGAAAATAAATTAAGT ATTCTGGCCTATTCTTA3TAATCTC: CAACCATGTCT (G: CC7? CTGCCACGAACGCAGGCTCT GGAGTCAAAATCA'TCΆTCAAGGCAGGTGACTGGCCTTG7ATΓTCCGGGATΆAACTGAAGTTC TATTCGCCACCCTTGTGCAAGCGCAGGAACAACAGTACGTAGAGGGCGGTGGAGGCTATT GCCCGTTCCGTCTGGTCCCTTTCTCTACTATC7TACCCGTCTCCTCCGTCTAAAGAATGTCA TAAAATACCTAACATGGGAGATTGGAAATCCCAGAT (GGΆGGAGACCAAGGCACAGCAAATT GTCCTGCAGTGACCCCCFCTGCTGGAGGGAGTGATGCG7AGCΆCGGGGACAATTGGCAACCA CTTCACACCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCTCCTTTTTGGGGGCGT CAACGAACCCTTGGAACCCAGCTTCCTCCACAGGGAT: 7GACCACAGCTTACAAGGACCCT AATGGATGTTCCTGAGCTTCCAACACCTGCTCCGAGG7ATT3GTGCGTTTTATGATGCTTG TAGGGCGCGCACCCTCTGGGTCAGGGATTTCGGCGGCCTTCATGGCGTTTAATAATTGGTT TGGCGCG.TCCTCCGAGTCCTCAGTAΆACTGCTTCG'T7ACTCCCATGTCCTTCACACGAGA TTCAGGAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTCCTGCTGTCTGTTGTAGAAT CTAGCTG (SEQ DD NO: 123) pMON28511

^{GGCATATGCTCTATAATGATCGATGAAAΓTATACA,} rcACTTA (AA7AGACCACTTGGTCTT TTACCCCACCCGAACCTTCCTCCTATGACG7TTGACGTCAΓCTATCCTGATGAAATGAAACATT CGAGCCACAAACCTGGAGΆGCTTCGTAAGGGCTGTCCAT37AA7TTAGAAAATGCACGAGGT ATTCACGCAAΓTCTTCGTAATCTCCAACCΆTGTCT (G7CCTCTGCCACGGATGTATAGTTT GCAGATAGCTTTCATCATCCTAGGCAGGTGACTGGCCT.A: 77ATFTCCGGGAATAACTGAGCTTT CACACGGTTACCCTT (ATGCCTAGCGCAGGAACCTTCA (GΓACGTAGAGGGTAGTGGAGCGTTC CTGGGTG.ATCCGTCTGGTCCCTTTCTCTACTATC7TTCCCGTCTCCTCCGTTTAAACAATCT TACAATCCTCC7AATGATGGGACCCACTTGCCTCTCATCCCTCCTGGGGCAGTTTTGCGGA CACCCGGGTGTCCTCCTTGGGGCCCTGCAGAGCCTCCTTGG7AA7CCAGATTCTTGGACAC GGGAGGTCCACAGCTCACCTAGGATCCC.AAΓGCCATCTTCCTGAGCTTCTAATATCTGTTC TGACGAAAGGTGCG'TTFCCTGATGCTTGTAGGAGG (GΓCCACCCTCTGCGTTAGGGAATTC ^{CGCGGCTACATGGCCGΓCTCCCGCTCCGCCTGCTTG,} T7ACCTCCGAGTCCTTACTAAACTG GTTAGTGACTCCCATGTCCTTCACAGCAGACTGAGCCAGTGCCCAGAGGTTCATGGTTTC CCTAAACCTGTCCT <A ^/, ΓGCCTGCTGTGGACTTTΆGCA TGG GAG7ATTGGAAAAGCGACATC GAGCTGACC7AT; 7GCACAGGACATTCTGGGAGCAGT (AT : CCTTCTGeTGGAGGGACTGATG GAACCAGGCGGATATCTA (SEQ DD No .: 124) pMON2 8512

GTTAACTGCTCTAT7TTTGATCGATG.AAATTATACA ^, rcACTTTATTGAGACAATCTGCATAT

TTACTGGACCCGAACJATCCTCAATGACG7TTGACGT (GΓCTATCCTGATGGAAAAAAAAATT

TAAGTTCC7ATTCCTGGAGAGCTTCGTAAGGGCTGTC / AA77AτGTTAGA_AATTATATCAGGT

ATTGAGGC7TATTCTTCGT2ATTCTCC7TTCCATGTCT <A: CCTCTGCCACGGAAATATTCTAT

AAACATCCCTTTCAT <ACTCAAGGCAGGTGACTGGCAAG7ACCΓCCGGGAAAAAATAATATTT

TACGTCGCCACCTTTAAATTAATGTAG-GAATGACATGTTAGTCAGGGCGGTAGAGGTTTC

184 424

CCTCTCTGGΓCCTCTCCTCCAATCTCTACTGTCΓGSCCCGTCTCCTCCGTCTGAGTGGCCT CGCGGGTCCΓCGGGCGTCCGAACCCAGCTTCCTCCACAGGGCACCACCGCGTCTCGCGGT CGCCCCGGCTCCGTCCCCCTGAGCTTCCCAACACCTGCTCCGAGTAGGGTTTCTTTTCCTT S / CCCTTCCS_CTGTTCCΓCGCCCTCTGCGTCΆGGGTGsTTCGGCGTCGGCGTTCCCTCTCCC TCTCCTCCTCCCTTTCGCCTCCGAGTCCTCAGT.?AA\CTGCTTCGTGACTCCCGTTTCCTT CGCGTCGTGCTTGTCCGCTGCCCAGGS3GTTCACCCTTTGCCTACACCTTTCCTTGTTCCC TCTTTTTGCTGTGTCTTTTTAGAAT (TcGSGCCCAGATGGAGGGGGCGGGGTCGGGGTGC GCTCTTCTGCCACTCACCCTTCTGCTGGAG (G3AGTGATGGCAGCACGGGTGCGGGTTTTG CCCGCTTTCCTCTCGCCCCTCCTGGGGCAGCTTTCTGGACAGGTCCCTCTCCTCGGTCCT CΓCCCCCGTGTΓCTCCCT (SEQ ID NO: 125) pMON28513

TΓTGGΓCTCCCCGTGGCCATCGATG7GGGTTATACATCACTTAAACAGACCGCCTTCGCCC TCTCTCCGCCCTGGCGSCCTCAATGACGίGG3ACGTCTCTATCCTTATGTGCCTGGGCCGT CTGCTTCGAGGCCTTTAGAGC TTCG TAAGGCGCC (3 TCAAGAACTTAGAAGGTTCGCCGTTT GCTTGTCCGGTCCCCCCTAATCTCCAGCCATGTCTGCCCTCTGCCACGTCCTCGGCCTCT cGGCGCCCGGTCGCCGTCAAGGCAGGTGACTGGCΓGG-AATTCCGGGAGGGGCTCGCTTTC TGTCTTTGTGCCGTTTGGCAAGCGCAG <cGGGGG: AGTACGTAGGGGGCTTGTGGGTCTCC CΓTTTTTGGCCTTCTGC-TCCAATCTCTACTATCΓGA :: CCGTCTCCTCCGTCGGGGGGGTCT CGTAGGTGCCΓGGGCGTGTGCAGGACCACAGCTCACCAG3GATCCCAGTTCCGTCTTCCTC GτCTTCCGGCGCGCCCTCCGAGGAGA3GTGCGTTTCCTGATGCTTGTGTTGTTCGCCGCC CCGTTCTGCGCTTGGTGCTGCGGCAACATGGCGTCTCCCGCTCCTCCGTGTTTGTGCCTC CTGTTCCTΓGTTGGGCTCCTTCGTGACTCCCATGTCCTTCACATCAGGCTTGTCGGTTTC CCGTGTTTCCACCCTTTGCCTACACCTGTCCTGCTGCCTGCTGTGGACTTTGCCGTTTCG CGGGTGGGGGCCCGTGTGCAGGAGACCCGG3GCACAGGACATTCTGGGATCGTTTGCGCTT CCCCTCTGTCTGTTTGTCCCΆGCACGGGGACAACTGGGACCCACCTCCCTCCCGTCCCTC ΓCCCCCCGCCTTTCTGGACAGGTCCGTCTCCTCCTTGGGGCCCTGCAGATCCTCGTTTTG GΓCCGCGTTCCTCCGCGC (SEQ ID NO: 126) pMONl8524

CCTGGCTTCTCTGTGGTGATCGΆTGGCGSCΓATACGTCACTTGAAGAGGCCGCCTGGGCCC TCCCTGTGCCCGAGCAACCTCAATGACG7GGCACGTCTCTΆTCCTCATGTGGCTGGG.CCTC CTGCCCCCGGGCCTGGAGAGCTTCGT.?GGGGCTGTCCGGGGGΓTTAGAAGGTTCGGCGCCT GCTTGCTCGGTTCTTCGTAATCTCCCGGCCATGT <CΓGCCCTCTGCCACGTGGGCGCCCTCT CTGCGCCCGGCCGTCATCΆAGGCAGGTGACTGGCΓGG-GATTCCGGGAΆAGGCTTACTTCC TGTCGCCTTGΓCcTCGAGCAAGCGCAGG-GS2.? GACAGTACGTAGAGTGCGGTTTGGTCTCC CCCTcTTGGΓCGTCTGGTCCΆATCTCTACTATCCGCCCGTCTCCTCCGTCTGAGTGACCT cGTGGGTCTΓΓAAGCATGGCTCACCAGGGATCCC: GTGCCATCTTCCTGGTCTTCGGGCGΓ CTCCTCCTGTTAGGGGTGCGTTTCCTGATGCTTGTAGGAGGGTCCACCCTCTCCTTCGCT CGGTTCTTCTGCAACATGGCGTCTCCCGCTCCGCCTGCTTGTGACCTCCGGTTCCTCGCC GGGCTTGGTCCTTAΓTCCCATGTCCTTCACAGCAGACTGAGCCATTGCCCGTGTTTTCGC CCTTTCGCCGΓACCTGTCCTGCTGCCTGCTGTGGACTTTAGCTTGGGATGGTCTGGGGCC ΓGTGTGGAGGAGACCGAGGCACAGGACATTCTGGTAGCAGTGACCCTTCTTCTTTGTTCG TCCGTTGCGCCACGGGGACCGG: TGGGACCCACTTGCCTCTCATCCCTCCTCTTTCGTCCT TCTTTGCGTCTCCGTCTCCTCCTTG (G3GCCCTGCAGAGCCTCCTTGGAACCCGTGGGCCT ΓΓGCGCTTCGCCGcCGΓG (SEQ ID NO: 127) pMON28515

184 424

ACCACCTGCTCTATATTGATCGATGCCGCTTATACACCCTCTGCGACACTCCTCCACCTTC CCACC1GACCCGACCACCCCCAΆTGACGAAAGCACCCCCCCCCCACCAACCCAATA.TTCC TACCCTCCACCCCTGGAGAGC ^ ChCGThATcGGCTGTCGGACCTCCGAGAAGCACCCTCAAC CCCACAGCAATTCCCCACGCTCTCCAACCGCACTCATCTCTCATCCTAACCATCCCCCTC CAGCCTCCTTCTCATCATCAAGGCAGGTGACTGGCCAAGCTCCCAAAGCGCGCGACCACCT CCCCCGGTTACCCTTGAGC.CCGCGCAGGCCCCAATGACGTACCACAAACAACAACAGCCTT TTAAATGAACCGTCTGGTCCTTTTCTCTACTATCAATCCACTCTCCTCACCCAATATGCTC TGCCAATCTCCAAACΆCGAATCCCAATGCCGCCCCCCCACACCCCT-TCTGTTCACCTCAC AAAAAAGTGCGTTTCCTGATGCTTGTΆGGAGGGTCTCCTTCCCACACTGAAACGCCCAAT

AA.CGCCTTCACCGCCCCCCATCTTACTCATCCACACCTCCGAGTCCTCAACACACCACCC CACACTTCCCATGTCCCCTACAGCAGACCAGACCGACATTTCAGAACCCGCTTCCCACTC CTATTCGTCCTGCTGCTTATTATAGACTCCGACCCAAACACGCAAGCACTCTAAGCAACA AGAGTTATGGCACAGGGCACTCTGGGAGCAGCAGTCCCCTCACCAACAAAGACAGTAGTC ACCCAAGGACAACTGGACTTCACTTGCCTCCCGCCCCCTTCAAAACAATCCCTCAACCCA ACTCATCTCCTCCTTGGGGCCCTGCAGAGCCTCCTCAACCTCCGATCCCCCTTCTCAAAT CAACTTCTCACCCCCAAA (SEQ ID NO: 12 8) pMONl8516

ATCACTTGCTCTGCAACACCCAATAAAACCGCGCGCCCTCCGAAACACCTGCCCATCTTC CCATCAGACCCGΆCCAΆCCCCACTGACGGGAGCACCCCTCCTCCACCAAACTAAAACGCC CAGCGCCTAAACCCAGGACACCCCATGGGAGTCACCAAACCCCCGACCGGCACCCCGAAC GCCACAACAATTCTTTACGGTCCCCACCTACACCCATCCCCCACCGCAACTACGCTCTTC CGGTGCCCAATCATCATCAΆGGCAG <GhGACTGATCAGTACCCCAAACCGCGTCACCACCT CGCCCAACCATCCTCCACACCCATAGCAAmCAGTACGTAGAGGGCAACAAGAACCTT CCAAACAACCCGCTTAACTCGGCTCCCGCCGCCGGCCCACTCCTCCTACCCGAAACCG'TC TGCCCATCTCCAAACACAACCATCCCCCCAGATCCCCCGCCTCCACCTCAGAACAAAACA CACCCTCTGATGCCTGCGAAGAAACCCGCTGCCCGTACCGAGACGCCCAACAACGGCGCA ATACTCCCCGCTCCGCCCATTTATAACCCCCACACCCCCCACCACCCACCCCACACTCTT TGCACTCTTCACAGCAAATCAGACCAATACCCCAGAACCTCTCCCCCACCCCCGCTCACT TCACCACCTGCTGTGGΆCCCTGACCTAAAAAACCAACGACCTCCAGCAAGAAGAGTTCCA ATCTC1AACATTCTAGAAACAATGACCCTTCCACCAAGAAACACACCAACGATGCAAAAA TAATCAGGACCCACTTGCCTCCCATCCCCCCCAAAACCACCCCCCAACCCAACCCGCCCT CCCCTCGGGGCCCTGCAAGAC <ChCCTTGGAGTCTAGCCCCCCCCGCGGAACGAAGCCGCC ACCCCTCGAAACTTTACC (SEQ ID NO: 129) pMONl8519

ATCGCTTGCTCTATAΆTACCCGATGAACTTACCCACCGCCCAGAAGACCCGTCCACGCTC

CCATCAAACCCGAACAACCCCAATGACGAAAGCACCCCCCCTTCAGCAAGCTAAAA.CCCC

CAGCCCCCAAACCTGGΆGGACTTCGTAAGGACCACTGGAAGTCCGACGGGCACGCTCAAC

CCCACAGCAΆTTCT'CCGTAΆTCTCCAACCACACTCACCCCTCACCCTAACCACGCCCCTC

CAGCCCCCAATCATCATCACAGCAAGTAACCGAGCAGCGCCCCAAAGCCCACTGGCACCT

CCCTCAATTACCCTTAAACGCACGCAAAAACATTAACGTACCAGAAACAACAAGAACTTT

CTAAACAAACCGTCTGGCCCAGTCTCTACTACTGGTCCACTCTTCCTACCCAGGACCCTC

CGCCTCTCTCCAAACATAAAGGTTCACCCTCCATGCGTGCTCACCCCACCACCCGCCACA

ACCCCCAGCTTGGGAGAACAAAGCACCCAGGCAAGAAGACTTACAACCCAGAACCCCTCA

AAGATTGTGACCCTTCTGCCAAAGGGAGTGACAACGACCTAAAACCGCTCGAAGCCCCTC

CACTCTTCATCCCTCCTGGGGCAGCTTTCTGACCGAACCCACTCTCCTCCCAAAACTCCA

CGAGATCTCCTTGGAACCCAGCTTCCTCCACGAAGTGAACCCCTGACCCCGCAAAGCCTT

CACATTATCTTCCTGAGCCTCCAACACCTGCCTCAGAACATAACATACCCCCCACCATCC

ACGAAAGGGTCCACCCTCCACACCAGGGAACCTAAGATCACAATACTCCCCATCCCATTC

184 424

1CTGCGCGCCGTCCGCTCTGCG1TGGGTT1TGGT1G1GCTTTTGT1GCTTGCGCG1CG1G

TTlGlCCGCTCCCCG (SEQ II No.: 130 pMON28520

1CTGGCT1TGCGGGGAG1GGT1GG1GGGGTGTGCGGCGCGTGGA1GCGCCGCCTGCGTCG GGCTTCGGCCTCGGAGGTTTCGGGlGTlAGGGClTCGTGGGTTClGGCCGCCCGGGCTTC TCGCTGCCAGGCCG1CG1G1CGTT1CAG11CCT1GCGG1GGTGCG1AGGGTCCGTTG11C GTTCGllTGGTTTGGClTGGGTGTTAGCTGGlGCTCCCCGCGlTCGCCCCCCCGCTCGTC TCGCGTCCGGGTGGCGGCGG.G1CGC1G1GCGCCTGACGGTTTT1C1GGGGGCTGGC1GGT GGTCTCCTTGCTTGTGGCTGGCC1TG11GGTGGAGCGGC1GG1GC1CCCGGCCG11TCTT CTCClGCGGCCCGTGGCGTCGGGCTCTGCGATTGGTCTCTCTCCGCCCGTTSGACGGTTG TGTGGGGTTCCGGGTGGlGGGCCGGTGTTTCGCTGGCGCCTTlTGlTCCACTGGGlCGGl CCGGAGGCCGGGGCCcGCGGGGGlCGcGTCGGClCGCACCGTGTGCGCGCGGCGGTGGTT TTGTTCCTC1GCCCGCT1GT11CG1TGC1CG1GTGGCG111GTTTGCGT1CCGCGCGCTT TGCCGCC1CTG1TGGGTG1CGCG1GGTT1TCGCTGCCGG1C11TCTGCCACGCCCGTTCG 11AGTTTGCTGGCCTCTGCGGC1TG11GTCGCG1CGCGCGG11GTCCTGGGCCCGTTCCT TGCA1CGTTCGGTGCCG1CGCC1G11GAGCCGCTCGTGTCTCGC1CGTCGGCGGG11GTT GTCCTCTlclTTGCCCAGTTCClTAGCGGCCCCCTTCTTlCTTTCTCGCCGGCGCGTTCT CCGCTCCGCGCTGGG.TTCTGCCCTCGCGCTTGGlGCCGTCGCGlCGCGCGGGGCCGCGGT TTGGGClTTTGTCCT (SEQ II NO: 131) pMON28521

CTGGGCTCCTCGGTGGGCGTClGTlGGGGTGTGTGTCGTTGGAGCGCGCTGCCGCCGTTG GGGTGGCGCCCCGGCAGCCGCSGTCGCCGGGGClTCGTGGGCTTCGGCCGTTGGGACCGT TlGCTGTCGGGTCGCCGCGCCGTTlGGGCCCCGlGTGACGGTGCGlGGGATGTGTCGllG GTGGGCCCGGTCCGGClTGATCTTTAGTTGGCGTGlTCTGTGCTTGCCCTCCCGCTTGTG CCGCGGCCGGGCGGCGGCGGGGCGCCTCGCGCCCGGCAGGTCCCCCGAGGATGGGCGTCC TGGCGC1GTGCTCGGCGCTGGCC1CGC1GGCGGTG1GGCCGG1GCC1TCCGGGGGGCTTT TTGClGCGGTClGCGClTTCGATTGTGGTGGTCAGCCClGTGTTGTCCGCGGGGCGGGAG TGGGGGGTGCTGGGCGTC1GCCT1TG1TTTCCG1TCCGCGGTG1TGTCCCGCGGGC1GGG GTCCGCGT11G1CGCGCCAGCCCGTG1GGCAGGTT1CCGCTG1GCGCCCTGCGCCT11G1 clGCTCGGllCGCCACCllCGTGGTTlllGCCTGCGGCCCCCGTGTCCCGCCGGGllTGl TTGGCGCCGCGlC ^r lCClTCGCCTTCTGlClCCTTTCTGlGlTTGCCGGCCGGCTCGlCGC CTGCCGCGCClTGCCGCCGCGlTTCGTGGllGGTCCGGGlTTGCCTTCCGCGCCGGTTGG TGTCGCCGTCCGCCGGG1CGGTCTTTTTG1GGCTGGCTGC1G111TCCGCCCGCT1CGCT GlcCGGGGTClTGGTGGCCCCGCGTτTlTGCCCTCTCCGTlTlGCTGCcCGCGCTGTGlG GAGCGlTTTTCGGGTGCCCGGCGTTTGTGCGCCGCGTGCGlTTGCGCCCCGCGGGGTTGT TTGGTCTCGGTACCG (SEQ II NO: 132) pMON28522

1TGGGCGCTGTTGTGGT1GGCGGT1GGAGTGGGCGGCGTTGAGG1GCGCTGTCGCCGCTC

TT1CGC1GTCT1GGCGGCTGTGGT1GT1GGCGT1GCGCGGGCTC1GT1CGCCCGGGTAGC

TlGCGTTTGAGTCTCCGlGlCTTTlCGGlllcTlTCGGCGGTGGGlGGGATCCAGCGllC

GGTCGllTGGCTCTTClTGGGCTTTGGTTGTCTTTCCCCGTClCTGClCcCccGCTCGTC

CcGTGGCCGGTCGGTGGCGGCGCGllGCGCGCCTGGCGATTCTCClG.GGGG.TGGGCCTGT

GGGTTC1TTGTTCTGCG1CGG.CT1TG11GGTGGTG1GACCTG1G111TCGTCCGG1CTTT

TTGGCGCGGCTlGCGCCGCCGGGCTCTGCGGGTAGCTTCTCGTTGCTCGTGGAGGGGTTG

TGTAGAGCTTTGGGCGGClCGlTlCGTCTTGCCTTCGCGlGGGlCGGAGcCTGCGGlGGl

1G1GCCAG11CGTGCCGCATGCT111G1TG1G1GTCCGGCT1TG11G1CCGCGGGTG1TG

184 424

GTCCGGGGCTCCCTGGGACCCACTTGCCTCTCTCC: TTTCCTCTTTTTCTTGGCTGTATCG GTCTTGCCTTTCC ^Γ ΓTGGGGCCCTGCAGAGCCTCCTGTTTCCCCTCTTTCCTCCACCTTGC CTGCCTATCTCGCACAAGGATCCCCAAGGCCΆCTCTTTTCTCTCTCTTCCACTTGCGTTTC GTAACGGGTCGGGTCCTGATGCTTGTAGGACTTGCTAACTTCTTCCTTTCGGCACTGTTTT AATCCGTTGCTTTCCGCTCCGCCTGCTTGGGΆCTTCCCTATCTTCTCTGCAATGCTGTGG TCTTTCTCTTTTTTτCACAGCAGACTGAGCCACGGGTTTCTCTGTCACTCTGGGCCGCTC TCGTTTCGGCGGCCC (SEQ ID Nh: 133) pMON28523

TTTACTCTCCTTCTACΓGATCGATGCACC] GΓACGCTCCTCCGCCCAACTATACCTGCCTTG CCTCCTTCCTCTAAC (CCCCTCCCCTGACGCCCACCGCTCTGCCCCCGCTGTACGTAACTCTG TτCTTGTCC.ACTCCTTAGAGCTTCGTCCC3GGTTCGCTCATCCCGTGACAACGCATTCTTG CTCTCGTτCCTTCTTCGTGCCTCTCCCCCCCATGTCTCTCCTCTCTCACTGTCTCACTTTTG TTCCCGTTCCCTCCCATCA? CCGCAGGTGACT (TT: TACCAA ^[, TCCTGG.CCCCCC: TGATTGGT TCGCTTGTGCTCCTCGAGCCCCGCGCA <TTCC: CCA: TATACGTGCTATTGTTGGGAGTTGTT CCTTGGGCACTTTCTGGTCCiCCTCTCTACTATCCAATCTTCTTCTCCCTGTCCCCGCCGTG TCGCAACCCTCCCCCATGGACTTTAGCTTG (TGATCCTGTACACCTACTCTGAGGATCCC ACTTCATATGACATCCTGGGAGCAGTGACCC1GTTGGTGGAAGTTATCTCGGCAGTCTTT GTCTCATCGTGCTTCACTTGCCTCTCATCCCTCCTCTGTTACTTTGCCGTTAAGGGTTGT CGTTTTTGGTTTTTCCTGCAGAGCCTCC'GΓ (TTCC: CCAGCTTCCTCCTCAGGGCATTCTT ATCTCGCCT.CCGTAGCCC (ACΓGCCATCTTCCΊGACGTGTCCCAACCTTTΊ ' TCGAGTC.ACT TTTTGGCGTTGGCT (CCTTGTAGGAGGGTCCACTCTCTGGTTCACTTACCGTGGCACTCGT TTTTCGTTCGTCTTTCCTGCTTGTGACCTCCGACTC: CTCACTGCACCCGTGCGTGCTTTC cCGTGTCTGTATCGGCGACGGAGCGAGTGCCCACACTGTCACCCTTTTGCGACACTGTGC TTGCTTCTGGCGTCT (SEQ ID Nh: 130) pMON28520

GTGACTCGTGTTCTAAGGAGCGAG ^{<TACCGΓAGGCACGACCG,} GCAATCAATACCGGCCTTG GTTCGGGCCCTTCCTCACCTCAATGACGAAGACGTCTCTATCCTTTACGACCGAACTTGG TGCCTGCCCAACTCGGΆGΆGCTTCGTGCA3GGTTGTCTCCTACTTGCTCCCCGCΆTTAGGG CGGGCTGTCCGTTTTCGTAATCGCC (CCC <TGGTGTTTTTTCTTTTTcTTTTGCACCTGTG TGCTCGTTCCGCCTTATCAΆGGCAGGTGAC ^ GT ^TTCCCCCG, CCCTT.JCCCACTGACTGGT TCTCGGGTTCCTTCCGAGCCACCCGCAGGTCCZ (CCACGGACTGCTCTτTTTGGGAGTTGCT TCTGGGGCCCCTTTCTGTCCAATCTCTACTA'G: TAACCGTCTCCTCCCTTTGCCCGCATCT CCGACCGTGTCCCCTAGGGGAGAATGGAAAACCCAGATG <TCT3AGACCCAA3GCACCTTCT CTGTGTTGAGTAGTTCCCCGGCTGCGGGAGGGAGGGAGGGCACGAATTTTTC (CCCTTTTA CTCATGTTCCTCCCAGCCCTCCGGGGGCAGCΊGTCTGTACACGGCCTTGTCCTCCGGTTT TTTTGTCCTATTCTTTTTGGAACCCAGCTTCCCΓCCACAGGGCAGGACTAAAGCTCCTACG TCTTTTACGGCTCTTTTCCTGCGTGTCCACACCTGCGCCGAGGTCCATTGCGGTGTTGG ATGCGGTCCTGATTTCCCCTCCGCGTCGGCA ^{(TcGtCGGCGGCC:} CCΆCGTCGGCGCTTTCT TTGTTGTCTTTTTATCGCCGAGGCCTCAGGjCCCTCGTTCCTGACTCCCAAGGCCGGCAT ^{CGTATACTGAGTCCTCGCCCAGAGGGGCACCCΊG,} TGCCTACACCGCTCCGGCTGCCGTTG TCGGATTTCAGCCCT (SEQ ID Nh: 135) pMON28525

TCGCCTGTCGTGCTCCTGATCGATGAAAGGAGACAGCAC ^, IG ^, CCCGACTCCACCTGTCTTG

TGTTGGTCTTTTCACAACCGCACTTACGAAGACGTCTCTAGCCGGAGGGACCGAACTTGG

TTATGGTCCCACCTGTAGAGCTTCGTAAGGGCTGTC (CCGjCCTTAGJCCCTGCATTCTTG

CTTGCGTTCCG ^, TCCCTGTAATCTCCAACCATGTCTGCCCTCTGCCACTGTCGCACTTGTT

184 424

ΊA (Ί (CΊΊAAAT (CΊ (CΊA (AAΊGCCCCGΊCCCΊGAAGACCΊΊACA ((A (AΊTA (ΊCCCΊ C (TΊTAACC (ΊΊΊTCC (CΊAAAΊAC (AAAAΊGAΊ) (CT (ΊCC (A (CCCΊAAGΊCAΊCCA ACCC A (ACΊC Ί (T ((ATΊGCΊ (A (Ί (CAAAACΊΊ (ΊCCCΊΊCΊCΊATΊΊΊCΊΊCCCAAΊAAΊGCCΊCCC (ΊAAACΊCCGCTΊΊCΊΊCGAAAACΊΊCCΊ (C (CΊΊCΊCCCCC ((ΊΊΊ (AΊGTCCCΊΊC.Ί (C CACAAA (ΊCAΊGACCΊAΊ ((AAACΊΊΊ ((CAΊΊ (CCTCΊΊCC (CΊCCΊΊCAC (cAAA ΊΊGCΊCΊ (A (AAGACACGTCΊTAAGACCCATAAAAAAATΊΊGCΊCTΊGATAGCAAAA (LCGGΊ CACA (Ί (CAAΊCCCCΊCΊCΊGCCCΊΊCCΊCCCCCGΊΊCΊΊCGCCΊΊTΊ (ATA (C.ΊCAΊCC ΊATAACGΊTTACAGΊCTGΊ (CAACAA (ΊCA (ACΊ (AGAΊΊC (A (AATGΊ (CCCTGGAΊCC (Ί (ΊΊCATCCTCΊCCΊΊCCΊGATAAA.ΊCCC (CΊCCAAA (C (ATCA ((A (CCCAAATACGC C (AAΊΊAAAACGΊ (AAGΊGCTCGAAA (CΊGCCC (ΊCΊTCΊCCΊCAA (ACA (ATA (TCCΊG ACACCAAAACAGCTC (SEQ ID No: 136) pMON28526

ACGA (ΊTACGΊA (C ((TAATCAAGAG ((TT (CGΊ (TCAΊCC (AGA (AAΊCACCGACAΊCC) TTACCAAACΊCC) ((ΊAACCTCAATA (CAACA (CCCCTCC (GΊCCAAGAA (CCA (AAΊΊTC ΊA (CCCCΊ (A))) (AA (GAC (TC (CCT ATGA (AACAATCCTCCATAAGCACC ((CC (GACΊCAΊCΊCΊTAΊCACAACCACACCCCΊT ΊA (C (TCΊAACΊ (GΊ (CΊAAAAC (ACCA (ΊCCCA) (AA (GCCΊCCCAAΊACACACΊTA A (AAACAAGAAAAA (: CΊΊ ΊΊAACCCCACCCTΊCACTΊΊA (GCCΊCACAACΊ (GΊΊCCCΊCCΊCΊΊACCT (A (AAAGΊC ΊAAAGATCACC (GACATAAA (ACCΊ (ACCTCΊTΊΊACAAAACAAAACCACAACTCAΊCAC C (CCΊΊGACAΊΊACΊCCΊΊCΆAAΊTTΊΊ ((Ί (ΊΊGAΊTΊΊA (ACAAAACCACATTCΊΊGC (CAΊCTAGAAA (AACTΊΊ (ΊCCACTAΊACΊACCC (ATTΊCCΊAACACCAΊATCCΊCΊCΊC ΊCCΊΊCACTTACA (ΊΊCΊΊCAAGΊΊTΊ (AC (AATCACTGΊACCGΊTΊΊΊ (GACΊΊTCΊ ( Ί (ACAAACTAAAΊCAACAΊΊCAAAAATTΊ (ΊΊΊTCGACTC (C (CΊCATΊΊTACGACCGAΊC AGAAACGGTAAΊTCAAA (AAAGAA ((G (CΊΊ (A (CAAAAAAAAΊΊ (AAACACAAAAΊ (CC ΊCAAC (ACACTA (ΊΊΊCCΊCACGAAAAAA (CCCGCACΊGAΊ (ΊCAAA (ΊAACGAAA (ΊΊΊ GΊCTACCTCGC (TΊΊΊCΊΊCAAAAΊACΊCCGΊCCCGΊ (CCCΊΊCCΊCΊΊTΊCGCAACCΊΊ ΊTACAAAAΊCTΊΊCC (SEQ ID NO: 137 ) pMON28527

ACTAAΊTACGCCATGAGAATCAATAAG (TC (C (Ί (GC (ΊTC (CAA) (C (ΊΊACTTAC (CΊG CTACCAAACCΊCGAΊ.A (ΊΊTCAAGΆAΊC ((C (ΊCCΊTΊTGCΊΊA) (CCTCC) ATTCCGΊAC (AGTTCCAAΊΊ (TATΊTACCΊCΊTACCATACCTAT (TCCTCC ΊA (C (TCΊAATΊ (TΊ (CΊA (AAC (CACA (CTACΊ ((AAGCCΊΊCAAAG (A (CGAACACGΊ CAGCTAAGGACCCTTAAAΊ (AACAΊAAA ((Ί (GCAAGAΊCCAA (AAATCAGAAAAAΊGΊΊ CCAAAGAAACCCGΊGAACCCAAGΊTCT (CGACΊGACCΊCTCTΊΊGCTACCGAGAA ((GΊC ΊATA ((GCACC ( GACAGAAACAAAAΊCAΊ (AΊTΊAΊ (ACC (TCCΊCAGACTAAΊAGCΊCA (ACTTCC (ACAΊΊCAΊCΊCA (AAAAACCCAΊAGCTΊΊCC (CAΊCTAG (CAAAACGCCAΊΊ ΊCCTACATCAAAA (ACCΊAAC (AΊAGCACCCΊCΊΊΊACCΊΊACΊCACCCCTAAΊCCΊΊC (CCΊΊCΊAAGG (AΊCAΊCCΊATAAΊCΊΊΊ (CCCΊΊTCΊAΊACΊAA (ΊGAGACCACCAΊΊΊ (AAAATCCACCCCGCAΊCCACACCTATCCTACTCΊΊTAΊTCCAAACTGC (ACAGAAAGAAA CCAAGAACCC (CACCCGAAAAACΊCAAAC (Ί (CC (Ί (CCΊCCAC (AC (CTAAΊΊCCC · ΊGC CTAAAAAAATAATAAΊ (ACACAAAA (CGAΊTCAA (ΊCΊ (ΊTTACCGΊCΊAAΊCCTCΊCA AAAC (ACGCGTGAA (C (CAGCCATCTCCTCCTCAAAACCCCCT (AAACΊTCCGGAΊA) (CΊΊTCNo.

184 424

1GCGACTCGTGGAGAAGGAGCGAG1AGGTTGGGGGGGGGCTAGGCG1GGGGCCT1GGCCT GT1GGGGGCCC1AACAACCTCAAGGAG1GG1GC1TCTCGGGGCG1GG1CACCGAGGCGTT GlGGTTGGAGGCCTGGAGAGCTTClTAGlCCGTCGGAGCAGGGTGCGAAATGCATGGllG GTGlGGlGAGGGCGGCGGAAGCGCGGACCGTCGGTlGGGTGTlGGGGCCGCGCAGGGTGG C1AGAGGCGGTCATCAGCAAGGCA11T1ACGC1GGA1GATTCG11CGGAGGCG1GC1TTG GATCT1GTTAGGGGGGAGCAAGCGGG11AGGGGCA1GGCCGG1GCGCGC1TG1A11CTCG GGlllGlAGGGCGCGGGGCC (GGGCGGTGCTGGCAGCGCCGGTGGGGGCGGGAAAGAGTGG GGCGAGGGTGCAAACAGGGCGCACAGllGTGGGAGTlGGGGGGGGGGCGlGGGCGGACGC GTCGGGCCGllGAAGGGGCGGGGGCGlGGCGTTlTAllACCCGGGGGGGGGGCCCTGGCl CAGTGC1CGAACAGGGCGGCGCCC1GTCC1GGG1GTTCTCGGCTGGCAGGCCGCA1TAGA GTCGTGGCGCGGGGCCAGGGCCGGCGGG1GG1GGT1G1GGGCT1GGGG1G11GTGGCCGG CTCGGTGGGGGT1GCCGGCGGCCG1CT1TC1GGTTTG1GGGCCCG1GGG1CGGAGGGCA1 GTCCGGlGCGGGAGGGCACAGGGCATTGGClCGlGGCTlAGGGGTGGlGGClGllCGlTl GGCCGACGGG1C11ACAGCGGG1AGGGGGGTCGGGGTGGTGGCTGGG11C1GA1GTGGGG 1CGGA1CGGGGGCGCCGCCGGGGG1GCCTCGG1G1CGGGGTT1GGGGGCAGCGGGGTCGA GGCllGGlCGGGGGG (SEQ ID NO: 2R9) pMON28529

1GTGACG1GTGGGGAAGGAGCGΆG1GAATCGGGGGGGGGGGAGACGCGGGGCGT1GGCGG GT1GTG1GGGG1GGCAACCTCAATGAGGGGGGG1GCGGGGGCCT1GT11GGCGCAGGCGG GlGGTGGGGAGCGGGGAGAGCGGClGAGllCGTCTGGGCGGGGGGlGAGGTCGGGCGlCG GGTlGGCGAGTGGGGCGGAGGCGCCAGGGGGCTGGlGCGTGGlGGGGCCGGCCAGGGTGG GCGGATCGAGGCAGGATCAAGGGAG1T1ACTCGGGG1GATGGCG11GAGAGCT1GC1TGC GGTGTG1TTACGCGGGAGCAAGGGGA11GAGGAGA1GGCCGG1G1C1C1CT11A11CTCC GGCClGlAGGGGGCGGGTCC (GCGCTGGACTGGGAGGGCCTGTGGTGGCGGGAAGlAGGGG GGTAGAGCGCCAAACAGG <GCGCCCAGGGGCAGGGGCGGGAGCTGGGGACACCTGCTGGlA C1GGA11GCG1TTGCCGGAGGCGTCGA1GG11CGGGGGGGTGG1GCGGGC11AGTTC1CC GAGGG11G1GGGGGCGCGCCGCGG1GGT1T1GGGTGG1G1TGCTGGCGAAGCG1CTGGCT CGGGCCCGGGGCCGTCACAGCAGAGGGAGCCGlGlCGCGlAlGCTGGCCCGGGGCCGGGA GGGCGGGGCCGlGGTCGTGlTlAGΤTTAGCGGGGGAGCCAGGGAAAACCCAGAGGCAllAl GGGAΆGlCACAGGACAGGCGGGGAlGAlGCGGGGGTGGCGGCcGlCCGGGGAGlCGGlGG G1CCGAGGGCT11CACCCACTG1CCTGTGATGGGGCGT1111CA1CGGTGGG1ACA1GTC GCGGGCGTGCGTCGGGCCCGGCAlGlGGTGGGGllAGCGGGCCTTGGTGGAGGlllGAll GGGGCACGTCGCGGl (SEQ ID NO: 240)

PMON28530

1CGAGCG1GGGTATAGTGATCGAG1AGAGGAGAGATCAGTGGGACGCGGCACGT1GACCG

CTCGGGCGGGCGAAC (GCCCTC (GGG1AC1AG1GG1GGTCTGTGCG1GC11GGG1AAGGCTG

G1GGGGGGAGACCGGGAGAGCGGC1TGA111GCCTGAG1AGCGTG1AGAGT1GATGG1CT

GGGCAGCGAAGGC'GTCGT.GCTCGCCGACCGT1GGT1GCGTGT1GGGG11GG1GGGCGTGG

GCGCAGGGAGGCAGCAGC (GCGGCA11GCGGT11GAGCAGTGGG1C1GAGGAGT1GG1TTG

GGGGGlCTGGGCCTGGAGCAAGGlCGllGAGGAGGlTAGCGGlGCClGlCGClAllGGGG

GGClGGCGAGCGGCGGGGCC (GCGCGGTGGGGGGAGGCCCTGGGCTGGCTGTGAGCGATGT

GGCGAATGTGGAGACAGGGCCAGGGGGGGCGCGTTGGAGGGGGTCGCGGlGClAGGlCTl

GCGTGCGGGAGGCGGGGAGGAGGGGGGGGGGTGGlGlTGGCCCGGGGGlCGAGGGGllGl

GGCGCCCGTGGGCCGGCGGGGGACGTGGCGCGGGTGGlTGGAGGlGGTGCTCGGTCGGGT lGGCGGGACAGCAGACGGAGCCAGGlGCGGCGlCGTGGGGGGTGGGlGTGGGlCGTGG

GG1CCGCCGGGGGACGGGTGCCGTG11G1AGT1CAGAAGGGGCGG11G1CG1ACCAG1CGG

GGCGACATGCGGGGAGCAGGGACCCTGCGCGTllGllCGlGlATllGGCGGGllClGGGG

184 424

ACCGGACCCAACTGGATGCTATCACTCCTGCCGAAGCTTTCTGCAAACCTCCCTCTTTCA GTTGGGGCTTTCGACAGGGTTCTCGGAACTGACACTCTTTCACAGCGGAGCACCAGAGAC GAGAACGATTCGAAC (SEQ DD No .: 141)

PMON28533

GGCAAGTGTTCCACAATGATCGACCAAATTACAAATCATTCAAAGTGAGCACCTGGACGC CCGCTCGACTCCAACAACCTCTACGACGAAGAAGCCTCTATCCTGACGCACTGATACCCC CAATTTTAAAATTGGACAGTTTTCTAAAGGCTCCGAAGAACTTAAAAAATGTATTAAGCA CGACCGAATTCTTAGCAATTTTGAAGAATCCGCGGCCTGTCTCACCGGCGTAACTTTTGC GATTTAATTATTATCAAGGTAA7CGATTGGGATCTATTCAGGGAATTATTGAAATTATAT CCCCTATCTTTGACAAACCGCAGGAACAAGACCTACCAGAGGGGGGTGGAGATTCCATGG TTAGTGTTTAGTACAATCTTTATTATTAATCTCTGTAATACGTCTTAAGAATTTCATTAA CCTCGAAAAATCGAGCTTCATA7TTTGATTAGAACTGTTATGCCGGCTGTTGTGGAATTT ACTTTGAGAAAATGCTATATTTAGATGGAGCAGACTAAGATACAGGACATTATAAGAACA GCGACGGTTATGGCGCTCGGAGTCACGGCAGATACGCGATAACCGGGACTTATTTGCTCA TAATGGGTTTTCGGCAACGTTTCCGGATACGCAACTCTCATCCCTCcCCTTTTGGAGAGG ACCGCTCGAACGGAGGTCGCTTTACACAGCACGTATATAGCTCATAAGGATTTCAATGGG TCCCTTCTGAGGTTGGTACATTTCTTGCGACCAAAGCTGACTTCCATCATGTTTCTAGGT GGCCCCATTCTGTGGCCCAGGGAATTCGGGCGGTATCGCGGCATTACCGCGTCCGGAGGG AGGCGTCCTTGCGAGCCGCGAGTCTTCACTAAAACGCTTTGTGATCGCCATGTCCTTCAC TCTACACTGAGGCAGTCGGCA (SEQ DD NO: 142)

PMON28534

GACAACTGTT7 CATTACGATCGATGAAATCACAAATCACTCAAAGACACCATCTGGACCC CTGCTGGAATTGAAGAATTTAAATAACATAGACGTATATATTTTGATGGATTCAAATCTT CCACTTTAAAACTT7AAGAGATTTGTAAGGCCTCTTTAGAATTTAGTAAATATATTAGGT TCTGAGGCAATTCTCGGCAATCTCTAATTATCTACGGAGTCCGGCAGGGTTGCATTTTGC GCATATTTAATTATGATCAAAGAAGGTAACTGGGAAGAATTTTGGCAAATAATGATATTG CATGTGCTTACCCTTGACGTACCCCACGAAGAAAAGTACGTAGAGGCGGGTGGAGGTTCG AAGCGTGAATAGTCCCCTCTAATTTGTACCACCAACCCCTGTCGTGCCTCTAAACAATCC AATAAATCTTTAAAGACGTTGTCTACAATCCCCACGGTCGCTCGTGCGGATTCTAGTTTG GCAGATTGGAAAACCCAGATGGAGGAGATCAACCGACAGGACACTGCGCGAGCACTGACG ATTCTGTTGGAGGGACCGATGCGACCATGCCGAAAAATGGGACGCACCTATCTTTCATCG ACCGTGGCGCACCTCTCTGGATAGCTGAGTCTCACTGTTGCCGGCATGCAGACCCTATTC CCAACCCAGCTCTTCCGATAGGCCAGCATAAGAGGTGATAAGGATGGCAATGGCATTTCA GCGAGTTTCTAACACCCGCTTTCAGCAAACCTGGGTCTCTTGACGCCTGTAGCAGGGTGA TCTCTTTGTGTCACGGAATTTGGACGGAACCCGGCTAATATGGGCTGCCAAGCCTGGCCC GATTCTCATTTCCGACTCCTAAGTAAATTCCCTCGTGATTTGCATGCCCTTTAGAGCAGA CCCACTCAGTGCTTACAGCTTTACCCT (SEQ DD NO: 143) pMON28535

CGTTATTGTTATATAATGATAGATGTAATTATAGATCATTTAAAGAGACAATTTGTAAGT

CCCTCGGATCTGAACAACTTCTATCAcGAAGAGGCCTCTATGGCGACCGATCCAAATGCT

AGACCTCCAAACGTCGTCAGCTCGGC.TAGCCGTGCCTTGTAGCCTCATAACGCATGAGGC

ACTGAAGTAATTCTTCGTAATTCCCAAAAATGTGCGCAATATCCCAGGGAAATATTATCC

GCATATTCAATTATCATTAAGGCAGGTAATTGGGAACAATTTCGGGTAAAATTGATATTG

CATCTGGTTATCGTTCTGCTAGACGAGGAAGAAGAGCAGCTACAGGCGGCTGCAGGTTAA

GACCCTGAACACTCCCGCGCAACCCCTAACATGAACCCGTTTCACCGCTTTTAAGAATAC

GATAAATCTAAAAACATGGTTTCGTTGTTTGTTGTGGATTTTAGCTTGGAAGTATGGAAT

184 424

GCCCGCGTCTGTGGGACCΓGGGTGGAGTACATTCCGGGAGCAGTGACCCTTCTGCTTGGT TTGTCTGTCTCAGCACCT3GGTGCGGGTTGACCCAGCTGTCTCTCATCCCTCCTGGTTCGT CTTCΓTTTGCAGGTCCGTCΓCCCCCTTTTTGCCCΓCCAGAGCCTCCTTGGAACCCATCGG CΓTCCACAGGGCAGGACCCSGGCCTGGΓGGTGGCCCΓGGTCCAGCTTCCTGAGCTTCGGG ^{CGCCCTCTCCTACGAGAGGTCTCTTTCCTGATGCTTGTAGGAGGGTCCACCCTC,} CTCGGC GTTTGGTTCCTCTGC.G \ CGTCCTTCGGGGCGCCTCCCCAGTGCCGCCGGCTTGTGGGCGC CTGCC _C GC _C CC _T AAACTGCCTCCTGAGGCCCATCTCCTTCGCAGCAGACTGAGCCATGTC CCGCGTTTTΓGCCCCCTTΓΓTACACCT (SEQ ID No: 144) pMON28536

TCTGGCGTCTCTATAATGATCCTGCTGGTTATACATCACTΓCGGG-AGACCACCTGGGGCT TTCCTTGGCCCTAA <GGGXTCΓAGTAGG (GGACGTCTCTATCCTGATGGACCGAAGGGCG CTGCTTCCAGGCCTGGAGAGCGTCGTCGG3G (GΓΓTTCΓGG-GGCTTAGJAGGGTGCATCGGTC S / CCGGTTCGGTTCTTCGTcGGCCCCΓGGCGTGTCGCCCCGCTGCCΆCGGCCGCACCCTCT CCGΓGTCCAGTCATCATCCGGTTGGTTTAGTTCTΓGGTGG? TCCGGG-GGSGGCTGACTGCG TGCΓCTTTCGCCCTTGAGCCGGCCCAGTTGG: CGGAGTACGTAGAGGGCGGTGGAGTCGCC CCTGTTTGACCGTCTGGTCCΓAGCGCTΆGTATCΓGCCΓGTCTCCTCCGTCTAGAGAGTCT CGCGGGTCCΓCAAACATGGCΓCTTTAGTTTAGCΓGGTGAGίGGΓGG (GGGTCCCAGATTTGT CGCGΓCAAGGCACAGGACAGCCCCTGGGCAGTTGGCCΓTCTGTΓCGAGGGAGTGGTGTCG CCGΓGGTTGΓAACTGGGACCCGGCTTTCCCTCAGCCCTCCTGGGGCAGCTTTCTGTGCGT TTCΓCTCTCCTCCTTGGGGCCCGTTAGAAT? CTCCTTGG (GG? CCAGCTTCCTCCACGTTTC SG3TGΓCACGGCTCACΓGGTTGCCCΓG.GTCCAGCGTCCCCGGCCTCCCGAACCTGCTCCGG. TCGGAGGCGCGTTTCCTGAGCCCTCGAGGAGGGTCCACCCTCTGCGTCAGGGGATTGTGC TTCGACGCCGGCAACATGGCCTCCCGAGCGCCCTCCGTΓTGTGACCTCCGAGTCCTGGTT GGGΓCCΓTTΓGCGACTCCCAGTTCCTTCAGAGCAGACTGAGCCAGTGCCCAGAGGTCCGC CCCCCTCCCGCGCCCTCΓΓCTCTCCCT (SEQ ID No: 145) pMON28537

CCTGACCTCTCTAT-GSΓGAGCCTGTTGGTTATAGAGCACTTCGGGAGACCACCTGCGGCT TTTΓTGGGCCCGAAC.? · GϊGCCCCGGCGGCTA.GAGCTCGCCAGCCTGATGGACCGAΆACCGG CTGΓTTCCAGGCCTGGAGAGTΓCCCGCGGTGCΓGTCΓGGΓGATTAGTGGGAΓGCATCGTTT ^{GCCTGTCCGGTCCTTCGΊ,} CGGCΓCCGAGCATGTCGGCCCGCTGCCACGGCCGCACCGTCG CCGΓATCCAATCATCATCΓGGTTAGTTTACTGGCΓGGTGTTCCGGG (GGGGGCTGACTTTG TGCCTGTTCACCCTTGAGCΓGGTCTAGGTACCGGAGTACGTAGAGGGCGGTGGATTCGCC CCCCTTCGACCGTCTGGTCCCAGCC'CGCGGATCΓGGCCGTCTCCTCCGTCTAAAGGGGCG CGCGGGTCTCCAAACATGGTGGTTCGCGTGGGΆGTGGFGG-GGGkCCCAGATGGAGTGGGCC GACGCACGCCACATTCTGGTGGTAGGCACCCTTCTGCTGGAGGGAGTGATGGCAGCGCTT TTGC-AACTCTGACCCACTTCCCCTGCAGCCCTCCTGGGGCAGCTTTCTGGACAGGTGCTG CTCΓCCCTCCGGGCCCTGCCGGGCGGCCΓTGGTGGCCAGCTTCCTCCACAGGGCATTGCC GCGCCTCGCGGGGATCCCΓGGTTCAGCTTCCTGAGCTTCCCGG. ACCTGC TCCGATTGGGT CTCCGTTTCCTGATGCCTGCTGTTGGTTCCACCCTCTGCGTCAGGGCGSTTCGGCGTCGAC TCΓTCCGAΓGTGGCGTCCCCCGTCTCGCCTGCTTGTGACCTCCGAGTCCTCAGTAGGCTT CTCCGTCACTCCCATGTCCCCCAGAGCAGACTGAGCCAGTGCCCAGAGGTTCACCCCCTT CCTGCGCCTTGCCTTCTTCCTGCTTGG (SEQ ID No: 146) pMON28538

TCCGACTGCTCTAT-GSΓGAGCCTGC (GGGC ^, TATAGATCACTTCGGAAGACCACCTGCGCCT

TCTΓTGGGCCCGAACCGCCΓCΓGGCAGΓCG _l GACGTCTCTATCCTGATGGACCGAAGCCTT

CCGCTTCCAAACCTG <GSGAGCGTCGTCGG3GGCTGTCCGGS-GCTTAGACGGSTGCATCGTTT

184 424

GCCAGAACCCCTC '] hΓCGTrAhTCTCCAACCGTGTCCACCCCTGACCCCAACTACGCTCCTC CACCGCCCCACCATCATCGGGGCGGGTGGCTGGTCAACCCCCTAAACCTAA.CCACTACCT CCCCCAACTGCCCTTGAGCGGGCGCAGdCCCTCACCTACGACAAACAACAACAACCTT TTAAACACACCATCTGGTCdGCGCTGCCGGCmCACTCCTTTTACCCCCGACGCTC TCCAACCCCCCCCCTCATGGGAGrCCCGGrCCGC: CCGGCCAAAAGCACTTAAAATCCCAACC GCCCCAAGGACGGTGGCCCTTCTGC'AGGA3GGGACAGTAACGACGCAAGAGCATCCAAAC CCCCTCCGCCCCTCGGCCCTCCTGGGGCGGCGGGCTAAACCAATTCACCCTTCTCCCAAA ACCCCACGAGGCCTCCTTGGGGCCCGGCTTCCTTCGTCAAACGAGGTCGCGACCCCCAGA AGCCCTGGCACCATCTTCCTGAGCTTCCCGCACCCACCCTAGAACACAACATACCCCCCA CCACCCACGAAGAGGTCCACCCTCT (C: GTTAGAACCTCTAACAATGCTAATAATCGCGCA ACACTTTCGACACCGCCTGCTTGTGGCCTCCGGACTCCTGACCAACCACCCTACACCCTT TCCACTCCCCGCGGCGGGCTGGGCCGGTGCCCGAGAACCTCCCCTCCACCCCCCTCCACT CCACCACCCACCACAACCCCCCATCCA (SEQ ID NO: 147) pMON28539

ACCGGC CACTCCGT · (G-TGGTCGGTGlGhΓTGTGTGCCACCCCAGACACCCCTCCATGCTC CCACCAAGCCTGrGCCGGCCTCGGTGGCGlGGCGCCCCCCCCCCAGCAAGCTACTGTTCC TACCCCCCCGCCCTGGGGGGCTTCGT (AACGGCTACTCCAACCCCCATCAGCACGCTCAAC GCCAGAATCCCTCTTCGTGGTCTCCGGCCGTGTCTGCCTCCCATCGCAGTCACGCCGCCC CAGCGCCTCCCCGTCGTCGGGGCGGGTGGCTGGC1GCGCCCCAAAACAGGCCACCACCT CCCCCAACCGCCCTTGGGCGGGCGCGGG (mCGATCCACCAGAAACAACAAGAACCTT TCAAACAACCCATCTGGTCCGGTCTCTGCTGTCCGCCCACTCCCCTTACCCAACAAGCTC ^{TGCGGGCCCCCCGCTCGTGGGGCCCGC,} rΓGCCTCCCGCCCTCCCCAAGACGACCCCTCAAG TGAACCCACCCCCTCCTTGGGGCCCTGCΆGΆGCCCCCCGAATACTTAACCCCTCCCGCTA AACGAACCCGCGGCTCAdGGATCCdTGCCACCTCCTCACACCCCdTGCCCACCT TAGAAGCGAACACGTTTCCTGGTGCTTGTGGGGAAACCTATCCCCTGTACCGAAATACCT AATAATGACAACGGC (AkCGTGGCGTCCCCGGCGCCGCCGATCCGCAGTCCCCACACTCCT CACGAATCACCTCGTGGCTCCCGTGTCCTTCGCGACCACCCAGATCCACACCTCACAACC TGCCTCCCACTTGCGCCTGTCCTGCTGCCGACCACAACTCCCGATCCAAACACGCAAACC CCTTGAACAAGGGAGΆCCAAGGCACΆGGACATTCTGAAAACAACAGTCCCCCCATCAACA AAGACAGCGATGGTGCAGAGACAACTG (SEQ ID NO: 148)

PMON28540

ACCGGTCACCCCATr'TCΓGATCGATGCCGhΓGATACGTCGTCCCCCACACTCGCCCATGCTC CCACCAAGCCCATGTGCTC (CTCAATGACGrCA3ACACCCCCCTCCCAGCAAGCCACTACCCC CAGCCCTCACA-CCTGGGGGGCTTCGT1GGGCTGCCCCAACCCCCACGCACACCCTGAAC CCCAGAACGGCCCTTCGTGGTCTCdCCATGTCCGCCCCCCATCGCAACCACCCTCCTC CAGCTCCdCC rCΓCATdGGCAGGTGACTGGdACCCTCCAAACGCCACCAGCATCT CCCTCAACCGCCCTGGAGdGCGCAGddCAACACACGACAAATAACAACAATCTT CCAAACACACCATCTGGTCdTCTCTACTATdCCCACTCCCTTTACCCTCAAAACTC CCCGA.GCCCCCGrτTCATGGGAACCCAGCTTCCTCCCCCAAATGGGCTTCCGACCTGTACG AGCCCdCACCATCTGCCTGAGCTTCdTACCTACCCTAGGACTGAACACACCCCCCA ^GCACCCAC, GGGAGGGTCCACCCTCTGCGTCAG <AGGCCCAACGACCACAACGACCACGCA ATACCTTCGACACCGCCTGCTTGTAGCCCTCACACTCCTAACCGGTCACCCCACACTCTT TGCACCTCCCGCGGCGGGCTGGGCCGGTGCCCGGGAAGCTGTCCCCCACCCCCCCCCACT CCACCACTCACCATGGGCGTGGGCGGGGGAdCAACAAGTTCCACCAACAAGACAdA ATGCCAAGCGCCTTGGGGGCGGGGGCCCCCCCGCCAACAAAGACACCAACGATCTAAAAC CCGCCAAGGGGCGCTTGCCTCTCATCCCTCCTGGAACGATTCGCGAAGCGAGCCCACCCT CCCCCCAAAACCTCACCACACCCTTCC (SEQ ID NO: 14 9)

184 424 pMON28541

GCCATGTGTTCTATTA.CGATGCACCAAATCATTCACAACTT.AAAGAGACCACCTGTACCT TTCACGGACGTGAAGAAACTGAACCATGTACAACCACCTATCCTGATGGACTGATAGTTT ^AGATΊ, TTTAAATCTGCAGAGCTTCGTAAGGGTTGTCAAGTACTTAGAAAATGTATAAAGT ATCCACGCAATTGTCCGTAATGTGGTACTACGCCTGGACTCTGCCACGGCTGTACACTTT TGACACGCAATAATAACGAAGGCΆGGTGΆCTGGCCTTGAATTCCGGG7ATAATCTGAAGTTT TACCTCCTTATTGTTGACCAAGCGCAGGAACATCAGTACGTAGAGGGCGGTGCAGGCTTT TCCCGCGAAGG'cTCTGCCCCAATCTCTACTATCCTTCCCGTCTCCTCCGTCTAATCAAT _TT TACAATTTCCCAAAGACCGGGAGGACCACAGCTCACCTAGGΆTCCC7TTTGCCATGTTCCTG ^{AGCTTCCAACAACTGCTGCGAGGAAAGGTGTGTTTCCTGATGC,} TΓGTAGGAAGGTTTAAA TTCTCGGTCAGGCAATTAGCGGGCCTACGGCGGCCTTCATGGCGTCCCCAGCGCCGACTGCT TCCCAGCTCCGAGCGCCGAGTTAACTGCTTCGTGACTCCCΆTGTCCTTCΆCAGCAGACTG ACAGAGTGGGGAGACGCCGACCCTTTGCCTACACCTGTCCTGCTGCC7? GCTCTGCACTTT AGGTTGGGAGAACCCATAACTGAGATGGAGGAGATCTAGGCACAGGACATTTTAGAAGTT. GTCACGATTCTGGCCGAGGGACTCATGGCAGTATGGGCACAACTGGGACCTATTTGTTTC TTACCGCTAGTGCGGCAGCCTCGTCCACACCTCTGTCCC (7TCCTTGGGGCTTTTGGACAGGACAGdtGGATGQACAGTCGATGQACNo5GATGQACAGTCGCAACTG)

GCTTAGTGCTTTATTATGATCGATCΆATT'Ϊ'ATΆCΆTCΆCTT? TAT7AGACCACCTGTAGAT TTGGCCGACCCAAACAAAGCCAATGACGATGACGTCTCTATCCTGATGGACCGAAATCTT TGACTTACAAAAGTGGACAGTTTCGTAAGGGCTGTCAAGAACTTAG7ATTATAAATTAGAT ATTCAGATAATTCTTTGTAATCTCCAACCATGTCTGCCCTCTGCCACGGCTATACTTTAT GCAGATGGATTTATGATGAAGCGACGCGATCGGCAACAATTCCGGG7AATAAATGAGGTTG TATATGCTCACTCCTCAGCAAGGGcACGATCATCAGTACGTAGAGGGCGGTGGACCCTTC CCCCCTCAAGTGTGTCCCGCAATCCCTACTATCAACCCGTCTCCTCCGTCTAAAGAATTT TATTAATCTGCAAAAATCGTTCAAAAGGΆTACTAATCCATTCTTCCTGAGTTTTCAACAC GTGGTCCCACGATAGCTCGGTTTCGCGATGGTTGTACGAGGGTCCACCCTCTGCCTCAGG GAACTCGCTCCTATTCGCCGCAACATGGCGTCCCCΆGC <GGCGCCTGCTTGTGATCTCCGA GTCCTTAGTTAAATGTTTTGTGACTCCCATGTCCTTCA (TT3CAGACTGAGCCAGTGCCTA GACCTTCATCTTTTACTTAAATCCCTGTTGGTGTTTACTGTGGACTTTAGCTTAAGAGAA TGCAATAGGCACACCCAGGACACCAAGGCAAAGGACATTCTGGGAGCAGTGACTTTTTTC TTCGAGGGAGTAATGGCAGCAAGGGGACAACTGGGACGATCTTGCCTCTCATTATTACTG GGCGAGCCTTGTGGAGACGCCTCTCCGCTTGCCGGACACCTGCAGAGCCTTTTTGCAATG CAGGCTCCCGTACAGGGAAGGAGCAGA (SEQ DD No. 151) pMON28543

CTTTATCGCCCTATAATGATCGATGAAATTATACATCTCTT.A? AT7AGACCATCTCGACTT

TTGTTGCATTCATAAAACTTTAATCACGAAGACGTCTCTATCCTGATGGAATGAAATTTT

CGAGTTCGTAACCCGCACAGGTCCGTATGGGCTGTCAAGAACTTAG7AAATTGCATCAGGT

ATTGAAGTTATTCTTCATAATTTTCAACCATGTCTGCTAΓCTGCCACGGCAATATCATTT

CGACATCCTATTATTATGTAGGAAGCTGACCGGCAAGAATTCCGGGAAAAAATGATGTTT

TATTTGCΊTACATTTGACTAAGCGGAGGAAAAACAGTAGGTAGAGGGCGGTGGAGGCTAA

TCGGGTGAACCGTCTGGTTTAATCTCTACTATCAACTGGTCTCCTCCGTCTAAAGAATTT

TATAAATTTCTAAATATGGATTTCATTGAGATCTTTCTGAGCTTCCAACAACTATTATGA

GGAAAAGTGTGTTTTTTGATGATTGTAGGAGGGTCTACCCTCTGCGTCAGAGAATTTGGT

GCGAATGGGGGTTACATGGCGTGAGGAGCGCCGCCTGGTTGTGACCTCCGAGTTGTCAGT

AAACTGGTTAGTGATTTTTATGTGCTTGACAGCAGATTGAGCCΆGTGCCCAAAAGTTTAT cGTCTGAGCACACATCTCCTCTTGGA'ΓGCTG ^Γ ΓGGACCCTAGCTTGGGAGAATCGAAAACC

184 424

GG1GGC1G11G1GGGAG1CCGGGC1GGATTCTGGGAGCAGTGACCCTTCTGCG11GC11G CTCGGCCGG1GGG111CGGGGCTC11GCCCACTTGCCGCTCATCCCTCCTG111GG1GGG TGGGGGGAllTGGlGGGGGTGCTTClCCCCCTGCAGAlCCTCCTTGGAACGCAGCGGGGT CGACAlCCGAllGCGGGGCCGGAGGAC (SEQ ID Ne 2 54) pMON28544

1CTGAGT1GGGGGGGAG1GTG1GTCAGGTTATACATCAGTTAAAGAGACCAGGTGGGCCT TGlGGlCGCCGlGACAGGGTCGATCGG <CAAGACGTCTCGATCCTGATGGAGGGAGAGCGG GlGGTGGGAGGGCTllGCGlCTTGCGGAGGGCTGTC (CAGAACTTAG _J AACATGGAGGGllT GTGGAllGGGTGCTTGCGAGGGGGGGGCCATGTCTGCCCTCTGCCACGGCCGGAGCGTGG CGAGGGCGGGTGGGGGGGGAlGCGllGlGCTGGCAAGAGGTCCGGGAAAAAGTGGClGGC TGGGTCCTTGGGGTTGGCGAGlGlGGCCAGC (ACCΆGTACCTAGAGGGCGGTllGllGTGG GGlllGCGGGGCTGGllGGCGGTGGGCGCTATCAACCCCTCTCCTCCGTCGAGAlGACGT GGGGGGGGTGGAGGGGGlCCGATGCGGGTGAGCTTCCAACACCTGCTCCGAGlAGAllGC GCTGGGGGlGTCGGGlGGllGllCGGGGCCCTCTGCGTGGGGCAA ^r TTCGlCGGCAGGllG CCCGAGGCllGCTGCCCGlGlGClGGTGGTTGTGACCTGCGAGTCCTCAlTAGAGTlCGT GlGlGGCGGGGGlTGGTTGAGACGGlGGTGAGCCAGTlCCCAGAGGTTCAGCCTGTCGGT GGGGGTCCGGT1CTCGCG1GG1T1CGG'CTTAGCTTGG1A1AATGGAAAACCGAGGGCGG1 1G1AGGAG1CGGCG11GGGTGCTC11GCCAGTGACCCGTCTGCTGGAGGGA1GGGT1CGG CGACllClGGAGCGCCCGGGGAGTGCGGTCTCATCCCGGGGCGGGCAGCTTGCTllGGGl 1GGC1GGTGGGGGTG1111CGCG1GGCGCCCTCCTT11AGGCCGGCTTCCTCGGGAC11G GClGGGGCGCGTGACGGCCATGGGGGC (SEQ ID NO: 153 5 pMON28545

CGGGAGGlGGGTGTAGTCGGGlGTlAGGTTATACATCGCGTAAAGAGACCACGTlCGGGT GGlGTlCGCGGGAGGAGGGTCAGTlGGCAAGACGTCTGTGTCCTGATGGACGlGGA.GGTG CGGCGGGCGGGCCTllGlGlGCTClTGAGGGCTGTCAAGAACTTAGAAAATlGATCGClG AGTGGlCCAGGTGGTGlGAGGCGGGAGGCATGTCTGCGGCCTGCCACGGCClCGCGGTGT CGGGAGGCGAGGATGATGAGllCAllTlGCTGGCAAGAGGTCCGGGAAAAAGTGAGCGGC GGTCGCCTGGGGGGG1GCGAG1C1GGCCAAC (GCCAGTACCTAGAGGGCGGT1GG11GGGG GGGllGlGACGlTCGlCGCGAGGGGGCGCTATCAACCCGTCTCCTCCGTCGAAGlGATGT CGGAGATGGCGAGAGAGllGGGGGAGT (lGCATCTTCCTGAGCTTCCCGCCACGTlGTGCCG C1AGA1GGCG1TGTGGT1AG1CTTCGGCGAGGGTCCACGGTCTGCGTCAG1GAATTGCCG ClCGAGGTllGlTCGGGGlGGCGlGGGCCTTGTGACCTGCGAGTCCTCAGGAGAGTCGTT GlGcAGTGCCGTCTGGTTGGGAlGGlGGTGAGCCAGTGGGCAGAGGTTCAGCGGTTCGGG GGACCGCGCCGCGTCCGGCGGlGllGGTTTAGCTTGGGAGAGTGGAGAGCCGAlGGClGC CGCGGGGA1CGGCGC1GGGGTCG111GCCAGTGACCCTTCTGCTGGAGGGAGG1AG11GG 1GGG1C11GGGGGTC1CGGGGGGTG1GGTCTCΆTCCCTGGTGGGGCAGCTTTCGG1GGGC 1GGG1GGTCGGGGGT1CCCCCGT1GGCGGCCTCCTTGGGACCCAGGGCAGGACCACGCGG GGGGAl (SEQ ID Ne: 1545

PMON15981

ATGGCCCACT GCTGTATTAT GATCGATGAA AGGTGGGGGC ACTTAAAGAG 51 ACCAGGGGCA CGCTGGCTGG ACCCGAACAA CGGCGAGGAG GCA ^ (^ _J ^ (^ (^ 'TC'T 101 CTTCGACTTC CTGTGCGGAT GlGTGGJAAC CGAGGGGGCl GAGCTTCGTA 151 AGACCCTGTCA AGJACTTAdA AAATGCATCA GCCTATCCAG CCA ^^^ f ^ G ^ CTTi

201 TAATGCGCCG CGGGGlGTGC GCCGGlGGGC

251 CAAGGTGGGG CGGGllAGGl GACTGGCCAAG AACT'CGGClG AGGCACTGGCG

184 424

301 GGTCGCTCCC CC (ΊTTTTC (ΑΤΑΑΑΤΑΤΑΑ A (AΊGAC (CC

351 TACCCCGCCΊ CΊTΊTCAACA ((CCAGCTAA CΊΊ ((CCCΊC

401 TATΊGΊΊCΊΊ ACTC (ACAAG TTTTATAAAT CTΊCAGAΊ (C

451 TGCCCΊTGTΊ TΊAGCAAAΊC ACTACTACTC AAAT (TCΊCT

501 TCACCΊCΊΊΊ TCAGATTTΊC ATTTTAATTA AATTTTATGA

551 ACCCCGCΊΊ (ATTTTATACC AATTATGTTT CΊC (ΊC (AAA

601 ACΊΊGCCGGC AC (C (TCCΊC TAAAGTCACT ΊCC (ΊCCCAA

651 ATTCCGTCCΊ AΊCC (CATTA CΊ (CTACCAG TGAATAATAA

701 GAACCACCCΊ ΊΊΊCACCCTA TGACCTACTC AAAACATTAT

51 ATTCΊGCΊGG TTCGACACTA AATAAAGAAA ATΊCCACCTA

801 AcGCGCΊCCΊ CCAC (AATCC TATGCTACAT CΊT (ΊACC (Ί

851 CCCCTCCTCC ΊCCCA (C (CA CTTGCGCTAT C (AATTTCAT

901 TTTΊ (CGCΊC CΊTCAΊGTAG CCCTGCAA (A ΊA (ACA (AC (

951 ΤΤΑΓΑΤΊΤΤΑ CΊAΊCΊCGAA GAA (ATTACA CACΊ (ΊCCCA (SEQ ID No: 155) pMON15982

ATCCΊC (CΊC CΊTΊC (GA (T CATTAAGAAA (TTATAC (CΊ

ATT (ΊΊCCΊG ΊΊCCCCCCAA (TCTAAATAA CCCC (ATCAΊ

101 TTCGTΊCCGC ΑΑΑΊ'ΤΑΑΑΑΤ CCTCA (CCGC TAGATCTACA

151 AACCΊGCGTG ACACTCTAAA AAGGATACT (ACCACGAAAC

201 TCACΊGΊΊAG ΊT (CCTCCAT TTCTTACTAC AATCACATTT

251 TAACTGCΊGC TA (CATAAAC AACTAATAAA A (CTTTAACA

301 GGTCGCTCAC CC (ΊCTGTA (ATAAACACAA AAATAATAAC

351 TAAGAAACAT CTTΊΊCACCC (ACTACCCAA CTTAATTCTT

401 TACTTΊΊCΊΊ CCTC (AAAA (CCTCACAAAT ΊTTTAAAΊAC

451 ATACACTΊΊ (TΊCCAAACAT ACCATAACGC AACACTACTA

501 TATΊ (CTCAA TGATAAATAA AAAAATGAAA AACAATCΊTC

551 CCATTTACCA CCΊΊ (TATTC CCCCTCACTC CCACTCTTT (

601 AAACCCAGTΊ CACCCACTAA CTAGCTATAA AATTTCCCAC

651 TTATCTCΊCG TATTATCTTA CACAACCTAC CAATAACCTC

701 TATΊACCGCC TΊΊCATTAAT CTTTGATTTT AAAATGTΊTC

751 TTACACTACC CCACAAAAAT TTAAAATAAT ACTATAATAT

801 ATTACCCCΊΊ (TTCATAAAT CATATTATTT TCAAAAATCC

851 AAT (TCΊCTC AAATATTTTT TAAATGTTTT GCAATCTΊCC

901 ATTΊCCT (AΊ CCAΊ (AATTA TCTAAATTAA TCTT (CACTA

951 TTATTGACAC TGTTTATAAA TTTGAAAAAA AAGACTTC (A (SEQ ID No: 156) pMON15965

ATGGcCTGCC CPATTTTAAG CPAGCTAGAA APGACAG (TC

ATTGTΊCCTA ΊΊCCCATCAC (TTTAAATAG TTTT (ACCAT

101 TTACTTCCAT AAATTAAAAT TCCTAATGCT T (AATTCAAG

151 ACCCΊCCGΊ ((CAATTTAAG ACAGAΊATT (ACGACAAAAA

201 GCACΊCΊΊ (A ΊΊ (CATTTAΊ TTTTTATTGT ACTTCTATTT

251 TC (GTGCΊAC TAGCATGAAę AATTAATAAA (AGCTTAAA (

301 GCΊGGGΊGCC GCAΊTTTGA (ATAAATATGA AAATAATACC

351 TAACCCGCCΊ CΊTTTAAATC AATTATTTAA CΊT ((GTCTC

401 TAT · ^^: CCTCAA (AA (GTTTATGAAG TCTΊ (AATAC

451 AGΊΊGCΊCΊΊ CCATAACAAC AATTTGACTC ATTGCTTATT

GTATAAAAAA

GΊCATT (ATT

CCΊTTATAAC

CCCATATTTΊ

TCAATAAATC

ATCTTGATAC

AΊATATGATG

GTAAAAAGAT

ATTAATTCAT

TGAATTAGTT

ΊGCATATACT

TAATGTTTTC

GAAęTTAAAC

TGA;

AΊTGAAAAAC

AAAAATAGTC

AAATGGTAC (

T (ATGTTTTA

CTTTAATATT

AAAATAAATA

ATATAAAAAA

ATGAATAATT

CTTGTTTAAC (ΊTTGATTAT

ATTTGATAAT

ATATTAAATA

AAATAGTATA

CATAGAATT (

ATATAAAATG

TTTAAAAAAA

CCATAATTTA

TTTTAATTAA

CTTTGATTTC

C (A;

TP (TAAAG (G

AAAAATAATC

AAAΊGGTATG

ΊAATGTTGTC

CTGTA (TAGT (AAATGAATC

GTCTAAAACA

GTT (ATAATT

CTTTATTAΊC

CATAAAATTT

184 424

501

551

601

651

701

751

801

851

901

951

CCTGGAlGCl GCTCGGACAT GGCCGGCGCA AGGGCTCCAT AGCGGGGGCT TCCTGCCCCA TAGCGGCCTT CCCCCGAGTT TTTGCCACCA CCTGCAGCCC (SEQ II Nr.

OCCTGGTlTT

OCGGllCCCG

OlTGGlCCGG

OCGCTTGCTG

TCCCTGCCCT

OlTGlCGCCT

AGllGlCCCC

OGCCGGAGTC

OCTCAGGCCGc

OTTGGlTGGC

ATCTGCGlCG

CCTGlTCTTC

AGGCGCCTGG

CTAGCCGCGC

GTCTCTCGCC

GGlCTCTGGC

GCTGGCCTTG

GTCAGCGGlC

GlGGCG (GGA (

CTTCGCCTlG

CCCGGCGGCG

GCCCCAGAGC

GCGATGGCGC

CACCCCGAGG

GCCCCGGAGC

GCCAACGCCA

GAAGGGATAT

CGTGGCGGAC

GGGCCCCGGC, AA pMON15966

ATdCTAACT (lCTTΓATAAT OCGCTAGClG (AGGAGACAGC ACTTAAAGGl 51 ACCACCTGCACCTTTGCTGG AGTTClGGTG (CCTGTGCΓGAG GAAGACGGCG 101 CGAGCCGGATGGAGCGAAAC CTCCGCGCTC ΟΗΚ / ΟΐασΑ GAGCGGCCGG 151 AG <^ <l ^ T <^ '^ <^^ G ^ C ^ ^ C ^ lG ^r ^' ^^ GJG AGGGGCAGCA GGTATTGAGG CAGTTCGGCC

01 T. ^ lGTCTCCA? LCCATGTCTGC CTTGTGlTAC GGCCGCACCC TCGCGACGGC 251 CrTCTCATCATC (GCJGCAGGT GCGCGGCTCGl: ^{^} GGΓTCCGGGA AGGGCTCGCC 301 TT <^ ^{^} CGGGA AGGGCTCGCC 301 TT <^ ^ Tj GAG <^ GCAG <^ GCAG <^ ' ACCTA ^ GH

51 CGGTGGAGGCTCCCCGGGTG., GCTTTlTGG TGCTGCΓCTCT ACTAICH ^ 401 CGGCGCCGCCGGCGAAAGAA TCTCATlGGG [ 'CTGTTGGKCAT OGOGA ^^ 451 CCGGCCTTCG CCTGCCCTGCAGCCCACCCA GlGlGCTTGG CCGCGGCGGT 501 CCAGCGCCGGGCAGGAGGGG TCTTGGlGCC TAGCCATCTG 551 CAGAGCGGCC TGGAGGTGTCGTACCGCGTT ΑΟσ ^ ^ ^ Α TTGCGCAGCC CGC-601 CGCCCCT TCTGACATGGCTACACCATT AGGlCCTGlC AGCTCCCTGC GeGAGACH 651 CCTGCTCAAA TCGTTAGAGC AGGTGAGGCGc GAGCCAGGGC ^ GAGaCC H 701 CGCTCCAGGAGlGGlCGGGGT (GT :: AC (Aaca AGCGGGGCCA CCCCCGGCGC 751 CCCTGGGCTC CTGGTGCTGCTCGGACACTC TCCGGGCTTC CCCGH ^^ AGCTGGCAGG CTGCTTGAGC 801 CTGCCCCAGCCAGGCCCTGC CAACGCCGGG 851 GCGGCCTTTT CCTCGACCAG GGGCTCTTTC AGGCCCTGGA ΑσσΟΗΚ ^ 901 CCCGAGTTGGGGCCCACCTT CAGCGGGACG GCGCCcGCGG GGACACACTG 951 TGCCACCACCATCTGGCAGC AGATGG7GC2A ACTGGGATlGC TAA (SEQ II NO: 158) pMON15967

ATGGCTAACTGCTCTATAAT GA ^ GAICm ATTATACATC GCTTAGAGGC 51 ACCAACTGCA CCTGGGCTlG ACCCGlGCTGc CCTCAATGAC lGGGGCCGCT 101 CTATCCTGΆTGGATCGAGAT CTGCGACTTC, CAGGTCTGGA lGCTGGCCGG 151 AGCCCTGTCAAGAACTTAGA Α / ΚΌΟΑΤΟΑ GGTATTGAGG TAATGCGGCc 201 TAAGCTCCAGCCAGGTCGCC CTTlGGlTAC GGCCGCACCC GCTCcGTGGC 251 CAATCATCATCAAGGCACCT GACTGGCTCG5 AATTCCGGGA GAAATGCGCC 301 TTCTATCTGG TTACCCTTGA GCTGl3CGCAG GAACTGlCAGT GCGGGCGCCC 351 CGGTGGAGGCGCCCCGGlGG AACCGGCTGG TCCTGGTCTCC GCTGGCGGCC 4 01 CGTCTCCTCCGTCTAAAGAA TCTCATlGGCΓ CTCCAAACAT CTCGGTTCGC 4 51 GGTGCCATGC CGGCCGGTlC CT <TΓGCTTΓC CAGCGCCGGG TAGGGCCGGT 501 CCTGGTTGCTAGCCATCTCT AGAGCTT · CCG GGAGGTGTCG 551 TACCCCCGGC TACGCCACCTTGCGCACTTT CCGSC GC ^ ^ ^ iSGC / r CTGACATGGC TGCGCCGGGG 601 GCCCCCGCCA GCGCCCGCCC CTAGAGCTTC CTGĆTCAAGT TGGGGCAGTG AGTGAGGAAGΆTCCAGCCCC ATGGCGCAGC 651 dTCCAGGAG ACCCCGCGCGC

184 424

GCTGTGCCAC CCCGAGGAGC 701 CCACCTACCTC TTTGCCTCTT TGGACATGTG 7 51 GTGGGCATCCCCTGGGCTCC CCTTCGCTCC TCTCCCCC3TT CGGCCCGTTC 801 GCTGGCCTCGC'GGC (TΓGCCTCC AACTTTATCG CTGCCTTTTC TCCGCCTCTG 851 GGCCCCGGCA GGCCCGGGAA GTTCCATCTT CCTTATTCTT CTCTCCTGGT 901 GACACACTGC AGCTGGACGT CGCTGACGGG GCCACCACCA CTTGGCAGTC 9 51 Α Α ^^ ^ ΑΑ ^C GGGGCCCTGG CCCTCTCCCG GTAGCCCTGA CCC (SEQ ID No: 159) pMON15960

ATACTGTCAT TCATGCCTGCT CGTTCGCTCT CTGCCCCAGA TCGGTTGTTT 51 CATCCTCTCTCGCTAACTGT TTCCTCTTCC GGGCGATGGC 101 TCATCGTGCC AGCTGCTGCT TTCGTTCAAC CATCCTCGGT TGCGCGTTGG GCCACCCCGA 151 CCCCTTCCTT T.CTCTCTTGG TCTTTCTTGG GCGCCCCTGA TTGTCGTTTC 201 CATCTTCATT CTTTACGTGG CCGTTTTCGG GAGCCCAkCGC CCGATCTTTC 251 TTTGTTTTCTCTAATGTTTC TTTCATTTCC TGGAAGGGAT CGTTTTTTAG 3 01 TTTCGGTCCT CCTCGGTAAC CTTTTCGTGG GACGTCGCCG CCGGGTTTAC 3 51 CATCACCGCC TTCTACTCTG CATCCTTGGT TTTCGGTCTT

001 CC.CTCCTCCT TCTCAATGCG TCCCCTTTTG CTGCTTTCCA TCTTTTTTTC 051 GGTTCTTGTC TTTGGCGTAG TTCCTCTCAG AGCGGCCGGG CTTGTGTTGC 501 CCCCTCTCTT cGTCACTTTG TTTCTTTTTT TATCTTTTTC CGGCGGCTCT 551 CACCτTCGCT C2C ^ CT ^^ C ^ C ^ C ^ CA (CCTTCGTTTT AGAGCGTCCT TTGTCCTGTT 601 GTAGAGCCTC; AGAGO / AGAG CCCTTTTGCG GGCGCAGCGC CTTAGGCTCC GCTTTTCTCT 651 ACCTACAAGC TGTTTTCCTT CGAGGAGCTG TGTCTTTGCT 701 GAGACTCTCT TTTTTCCCTT GGAGCTCCTG TTTTAGTTCG

01 GCTTTCCΆGC TGGCAGGCTG TTTTCTTTCC CGCCAGAGCG GTTGGTGTTG 801 ΑΤΑ Οσ ^^ ^ CTCCTGCAGG CTCCTTACGT GATATCCCCC 851 TCTGGTTTGT CCACCTTGGACACACTGCAG TTTTCTTGCG CCGACTTTGC TCTTCTTCGC 901 GGGCAGCAGACGGCCCCTCCCG GTTCACTGTT CCGGCCCGGC CTTTTATTCC 1001 TCCTGCTTGG TAGCCATCTG CCTCTTTTTT TGGATGTGTC GGATTTTTGT

1051 CCCTTTCCTτ CTTTGCCTCT TTTCCCC (SEQ ID Nh: 160) pmON32132

TTGCTTTCTCTGCCTGCTTGTGACCGTCGAGTCCGCAGG _J CCACTGCTCCGTGACGCTTCG TCCTGGCCTCGTCGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTTTGG CTTCTGGTGGTTTACTTTAGCTTGGGAGAATGG2CCACCCCAGATGGAGGAGACCACGTTA TCGTCTCTCCGTGGAGCAGTGACCCGGCTGCTGTACGGAGGGAGGGCAGCACGGGGATCC TCTGGCCCCCCTTGCCTCTCATCCCTCCTG (TCGCAGCTTTCTGGACAGGTCCGTCTTTGT CGGGTTTTTTGGCAGAGCCTCC · · GΓGGAACĆ CAGCGTCCGCCACAGGGCAGGACCACCTCG CCCCATTCTCTCAATGCCATCGGCCGTAGCTTCCCCCCACCGGCTCCGAGGCCCCGGGTTTG CTCTTTCTTCTCTCCGTCTTTGTTCCCCTTCTTTGTATG (SEQ ID NO: 20 9) pMON32133

TTCTTCGCGCTTCCTGCTTGTGACCTTCGAGTCCTCAGTGACCCTGCTTCGTGACTCTTAG

TTTTGCCCTCTCAGACTGAGCCAGTGCCCAGAGGTTCACCCTTTGCCTACACCTGTTTTT

CGGCTGτTTTGTGACTTTAGCTTGGGAGAATGGCACCCCCAGATGGAGGAGACCAAGTTC

TCTTACCTCTCTGGAGCAGTGACCCTTCTGCTGGAGGGAGTGATGGCAGCACGGGGATCC

CTGGGCCTCCTTCGCCTCTCATCCCTCCTGGGGCAGCTTTCTGGACAGGTCCGTCGTTGC

CTTTTGTCCCGGCAGAGCCTCC'GΓGGACCCCAGGGCAGGACCACAGCTCACAAGGAGTTT

184 424

AT.TGCCTTATTTTTGTGACTCGTTCT.GTTGGCAAGAGGATTCGTGCCTTTGCTCTTATTC

GTAGGAGAGTGGATCCCACCCGTGAGC (SEQ DD No .: 250) pMON32134

TACCGAGTGCGGCCTCACCCTGAGTTTTGAGCGACGACCAAATTGCTTGCTCAGTCCCAC CTCTTTAAAAGCAGAACCACCAAGTGTTTACAGGCTTACCTTTTCATTATATTTCTAATC CTCCTTAATATCGTATTTTGTTTAAATATATCGATTTTCCTATTAAAAATATCTTAGATT GAGGTGTTTCCGAGTGAAGCGTTCTTTTTGGTCGTGGGTGTGTTGGCTGCTGGGGGTGTT CCCGGACTAACTTGCGTGCGATTCTTTCTCGGCAACCTTTCTAGACAGGTGGGCCC · CCCGGGGTATCCCAGACGACGTTTGGAAGACAGACCCTCTCATAGGCCAGGACCACAGTT CTGAACGATCGATTCCGGACCTTCTTGAGGTCGATAGAATTGTTTCCAGCAAAGGTGCCC CCGCTCATGCCTCTAGGAGCGTCGACTCCGCGACCGACG CCTG (SEQ DD NO: 251)

Pmon13181

CtGT ^ G ^ C ^ GC ^ T ^ IAT GCGATGTATA ATTGTTGGTC 7 to AATTATAGA TCACCTAAAC 51 AGACCACCTG GAGGCTTGGC GCACGGGGAC TLAGTTCTATG ATGAAGATCT 101 CTCTATCCTG TCGCATTCTA ATCTCCAGTC CCCATACCTC GAGAGTTTTG 151 TAAGGGCTGT GATCTAATTA GGAATA? CGAT AAGCCATTGA GGGAATTCCT 201 CCCTTATTCTCC AAGCATGTCT GCTCCCCTGG AGGGCCCCAC TTTTCTGATA 251 TCCCATTCATC TTAATCCAGTG GGCACGCCCA ACAATTCCGG GAAAAACTCA 301 CGTTCTATCT CCTCTTTGTT GAGC7CTGTG TGGTAGTAGT GTAGGTTgag 351 ggcggtggag gctcCATGAG TGGTCGGCCA CCTTGAATCT TTACTACCAT 401 CCCGTCTCCT ACGTGTTTAGTCCATTTC ATTAGTCCATTTC ATTAGTCCATTC ATTAGTA TCTTTC

451 CCGCATGC.TA CCCC (SEQ DD Nrc 257)

Pmon13180.Seg

CCATGGCTAA GTCCCTTTTT ATGATCGGTC TAATTATAAA TTAGTTAAAC 51 AGACCACCTG CTGACTTGTT GGACCCGTTCT TAGCTTAATG ATGAAGACCT 101 CTCTATCCTG ATGATTTATT ACGTTCCACT TGGAAACTTG AAGTGCTTCC 151 TAAGGGCTGT GTTGTTCTTA GCTATTGCAT GAGGTATTGA GGGAACCCTT 201 CGT.CTTCTCC CTGGATCTTT GCGCTCCCGC ACCATTGCAC CTTCTGCTCT. 251 TCCAATCATC ATGTTAGCAG GTG7TCTGGC / C TGAATTCTAG GTATAAGTGA 301 CGTTCTATCT CGTTATGCTT G7T7C7TTGCCC ACGAAGAACA GTTGCTAgag 351 ggcggtggag gctcCCTGGTG gctcCCTGGTG gctcCCTGGTG

401 TCATTGGGCT CCCTTCTTT (SEQ DD No .: 258)

184 424

Table 3

Protein Sequences ·

PMON26458pip

SeePeoAiaProProAlaGjsAspLluArgValLluSlgLyyLluLeuArgGspSerHiy ValLluHiySerArgLeu.SerGln (GcyPrylluValHiyPryeeuPryGhrPryValLeu eluP: roAlaValAspPheSerLeuGlyGlu.GgpLyyGhrllneetllulluGhreysGla ClnAypIllLeuGlyAlaValThrLeuLeuLeull · uGlyValMetGlaGlaGegl lyGln eeullyProThrGjSLeuSlrSerLluLeuClyllnLluSlrllyClnValGAgLluLeu LeullyAiaLluGlnSerLeuLeuGlyThοllnLluPgyPryGlnllyGAgThrThrAla Hiyeys.GspProAsnAlaIlePheLluSeοPhlGlnHiyLeuLeuGggl lyeysValGeg _{PhleeuMεtLeuValGlyGlySe;} ιeThrLeuCyyValGggCluPhl (SEQ ID Ne: 2625 pMON28548pep

SeeProAlaProProAla <GjSAspLluAggValLluSlgLyyLeuLeuArgAspSlrHiy ValeluHiySerArgLeuSerGln <GcsPοyCluValHiyPryLeuPryThePeoValLeu eeuPοoAlaValAspPheSerLeuGlylluTrpLysGhAllnMltCluCluGhreyyAla llnGypIleLeuGlyAlaValThrLe · uLluLeulluClyValMltAlaGlaGggl lylln elullyProTh: ο (GjsLeuSerSerLeuLeullyllnLluSlrl CyGlnValGrgLluLeu LluGlyAlaLeuGlnSerLeuLeuGlyThAllnLeuPgyPοyllnll · cGAgThgThgAla HiyeyyAypPryAynAlaIlePheLeuSeοPhellnHisLeuLluAegllyeysValGAg PheLluMluLluValllyllySlrThοLluCyyValGgglluPhlClyllyAynMet.Ala SerProAlaProProAla (CjsAspLluAοgValLeuSerLyyLluLeuGAgAypSlrHiy ValeluHiySlrArgLeuSerGln ^ ysPgylluValHisProLluProThePryValLeu LeuProAlaValAspPheSerLeuGlyGluTοpLysGhgllnMltllulluThοeyyAla ClnGypIleLeuGlyAlaValThrLeuLeuLeullullyValMltGlaAlaAοgclylln LeullyProTh: οGjsLeuSl: οSe: οLluLeullyllnLeuSerllyllnValGrgLluLlu eluGlyΑlaLeuGlnSe: οLeuLeuGlyThgllnllyGrgThrTheGlaHisLyyGspPry GsnGlaIllPheLeuSerPheGlnHiyLeu.LluAAgClyLysValGrgPhlLluMetLlu ValllyClySerThrLeuCysValAog (SEQ ID Ne : 162 5 pMON48500

SleProAlaProProAla ^ ysAspLeuAggValLluSlgeysLluLluGggGypSlrHis ValeluHiySerArgLeuSe: ACln <GjyPrylluValHiyPgoLluPgyThrPgoValLlu LeuProAlaValAypPheSerLeuGlyGluTοpLyyThAllnMecGlulluThrLysGla Cl] nGypIleLeuGlyAlaValThrLeluLeuLluGlullyValMltGlaAlaAAgClylln eluGlyProThr (GjsL eu S ERSE r LeuLeullyllnLeuSegllyllnValGAgLluLlu LeullyAlaLeuGlnSerLeuLeuGlyThAllnLeuPoyPoyllnllyArgTheThrAla HiyLyyAspProAsnAlaIlePheLeuSlrPhlllnHiyLeuLluGrgllyLyyValAgg Phelan ^ UletLeuValGlyllySerThgLeuG: yyValcrgcGluPlcGCyyοnMetGlaSle PοoAlaProProAlaCysAspLeIUCrgValLeuSlrLyyLluLluGrgAspSeοHiyVal eluHisSer, GοgLeuSerGlnCysProlluValHiyPgoLeuPeyTheProValLluLlu PgoAlaValAypPheSer] LeuGlyGluTgpLyyGhrllnMltGlulluGhrLyyAlalln GypIleLeuGlyAlaValThrLeuLluLlullullyValMltA.laAlaGAgGlyllnLeu ^ClyPro, τhr (GjsLeluSerSerLeuLeuGlyCl: nLeuSerllyllnValGrgLeueluLeu ClyGlaLe ^ uGlnSe: οLeuLeuGly ' Thrlln.eluPryProClnllyArgGhrGhοAlaHiy

184 424 eysAsprroAsmcLeIeeurιhUeubsrPhGlnHH £ LeuUeuU.AgGlyLysVaeGrgrhu eeuMeteebVaeGeyGlySerThrLuuCysVαeAog (SEQ ID No .: 163) OMONl8501

SeoPgzAlaProProACιCGsAcpOytbc: 'gValLeubsrOyΞLeuLeuArgAspSegHis

ValyeuHlsSεr: A-oLyubsrrlrlCGΞPrgGluValliiPrΌOeuProThrPrzValLeu yeuPooλlaValAspOheSsrOyub1yGluTrpLysTCrOC..ιnIetGluGlu'ChgLysGla

AlnCspDleLeuGC.ιAClVall’CrgyubyuUyuUlιUl · ιVallίeϋAlaAlaCogGlyAln

LeuAlyProThr: GyLyubsrrsrLe ^ .b, euGlyG] lΛyubsrglyG (LnValArgyeuyeu euuAeyAlaLeuG (nGsuOeuUeudnS-'haGlnLeuUrrOrrGlnClyAreg

HisyysAsoPozCsnAlaDlePh.eLebSegPheAlItfίiΞLeuLeluAogGlyLysValGgg

PhueebeeiLeuValGlyGlySerChreeuTysVαeGrgAebrhuAeyGlyAsriMutAeα

SeoPooΆlaPro? RoACιCGsAcpOyuArgValLeubsrrysLeuLeluΆrgAspSerHis yalLeuKi sSerOA · ggeubsrrlιOGs PrgZCLuValnHiProOeuProThrrroVaeyeuGuThuurgoArłaThrrroVaeyeuGuThuurgoAuhluGuMeurgoAreaThrrroVaeyeuGuThuurgoOułaThrrroVaeyeu;

AlnAspΐleLeuGlιACιVall'Crr · yuUyuLeuUlιUlιVallίetAlHaAogAlyAln yebAlyProThr <C / sLeuSerSerLeuLeuAlyAlnLeuSerAlyAlnVαlGrgLebyeu yeuAlyAlaLeuGCllSsrgyuUyuUlyThrGlrHJeubrgOrrGlltGlyArgThoChrGla

HisyysAΞoPozAsnAlaDlePheyeuSeoPheAlItfiisLeuLeuArgGlyLysVaLCgg

PheyeuMetLeuValGlyGlySerThryeuCysValTog (SEQ ID No: 164) pΜΟΝl850l

SeoProAlaProProACιCTsAcpOeebG: 'gValLeetbseryΞLeuLeuArgAspSegHis G ^? alyeuHysSerAroLyubse'r 1lCGsPrgGl.ιVaΓHliPrrLyeiProThrProValLeu LeuPrzAlaVAlA (S) OheSsrOeuGlyGluTίrLysT- ^ o :: lIttίetGluGluThgLysClα AlnAspDleLeuGlιACιVaaι-Ώ: ryebyuLeeιGlιUlιValMeLA (LaAla.AogAlyAlr 'LeuAlyPgzChgCysLeuSegSeryebLeuAlyAlInyeuSerGlyGlnVαlCogLebLeu LeuAlyAlaLeuGcιnsrgyuUyuUlιy'hrGlrti _J euUroOrrClnGlyArgThoChgGla HisLysCsoPozCsnClaDlePheLebSerPheAltf ^Λ ^ isLeuLeuAggAlyyysValCgg PheyelUMetLeuValClyGlySsrOCrLyuCC εValAAgGAιUheGlyGlyAΞ: ΩGlyAly GsRMetAla3erProZAιargo ^J rΌACιaysAτρ0eeb_cgVallyuSerLyΞLebLeucgg GspSurHisValLeubHiSsrOArgeubsrGlnCT <sPrrCluValHisProyuurroChr PgoValL · e ^ JLeelPrΌACιValAcpOheeseTyuUlιGlιUrpo.ysThrGlϊτMepAluΆlb ChgLysAlaGlIϋGs> OIιLLuUlyAClValΊCΏ · ^ LeebyubL lUluGlyValMet.GlaAlα GrgAlyAl] i] yeuGC.ιPrgOCrOGsLyuSerSerLeebyuUAιGlIlLeuSeoAlyAlnVal GrgyeuLeuLeuGlιACιLyuUlιSsrgyuUeuGlιTCrOlιLyuProProGlnAlyGgg ThoThrd aHis LysAsp ProGsnA.laDl e PhuLeuS erPheG InHłi sLeuLeuArgGly yysValCrgPheLel.U4eeLeuValGlyGlySerhhrLeuCysValGog (SEQ ID NO: 165) ~

13182.Pept

Asn Cys Cheese j. Ie Aee He Asp Glu lie How much His His eru Lys Arg Pro Pro Gia P AFTER Alu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Cheese L Le Aee Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Cheese Phe VaV Gęg for Vai Lys Asn Leu Glu Asn Ala Cheese Gly How much Glu Ala How much e_ Le Απο Asn Leu Main Pro Cys Leu Pro S born da Thr Ala Ala Pro S sr lAr His Pro How much How much lle Lys Ala Gly Asp Trp Main Glu Phe? λΑΤΟ Hu Lys Leu Thr Phe Tyr Leu Val Tho Leu Glu Main Ala Gin g Gl Din DJLn iyr Val Glu Gly dy Gly Gly Cheese Pro

184 424

Gly Gly Gly Ser Gtysly Tly Cer His Pro Glu Glu Leu Vc.l Ter Cer Crp Ala Pro Ueu Ser rSe thous Apo Gly Tys Ueu Ser Gin Lee Aii Csu Ueu Ueu lin Ala Leu Vlu Tly SDe Ueu Asp Chr Ueu Gin nee Ατρ Sal Crp Gln Gin Met Glu uli Teu Sty Ghr Gln Gly Tla Met. Prr TTi SPh Ala Gly Cly Vai Lee Val ATu Csu Val Ser tyr Arg Val L eu Ato 77ii. Aly Gly Cheese Gln SSe SPh Au. Trg Uys Diu Gln Glu Ατρ Tly ATu Tla Ghr (SEQ DD No .: 166)

Ττπ TMU ATe Ter Les Teu thousand TCy Ais; Csu Teu dy GDi Po Τ ^ ι; on Acn Ter du Teu Trump dy Leu Tli hu Teu Tyr du dy SSr Po Tui Teu Gly Po Thr Ala Acs PllhU ATe Thr Thr IDe Underworld ATa Po (TTi Leu on Pro ATe Gsu Trump PtlGU Main Tao And this Ais Leu on Sir Phe Leu du Teu Trump on Po Cheese Jan Gly A ^ u Sus G ^ r Leu du di Val Tc Te Leu Main du Lys Leu thousand

13183 Pep Asn Thousand Cheese Dlr Underworld; And Dl Ttsp du Pro Pro Ala Pro Leu L Ue Ats Spo Vai Cheese Dle Uru Underworld Acg 7to Acn Cheese Phe Vai Arg Ala Val Sus Acn Alu Ala Dle Uru Arg A τη S ^ u on Ala Ala Pro Cheese Arg H ii Sieve Ili Main Glu Phu Trg Glu Lus Leu Thr Main Ala Ain Glu Main GCu tyr Val Gly Glu Pro Cheese Gly Po TDl S & r Cheese Uys Glu Cheese His Lus Gsu Po His Pro Glu Glu Leu V al Leu Leu Crp Tla Pro Ueu Cheese S «r Thousand Pro Gly Cys Ueu Srr Main L eU His Cheese Ueu Ueu Main Tla Leu G le Jan How much Uru Tsp Chr Ueu Main Luu Asp Val Crp uin ropes Underworld Glu G le Leu Gly Chr Main Gly Tla Underworld Spo Ala Phe Ala Gly Gly Val Leu Val Ala Cheese Vai Cheese Cyo Trg Val Luu Trg His Cheese Gly Gly Srr Main S Sr The Leu Arg Uys Dlr Main Gly Ατφ Gly Ala Ala Chr (SEQ DD No .: T67 )

How much How much Kii His Leu Lys (eg Asn Asn Leu Asn Asp Glu Asp Leu Arg Leu Pro Asn Leu Glu Leu Glu Asn Ala Cheese Gty How much Pro thousand Leu Po Cheese Ala Thr How much How much Lys Ala Gly Asp Tir? Phe (type Leu Val Thr Leu Glu Glu Gty Gty Giy Gly Cheese Drank Tlhr How much Asn Pro Cheese Pro Pro Asn Underworld Ala tyr Lys Leu thousand Gty His Cheese Leu Gly H <u Pro Cheese Main Ala Leu Main Leu Ala Gty Leu Phe Leu Tyr Main Gly Cheese Pro Glu Leu Gly Pro Thr Ala Asp Phe Ala Thr Thr How much Mut Ala Pro Ala Leu Main Pro Ala Cheese Ala Phe Main Arg Arg His Luu Main Cheese Phe Leu Glu Leu Ala Main Pro Sur Gly Gty Leu Lys Cheese Leu Glu Gin vai Ala Luu Main Glu Lys Leu thousand

13184 Pep Tsn Thousand Cheese Dle Mee G De Asp Glu Pro Pro Ala Pro Lee L er Asp Pro Vai Srr Dlr Uuu Mee Tcs Arg Asn Cheese Phr Vai Trg Trump Thallium Lys Asn Alu Tla Dlr eru Arr Ττπ Leu Main Ala Tla Pro Sur Arr A is Pro How much Ain Alu Phr Trg Gly Aus Leu Thr Ain Tla Prices Alu de T In tyr Val Gly Gly Gly Cheese Gty A ly Gly Cheese

How many How much His His Luu Lys Arg Asn Tsn Leu Asn Asp Glu Asp Luu Arg Leu Pro Asn Leu Glu eru Alu Asn Ala Sur Gly How many Pro Cys Luu Pro Sur Ala Thr Hu How many Lys Ala Aly Asp Crp hhr “C ^ r Luu Val Thr Luu Glu Glu Aly Gly Gly Giy Cheese Pro Asn Mut Ala Pro Alu Uuu Aly

184 424

Pro Tho Leu Asp Thr Leu Cln Leu AS ( Incl , Αι Pcp Phe , Αι PGe Thr How much Trp Cln Cln Underworld Alu CUu Leu uAy , eL , Αι , ρο ACu , 6:, 1 Cln Pro Thr Main Cly Ala Underworld Pro Ala ahe , Αι , Ee ACl PPe , Αι Arg (rg Ala Gly Cly VaU Leu ViU Al A 1eu , Ηδ , Αι Seu Phh Leu Alu Val Cheese Tyr Arg Va1 Leu Arc HH p PeL , Αι , Τη Po , EU Cly Cly Cheese Gly Cly Cheese Cln Cheese Phr Lee , Ε, Lll Cln Va1 (rg Lys How much Cln Cly Asp Gic But , Αι Pee , Αι GTu Leu Thousand (la Thr Tyr Lys Leu Thousand HiH Pro , Τυ , Cu Lee Val Leu Cly His Cheese Leu Cly How much Pro TrT A.Cl PPO , € ^ U , Ε, Seu Pro Cheese Cln Ala Leu Cln Leu (la Gic C (S , EL , Τη Llu , Hs Cheese Cly Leu Phe Leu Tyr Cln Cly LeL Ijeu , Αι , Αι Peu GTu , Αι lie Cheese (SEQ ID No .: 168)

13185, Pt

(pp Thousand Euo How many Underworld How many Asp Alu How much Hives , hs Hhs Leu Lus Well Pro Pro Ala Pro Luu Luu Asp Pro Asn Am Ann Asp GAu Ans VaU Sur How much Luu Underworld Asp Arg Asn Leu Aro , ρο Asn Lll GAu Euo Phu Vil Arg (li VaU Lys Asn Leu Glu , cn ACe Cheese GAy How much Alu Ali How much Leu Arg (sn Leu CUn Prr CTy , ^ u Pro Cheese Ala TTr Ala Ali Pro Cheese Arg His Pro How much Hi Hives Lys A.Aal Glv Acp Ttp Cln Alu Phu Arg Alu Lys Leu Thr Phr Lyr , 6 :, Val Thr Lll Cln Ali Cln Alu Cln Cln Tyr Vil Glu uly , Τγ Gly Seu Pro Cly Alu Pro Eur Cly Pro How many Euo Thr Background Asn Drank Cheese Pro Pro Eur Lys Alu Eer His Lys Eer Pro Asn Underworld But Pro Glu Lll GAy Pro Thr Luu Asp Thr Luu Cln Luu Asp Val de Acp Phe Alu Τίτ Thr Hle Top Cln Cln Underworld Alu (Uu Leu Gly Underworld Ala Pro Ala Leu Cln Pro Tho Cln Cly (li Underworld Poo Ala PPie Ala Sero Ala PPe Main Arg Arg (li Cly Cly Val Luu VlU Ala ^ ear His Leu Main Vulture Phe Luu Alu Vil Eer Tyr Arg VaU Luu Ar co His Leu Ala Main Pro Cheese Cly Cly Suo Cly Cly Eer Cln Euo Phi; Leu Leu Lys Cheese Leu GAu Cln Vll Arg Lys How much Cln Cly Csp Gly Ala Ala Leu Main GAu Lys Leu Thousand Ali Thr Tyr Lys Leu Thousand His; Pro Glu Glu Leu Val Leu Luu Cly His Eur Luu Cly How many Poo Trp Ala , ρο GeL Cheese Seu Cys Pro Sur Cln Ala Leu Cln Leu Ali Gly Cys Leu SEU Main Le: u His Eer Cly Luu Phu Luu Tyr Cln Cly Leu Leu Main Ala Leu Glu Gly How many Euo (SEQ ID No .: 169)

13186 Pep

Asn Thousand Euo lie Mut IUu Asp (Uu How much: How much His His Leu Lys Arg Poo Poo Ali Pro Leu Leu Asp Poo Asn Asn Leu Am Asp Glu Asp Vaa Sur IUu Luu Underworld Asp Arg Asn Leu Acrg Pro Asn Leu Glu Euo Phu Vi1 Arg Ali VaU Lys Gss Leu Glu Asn Ala Cheese Gly How much Alu AUi IUu Leu Gog Asn Luu (Us Pro Cys Leu Pro Cheese Ala Crowded (la Ali Poo Eeo Arg His Pro IUu How much: How much Lys Ala Gly Asp Trp Als Clu Phu Arg (Uu Lys Luu Tho Pho Tyr Leu Vai Thr Leu Glu CUn Ali CUs Alu Cln Als Tyo VlU Glu Gly Gly Gly Gly Cheese Pro Cly Cly Cly Euo Cly Cly (Uy Euo Asn Underworld. Ala Underworld Ala Pro Ala Leu CUn Poo Thr (Us Cly Gli MUt Pro » Ala PP h, Ala Cheese Ala Phe

100

184 424

Main Arg Arg But and you Gly Val Llu tv1 Tla Her HHi Llu Hln Ssu Phe Leu Glu Val ler oyr Ar; wi Llu Tc; 0; HS Llu Tla Hln After; Cheese Gly Gly See Oly Gly Cheese Hln 0er The Llu Llu Crackpot Heu Llu Glu Tln Val Arg gys How much Main Tly Tep Tly H.la Ala Llu Hln ltu Lys Leu Cys Ala aTh oyr Lys Llu (0ys HHi PPO Llu Llu Llu Val Leu Leu Gly HiH Cheese Leu G ^ Her Hor Lto Tla PhO Llu Her Cheese Cys Pro Se; Glu aIu Leu Glu Llu Tln Tly Thousand Llu Her Hln Llu His Cheese Gly LeL Phe: Leu iyr Main Tly Llu Llu Main Ala Llu Hln Gly How much Cheese Prp oin Leu Gly POO Thr Llu Asp Thr Llu Hln Llu Asp Val Ala Ace phie Ala Tter Thr 0ia Tir;) Hln Main MeU Hln Glu Leu Gly (SEQ ID No. 1 ^ 0 )

13187.pept

Asn Thousand Su; Ili Ueu How many Asp Glu Iia How much Hii Hi s Leu Lys Arg PhO Pro Ala Pro ouu Ueu Asp Po Asn Asn Leu Asn Asp Glu Asp Val Se; How much Leu Me U Asp Arg Asn Leu Arg Leu Po Asn Leu Glu Se; Phe Val Arg gla Val Lys Asn Leu Glu Asn Ala Cheese Gly How much Glu Ala How much Leu ug; Asn Leu Gla. Hor Cys Leu Pro Cheese Ala Toll Ala Ala Poo Ses Aag His Pro How much How much How much Lys Ala Glv Asp 1103 Main Tlu Phe Arg gul Lys Leu Thr Phe Tyr Leu Val Tiar Leu Glu Main Ala Tln Glu Main lln Tyr Val Glu GIv Gly Gly Gly Cheese Pro Tly Tlu After Ses Oly Pro How much Cheese Thr How much Asn Pro Cheese Pro Pro Se; Lys Tlu See Lys Cheese Pro Asn Underworld Ala Underworld Ala Poo Ala Leu Main Poo Thr Main Tly Ala Underworld Pro Ala Phe Ala Cheese Ala Phe Main Arg Arg Ala Gly Gly Val Leu Val Ala Ssu Has Leu Main Cheese Phe Lru Glu Val Cheese Tyr Arg Val Leu Arg His Leu Ala Gin Pro Se; Gly Gly Ses Giy Tly Cheese Main Cheese Phe Leu Leu Lys Cheese Leu Glu Main Val Arg Lys how much Main Gly Asp Gly Ala Ala Leu Main Glu Lys Lru Thousand Ala Thr You; Lys Leu Qys His Pro Glu Glu Leu val Leu Lru Tly His; Cheese; Lru Gly How much Pro Trp Ala Pro Leu Cheese Cheese Cys POO Cheese Main TCLa Lru Main Leu Ala Gly CC / S Leu Cheese Main Leu His Cheese Tly Leu Plre Lru Tyr Main Gly Leu Leu Main Ala Leu Glu Tly Ilr Cheese Pro Glu Lru Gly Pro Tiar A letter Asp T11r; Leu Main Leu Asp Val Ala Asp Plie Ala Thr Thr How much Trp Main Main Underworld Glu Glu Lru Tly (SEQ ID No .: 171)

83888.Pept

Asn Thousand Cheese How much Attorney ilr Asp Glu How much How much His His Leu Lys Arg After Pro Ala Pro Leu Lru Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Se; how many Leu Underworld Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Se; Phe Val Arg Ala ViU Lys Asn Leu Glu Asn Ala Cheese Gly How much Glu Ala how many Leu Arg Asn Leu Main Pro Cys Leu Pro Cheese Ala Thr Ala Ala Pro Cheese Arg His Pro How much How much How much Lys Ala Gly Asp Trp Main Tlu Phe Arg Glu Lys Leu Thr Phe Tyr Leu val Thr Leu Glu Main Ala Tln Glu Main Main You; Val Glru Gly Gly Glv Gly Cheese Drank Gls Tly Tly Cheese (You Gly Gly Cheese Asn Underworld Ala Thr Main Gly Ala Underworld Pro Ala Phe Ala Sr; Ala Phe Main Arg Arg Ala Gly Gly Val Leu Val Ala Cheese Has Lru Main Cheese Phe Leu Glu Val Cheese T / y Arg

184 424

101

aal Leu Ars HSs Geu Ala Main Gpo Dog Main Main ise Gln Gly Cheese Tln Sio Phr Ili Leu Lys SSE Lli how many Main wa Lgo GUS PIe Main Gly Gsp Gl— rsn But Leu Main Main GUS Geu Cas Lle GCh iyr Lys Leu Gys His Pr o Glu Glu Lee aa Geu Gli Main HSs 1n Leu Gly How much Pro Trp ASn iro Leu SSE Sn Lcs Cf. SSE Main VSe Leu Main Leu Ala Gl— ((r iee Cheese Main Gli Lśs ise Main Gee iPe Leu Tp ^ r Tln Cly Leu Uli Main Ala Lee Glu iln PIe SSE Spo Glu L ^ u Gly Pro Thr Leu Asp GGr Leu Main Gli Gap Gaa Alu Ass iPe Ala Thr Thr How much Trp pin Main Underworld Main iln Gli Lly Underworld AAl iro Ala Leu Tln Poo (SEQ ID No .: 172)

13189 Pep

Gsn Cys Cheese How much Underworld How much Asp Main IIe PIe His HSs ieu Lys Arg Poo Poo Ala Pro Leu Leu Asp irr Asn Asn Leu Asn 1.sp Glu Asp Val sio Il € 5 Leu Underworld A ^ pp Ago Asn Geu Arg Leu Cf. Asn Leu Glu cheese Phe Val nsrg AS a Val Lus AGP Geu L lu Asn Aln ise Gly How much Tlu Gla I1i Leu Arg Asn Lee Main ioo Lys Leu Cf. Sn Ala Thr Gla Gla Pro Cheese Arg His Pro PIe iIn He Lys Ala Lly Asp Trp Tln Clu Phe) JGrg Giu Lys Lee GCh Ghh iyr Leu Vla Ghr Leu Glu Tln Gla Main Glu Gin Main IGr Val Glu Gly Gly Gll ' Gly Cheese Pro Cly Clu Pro Cheese Gly Pro IIe Sn GCh How much Asn Poo Cheese Pro Pro cheese Lys Glu Cheese His Lys Ssr Pro Asn Underworld Ala TTr Main Gly Ala Underworld Pro Ala Phe Ala Cheese Aln PPh Main Arg Arg Aln Gly Gly Val Leu aal Ala Cheese His Leu Main ise Sweat Leu Glu VvV Ssr ip / r Arg aal Leu Arg His Leu Ala Main Pro in Gly Gly SSE Gly Gly Cheese Main sio Phe) Leu Leu Loess Cheese Slu Llu Main vai Asg Lys How much Main Cly Gsp Gly Ala Ala. Leu Main Glu GUS Leu CC / s Aln Thr Tyr Lys Leu Ays His: Pro Glu Glu Leu La a Leu Leu Gly HSs: Cheese Leu Gly How much Pro Trp Ala Pro Leu Sn in Crimson Pro Cheese Main Ala Leu Main Leu Gla Gly ((ys Leu Cheese Main Glu HSs Cheese Gly Leu Phe Leu Tso Tln Gly Leu Leu Main Ala Llu Glu Main How much Cheese Pro Glu Leu Gly Poo Thr Leu ussp Thr Leu Main Glu Asp Val Ala Asp Phe Ala Thr Thr How much Trp, Main Main Underworld Glu Glu Geu Gly Underworld Aln Pro Ala Leu Main Pro (SEQ ID > No: : 173)

13190.Pept

Gsn Cvs Cheese How much How much Asp Glu PIe How much His His Leu Lys Arg Pos Poo Ala Pro Leu Leu Asp Cf. Asn Asn Leu Asn A ^ £ p Glu Asp Wow cheese How much Leu Underworld Asp Asg Asn Geu Arg Leu Pro Asn Leu Glu sio Phe Val Arg Ala llal Lus Asn Geu Glu Asn But Cheese Gly How much Clu Gl a How much Leu Arg Asn Leu Main Pro Cys Leu Prr Cheese Ala Thr Gla Gla Pro Arg His Pro He IIe How much Lys Ace Gly Asp Crp Main Tlu Pho Arg Glu Lys Leu GCh Sweat Tyr Leu Vai Thr Leu Glu Main Gla Main Glu Main Main Ter Val Glu Gly Gly Gly Gly Cheese Pro Cly Cly Gly Cheese Gly Gly Gly Sn Asn Underworld Ala Sn Ala Phe Main Gog Gog Ala Gly Gly ilal Leu Val AS a Cheese His Leu Main Cheese Phe Leu Clu Val Cheese 1Τ ((, Arg val Leu HCg His Leu Ala Gla Pro Cheese lly lly Cheese G ly Gly Cheese Main i ^ r Phe Leu Leu Ler Cheese Leu Glu

102

184 424

Cln Val Aog Lys How much Main Gly Aas oly Ola Ola Olu OCn 0 Cu Oys Leu Cys Ala Thr Gye Lys Lee. Ccc Oii Opo Alu OCu Olu Oal Olu Leu Cly His Cheese Leu Gly He Apo Aeg Ola Ore Olu Osu Osu Cyy Pro Cheese Cln Ala Leu Main Lee Olu Oly Agc Alu Osu Ola Olu Aii Cheese Cly Flax Phe Leu Tyr Glu Oly Oli Olu OCu Ola Olu Alu Cly How much See Pro Clu Leu Gly Pre CTr Oli Oas CTr Olu OCu Aei Cas Val Ala Asp Phe Ala Thr TTe OIe Ocg Aln rin Μβΐ OCu OCu Oeu Cly Underworld Ala Peo Ala Leu Gla Aro CTr But Oly AAu Οθΐ Orr Ola Phe Ala (SEQ ID Well: 174 5

13191 Pipt

Gsn Gys Aug Ili Myth How much Ass Clu OIe 0 Iu Hii Hii Olu Cyc Acg Peo Pro Ala Peo Liu Leu Asp Oro Ass Asn Leu Asn Acs Olu Ols Val Cheese Ili Liu Myth Asp Acg Oss Oee Ccg Llu Pro Ass Clu Olu Sir Pooh Val Arg Ala val Lys Asn Olu OCu Acn All Oee Oil OIe Glu Ala How much Leu Gog Asn Llu Cll Ore Cyc Llu Pro Axis Ola OTr Gla Ala Pro Sir Grg His Pro He Oll He Lys Ala Oll Ccs Ccg Main Glu Pooh Grg Clu Lys Leu rCh orh oyr Llu OVi1 OTr Oei Olu Cln Ala Cln Clu Cln Main Tyr val Olu Glv Gly Gly Olu Osu Opo Cly Clu Pro Aug Gly Pro H.e Osu OTr OIet Asn Pro Oei Ore Ore Sir Lys Clu Sir His Lys Cheese Oro Asn Underworld Ala SSE Ala. OPie Olu Arg Aog Gla Cly Cly Val Leu Val Ala Cheese His Leu Olu Osu Ohe Leu Glu Val Cheese Tyr Arg Val Llu Ocg His Leu Ala Bullfinch Oro Osu Cly Gly Sir Cly Cly Sir Main Ssr pre Leu Leu Lys See Oeu Olu Main Val Aeg Lys 1li Cln Gly OGp Gly Ala Ala Leu Glu Shhh Oys Liu Cys Gla The Tyr Lys Leu thousand His Pro Glu Glu Llu Val Lei Liu Gly His See Clu Gly How much Pro Tcg Ala Pro Leu See Ssu oys Peo Cheese Main Ala Oeu Main Leu AG u Gly Cys Leu Cheese Main Lei Hii Sir Cly Leu Phe Oeu circus Main Gly Lei Leu Main Ala Leu Giu Bullfinch 1li Sir Pro Glu Olu Cly Pro Tter Lei Asp Thr Leu Main Leu Asp Val Ala Asp Phe Ola Thr Thr He Tcg) Main Main Underworld Glu Giu Llu Cly Underworld Ala Pro AC u Leu Main Drank Thr Main Gly Ala Underworld Pro All Pooh Ala (SEQ ID No .: 175)

2r192.Pept

Gsn Cys Cheese He MmI How much Asp Glu He How much His His Leu Lys (cg Pro Pro Ala Pro Leu Leu Asp Pro Am Asn Leu Asn Asp Glu Asp Vaa See How much Leu Underworld Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Cheese Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Cheese Glys He Clu Gla How much Leu OGg Gsn Leu Main Pro Cys Leu Pro Cheese Ala Thr G1i Ala Pro Cheese Ocg iis Pro How much He How much Lys Ala Glys Asp Tto> Cln llu Phe Arg Glu Lys Leu Thr Phe Tyr Leu val Thr Leu Giu Main Ala Main Gili Gin lln Tyr Val Gin Gly Gly Gly Gly Cheese Pro Gly lly Gly Cheese Gly lly Gly 'Ser Asn Underworld Ala Tyo Lys Leu cys iis Pro Glu Giu Leu Val Leu Leu Gly His Cheese Leu Gly How much Pro Trp Gla Pro Leu Cheese Sir Cys Pro Cheese Main Ala Leu Main Leu Ala Gly Cys Leu Cheese Main Leu His Cheese Gly Leu Pooh Leu Tyr Main Gly Leu Liu Main Ala Leu llu Gly How much Cheese Pro Glu Leu Gly Pre Thr

184 424

103

Leu Asp Thr Leu Cln Leu And 1? Incl , 13 Asp Phe Alley TGr Thh IIl Trp Main Cln Underworld llu Glu , LU Underworld Ala Pro AAl , LU on Po Thr Main Gly Ala Underworld Prr , Al , Pe Ala Cheese Ais PPe on Λιο Aan Ala Gly Gly Val Leu wa , Aa SSE His Leu Main SSE , Ρτ , LU giu Val Cheese Tyr Arg Val Llu , -Γς , is , eu Ala Main Po Thr , ro Leu Gly Pro Ala Cheese Cheese Llu , AFTER OCe , er Phe Llu Llu , ys "Er Leu Clu Main Val Arg Lys How much , Gl oce Asp Gly Ala AAl , eu on G1u Lys Leu Cys Ala Thr (EQ, I, No .: 176)

13193.Pept

Asn Cys Sro How many Underworld IIl, ιρ OCe How much How much His Hii Leu , ys Aso Pro Poo Ala Pro Leu Llu , ΡΟ Asn Asn Leu Am A ^ j5 Glu Asp Val Sro How much Leu Underworld Ais, 10 Leu Aog Leu Pro Asn , eu Main Sun Phe Val Arg Ala wa, 'ν'Ξ Leu Glu Asn AAn Cheese dy He du Ala How many Lru Arg Am, eu on Poo Cys Leu Pro Cheese Al a Thr Ala Ala Poo Cheese Arg Hii, ρ ^ ο IIl How much How much Lys AAn dy Asp Ttn) Main Clu Phr Arg Clu Lys, eu TTn Phe Tyo Leu WI Thr Leu Gcu Main Ala Cln Glu Cln for TT ^ r in i Glu Gly Gly dy Gly , er Pro Cly Glu Pro Sro Cly Pro Ose Tho How much Asn Pro Cheese Pro Pro Sro Lys Glu Sro iis Lys, ^ r Pro Asn Mrt Ala lyr Lys Leu Cys iis Poo Clu Glu Leu wi, eu Llu Gly His Cheese Leu Gly How much Pro Trp Ala Pro Leu Cheese CCs cheese Pro Seo Main Ala Leu Main. Leu Ala Gly Cys Leu Sro Cln Leu, is See dr Leu Phe Leu ST ^ 3r Main Gly Leu Leu Main da Leu for Un Seo Pro Glu Leu Glv Pro Thr Leu Asp Tho Lru Cln Leu, sp in i Ala Asp Phe Ala ΤΗ Thr He Trp Main Main Mrt llu dl, eu dy Underworld Ala Pro Ala Leu Main Pro Thr Main Gly Ala Mrt Pro Ala PPh Ala Sro Ala Phe Main , 1 ^ TGsg Ala Gly Gly Val Leu wi Ala See iis Leu Main Cheese Phe Leu Glu Val Cheese Tyo Arg Val Leu Arg His Leu Ala Main Pro Thr Pro Leu Cly Pro Ala Srr Seo Llu, ρο on Seo Phe Leu Leu Lys Cheese Leu Clu Main Val Arg Lys Ul Gln Gly Asp Gly Ala Ala Leu Main C-lu Lys Leu Cys Ala Tho (SEQ H ^N o: 177)

25190.Pept

Gsn Crs Cheese How much Underworld Hn Asp GAu How much How much His His Leu Lys Tirg Poo Poo Cla Pro Leu Leu Asp Pro Gsn Asn Leu Asn Asp Glu Asp Val Cheese How many Lru Mrt Ass , 1 ^ Asn Leu Aog Leu Pro Asn Leu Glu Seo Phr Vαe Aog Cla wa Dys Asn Leu Glu Asn Ala Cheese Gly He Clu Gla How much Lru Gog Am , eu Main Poo Cys Wow Pro Cheese Ala Thr Gla Gla Pro Sro Gog Hhs Pro IIl How much How much Lys Ala Gly Asp Ttop Cln du Phe Aog Clu Lys Leu Thr Phe TyN Leu Incl Thr Leu Glu Cln Gla on Glu Cln GGu , νΓ Incl Glu Gly Gly Gly Gly Cheese Pro dr Gls dr Sro Gly on Gly Cheese Csn Underworld Ala Pro Glu Leu C-ly Poo Tho eeu Asp Tho Llu Main Leu Gsp aae Ala Asp Phe Ala Thr Tho How many Top Main Cln Mee Glu G'lu Leu Cly Underworld Ala Pro Ala Leu on Pro Thr Main Cly Aln Underworld Pro Ala Phr Ala Cheese Ala Phe Main Gog Gog Cla Gls Hy WI Leu Incl Gla Sro His Leu Main Cheese Phe Leu du Val Seo Tyo Aso Incl Leu Gog HSs Leu Ala Main Pro Thr

104

184 424

Pro Uuu Gly Spo Ala Cheese Cheese Leu Pro Main Cheese Phe Leu Leu Les Sur Uuu Main T ln Val Trg Lys How much Ain Gly Asp G? LV Ala Ala Leu Main Clu Lys Teu Cys Ala Thr tyr eyn Leu (thousand Hii Pro Glu Glu Ueu Vai Leu T eu Gly Hin Cheese Leu Aly IDe Pro Trp Ala Pro Leu Cheese Sur Cys Tpo Sur Main Ala Leu Ain Leu Ala Gly Cys Leu Cheese Ain Uuu Hii G ^ r Cly Uuu Phe Leu tyr Main Gly Leu Leu Glu Ala Ueu Clu Gly T De Cheese (SEQ ID Tr: 1.78)

pMON25191.Pep

Tsn Cys Cheese Dle Mut Dlu Asp Ulu Dlu Dle Hin Hi? Uuu eys Trg Pro hro Ala Pro Uuu Leu Acs> Trr Cts Acn Teu Acn Ατρ TUe Ατρ Val Cheese Dle Uuu Mut Asa? And this Acn Teu Acr Teu Tpo Acn Teu TUn Sur hhu Val Arg Ala Incl ces Acn Teu SUu Acn Background Dec Aly GDe Glu Ala Dle Uuu Arg Asn L eu Background Trr S / s Teu Trr Dec ATa TCh Ala Tla hro Cheese Arg Hii Trr TDe GDi TDe Thes ATa cle Ατρ Tgo Gin Clu Phu Trg Glu Lys T eu ACh CPi you' Teu Thallium TCh Teu TUe Main Ala Aln Alu Cln Main you: Av1 TUn HERE HERE HERE TUn Dec Srr Aly Clu hro Sur Uly Prr G De Ter ACh TDe Acn Tpo Dec Spo Tpo Sur ess Glu Sur Hin Lys G ru Sro Acn Teu ATa Tpo Alu Teu HERE Pro Chr Uuu Tsp Chr Leu T Un Teu ccn Thallium ATe Ατρ Phh Trump TCh Chr Diu Grp Main Main Meu T Uu Alu Teu HERE Teu ATl Aro ATe Teu Main Pro Ghi Gin Aly ATe A eu Aro TC e gpi ATe Cheese Trump Sleeps Tln Arg Trg Ala Uly Gly Incl T eu Cv1 But Dec Tin Teu TUn Dec Sleeps Uuu Giu Val Sur tyr And this Incl Teu Tao Yee Teu Trump Background Spo ACh Pro Uuu Uly Pro Tla Ssu Dec Teu Pro Sln Dec PPh Leu Teu ces Cheese Ueu Alu Uin Val And this Thes GDu TCn Tly Ατρ HERE But But Teu Main Glu Uys Uuu thousand Trump Thr tyr Thousand Teu T / s Hin Prr Tlu Alu Ueu Val Ueu Uuu Aly Hii Dec Teu HERE TDe Prr Tco) ATe Tpo Leu Sur Sur thousand Pro Sur Main ATe Teu GUn Teu ATe Gly C / s Teu Cheese Aln Uuu His Sur Uly Leu The Teu you' Tln HERE Leu Leu TUn STi Ueu Glu Aly Dle Cheese (SEQ dd No .: 179)

13194.Pept

Asn Cys Sur Dlu Mut IDe Asp HERE IDe GDe Tin Hii Leu Thes Alg Pro Pro Tla Pro Ueu Leu Asp Pro Asn Acn Teu Asn Asp GUu Asp Val Cheese Dlu Ueu Mut Ατρ Arg Acn Leu Trg Leu Po Asn Teu Glu Sur Phu Val Trg Tla Incl Thousand Asn Leu SUu Asn ATi Cheese Tly IDe Ulu Tla Dlu Uuu Arg Acn Teu Main Pro Sys Leu Pro Cheese Ala Thr Ala Ala Pro Sur Arg Hin Sro IDe IDe TDi Les ATa Gly Asp Tęp Uin Ulu Phe Trg Glu Les Leu Thr Phe Tyr Leu Incl Thr Leu Glu Uln Tla Uin Glu Cln Main tyr Incl Glu Gly Gly Gly Gly Cheese Pro Uly Uly Aly Sur Uly GUy Gly Cheese Asn Underworld ATa Underworld Ala Pro Ala Ueu Cln Pro Chr Cln GUy GTa Underworld Pro Ala Phe Ala Cheese Ala Phe Main Arg Trg Tla Gly Main Thallium Leu Incl Ala Cheese Hii Leu Glu Cheese Phu Uuu Alu Vll Sur you' Arg Incl Leu Arg His Leu Ala Main Pro Chr Pro Uuu Uly Pro ATe Ter Cheese Leu Pro Main Cheese Phe Leu Leu Uy? Cheese Uuu Giu Main Incl Arg Lys How much Glu Gly Asp Gly Ala But Uuu Cln Glu Uss Uuu Cts And Cei Thr tyr Lys Leu thousand His Pro Glu

184 424

105

Glu Leu VaV leu Alu Uly Hii Ssr Leu dy II ^ Pro Trp Ala Pro Leu Cheese Ses Ocs Po Cheese Gili Ala Leu on Leu AA ^ a Gly Cys Leu Cheese Main LeL His Ssu Uly Leu PPe Leu Yttrium on GGu Leu Leu Main Ala Leu Glu bCuy Hu Cheese Pro Glu Leu dy Pro Thr Leu Asp Thr Leu Hn LeL Asp Incl Ala Asp Phe AIi TTh ^ Thr He Trp Main Main Underworld Glu Glu ueu Gly (SEQ ID No .: 18) )

12395.rept

Asn Cys SeS ZIe Underworld. How much Asp Glu How many He His His Leu Lys Aog Pro Pro Air Pro Le ^ u Leu Asp Pr ob Tsn Asn Llu Asn Asp Glu Asp Val Cheese IIi Leu Underworld Gsp Arg Asn Leu Arg Lluu Pro Asn Leu Glu Cheese Phe Val ler Ala Val Lys Asn Leu Glu Asn Ala Cheese Gly How much Glu Ala IIi Leu Carg Tsn Leu Main Pro Cys L € iU Por o Cheese Ala Thr Πι Ala Prr oer Arg His Poro Ilit How much liii L ^ ys Ala Gly Asp Trp on Glu Phe Arg du Lys Leu Thr Phe ΊC ^Λ S ' Leu Incl TTu: Leu Glu on Tui Main Glu Main Main Tyr Incl Ulu GG.y dy Gly Gly Cheese Pro dy Glu Prr oer Gly Pro How much Cheese Thr He Asn Pro Cheese Pro Drank Cheese Lys Glu Cheese Hi and Lys Cheese Pro Gsn Underworld Ala Underworld Ala Pro Ala Leu on Pro Z ^ (a2: Main Gly Ala Underworld Pro Alu Phe Ala Cheese Ala Phe on Tog Arg Ala Gly Gly Incl Leu Val Ala Cheese His Leu Main Cheese Phe Leu Glu Incl Cheese Tyr Arg Incl Leu Arg His Leu Ala Main Pro Thr Pro Leu Gly Pro Gla Cheese Cheese Leu Pro Main Cheese Phe Leu Leu Lys Cheese Leu Glu Main Val Arg Lys How much Main dyy Asp Gly Ala Ala Leu on Glu Lys Leu Cys Ala Thr Tyr Lyy Llu CC / s His Pro Glu Glu Leu Val Leu Leu Uly His Cheese Leu Gly He Pro Trp Ala Pro Leu Cheese SeS 0 (/: 5 Pro Cheese Main Ala Leu Main Leu Ala Gly CC / s Leu Cheese on Leu Hi s Cheese Gly Leu Phe Leu TT / y on GUiy Leu Leu Main Πι Leu Glu Gly How much Cheese Pro Glu Leu Gly Pro Thr Leu Asp Tho Leu Main Leu Asp Incl Ala Asp Phe Gla Thr Thr He Trp Main Main Underworld Glu hive Leu Uly (SEQ ID No .: 181)

13196.Pept

Gsn Cys Cheese He Underworld How much Asp Glu How much How much His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Gsn Asn Leu Asn Asp Glu Asp Incl Cheese How much LeU Underworld Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Hundred Phe Incl Arg Ala VaU Lys Asn Leu Glu Asn Ala Cheese Gly How much Glu Gla How much Leu Arg Csn Leu Main Pro CC / s Leu Pro Cheese Ala Thr Gla Gla Pro Cheese Arg His Pro How much How much How much Lys Al a Gly / Asp Top Uln Ulu Pho Arg Glu Lys Leu Tlho Phe yttrium Leu Incl Thr Leu Glu Uln Gla Main Glu Main Main T ^ r Incl Ulu Gly Gly Gly Gly Cheese Pro Uly Uly Gly Cheese Gly Gly Gly Cheese Csn Underworld Ala Thr Main Gly Ala Underworld Pro Ala Phe Ala Cheese Ala Phe Main Arg Arg Ala Gly GIu / Incl Leu Incl Ala Cheese His Leu Main Cheese Phe Leu Glu Wi Cheese Tyr Arg Val Leu Ar At His Leu Ala Main Tho Pro Leu Gly Pro Ala Cheese Cheese Leu Pro Gin Cheese Phe Leu Leu Lys Cheese Leu Glu Main Incl Arg Lys How much Main Gly Asp Uly Ala Ala Ljtui Main Glu Lys Leu _Γ / ξ Ala Thr Tyr Lys: Leu CC / s His Pro Glu Ulu Leu Incl Leu Leu GIu / His Hundred Leu Glu How much Pro Top Ala Pro Leu Cheese Cheese CC / s Pro Cheese Main

106

184 424

Gla

Pooh

Clu

Phe

Pro

Liu Gln Llu Olu lly Cys Leu See Gln Leu Hii Osu Gly Alu Liu TyrGlu Cly Leu Llu Gln Ala Leu Glu Gly OIe Gee Pro Liu Gl (Pro OTr Leu Asp Background Leu Gln Leu Asp Oć ^ J. But Asp Gla Thr Background OIe Top Gln Gln. Mit Glu Giu Lei. Gly Mei Ale Cla Leu Cln Peo (SEQ id Ne: 1825

13197.Pept

Csn Gyy Sir Hi Underworld How much Asp Giu How much Ili His His Llu Cys OAg Pro Peo Gla Pro Llu Leu Asp Drank Gsn Asn Liu Csn Asp Glu Asp Val Aug How much Leu Underworld Asp ocrg Asn Liu Arg Liu Pro Aces Llu Glu Sir Pooh Val Arg But Val Lys Asn Liu llu Csn Cla Cheese Gly How much Clu Cla How much Lett Amg Asn Leu Main Pro Cys Liu Poo Cheese Ala Thr Cla Cla Pro See Aig His; Pro How much Ili Ili Lys Cla Gly Asp Trp lln Clu Pooh Arg Glu Lys Leu Thr Pooh Tyo Leu Val The background Lee Glu lln Gla Cln Glu Main Main iyr Val llu lly Gly Cly Gly Cheese Pro Cly Clu Pro Cheese Gly Pro How much Cheese Thr Ili Asn Poo Cheese Pro Pro Aug Lys Clu Cheese Hi s Lys Cheese Drank Gsn Underworld Gla Cho Main Gly A la Underworld Peo Cla Phe Ala Cheese Ala Pleats, lln Gog Gog Cla Gly Gly Val Leu Val Gla Cheese His Leu Main Cheese They drank Liu how many Val Cheese oyr Ocrg Val Leu log His; Leu Ala Main Pro Clio Pro Liu Cly Pro Ala Cheese Sir Liu Pro Main Cheese Phe Leu Leu Lys Sio Liu Clu Main Val Olrg Lys Ili lln Gly As p Gly Ala Ala Liu lln llu Lyy Leu oys Ala Tho Gye Lys Leu Cys His Pro Glu llu Leu Val Leu Leu Gly His Cheese Leu Cly How much Pro Trp Ala Pro Leu Aug Aug Cys Drank Cheese Main Gla Liu lln Leu Ala Gly Cys Leu Sio lln Liu His S ^ r Gly Leu Pooh Liu Tyo Main Gly Leu Leu Main Ala Leu how many Cly How much Cheese Pro llu Leu Cly Pro 'Games Leu Asp Thr Liu lln Liu Cyp Val Ala Asp Phe Gla Thr Thr How much Trp Main Main Underworld Clu Clu Liu Gly Underworld Ala Pro Gla Liu Main Pro (SEQ ID Well: Z835 )

13198 Pipt

Tin Cys Cheese Ili » tert How much Asp Glu How much Ilto His His Leu Lys Arg Pro Pro Cla Pro Leu Leu Asp Pro Gsn Csn Iru Csn Asp Glu Asp Val Aug Ili Leu Myth Asp Arg Asn Leu Gog Liu Pro Asn Leu Glu See Phe Val Arg Ala Val Lys Asn Leu Clu Asn Ala Cheese Gly IlLe llu Ala How much Leu Arg Asn Luu Main Pro Cys Leu Pro Cheese Ala Thr Gla Ala Poo Cheese Arg His Pro How much How much How much Lys Ala Gly Asp Top lln llu Phe Arg Glu Lys Leu Thr rhe Tyr Leu val Thr Leu Glu Cln Ala Cln Glu Main Main (tyr Val Clu Gly Gly Cly Gly Cheese Poro Cly lly Cly Cheese Gly Gly Gly Cheese Tin Underworld Ala Aug Ala Phe Main Gog leg Cla Gly Gly Val Leu Val .Ala Aug His Leu Main Cheese Phe Liu llu Val Cheese Tyo Aeg Val Liu Arg His Leu Ala Main Pro Thr Peo Liu Cly Pro Gla Sio See Liu paoo lln Cheese Phe Liu Liu Lys Aug Iru Clu Main Val Aog Lys Ili Cln clay lys Asp Gly Ala Ala Leu Cln Clu Lys Leu Cyy Ala Tire (Tir Lys Leu Cys His Pro Glu Glu Liu Val Leu Leu Gly His Aug Liu Cly Ili Poo Crpo Ala Pro Leu Aug See Cys Pro Aug lln Ala Liu lln Leu Ala Cly Cys Leu Seo Cln Leu His Cheese Cly Liu Pooh Liu cye lln (Sl ^ y Leu Liu Main Ala

184 424

107

Leu Clu Gl— SIl Cheese Pro Ple Leu Gly Pro TGh lee Vsp GCh Lee Main Leu Ass GiI Ala Asp Phe Gla Thr Thr IIn Hco lle Main Underworld llu Clu Lee Uly Underworld A Ce log Gla Leu Main. Prg GCh lle Lly ASa Underworld Pos Ais ahh Ala (SSE VI HO _: 184)

23199.OlGt

Gsn Ars Ses OIi Underworld IIe Asp Clu Ilr How much HSs GSs leu Lys larg Pos Pos Ais aoo Leu Leu Asp Prs Gin Asn Leu LSP Mr Glu Asp aal Sio I1i er Underworld Asp lag Gsn Lru Arg Lee Pog SAP L-eu Glu Seo pIi vaa lag Ala Val Lus Gin Lru Glu Asn Ala Sn Gly How much llu Gla IIi Ili larg Asn leu lln Pos ccrs Lee log Sn Ala Thr Gla Gla Pro Ssi Arg HSs Po How much Ilr How much Lus Aln Gly Asp Trp Main Clu Pho Usg Glu Lys Ler Cho Phe / pyr Lee La i Η’ητ Leu Glu Main Gla Bullfinch Main Main Gla ipr aal llu Gly Gly lly lly Cheese Pro lly Clu Pro Cheese Gly Pro He Cheese Tho How much Ass Po Sn Pio? Pro Sio Lys Bullfinch Usi His Lys S € ^ 37 Pro Gin Underworld Ala ise Ala Phe Main Grg Grg Ais aly Gly Val Leu aal Gla Cheese HSs Leu Main Cheese Phe Leu Clu V31 Ise Chyr larg Val Lru Gog His Leu Ala Main Pro Thr Poo Leu Gl— Sog Ala Cheese Ssr Lru Prs Main Ssr pen Gee Leu Lys Sio Leu Bullfinch Πη Val market Lys How much Tln Gly Asp Gly ASa Ala Leu ropes Tlu Lye Pee Ars Ala Thr Tyr Lys Leu Cas HSs Pro Glu Glu Leu aal Leu Gee Gly His Cheese Uru —Ir How much Pro Tt, Ala Pro Leu Sio Sio Cyc Pog Cheese Main Ala Lru —Ig Leu Ace Gly Has Leu Cheese lln Leu His ise Gly Leu Phe Lru Tyo Main Gly Lee Leu Gin Ala Leu Clu Gl— GIi Cheese Pro Glu Uru Gly Pro TTh, Leu Asp Thr Leu lln Leu Ass pżaa. Ala Asp Phe Gla Tho Thr IIe This Main Gla Underworld llu llu Lee Uly Underworld Ala Pro Gla Leu Main Pro Thr Bullfinch. Gly Ala Underworld Pos Ala ahe Ala ((EQ ID No: 1.85 )

31104.Pup

Lru Jul Pro Asn Asn Leu Asn liG Clu Asp Val Cheese He Leu Underworld Gsp Ggg Asn Gee Arg Leu Piso liG Lru Giu Sn Ρήε Val Arg Ala aal Lys .Asn Geu Glu Asn Ala Sro Gly How much Main Ala How much Leu Arg Gsn Lru Main Gro CCSi Leu Pro Cheese .Gla Thr Ala Ala Pro Cheese Arg HSs Pos IlI He How much Lys Ala Gly Jul Top Gla. Glu Phe isog Glu Lys Lru The Ohie 11 (0 Leu val Tho Uru Glu Main Ala Main Glu Main Tln lly Gl— Gly Cheese Asn CCys Sio Ilr Underworld How much Asp Glu How much How much SSi Sis Leu lys Arg Pro Pro Gla Pos Lru Tyr Val Glu Gly Gly Gly lira Sn 1 = 070 Gly Glu Pro Sro Gly Pro How much Cheese TCn How much Asn Pos Seo Pro Sro Cheese Lys Glu Sro Sis Lys Cheese Pro Asn Underworld Ala Thr ropes Gl— Gla Underworld Pro Ala Phr Gla Cheese Ala Phe Main Arg .Gog Gla lira Gly GżćaJ. Leu Val Ala Sro Sis Leu Main Sn Phe Leu Giu aal Seo Tyr OGrg Val Leu Arg SSi Uru Ala Main Pro Cheese Gly Gly Seo lira Gly Cheese Main Cheese Phe Leu Lru Lys Cheese Leu Glu Main Val log Uys IlI Main Gly Asp Gly lia lia Leu Gla Glu Lys Leu CCrs Gla Cho Tyr Lynx Leu CC / s His Pos Tlu Glu Leu Val Leu Leu Gly Sis Sio Leu uly How much Pro Trg) Gla Pos Leu Sn Sn Cvs Pro Cheese

108

184 424

Tln AlaLeu Gln Llu Ola Gly Cys; Leu Ser Gln Leu Ηί =; Cheese Gly Luu Phe Lei Ghr Gln Tly Luu Llu Gln Ala Llu Glu Gly Ha Ssu Pro Glu Leu Gly Ppo Thr Leu Alp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Tłir Thr Iia Trp Gln Gln Met Glu Glu Luu Gly Meu Ala P; o Ala Luu Tln Pro (SEQ lD No .: 186)

31805.0uo

Asn Ala See Oly Iia How many GCa How much Llu Ocg Aen Llu GIu. Po cys Uuu Pro See Ala ohr Ala Ala And after Her Arg HH. ^ Po Ole Zler How much: Lys Ala Gly rep E.t.c Hln Tlu Ihr Lep Glu Lys Llu Thr Phe oyr Luu Val The Olu How many Tln Ala Hln Alu Main Main Gly Gly Gly Cheese Asn Cys See How much: Underworld Ilet Asp Alu Ole How much OHi HHi Leu Lys Arg Pro Pro But. And after Leu Llu Asp IhO Aen Asn Leu Aen Asp Glu Acp Val Cheese Ili Ulu Underworld. Asp Ar; Asn Luu Arg Leu Drank Asn Leu Glu Cheese Phu VaV leg 0.la Val Lys Aen Huu Glu Oyr Vaa Glu Gly Gly Tly Gly See And after Gly Tlu Drank Cheese Gly Pro How much Ssu Thr How much Asn Pro Cheese Pro ooo Cheese Lys Glu Cheese HŚS Lys Cheese Drank Asn Underworld Ala hhn Tln Gly Ala Underworld Po Ala Phe Ala Cheese Ala Phe Main Arg Ocg Ala Gly Gly Luu Val Ala Her His Leu Main Cheese Phe Leu Glu Val Su; You Arg Vnl Leu cerg His Leu Ala Glri Poo Cheese Gly Gly Sur Gly Gly Cheese Main Cheese Phe Leu Leu Lys Cheese Leu Glu Gla. Val Arg Lys How much Uln Gly Asp Gly Ala Ala Leu Gin Glu Lys Leu cys Ala Th; Tyr Lys Leu cys His Pro Glu Glu Leu Val Leu Leu Gly His Se; Leu Gly How much Pro Trp Ala Poo Leu Cheese Cheese CyS Pro Cheese Tln Ala Leu Main Leu Ala Gly cys Leu Cheese Main Leu His Cheese Gly Lru Phe Leu : ^ 21 Main Gly Leu Leu Main Ala Leu Glu Glv How much Cheese Pro Tlu Leu Gly Pro Thr Leu Asp Thr Leu Main Leu Asp Val Ala Asp Phe Ala Tir; Thr How much Ττρρ Main Main (Underworld Glu Gla Leu Gly Underworld Ala Pro Ala Uuu Main Pro (SEQ id No .: : 187)

31106.Pup

Ala hro Cheese Arg Hi s Pro How much How much How much Lyn Ala Gly Asp Trp Main Tlu Phe Arg C ^ Iu Lys Leu Thr Phe oyr Leu Val Thr Leu Glu Main Ala Tln Glu Main Main Gly Gly Gly Cheese Asn (Thousand Cheese How much Underworld How much Cnp Tlu He How much His His Leu Lys Arg Pro Piro Ala Pro Leu Leu Anp hro Asn Asn Leu Asn Asp Glu Asp VaU Cheese How much Leu Underworld Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Cheese Piet Val Arg Ala Val Lyn Asn Leu Glu Asn Ala Cheese Gly How much Glu Ala How much Leu Arg Asn Uuu Main Pro cys Leu Pro Cheese Ala Thr Ala Tyr Val Glu Gly Gly Tly Gly Cheese Pro Gly Glu Pro Cheese Gly Pro How much Cheese Thr How much Asn hro Cheese Pro Q: ro Cheese Lys Glu Cheese His Lys Cheese Pro Asn Underworld Ala Thn Tln Gly Ala Underworld Pro Ala Phe Ala Cheese Ala Phe Main Arg Arg Ala Tly Gly Va.l Leu Val Ala Cheese His Lru Main Cheese Phe Luu Glu Val Cheese Tyr A; rg Val Leu Arg His Lithium Ala Main Pro Cheese Gly Gly Sur Tly Gly Cheese Main Cheese Phu Leu Leu Lys Se; Leu Glu Main Val Arg Uyn How much Main Gly Asp Gly Ala Ala Leu Tln Glu Lys Ltu Cys Ala Th; Tyr Lys Leu (Thousand His Piro Glu Glu Leu Val Leu Ltu Gly Hin Su; Leu Gly How much Pro Trp Ala Pro Luu Cheese Cheese Tin After Su;

184 424

109

Gln Ali Leu G (y, 6,, 111 PCy Cts Lee Eeo GCn, 6, Ahs Asm G (y Ulu Phe Leu UfA P (n G (yp ^ lu Leu GCn Aea Leu, Τη, Τη Ple Sel Poo Alu Leu UCy Poo GAe, 6, Asp Thr Leu GCn Leu Ans Vv1 Ala Asp Phe Ala TTr CAe Glu Ci »CAn GCn Met GAu GCe Ceu C (y Met Ali Poo Ala Uuu Cln Poo (EEQ ID No: 188)

31107.Pup

Ala Cly Ace pro Glu Alu Phr Acg GAu Lys Leu ATe Phr Aga Llu Val Thr Leu Ulu Glu Cle Main Glu Main Cln Gly ⁷ Gly Gly Prr Asn Thousand Euo How much Me, PIe Asp GAu But; How much, His His Lul -us Ga » Pro roo Ali Prr oeL Ceu Asp Pro Asn Asn Leu Asn Alf) Alu Asp Incl Cheese IUu Leu UeL Pcs PA » Asn Leu Ca » Luu Pro Am. Peu PAu Cheese Phe VaU Ara ACe Inch Thousand Ann Puu Glu (sn Ala Seu PAy PIe Glu Ali ea, Leu Uc » Ann Peu GAn Poo CT / s LUU Pro Seu Ala Thr Ala Ala Pro Cheese Ooh GHs Pro He PIe How much Lys Tyr Incl Ple Gly Gly Cly Cly Cheese Pro Gly Alu Poo Prr Gly Poo With you Sr, TTr Ple, Asn Pro Seo Prr Poo Dog aus Main Prr His Lys Cheese Poo Cm Underworld Ala Tho Cln Glu But Ce, After" Ala Phe Ala Slo Ala PPe Ple Ccrg CG » Ala Cly Glu Vv1 PLL Incl But PS3 » Hhs Leu Main Sel Che Peu Glu VaU Cheese Tyr Oa » Vv1 Leu Pc » His Leu Ali Main Poo Dog AAn Gly Suo Gly Gly Sel Main Cheese Phe Leu Leu Lys Cheese Lee PAu CCln Arg Lys How much: Lln Gly Asp Gly Ala Ala Leu Main GAu Lus Leu CTys Ala Ghr Tyr Lus Alm Puff Hhs Pro Glu Alu Leu Val Leu Leu Gly His Eeo Lee. Gly PIe: Pro Trp Ala Pro Leu Cheese Seu CTs Pro Cheese Cln Ala Leu GCn Peu Ala Gly cca ^ Leu Emo Main Llu Hhs Cheese Gly Leu Phu Leu uyr Main Gly Leu Leu Main Ali Leu CAei GAy He Cheese Poo Alu Leu GCyz Pro Thr Leu Asp The background Leu Main Lul Alps val Ala (sp Phu Ala Thr PGe ie ^ <e Tty Main Main Underworld Glu GAn Leu Gly Underworld (la Poo Ali Leu Cln Pro (SEQ ID No : 18 9)

31108.Pup

Ulu Asp Pro Asn Asn Leu Asn Asp Glu Asp Incl Cheese How much Leu Underworld Asp Arg Asn Leu Ac » Leu Pro Asn Leu Alu Cheese PPe Incl CA » Ala Va1 Uys Asn Leu Alu Asn Ala Cheese Gly ILu Glu Ala Il ^ ee Leu Arg Asn Ulu Main Poo pta Leu Pro Cheese Ala Gho Ala Ala Poo Cheese Arg His Poo How much How much PIe: Lys Ala Gly Asp Gop Main GAu Phe CA » Glu Lys Ulu Thr Phe Pyr Leu Incl Thr Leu Alu Main Ala Main Glu Main Cln Gly Gly G Te- Asm, ' Gly Gly Gly Cheese Gly Gly Gly Cheese Asn cys Sur How much Underworld: lle? Acp CClu How much IZL (m His His Leu Lus Arg Pro Pro Ala Poo Leu uyr Incl Glu Gly Gly Gly Cly Cheese Poo Gly Glu Pro SLO Cly Pro lle Cheese Thr He Asn Pro Se » Pro Pro Cheese Lys Glu Emo His Lys S er Poo Asn Underworld Ala Thr Cln Gly Ala Underworld Pro Ala Phe Ali Cheese Ala Phe Main Arg Arg Ala Aly Gly Incl Leu Incl Ala SLO His Leu Main Sel Phe Leu Glu Incl SLO Tyr TG » Val Leu ΤΑ » His Ulu Ala GCn Po Cheese Gly Gly Cheese Cly Gly Cheese Gla. Cheese Phe Ulu Ulu Lyu Cheese Lll Main Main Va1 Aog Lys How much GCn GAy Asp Gly Ala Ali Lee, GCn PAu Lys Leu cys Ala Ghr TC / r Lus Leu cys His Poo Alu Glu Leu Incl Leu Leu Gly His Eer Leu GAy How much Pro Trp

110

184 424

lla Pro Lru Seo Seo CyC Pro Cheese, 1ι Gln Lur Alu Un Cys Leu Seo Main Leu His; cheese , Η Geυ , Ρ ^ , ^ u 'iyr Glu, ΐη Leu Cln lla Lru Clu Gly IIe Per, ΡΟ , Ιιι Gly Pro TGr Asp Tho Lru Cln Leu Asp νει! Ala Alp TPe Λΐι Background: Tłur Ha 'rrp Cln Cln Mrt Clu Clu Leu Gly Μη , ΡΟ , 411 Luu Gla, ΡΟ (SEQ W Well: 190)

31109.Prp

Gsn Gla Srr Gly How much Glu uGla IIe , LU , 10 Asn Leu Main , ΡΟ Gτs Leu Pro Seo lla Tho Ala Ala Pro Κυ , 10 Pro IIl Ha IIe Lys Gla Cly Asp Trp Main Glu Phe HO , ΐη Lys Leu Thr Phh Shs Lru Val Grr Leu Clu Main Ala Gla , 1ι Main Main Gly Gly Gly Cheese Gly Cly Cly Seo Cly Gly Gly Cheese Ais Aτs , βΓ How much MM ^ t IIe Aip Clu Ilr Ilr iis iis Leu iurs Arg , ΡΟ , ΡΟ Ala Pro Ler Leu Asp Poo Gsn Asn Leu Csn Asi) Glu Asp Incl He Leu MM ^ t Ais Urg Gsn Lru Gog Leu Poo Asn Leu Glu Κυ ΡΡτ Incl Arg Ala in i Lys Gsn Leu Glu This Val Glu Gly Gly Gly , ly Cheese Pro Gly Glu Drank Seo Gly Poo How much Seo Thr How much Asn Pro , (Γ Pro Pro Cheese Lys , ΐ'ΐ Seo Hśs Lys Seo Poo Asn Underworld Ala Κητ Glu Gly Ala Underworld Pro Ala Phe Gla Sro Gla Phe Main Arg JC ^ g Ala , 11 Gly wi Lee in i Ala Sro iis Lru Main Seo Phe Leu Glu Incl Cheese Tyr Arg Incl Leu Arg iis Lru Ala Cln Poo Cheese Gly Gly Cheese Gly Gly Cheese Main Cheese Phe Leu Lru Lys Seo Leu Glu Main Incl Lys How much Main Gly Aip Gly Gla Ala Leu Main llu Lys Leu cys Ala Thr T / y Lys Leu His Poo Clu llu Leu Val Leu Leu Gly Hiis Cheese Leu Gly IIe Pro Ttn? Gla Poo Lru Seo Seo Cys Pro Cheese Gla Ala Leu Main Leu But Gly Cys Lru Sro Cln Leu His Cheese Gly Luu Phe Leu T / y Main Gly Leu Leu Cln Ala Leu llu Gly How much Cheese Pro Glu Leu Gly Pro Thr Leu Asp Tho Leu Cln Leu Asp Incl Ala Al p Phe Ala Thr Thr IIe Trp Cln Cln Mrt Clu llu Leu Gly Underworld Ala Pro Ala Leu Main Drank (SEQ II Well: 191)

3111O.Prp

Gla Poo Cheese log iis Pro How much How much He Lys Ala Gly Asp Trp Main Clu Phe log Glu L / s Leu Tho Phe TT ^ -r Leu Incl Thr Leu Glu Main Gla Cln Glu Cln Cln Gly Gly Gly Ssr Gly Gly Gn- Cheese Gly Gly Cl / Sro Asn C / s Hundred How much Underworld lit Asp Glu How much ili His His Leu L / S log Poo Pro Gla Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp llu Asp Val Srr How much Leu Mrt Asp Arg Asn Leu Aog Leu Pro Asn Lru Glu Seo Phe Val Arg .Ala Incl Lys Asn Leu Glu Asn Ala Cheese Clr Ilr llu Ala How much Leu Arg Asn Leu Main Pro CC / s Leu Pro Cheese Gla Tho Ala This Val Glu Gly Gly Gly Gly Cheese Pro Gly Glu Pro Seo Cl / Pro How much Hundred Thr How much Asn Pro Cheese Pro Poo Cheese Lys Glu Seo iis L / s Seo Poo Ain Mrt Ala Thr Main Gly Ala Underworld Pro Ala Phe Gla Seo Gla Phe Main Arg Aog Ala Gly Gly Incl Leu Incl Ala Seo iis Lru Cln Hundred Phe Lru Glu Incl Cheese Tyo Aog Incl Leu Arg iis Lru lla Main Poo Cheese Gy / Gly Cheese Gly Gly Cheese Main Cheese Phe Leu Lru L / s Sro Leu Glu Main Incl H-g Lys How much Cln Gly Asp Gly Cla lla Leu Cln Clu Lys lru <C / η Ala Thr Tyo Lys Leu His Pro Clu llu Leu Val Leu Leu Gly K.1S Cheese Leu Gly How much Pro Trp

184 424

111

Tli Pro Lee ure Gsu thousand Tpo Dec- GUn SAiei Leu Glu Teu GTa Gly Tin Uuu Ses GUn I eu Tin Gsu dy Leu Phe Leu Tτr Tln dy Teu Ueu Main Alc leu TUu Tly Background Cheese Po Glu Leu Gly Spo TAh Teu Tsp Lee uln Teu Ατρ A ^ jL Alley At? Phe Ala TAh ATh GDe Trp Main Cln Underworld Glu GUn Teu Gly Underworld Ali U; Pro Ala Leu TUn Cpg (SE Q DD No .: 192)

31111.Pep

Tla Uly Ast Pr- Main du Phr (Arg Glu Lys Leu TAr The you' Teu Val Chr Lee. hive on Alu Main Glu du. Main Gly Gly dy Cerium Gly Uly Cly Cheese Gly Sly dy Srr Asn thousand Cheese How much Meu Cle Ατρ Glu Dlu Dlu Hii His Teu Les Arg Pro Po Ala Pro Leu Teu Asp Pro Tsn Ann Lee uin cip du Asp Incl Srr How much Leu Mmu Gap Ang Asn euu Arg Lee EPO Ais Lee Glu Cheese Phe Incl market Ala Gć ^ l Ces Asn euu Ulu Asn no Tse Gly How much Glu Alley How much Leu Arg Gan Teu Main Pro Ass Lee. uto Tse Ala Thr A. la Ala Pro Cheese Ang Tin PPG How much Diu Dle Lye pyr A ^ l Glu Gly Gly Gly Gly Cheese Po dy du Pro Sur Gly Prr How much Tse TAr How much Asn Pro Cheese Pro Prr Dec (thousand Glu Sur His Lye Srr Po Ann Underworld Ala Thr Main C-ly .Alu. Meu Prr Ala Phu Ala Cheese GTe The on market Arg Ala Gly Gly Incl Teu Incl Ala Sur His Lee on Gsu Phr Leu Glu Incl Cheese tyr A-Tg Incl Leu market Hin Ueu Ali. aln Gro Sru Gly Gly Cheese Gly Gly Cheese Cln Trr Phe euu Uuu Lye Her Leu Main Main Incl Arg Loess How much Main dy Asp Gly Ala Ala Lee Main Clu Lys Leu thousand Ala Thr CTsr Les Teu thousand His Pro Glu Glu Leu Incl Leu Leu Gly His Cheese Leu Gly IDe Pro Trp Ali Pro Leu u er Ssr thousand Pro Cheese Main Ala Leu Main Leu Ala Gly Ays Ueu Ses Main Teu Hii Cheese Gly Leu Phe Leu tyr Main Gly Leu euu Uln Ala Leu Slu Gly How much Cheese Pro Glu Leu Gly Po Thr Leu Tnp Thr Leu Main Teu Asp Incl Ala Asp Phe Ala Thr Thr How much Trp Uln Uln Meter G1u Glu Leu Giy Underworld Ala Pro Ala Leu Bullfinch! Pro (SEQ DD No .: : 193)

pMON15981 eutAlaTsnArsSerDluMutDluAspGlvDiuDleHnnHiseuuUysArgProProC.la PoGLeuLeuAspProAsnAsnneu Asinisp G lTuCspyalSurDlueuuMutAnpArgAnn eeuTrgUuuProAsnLeuGluSerPheValiτrgAlaValLysAnSeuvAivAnsTlaSur GlyDleUlvTlalluL · · euAτΓgAsnLeuGinProtyΞL euProSurAlaThrTlaTlaPrG rerTrgHisProDlulleleuUysAlaGlyAHpTrpGlnGiuPhuTrgdvU: HeuvThr PrutyrLuuValThrLeuGluGlnAladnGludnGlntyrValdudyd: d: Dr. SurPr <ollyGluProSerGlyProIleSerChrDluAssProSurProProeerernUlu rurHisLysSerProAssStetAla tyrLysLeutyΞHisProGiudueevWleeueev AlrHnneereuuUlyDluProTϊηpAlaProLuuSerSer ^r ^ rnrroeurUiSLAiaeuvAin euuAladytysLeuSerduSeu.HisHerdyLeuPheLeuTyrGlndyUuvUuvdn AlaeuuAluGlylluSerProGluLeuGlyProThrLeunspThrUuuAineuuTspWi AlaTspPheAlaThrThrlluTrpGlnGinMutGiuGluLuuGl: MuGTiaPGoTlaUuu GlnPGoThGdndyAl <HetProAlaPheAlaSerAlaPheGlnAGgTGgTlaU ΙιΑΙ: WlUeuWlAlaSerHisLeuGlnSerPheLeuGluWlSertyGTGgWieruTGgHns UuuTladnProdyGlydySerAspMetAlaThrProLeuGlyPGoTlaeeGeeGUuu PGodnSerPheLeuLeuI.e ' sSsuGeudeden / alyτrLysIleGlndyAspdyAll TlaeuuGlnUlverseuvCrs TlaThr (SEQ DD No .: 194)

112

184 424 pMON15982

MitClaCsnCysSioIliMitlliAsplluiarlliiisHisLiuLysGogPeoProGIa rroyi _in LeuAspreoAynAs] nietuAsinAspGluAspVaeSurIleLeuMutAspG _r Gayne LluCogLeurroGsnLeuGluSerPheVal.iSogAlaValLyyGsnyeulIuGsnGllSlr ClyIleGl-aCl _and iliLe'u ^ ^ <^. ^^ and ^ r ^] ^ <^; ^ C ^ i ^ nP ^ <^ (^ s, _J eurroSieClaThrClaClap _r o ^ Gl SeACrglisrroIllIllIllLysAllGlyAypTrplInGlurheGrgGluLysLuuThr PhlTyryluValτrrLeuGluGlI aG lnGluGlnGlnTyrValCluGlylIyCIylly SerrrollyGlurroSerIłyProIluSerThAlIuAsnhroSerProrAoSirLyyilu SiriisLyySurProAsnMet. AlaPr oG luLeuGyyProThrLiuGspThrLiuCinLlu AspValClaAspPhiAlaChrThrIIeCApGlnlInMitlIulluLeulIyMitGlaPro AlayluClnrroτrrGlnGlyAllαίetProAlaPheAlaSerAlaPrlllnArgArgCll ClyClyValLiuValcaaeieiisyeuClnSiAPheLiulluValeirTyACrgValyiu CrgiisLiuAlallnProGyyiłyGłySerAspMetAlaTheProylullyrroClaele eirLiuProGlnSirPheLeuLeuLysSer] IeuGluGlnValArgLysIliClnClyCsp ClyClaCllL, luClnGluLysLeu ^<r ΤjsAla ^Cer, CyrLysLeuGysKisrroClulIuLeu ValLluyeuClyHiseerLeuGlyIleProTłepSlaProLeuSleSlrGyyPeoeloCln GlaLluClIϊLlu.caaGly (GjsLeuSerGlylL euHisSerGlyLluPreLuuTyrClnlly LiuLiuClnAlayiuGluClylliSie (SEQ ID No: 195 5 pMON15965

MutGIaAynGyySeAIluMutIllAyplIuIluIluHiyHiyLuuLysAAgProrroGIl ProyiuLiuAspProAsnCs: inieuAsnAspGluAspValSurlliLiuMutAspCAgAsn LuuCrgLeurAoAsnyuuGluSerPheValArgAlaVaaLyyAsnLeuGluAynAlaSer llylliGluAaalliLeluAogAsrLLeuGliiProCysLiurroSieClaThAAlaAlaPro eirCAgHisrrollillilleLysAlaGłyAspTrpGinllurhlAAglluLysLiuThr rhlCyrLeuValThALeuGluGlrlllaGlnGluGlnGlnTyrVaIlIuGlyGlylIyGly SerPeollyGlurroSerllyProieeSurThAiauAynhAoSeArrohroSerLyyGlu SerlisLyySurhroAynMetAlaSerAlarhelInGAgGAgAIaCIyGIyValLeuVlI AlaSieiisLiuCyneirPhejIeuGluValSer ^r · TsrArgValLeuCAgHiyLiuGlaGlr rAoClyClyllyeeeAspMetAlaThrProLeuGlyProAllSerSlrLeureoClneer rheLluLeuLyySeryuuGluGlnValllrgIessIleGlnGlyAypGlyAalAllLuuGln GluLysLeuGysGllThrTyrLysLeu <ΤjsHisProGluGluLluValLl'uyluClyHis SurLiullyllirooTepAlaProL eus <no SerACssOroSrolInClaLiuClnyiuAla llyGysyluSlrlenLluHisSerGlyLeuPheLeuTyrGlnllyyluyeullnAlaLeu l luClylliSie ProGluLeuGly Pr οΤίοτΑβιιΑδρΤίοτΕθΗΐιΙΕβτιΑερνβίΑΠΑΞρ rrlClaThrThrIllTrplInlInMltlIulIuLuuClyMutAlaProGlaLluClnr eo ThrlInlIyGlaMuthroAllrheAla (SEQ ID No: 196 5 pMON15966

MitClaCsnCysSroIliMitlliCspGluIlilliiisiisLeuLysGogrroPooCla rroLluyluAsprroGsnAsnLeuAsIl AspGluAspValSerIllyluieetCspGegCsn yuuCAgLlurroArgAynLurroArgAheulVlualeeGerLeulla

ClyIllCluAlaIllLlluAogAsnLeuGlllPro (GssLlurroSlrClaThrClaClαPeo eueAegliΞProIllIllIllLysAlaGlyAspTrpClnGlurhlCoglauLysLluτre

PhlCyrLeuValChoLluGluGlrl.llaGlnGluGlnCln ^, CyrValClulIylIyllyCly

SerProGluhAoSerGlowProIleSerThAiauAsnhroSerProrAoSeryyslIu

SioiisyysSioPooGsnMitClaMetAlarooAlaLeullnreoGhoClnClyClaMit rroGlarheAlaSeoGlarhiGlnirgiCrgAlaGlyGlyVaiyeuValAlaSieiiyLuu

184 424

113

AlnSerOheUuuUluVαlrerCyr1rgVllUebCogHisUubClaAlnOrzAlyAlyAly SerCspMetClαChrPrzUeuAlyOroCllSeorerLeuProuenrerPheeeuLeuLys rurUeuAluUlnVllCggLysIleAlnAlyCsoAlyAlaAla.LuuAlnAluLysLeuCys ClaChrCyrLysLeuTysHisOrzUlbAluLebValUubLuuUlyHisSurLeuAlyllu PozCgpClaOrzLuureoSuoCysPgzSurAlnCllLeuAlnLuuClαUlyTysLeuSuo AlnLuuHisSerGlyLubOheLeuCyrAlnAlseeu] LuuGlnCeaUeuGluAlyeleSur OooAluUeuAlyOroChoUebCsoChgUeuAlGeuuCso'lαlClaCsoPheCllChrChr IeuCroAenAenMutUluAlbUeuAly (SEQ ID NO: 197) pΜΟΝl5927

MetClαCsnTysSureleMeteleCsoUlullelleHisHisLuuUysCrgPozPozCla OroLeuUeuCsoOrzCsnCsnyeuCsnCspUluCsoVαlSuoeleLuuMetCspCrgCsn LuuAggUeuPrzCsGLeuAluSegPhuValCogCllValLysCsnUeuAluCsnClaSeo GlyeluGlbClaeluLubCggCsnLebUlnPrzTysLuuProSuoClaChoClaClaOgo rugCogHisPozelullueleLysClaUlyCsoCrpGlnGluPhuCogUlbLysLubCho ^{PheCyrUeuVαlChoUebAluUlnClaUlnAluAlnGln,} G / rValAluAlyAlyUlyUly SuoProGlyAluPooruoAlyPrzeluSuoChrlleAsnProrugPooPooSuoyysGeb SurHiseysSεrPozCsnMetClaChoUlnAlsCllMeLPrzClaPheClαSeoClaPhe GlnCrgCggC.lαUlyAlyValLeuVαlCllSeolisUeuAlnSurPheLeuAluVαesuo CyrCrgValUebCogHiseeuC.laUlnPrzAlyAlyAlySerAsoMetClaChrProLuu UlyPgzClαSegSerLeuProAlnSerPheUeuUeuLysSerLubAluAlnValCrgLys lluUenUlyCspUlyCllClaLeuUlnGluLysUuuCysAlaThrhyoyysLubCysHis OroAluAluUeuValLebUebAlyHisSerLeuAlylluPrzCrpClaPrzLuuSerSur cysPrzSurAlnAlaLebAlnLeuCUaAlyCyseeuSeoAlnLuuHisrerAlyLubOhu LebCyrUlnUlyLuuLebAlnClαUeuAluUlyIleSerProGlbLuuAlyPozChrLuu CspChrLeuUlnLeuGsoValClaCsoPheClaChoThreleCrpAlnAlnMutUlbAlu LebAlyMecClaPozCll. UuuUlnPrz (SEQ ID No: 198) pMON 1112 .pep

Met.ClaCsnTysSuoCsnMuteleCspAlullelleTh: oHisLubLysAlnPgoOroLuu

OroLuuyuuCspPhuCsnCsnyuuCsnUlyueuCsoGenAspIeuLuuMutAspCsnCsn

OrCggArgPooCsnyuuAlbClaPhuCsnCrgCllValLysSurLeuUlnCsnClaSur

ClllleGluSereee OrUysCsnOrLeuPozTysLeuProUuuAlaChrClaClaPoo

ChoCrgHisPrzeluHiseleUysCsoUlyCspCrpAsnGluPhe.CogCggLysLebChr

PhuCyrLuuLysChgyuuAeuCsnClaAlnCllAlGGln ^Γ CsrValAluUlyUlyGlyAly

SeoProAlyAluPooSurAeyOrzlluSerChrlleAsnProSurProProSurLysUeu

SerHisUysSerOooCsnMetClαChgGlnUlyCla] eetProAelPheClaSuoClaPhu

AlnCggCogClaUlyAlyValLeuVllClaSurHisLeuGln ^ uoPheUeuUluVleSur

CyrCggVαlLeuCggHisLuuClαAlnPrzSerAlyGlySerGlyAlySerAlnSurPhu

LebLuuLysSerLebAlbAlnValCogLysIleAlGGlyAspGlyClaAlaLubUlnUlu

LysUuuCysCllChoCyoLysLuuCysHisPozAluGybUeuValLeuLeuAlyHisSer

LeuAlyllePrzCopcn.aPooUuuSerSerTyserzSeoUlnAlaUeuAlnLeuClαAly

TysLuuSurAlnLuuHisSurAlyUeuPheeeuTyoGlnGlyLuuUuuAlnClaLeuAlu

UlyIleSerPrzAlu orAlyOrzChrLeuCsoChgLeuGlnLuuCspValClaCsoOhu

ClaChrChrlleCgpUlnAenMutAluUluUeb1lyMetClaPgzClaLeuAlnPrz (SEQ ID No: 199)

114

184 424

OMON31112 .pep

MutC.llAsGCysSerAsnMetlleAspGluelueleChrHisLuuUysUlnPrzPrzLeu PooLeuLeuCspPheAs: nAsnLeuAsnGlyGluAspGlIn \ spIleLebeutGlbCsnCsn LeuCrgCrgPrzCsGyebAluCllOheCsnCggCla'ValLysSerLuuUlnAsncyaSer ClalluUluSeglleLeuLysCs: IGLelbJeuPro (C / ΞLeuProLe ^ bglaThoClαClαOgz ChoTogHisPgzlleelelluTrgAΞpGlyAspTrpAsnGluPheArgArgLysLeuChr PheCyrLeuyysChrLeuGluAsnClaGlIlAlaGlnGyιGGsoValGluGlyGlyGlyUly SerPrzAlyUluPrcSerUlyOrzlleSerThrlluCsnP: ozSuoPooOoorurUysUlu SerHisUysSerOgzCsnMetClαChrGlnGlyClleetProAlaPhuClarurClαPhe UlnCrgCggCllAyyAlyValLeuVaUClaSegHisLeuGlnSurPhuLebUluValSeg CyrCrgValLebCrgHisLuuAlaAlnProChrPooLeuGUyP: ozAlaSurrerLeuPgz GlnSerPhuUeuLeuLysSerUeuAluAlnValCrgyyseleGlnAlyCspGlyClaCll LuuGlnUluLysLeuTysClaChrTyrUysyuuCysHisProGluUluLuuValLubyuu UlyHisregUeuAlyllePrzCroClaProLeuSuoSer (T / ΞP: ozSegGlnAlaUeuAlG LeuCllAlyTysUeuSurAlnLeuHisSerGlyLe · bPheLeu'CyrGlnUlyLuuUeuAln AelLeuUluAlyIleSerPrzAluLeuGlyProTh: oLuuAspTh.rLebAlnLeuCspVαl Cl aCspPheClaThrTho lleCrpAln1 lnMetAlbUlbLebUlyMetAl a ProCU aL e u Ulny (SEQ ID No: 200) pMON31U4 pep

MuLClaTsnTysSerCsnMuteleAspGluelulluChoHis: eeu.UysAlnOozPrzUeu ProUeuUeuAspPhuCsnAsnyuuGsnGlyGluAspGUnAspIluLeuMetUluCsnGSG LuuGogAggPozCsoyeuUlubAuaheAgnAτgJA..uValUysSerLeuGenGsnClαSur ClalluAluSegeleLeu.LysCsnLelbLeuPro ^ ^ ysLe UOroLelbAlaThrClaAUaPgz ChgCggHisPo · ^Γ zelueeueluArgAspGlyAsp'GgoAsnGluPheArgAogLysLeuChr PheCyrUeuUysChgLubAluAsnClαAlnAlaAlnGln CyoValGlbGlyUlyAlyAly SeoPrzAlyAluPgzSurAlyPrzIlererThgeluGsnProSerPooPoorurLysAlu ruoHisLysSerProGsnMutClaChgGlnUlyClaleutProAlaPhuGlaSeoGlaPhe UlnCggTggCllAlyAlyValLeuVαlAlarerHisLuuGlnSugPhuyubGlbVαlSeg CyrCggValLuuCogHisLeuClaAlnOroSurAlyGlySerGlyAUySuoGlnSegPhu Lu'uLubLysSegLeuAlbUlnValCogLyseleUenGeyAspGlyAeaGlaLubAlnAlu LysLubTysClaChrCyoLysUeuTysHisPooUlbUluyuuValLebLUbUlyΉisSeg LuuAlyIlePozTrpAlaProLeuSerSer C / sProSerGlyn (laLeuGlnLuuGlαUly CysUebregAlGyebHisSerUlyLeuOhuLubCyoUUnAlyLuuLebUlGA.laLeuAlu UlyIluSeg0rzGluLeuGlyProThrLel · UgΞpThrLeuGlyG _J elb1spValGlaCspPhe GlaChoChgeleTrpGlnGlneutGluGluLeuGly] eutAlaP: ooAel orGlnPrz ( SEQ ID No: 201) pMO ^ mS. pep

MutTlaCsnTysregAsn] eeteleAspGlullelleChrH.isLubLysUlnPozPrzUeu

PgoLuuLeuAspPheAsnAsnyuuCsnGlyGluAspGenAspIluLuuMut.AspCsGGsn

LuuCrgColPgzTsGUeuUluClaOheAsnAogAlaVaeLysSerLubGlrlAsnCllSeg

TlaIleAyureglleUeuLysCsnLeuLeuPgoCysLuuProLuuAlaChoClaCllOrz

ChrCggHisPrzlleHiseeuLysCspGlyAspTrpAsnGluPheAogAggLysLuuChr oheCygLeueysChrLuuAluAsnClaGlnAlaAlnAenGs: oValUlbGlyGlyAlyAly

SegPozAlyAlbOozSurAlyPrzllererThrlluGsnProSurPgoOgzSeoUysAlu

SurHisLysSegOgzCsnMetGlaChrGlnGlyAlaMutProAlaPhuGlaruoClaPhu

184 424

115

ClnAAgCrgGlaClylIyValyuuVlIClaSeeHisLuulInSlrrhuLuulIuValSlr CyrArgValLiuCrgHisyiuAIaClnPooTheProLeulIyPeoClaSieeiryiuPoo ilnSiePhiyiuyeuLyseiryiuilulln'ValArgLysIliilnilyCspGlyAlaCla yuulInCluyysyeuGysClaThrCyoLysyeuGyslisProlIuCluyeuValLluLlu ClyliseleLluClyIlePooTrpClαPeoyluSlASurGysPeoelrClnAlaylulln LluClαClyGysyluSlrClnLlulisSlrClyylurheLluTyrllnllyyluLeulln GlaLlulIuClyIllSloProlluyluClyPro'chrLuuAspTrryluClnyeuCspVaI ClaAsprhlGiaThAThrIleTApllnllnMutlluGluLuullyMutCiaPeoGlaLeu ClnPro; SEQ ID Ne: 2025 pMON28505 caaAsnGysSeoIluMetIleAspGluIleIlllislisyuuyyslAgProProAllPro yeuLiuCspPooGsnGsnLiuA.snAsplIuAspValSeriauLuuMetGspGrgAsnyiu GAgLlurroCsnylulIuSlrrheVal.lAgGlaVleyysAsnyeulauAsnAIaSerlIy IluCluΑ.laIllLluCrgΑsnylullnPooGysLluhroSerGlaThoΑlaClaPooSlo S.AglisrroIllIllIllLys.AalGlyCspTrpGlnGluhhuGrglIuyysLeuThrrhl TyAyluValτeeLluCluCInAaalInClulInClnTyrValCIuClyllyClyGlySlo rroClylIuPooelrClyProIleSlrcroIllGsnrroSerrroProSleLysGluelo lisyysSleProAsnMltCluVlaHisPooyluProThrrroVa | yeuyluProGlaVal CspPrlSleylulIyCluTΑpLysThΑClnMltCluGluThrLysClaClnCspIllLlu lIyS-lαValτreLluLluyluGluGlyValMeŁAlaAIlGAglayCInLluClyrroτno CyyLiuSioSroyiuLiuGlyGanyiuSioClyGlnVaaGAgyruLeuLeulIyAlaLeu lanSieLuuLeullyThrIlnyuuhroProCinllyAAgThAThrAaaHisLysAsprro GsnAlaIalrhlLluelePhlGlnlisyluyeulrgGlyLysValSAgPrlyluMltyeu ValClyGIyeleThrLluGysVlaGAgCluPhlClyGlyAsnMltGlaelrProAlaPeo rAoAlaCysAspLluCAgVleyuuSlrLysLeuLluArgAspSurlisValLeuHisSeo GogLiuSerllnCysPro (SEQ ID No: 2035 of pMON28506 cyaGsnCysSiollrMitilrAspGy.ullilliHisH.isyiuLysGegPOoPooi.yaPo-LeuLiuAspProCsnAsnLiuAsnA.spCluGspVaasirIIeLiuMetGspGAgAsnyiu GrgLeurroGsnLiuCluSiArhuValCrgGlaValLysGsnyiuGauAsnAIaSirCly IlelIuAIaIleLeuCrgAsnyeuGInrroGysLluhAoSerAelThrAlaAIarroSer lAgIisrAollillelluLysAaaiłyCspTrpiInGaurhuArgGauLysLuuThrPhi T ^^ rLeuValThryeulluClnAIaClnCluClnClnTyAVaIlIuGlyClyClyllyeie PeoClylauProeerGłyrroiauSiAThelliGsnrroSerrrorAoSeryysCiueeo ^{iisLysSeoPeoGsnMicLiuroo'choPooV,} alyiuLiuPooAlaValAsprheSieLia llyGluTopLy sThrGlnMetiaulluChr LysAlaGanAspIllLeullyCllVllThA LeuLeuLeul IullyValMi tAlaAlaArgllyi Iny eul lyPooThoCy sLeuS ir S er L luLeuGlyl lnLeuSiri lyiInValCrgLeiuii IUL heat lyAlaLeul InSerL euLeu IłyThAGanLeurrorrolInGeyGAgThrThrAlaHiyLysAsphroGsnClallePhi LiuSierhilInIisLiuLiuAogiIyyysValAegrhiyiuMitLeuVaIilyllySio ThrLeuCysValArgGlurhuieylayCsnMetAlaSuAProAIarrorroGllGysGsp yeuCAgVllLlueerLysLluyuuArgCspeerllsVaaLuulisSerGegLeuSlriIn GysPeoiluVallisPro (SEQ ID No: 204 5 pMON28503 claCsnCysSielliMiclInAspiaullelaeHisIiyLuuyysArgPeoProClaPeo

116

184 424

LuuyuuAspPgzCsnAsnLeuAsnAspGluCspValSureluLuueetAspAggGsnLuu argLeuPozCsneeuAluSerPhuVllArgClαValLysCsnLeuAlu? ΧSnAlaSerGly eluGlbAlaeluUe ^ UAg3AsrGSeuGlnPre (TysLeuProSuoAlaThrAllAllPozrug CrgHisPgoeeelleeluLysClaUeyGspCopuenUlbPheAogAluyysyuuChoohe CyrLeuValChoee'b1ϊ'dGl: rLalaGlnUluAlnAlnCyΌVllUlu1lyAlyUlyAlsSuo OgoAlyGluPozSeϊ0clyProIlerugChoeeuCsnOgoruoOgoPooSuoLysGlurur HisLysSurPgoAsIMίutValLubIJUuPrzAlaValCspPheSereeuAlyGlu ^r FrpLys ChgAln] ^eetAluAlu, hh: oLysAlaAenAspeluUeuUeyGllVαechgLebyuuLeuGlu AyyValleutAlaAlίagrgGlyGlnLebGlyPrzTłb: oGssLeuSerSerLeuLubAlyUln eeureoUlyAlnValArgLebLubLubUlyClaUeuUlnSegLubUeuAlyChgAlnyeu PgzOgoUlnAlyar ^ ^glhr, jGhoAlaHisLysAspOgoAsGAlaeleOheLeureoPheGln HisLubyubCggAlyLysValArgPhuLubMutLeuVllGlyGlySegThoLubTysVαl TogAlbPheAlyAlyAsIGeetAlaSugPrzAlaProPro.aeaCysCspLuuGogValyuu SereysyeuUeuTrgAspSerHisValLebHisSerAggUeuSeoAlnCysPooAluVal HisegoLeuOgzChgPrz (SEQ ID No: 205)

OMONl8508

ClαAΞnCysSuglleMetlleAspGlbeeeeleHisHisUeuLysCrgPozOozClαPoz LuuUebAsoPgzCsnAsnLeuAsnAspGluAspValSuoeluLuueutAspGggCsnyuu TggeeuPrzCsneeuGe ruoPhuValCggClaValLysGsnyeuAluCsnAlaSegAly IleGlbAlalleee ^ ^ baogAsrϊLebGlnProC / sLebPrzSerAlaThrAlaAeαOozreg CogHisPgzeleIleeeuUysAelGlyCspCgpUlnGebPhuAogAluLysLuuChrOhe CyreubValChgeeuAlbAenAeaGenUluAlnAlnCyoVaeAluAlyAlyGeyAlySug PrzGlyUluPrzre: 03lyPraIluSuoChoeleAsnPozSerPrzerzSerLysGluSug HiseysregOozTSGMutClaVaeAsoPhuSegLebGlyUluCopLysChrGUG.eίetGeu AluChoLysCllAlnAsplleLubGeyClaValChrLubLebLeuAluAlyValMetAlα ClaCogGlyGenLeuGlyPra'ChrCysLeuSerSurLubyebUlyUlnLebruoUlyUln ValCrgLuuLuuUeuAlyAlaLubUlnSeoLebLeuGlyChoUlnLeuProPozAlnGey CogChoChrGllHisLysAspOroGsnAlaelePheLubSurOheAlnHisLubLeuArg AlyLysValCggPheLebϊeetLuuVleulyAlySerThgLeuCysValArgGlbPhuUly AlyCsnMetCllrerP: ozAlαOozOooClaCysAspLuuAogVaeLeuSeryysLeuLuu TrgCspreoHisValLubHisrugCrgLuuSeoUlG.CysPgzUluVαlHisOgzLeuPgz ChgPooValLeuUeuOgz (SEQ ID No: 206) pMON28509

ClaGsriCysSegIleMeteluAsoUebeleIleHisHisUeuLysAogPrzOooClaPoz LeuLuuAspOozCSIϋa3IGLe ^ basnAspGluAspValSuglluLuuMetAspAggCsnyuu TggLubOgoGsnLeuGluSerPhuVlecrgGeaValLysCsnLubGeuAsnAelreoGly lleGlbGlaeleeeblogASIGeubGlnPozCysLuuOgzreoAlaChrCllAlaPgzSug CrgHisPgoelellueluLysAllGlyAspCrpUlnGUbPhuAggUluyysyubChoOhu CygLebValChgeeuGluGl: GAeaUenUlbAlnAlnTygValGlbGlyUlyGlyUlySeg PgzGlyGebPooSe] 0GlyProIlurugThglluAsnOgoSeoPooPozSugLysUlbrur HisLysrurPrzCsGMetAspOhurugLuuUlyGluTrpeysChgUlneutGlbUlbChr LysGelUenAsoIleLuuGlyAeaValChoLuuLeuLubAlbGlyValMutAlaGlaCog UlyAlnLeuAiyOgzThrCysLuuruoSerUeuUebGlyAlnLubSegUlyUiGlValCrg UeuUubLuuUlyClleeuGlnSurLubLuuAlyThrGenUebOgoPooGinG lyCogChg ChgClaHisLysAspPraAsnAeaelePheUeuSerPhuAlnHisUeuLeuGrgAlyLys VαlTggPhuLubeetLuuValUlyUlySuoChoLuuCysVaeGggAluPhuGlyAlyAsn eetClarurPrzTlaProProAea <GssGspLeuArgVllLubruoLysLuuyubCrgCsp SegHisVaeLuuHisSerArgLuuruoUlnCysPraGlbVaeHisPooLuuPooChrPoo

184 424

117 aaleeveeuProTlaall (SEQ DD No .: 207) pMOr2851O

TlaTssTyHrerlleMuGDluTHpUlullulleHisHisLeuUys.CrgProProTlarro eevUuvTHpProAsnTHneuvAHsTspCluAspVaereGlleeeveuGAspArgTssιeuu AGgUuuPooAsnUuuCUuSeGPhuValArgAlaValLysAsnLeuGluAsinilaeurUUy DluGluAlaDiuUuuArgAsnLeuGlnProCAsLeuProSerAlaThrAlaAlaPGoeeG TrgHisProDiulleDluLyHTlaAlrTspTrpGlnU | vrhuAGgGluLysjeeuThGrhu TyreuuValτrLGeeuCluGiSLTlaUlnGluGlnGlnTyrValUluGlyGlyGlyUl Sur ProUl: UlvPGoSuGClyPGOlluSurThrlluAHsPGoSerProProSuGU: sUlvSuG Hise: seuGPGoTsnMutGl: UlvTGpersThrGlriMeGGluGlvThrLysAlaUlnTsp llueuvAl: T.laValChrUuvUuuUuuUluAiyVal] euGAlaAlaCrgGlyGlseuvUl: ProThrArpUuveurSuGUuveuvAl: UlneuuSerGlyGlnValArgLeuLuvUeuU ly TlaeeuUinSereeueuvUl: ChrUlnUuvProProGlnGlyArgThrThrAlaHisU: s THpProTsnAlaDluPheLeuSerPh.eGlIS iεLeuLe ^ '^ UAGgGlyLysValArgrhueev MuGeuuVaiUl: AlrSuGThreeuArsValTGgGluPhuGlyGlyAsIStetAlaeuGrro AlaPGoPooC ^ laCs ^r snspUuuTrgValUeuSur; ^ ;; sseeuUu ^ TrgnspSu: ^^ nsValUeu HisSeGTG'geeuSuGuUnc'yHPGoUluValHnsP: ^ xjLeuProThrP: ^ - oUaluPro: ^ - oUaluPro: ^ - oUaluPro: ^ - oUaluPro: ^ - o

ΡΜΟΝ28511

AlaTssAsHeurliuMuGlluTspAlulluDiuHiHHnsLeueyHArgProProTlaPGo eeueuuTsprroTsnTsneeuTsnTspGlvTspValeerlluUeveeGAspArg.Tsseeu TGgeevPGoTHseuuUlururPheValTrgTiaVaeLγsAsnLeuGluAsnAlaSuGUl: llrAluTlaDlrUuuirgAsnLuuGlnProtysLeu ProSerAlaThrAl aAlaProSer AGgHnHrGolluDluDluUysTlaUl: TspTrpUlnGiurhuTGgGluLysLuuAhGrhu T: reeuVaiTtlreeuCluUlsTlaUlnUluGenGlnTyrValGluGlyGlyGlyUl: rug PGoUl: AlvProrerUlyPGOllererChrliuAsnPGoSeGProProSerLysUlurur HnseysruGPGoTsnMuGUl: ProThGTrseuuSerSurLe'uLuuGlyGl] sLuvrerGly Ulsaal.TGgeeuUuueuvUlrTiaUuuUlnrurLeveuvGlyThrGlnLeuProPGoGin Ul: TGgThGAhr 'AiaHnsU: sTHpPGoTsnTiallurhuUuvSuGPheUlnHnsUuveuv TGgGlye: HValTrgPreeuueίeGUeuValCiyGlyee: GyrrLeuAysValArgAivPhu GI: Ui: TsnMuGTeaSuGPGoTiaPGoProTiaAIHAśpLeuAGgValLuuSUGU: HUuu eevTrgTspSerHnsaaleuuHisruGCrgeuuSe: GGlnArsProGluValHiHrGoeuu ProChGrroValeeveuuProTlaValTspPhuSureuuGlyUluTrpLysThrGlnMeG UlvGlvAhGL · ysTlaClsAsplleeuuUlyTlaVaiAhGUeueuueevUlvAi: VaiMuG TcuaAlaTrgGlyGlneuu (SEQ DD No. 209)

PMON28512

TlaTssArHeurlluetetDluTHpUlullulluHisHiHeeuLysArgrroPGoTlaPro euueuvTspPGoTHnTsnUeuTHsT.spUluTspVaUSUGDluUeuMeGAspArgTHsUuu ArgUeurrol ^ s ^ l _J euUlururPhuValTGgTlaValL: ssAsnUuuGUuTs] nnlaeerUly DlrGliuTlaDluUeuTrgAsnLeuGinPGOtysŁeuProSerAlaThrAliaAlaProSeG TrgHisProllelluDieLysAlaGlyTspT tgpG 1 nGlu Ph eArgGluLy sLruThrhhe T2 / reuvaalτhGl, evUUvGlnτlaGlsiclvGlsClsA ^ ^/ ^ GaalGlvCe · ^| GYY (^ 7ly7CUrreG PGoUlyAluPGoeerCUyProllrreGThrlleAsnrroruGPGoProSurLysAlueur HnseyHeeGPrc> TssMutGl: ThGGlneuvProProUlsClyTrgChrThrAlaHiseys TspProTsnAlallePheLeuSerPheGlnHisLeuLeuArgGlyLysValArgPheUru MeteuvValGlyUlrSurThreuuCrsaalTrgGluPheGlyGlyAsnϊtut; AlarerPro

118

184 424 aii p _and r _OS sAiaCC _g / ΞP.5g) Geel.AGgHlllLeuSerLy sLeu.LeuArcgSipSrrHssaalL _ru HsiSl GrgLeuSerGleGGGProOllValHisProLeuProThrProValLruLr _{U 0} r ₀ c ^{GiaaliGiGPelrrrLeuGlyGlu,} ropUysThrlInMetCiuTiuThoLGsalaClnaPG lIeLluGiyAlaValThrOeuI.ιeuUeuGlu (3 C_nVolMe et this laAlaArgGlyGInLeuGir rooThrCysLeuSerSeG0LIU _J euGlyGlLnJeuSerGlyGlnValArgUeuUeuUeuGlG llaLeuCinSroLIuUru (SEQ ID NO: 210 )

GMON28513 liaGsGAGsrlglirMltlieAspCl'ullellrHSsHSiLruLysaogrosrosG_iaroo LruLIuGΞpProAsrGl; nneIUGnAΞpGllUGspValSerIleLeιGertAsGaoHS..snUru loHelu0osAsnLeuGluUeePheVal · eG7gAlaValLUGsAsnLeuGiuApGalaSeoGly lirTiuaiaIilLG ^ .UGogAsnLeuGlnP: ooιCysLeuPrsSlrAlaTholIaalaPrsrrr GoHHisPgslllIlrIirLysAlaGnyAspTopGl: GGluPhrArgTluLysLruThrPel TGoLlUlalτerLluGluGlIGSlaGanTluGlGGaGTGrlaiCluTl · GTlGTlyTiGrer rosCiyllu0roSerGlyProIleSer'PerlirAsnhrsrlrProPooSeoUGiCiurlr HSieGsSlo0roAsIG4etGlyArgTThgΓhrAlaHiΞLysAspProAs] GGlalIl0hrUru rroPhrGnGSisLeIG _J eIUAgGlyLysVallG7gPheLe · ιUeetLeuVaIGaGGIyreoP'hr UruCysaaiArgGlu Ph iIIiG lyAsrGiet Ala S erProAl aProProAlaAriliGUru GoglalLlurerLysLeuLeIUGrgAspSerHisValLeuHisSerAogLeurroTlGGGi rrslluValHisProLeuUprTCrProValL · elUeeJProAlaValAipPhrrrrLruGlv CluCopLysThrGlrG4etGluGluThrLyΞAlaGlrGAΞpIleLeuGlyGlalaiChoUru UeuLeuTiuciyVlyeetAlaAlaArHGΊyCInUeuGlGPooProGypUGureoSerUeu UeuCiyClnLru S er oyyGlnGaaAsgLeuLeuL EUG lyAlaLeuGinSeoUeuLruTiy TholinUlu0gsrosCln (SEQ ID No 211) pMONl8524 alaasnΓGsSlolieMrtlIeappGIulIelIrHipHSpLeuLGilogroorosGlahro UeuUrulsprroAsIGa3nLeIGG3IGSspGluAspVaerrolIeUeueetaPGlogGsGUru lrgLluPrsAi] GeeuGluSerPheVal.AogAlaValLysAsnLeuGluAPGalaSeoTlG lleliuAlalllLeιuArgAsnLeuGlnPro ^ ysLeuProSrrAlaTholIaalaPrsrrr GoHHSprosllrlIrlleUypalaGlyaPGToGGaGGlurheaoHGluLGPUeuThrhhe TGoeeulalτerLeuGluGllGSlaGlnGluGlnGlnTyrValGl uTlyT · 1 (11 (11 (0 ^ ^{rosClGCiuProSerGlyProIleSer,} PerllelsGrrsrrrrosrrsrerLGsClurro HSsLyirlrProAsIneelAlaHisLysAspProASIGSlaIlePheLeureorreClnHSi eruLru.GoHGiyLysVallG7gPheLe ^l ιUeet; LeuValGlyGlySeoThoLeuGGsaalaog CIureeTlyGlyAsInlet: a.aSerProAlaProProAla <GGSAspLeuAoHValUeurro LGsLIuLruArgAspSerHisValLeuHisSer.ISrgLeuSerGlnCypPooGluaalS [ii PosLruProT ] erProVlleeuUeuProAlaValAspPheSerLeuGiyTluPoGLGiTho ^{TlGMetTIuTlu,} rhrLy sPlCLaG liGSspIleLeuGlyAlaValThoLruUeuUeuCluTiG lalMrtalaAiaArgGlyGlIGeeuGly: hΓoThr <CssLeuSerSeoUeuLeuGlGClGUeu SeoliyClnValArgLeuLeIUJeuGlyAlaLeuGlnSerLeuLeuGlyThoTaGLruros PoolinClGGogτeoτeo (SEQ ID No : 212)

GMON28515

GlaGsGCGsSroIiIIeetIleAipGluIlrIlrHisHSsLeuUyiGogPoorosGiaroo erueIuAspProAsΓGG; nLe ^ uAsnAΞpGluAspValrlolieLeu.ertasGSogGinUru

Gogelu0osAinLeuGluSerPheVallSogAlaValLysAinLruTiuGiGalaSroTiv

IllliuGlallrLGGGrgAsnLeuGlnProCysLeuroorerAlaThoGiaala0osSlO

GoHHSiPoslllllrlllLypalaClyaspToGClGTlurheGogCluLGiUruThorel

184 424

119

GrrLupVαlτrpLeuUlu ^ lnAllUanUlpUanUlnGrIaαlUluTlrUlrTlyUlySu; O; oTlyTluhroSurUlrO; olleSerTrrlleCsnP; ose; ProProSu; LysTluSei HisLrsSurPΑoΑsnMutCsoProAsnClallePruLeuSurPruTlnHisLupUupe g TlrLynValApgpruLeueUitUupValTlrTaySeAGhrLeuTynVaaArgy | ppruTly UlrAsneίutAll.SerO; oAlαOroProAlαTysCsoUupCrgVaaLeuSurLynLeuLup CrgAnpSurHisaaaLupHisSerAAgLeueurUlnCysOroGluValHisPrpLuuh o ^r τrIOroaαlLepLeuOroAlla alAspOruSerUuuUlrUluGroUrsτr; UlnMutTlp UUpGrIUrnAlαTe.Γerp; oUluUupUlyAllVllTrrLupUuuLeuTUpUurVαaMetAll ClaAAgUlyUlnLuuUlyO; oTriyrsUeuSerSurLeuLuuTlyUlnLuuSurUUrUln aαlAAgLuuLuuLuuUlrClαLupUanSurLuuLeuTlrCr; ylnLuuOIoOroUlnTlr AhghhoGhrAlaHisUys (SEQ lD NO: 213) pMON ^T 2E ^ 5 ^ 6

ClαAnnyrseuhlluMetlle.AspUlpllelleHisHisUuuLys.grgPopPAPAlaPro UeuUeuCspOooCsnCsnUeuAsnAsoUluCsoaαlSehlluLuuMutCsoAAgCsnUup CogUepOhoCsnUepylpSuIPruValCogAlaaalUrsCsnLepUluCsnAlaSuhUlr lleyluAlaaleUuuCrgAsnUuuTlnOloeysUuuPooSerAlahhhAlacaahroeuh CrgHisPholaellulleUysΑlaτayAspTopUlnTluPruΑΑgTluyysUuphhohhe TrIUeuaαlThhUepUlpUlnAlaUlnUluUlnUlnhyIaαlTlpUlrUlyUlyUlySuI OooTlyUluOroSuoTlrOhPlluSuhTrolluAsnPIpSurPooPooSurUrsUluSuI HinUrsSuoProAnnMetAlalluPhrUeuSuoOhrTlnHisLeuLuuAhgTlrLrsVal cogρheUepMetUeρ ll'iluUrUUr'SerTe.hUuuCysValg.IgUlupreUe.rUlyAsrA'ίut ClαeerPhoAlαProPooC.lαCysCsoUuuArgVαlUeuSuoUysUruUeuCpgAsoSeI HiΞValLepHisSuoeA · gUuuSerUlnCrsPAoUluValHisPooUuuPhoTrpProVal UeuyuuPooAlaValAΞoPhuSehUeuUlrUluThoLrsTrhUlnMutUluUluThoUrs AlaUlnc-splUuLu: ^pGn.yrUll, alThoUupUuuUuuTlpUlyValMutCulClacogUe.r TlnyuuUlrF-oThoCysUeuSuhSuhUuuUeuUlrylnLuuSerTlrUlnaaaArgUep UeuLuuTirAlaUruUinSuhUuuUuuUIrThoUinLeuPioPhoTlnUłyCpgThrTri AaaHinUrnAsoProAsn ( SEQ lD Ni: 210) pMON2 8519

AlaAnnCynSuollUMutlleAnpTapllelauHinHinUupLysAAgPhPPAPAlaPho UuuLeuAspPhoAnnAsnLeuAsnAspUlpAsoaaleeolluUupMutAsoAAgAsnLup AAgyuuhooAsnUuuyauSuhhruVaaArgAaaVaaLysAsnLuuUluAsnAaaSuoTlr lluyauAlalluLuuAogAsnLuuyinOroCysLeuhooSurAlaThoAlaAaaProSul ArgHis Poo ilullr lluLysAl αTlrAsoTPOU InTluPruAogUluUr sLuuThoPru TrrUeuValτroUruTlpUlnAlaUlnUlpUlnUln'hrhallUluUlyUlrUlrUlySuI PhoTlyUluPhoSupiTlyi ^ ^ rolleSerhrriauAsnpooSuoi ooPAoSuhUrnUluSui HisLrneurhroAsnMutyauValHisProLuuProThrPooValyupUeuhAPAlaVal AsohhuSeoUepUlrTlpTrpIynThrUlnMutUluTlpTrrUrsAlaUlnAnolluUup UlyClαaalτrhUuuUeuUeuUluUlyaαlMutAlαAlαeIgUlyUanLuuUlyPooTrh yrsUuuSeoSehUuuyeuylrUlnLeuSeATlyTlriaalAhgUuuUuuUuuUlyAlaUup UlneurUeuUuuTlyhhhTlnLeuOooPIoUlnTlyAhgτrrTrhAlailsUrsAsoPhO AsnAlαlleOheUuuSuoPreTlnHisLeuLeuArgGlyLysValAogOruUeuMetUup allTlyUlySeoThoUuu (ysaalAAgUluPhuUlyAsnMutAlaSehOIoAlaPooPIO AlαCrsAsoUeuAogValUuuSehUysUuuUuuAhgAspSuhHisaalUupiisSuhAhg UtuSerUlnCrsPro (SEQ lD Ni: 215) pMON28520

120

184 424

Cl _{and S} c _and p nGysSlrIllMltIllCspGluIllIllHlSlisLluLys.CogProrroAa _0o yeuLiuAsprroAsnAsnLiuAsnAspGluAspValSieIliLuuMet; AspArgAynye _at C _A gy _IU PeoAsnLeuGl'uSerPheValycAAlaValLysAsnLeuGluAs] LALLS _UA Lyc Il ^Λ _l iluAlaIllLluArgAsIϊLeuGlnPpeCG sLeuProSerAl _and τłerAlaAlar _{axis ee} AegIisrroiaellelleyysAlaGłyAspTiepGanGluPheArgGl uLysLeuTh rh _{r l} TyeyiuValChrLiuilullnAlaGlnGluGlnianTyrVaIlluilyllyllyi lyse PeoiłyilurroeurllyreolliSioThrIleAsnreoSirProProSerLyslIuSie IisyyseirProAsrUetLeuProThrPrroZalLeuLeuProAlaYalAsprheSerLiu ilyiluTrpLysThrGlrleetGluGluThrLyΞAlaGl] nlspIleLeuGlyAllValThe LeuLiuLiuGluGlyVa M & tAlaAlaAseGlyGlnL EUG lyProThręyyLiuSioSir LiuLiullyGlnLuuSerGlyGlnyallcgLeuLUjeuGlyAlaLeuGanSurLuuyeu ilycrAilnLluPeoProiInllycrg'TerThrAlaHisLysAΞpProAsnAlaIlerhl ΙιΉιοΡΠΐ1η] ϋ2Β6ΐι] ΙθαΑΐφΗη1ι ιν3 · e ^ i ^ l] D ^ l ^ e ^ you; eu € ^ tt and LenV alilyllySie crrLluGysValArgGluPheGlyAssnleIAlaSerProAlaProProAlaGysAspLlu CrgVaILluSerLysLeuLeuArgAspSerHisValLeuHisSerArgLuuSuAlnnGys ProlluValIisPeo (SEQ ID No : 2165 pMON48542

ClaAsnGysSleIleMltIleCspl1uIllIllHislisLluLysAegProrroA1aPeo LeuyiulspProAsnAsnyeuCs] nispGluAspValSieIliyiuMetAspCAgAsnLiu lAgLeuProAsnLeuGluSerPheVa] nArASaValLysAssl.ιeuGllLAsnAalSeAl1y Illi1uClaIllyluArgAΞnLeuGlnPreCG / sLeuProSerAlaTłrrAllAalrroSlo CegIisProIliIliIliLysAlaGlyAspT: rpGlnGluPheArgGlu ± ecsLeuThrrhi TyeLeuVlnτhrLeuGluGlnAlaGlnGluGlnGlnlCyValGluGlyGlyGlyGlySee ProilyilurAoSurlayPAolliSeeThrIleAsnrroSerrrorAoSuryyyGluSie ϊisLysSlrProAsnleetValLεuL · euPpeAlaValAsp? PΊeSerL · euGlyl1uTrpyys; ThrilnMet.GluGluThrLysAlaGlmpIleLeuGlyAlayalThrLeuLuuyiuGlu l1yVaaMetAlaAlaArglIylanLluGlyProTleo ^ · ysLeuSerSerL uuLuuGlyGln yiueirllyGlnVal.AogLeuLeuLeuGiyAlaLeuGliiSerLeuLeuGlyThAGlnyiu PeorroilnIlyArgThrThrAlaIisiLjsAspProAsnClallePhiLeuSerrhelln HisLi'uyruAG'gGlyLysyValArgPheLeuMePLeuValGlyGlySerThoyiuCysVal Argl1uPreGlyAs] neetAlaSerProAlaProProAla (G / sAspLeluAogVllLeuSlo yysyluylulrgAspSerHisValLeuHisSer ..] lrgI _J euSerGln (GjsProGluVaaHis reoLiureoThrPro; Ne SEQ ID: 227) pMON28522 l1aCsnGyselrIau] eltιalCspi1uIllIlelislisLluLysArgProrroClaPeo

LluyluCsprroAsnAsnLuuAsnAspGluAΞpVlleerIleLluMltAspArgAsnLlu

CrgyeuPeoAsnLeuGluSerPheValyA'gAlaValLysAssn _J euGluAsnAlaSioily

IlllIuClaIllLuuArgAynyeuGlnPro (Τ'sLeuProSerAlaThrAaaAIahAoSle

CAglisPool1lIllIllLysAlai1yAspTrpGlnGluPheArgGl <ueysLl'uThrrrl

TyryluVl1'Thr] IeuGluGlϊl · AlaGlnGlyGlnGln ^r lCjrValGluGlyGlyGlyl1yl1yelo

PeOiIyl1uPeoelrl1yProIlleloCrrIleAsnProSlrProProelryysl1uSlo lisLysSlrProAsϊiMetAlaValAspPheSerLeuGlyGluT _A pLysThrl1nMltl1u lluChralAleNeLualTuLuLuLeLiuGlinTly

ClaCrgi1yGlnLeuGlyProTłh0Τ'sS.euSerSerLeuLeuGlyGlIl] IeuSerl1yl1n

ValCrgyluLluLeuGlyAlaLeuGlnSeeLeuLeuGlyTłhAllIϊL euProrrol1ni1y

CrgThrτrrAlalisLysAyprroCsnAlaIlerheLluSlrPhulInliyyuuyeuAAg i1yLysValCrgPheLluMutLluVa1i1ylaySurτrALeuGysValAAglIurhul1y

CsnMlt.clαSlePeoClarAoProCllGysCspLeuCogVαlLluel: rLyyLluLeuCog

184 424

121

GsoSeoHisVllLeuHisregGggUeurerGln (CssPrzUluVllHisPgoLuuProChg

PrzValLebyeuPgz (SEQ ID No: 218) pMON18513

ClaGsnCysSugeleMeteluGspAlulleeleHisHisLeuLysArgPgoPgoAlaPgz eeuUebAspPgzCsnCsnUebGsnGspAluAspValSerlleUebeetAspAogGsnLeu CggUuuPgzGsnLeuAlureoOheVαlAogAllValLysCsnLeuAluAsnAearurUly eleGluClaIluLeuAggTsnyu'bUlnProeysLuuPozSugClαThrAlaAeaPooSeg TrgHisProlleIyeeleUysClαAlyAspTrpGlnUlbPheCggAlbUysLubChrPhe CyrUubValChgLeuAluAlnC.laUlnAluGln1lnCyrValAluAlyGlyGeyAlySeg OrzUlyGluPrzSerGlyPooeleSeoChreleCsnPrzSerProPrzSerLysUluSer HisLysrugOooCsrϊMetGspPheSurLeuylyUlu.CgpLysChoAlGMetGlbGeuChr eysClaGlnGsoeleLeuAlyAlaValChrLuuLuuLuuUluUlyValίeetAeaAllA.gg ΑlyUlnLeuΑlyPrzChoTysLuuSuoSerLubeuuUlyΑlneebSegΑlyUlnValTgg Luue · euLeuAlyTlaUeuAlnrugLeueeuGlyThrGlnLuuPgzOozAlnUlyCogChg ChgClaHisUysAspOrzCsnAlαeleOheLeuSerPhuGlnHisLebeeuA.rgGlyUyΞ ValCggPhuUeueIetUeuVaeGlyΑlySeoChoeubCysValCggΑlbPhuUlyCsnMet ClαSurOrzTlaPgzPrzClaTysGsoeeuAogVαlLuuSugLysUuuUe · bAggAspreg HisValLeuHisSurCggUebreguenTysOroAluVaeHisoozeeuOgoChgPozVal LeuLubPooTlaVal (SEQ ID No: 219) pMON28524

ClaGsnCysSuoeleMuteleAspGeblleeluHisHisLuuLysCrgOroPgoGlaOro LuuLubg.soPgzCsnGsnLubAsnAspAluAspVaesureleLe'beetΆspAggGsnyeu CogUuuOooCsnUeuUluSegOheValAogAlaValLyΞCsnLeuAluAsnAlaSurAly eluGluAlleluLuuArgAsnLuuUenPro <GssLeuProSugAlaThrAlaAllPgoSeg CogHisOroeluelueluLysAlaGeyAspTopGenGlbPheAggUlbLysyubChoOhte CyoLubValChoLeuAluAenAlaAenAluGlnAlnCyrValGlbAlyAlyGlyUlySeg PozAeyGluOozSegUlyProeeuSurChreeuGsnPozSurPgzPgzSeoLysAluSeg HisLysSuoOozCsGeetueyGluCgpLysChoAlrieutAluUluChoLysAlaUlnGso lleLuuGlyGlαValChrLebyuuLuuAluGeyValMutTlaT.lαAogAlyGenyeuUly PrzChoCysLebSurSerLubyuuAlyAlnLubSuoGlyAenVllCggLuuLubLuuUly ceaLuuGlnreoUeuyeuUlyChgAlnLeuOgoPooUlnAlyTogChoChrAelHisLys CspPgzCsnGlallePheLeuSuoPheGlIGF ^ iΞLeuLeuAogAUsLysVaeAggPheLeb MutLeuValGlyAlySerChgyeuCysVαlCrgAluOhuAlyCsGMetClaruoPozCll OrzPooClaCysTspUeb.aggValLuuSegyysUebye'uArgCsoSegHisVllLuuHis SeoGogLeurerUlnTysProUlbValHisOgoLebProChgPgzValUeuyubOgzCll VllGspPhururLuu (SEQ ID No: 220)

OMONl8525

GlαAsnTysSeglleMetlluAsoAlulleeleHisHisUuuUysAggPgzOgoClαPrz

LeuLubT.soOrzTsnAsnUebGsnCsoAluGspValSeolleUebeetCspGggCsnLeu

CggLubOroCsnLuuAluSurOhuValAggGlaValUysTsne ebUluAsnAllregUly lleGluGlaeleUeuAggAsnLuuUlnProCysLeuPgorugClaThgAlaAUlPozSeg

CggHisPgzllelleIleUysGlaAlyTspTrpAlnUluOheCggAluLysLubChgPhe

CygLebValChreuuAlbAlnAlaAlnAluUlnAlnCyoValAluAlyAlyGeyUlySeg

PozAlyGluOozrerAyyPgoeluSegChreluGsnPgzSegPgzPgoSerLysUeuSeg

HisLysregOozCsGeetAlyOgoChoCysLeuSerSeoUeuLeuAlyAlnLubSurUly

UlnVllTogLeuLuuUeuGlyAlaUeuAenreoLubLebAlyChrUlnUeuOgoOooAen

122

184 424

AlAGrHC ^ rce »· AlćH ^ isLysAshOzΌAsGn.lnlMeFlleL · <suSeoPheGUnHisUeGUeG aoHPheLeGMetUeGai1ClAclAeeoGr» Lu'GCAρ'aiU (rHAe _G p ^> h _M

CUyAP LAliSuoPozAeaPozPooAlaTASGspUUGArHVilLLGEMOLAPLM _S M _{E G G} LM _(O gA _P sE _EO HipailLMGHSsSeoAoHLuGEuoClnTyphooAlGailHSsPrzL _{UG Oz} CH _O p p v _{and rZ} eueGUMGPozAeaaalAspPhuEeoLeGAlyAlGrosLAPThrClnM _{U G} ClGThoLypAlaAlnAppeeLUeGAly TCL (laVa1ChoUeGUuGLLG (lGAlAValMMtAli (1iAoHClyGlnUuG (EEQ ID NO: 221) pMON28526

GliApnCypSuoSlM! EuteeeAssAlGeleeluHipHSsUuGLysnoHPozPrzA1iPrz LMGUuGAnpPrz (sn.GSΊsLLGGsnAssChIAspValSuoe1eLuGMLtAspAoHGpnLeG GrgLMGPozApnLMGCeGELoPhMValGrg (1iVaeuypApnUuG (LG (pnAliSuoAlA l1eAluAeieleUuuAogAnn.LLGAenPozTypLLGPozSeoAlaCho (laAliProeer GrHHSpPooeeMelMl1eLAPAeaA1y (spCosClnClGhheArHClGLypLuGChoPhu AArLMGaalGhoLMGAlGCen (.1iA1nClGAlnAlnAAoValClG _(UO lAClAAlAA1yE ProAlyGeuPozEMoGlyPrzeeeEerChreluAsnPozeuoPozPozEurLAsClGEuo HSpLAsEeoProApnMLtAlAGhrAenUuGPozPrzAenGlyAo ^ AhoChoGlaHSpLAP (ppPoz (pnAlaelMPheLLuSLoPhuAlnHSpLeGULGArHClALApailArHPhMLuG MutLMGVieAlAAlAeLoCh.oULGTAPVilAoHClGPheAlA (snMLt (p 1aSurPooAli: ooPAZ '( 1aTyP (pSLeGAoHValUuGSuoLypLLGLeIInr'HAPSEMoHssvilLuGHsp EUoGoHLeGeuoAlnTysPozAlGValHSpPrzLeGProTr Delay _1; VilLeGLMGPozAli aaeAPsPhLeMoLLGClAAeGTosUAPThoClnMetAlGAlGrł "LAP (1iAlnGssllu LMGAlAAeiVilChrLeGLeGULGAlGClAVileίLt.GllAliArH (UAClnUuGAlAPro ChoTAsLLGSerEuoUeGULGAeyAene.UGeerclyGlnVal1 ^ OHeLGLMGLMGAly (1l LMGClnELoUuGUuG (SEQ ID No: 222) pMON28527

AlaApnTyneeoilM! EutseMAppAeGlluileHisHSpUUGLAS (rHPozPrz (1iPrz LLGUeGAnshooApnApnUMGAnnAnpCeuAspValSMoeeLUuGMutAPsAogApnUuG ^(τ OgLLGPozAsnLMGClGeLoPhea alAogAliValLysG.prLeG (LG (sG.AllSuoAlA l1eClGAlieeuLMu.C: ogAnnUeGAlnPrzTypLeGPozSeo ^ G ^ laChrGlaGliPozSMO (ogHSsPozeluelMelLUAsAeaAlAAPpTopAlnAlGhhLArHClGLAPUeGThoPhe ryoUuGVaUAhoUeGAeGG enAeaAenClGClnAenCyrVaec lu (LYG lyGlyG lyUo r PrzClyAlGhooSurA1yhozeeLSLrGhoeleAnnPozSLoPozProSeoUAsAlGSeo HSsLAsSMoPoz (pnMetAeAAoHThoChoAlaHSpUysAssProGpnAlal1uPhuLMG EMopreAlnHiPLMGLeGAogAlyUypValArHPheU'LGeίetLMGVilAlyAlASuoTrr LuGΊAsaaeAOHClGPheAlAAsnMetAlaEuoProAeaPo ^ oPooaliTA ' pAssLuuAoH ailLMGeLoUAsLUGLuGAoHAssSerHisaalLLGHiseeoArHLMGSeoAlnTAsPoo ClGaalHSshrzLLGPrzrhrProValLeuLeuProAlaVeCAspli.uEerUeGAlyAlG CosLAnChoG1nMLtAlGAlGTrrUAPAlaAlnAPseleUuGClAGliValChrUeGUUG LUGClGAeAValMLtAlaAelArgClyClnLMGClyPrzGhoTAsLMGSuoSurLeGLUG CUAClnUeGSuoClyAlnaieAoHLuGLuGUeGAlAAlaUuGClnEMrLuGUuGClyThr ClnUUGPozPooAls (SEQ ID No: 223) pMON28528

GlaGpnTAPSuollMeeteeeAppClGl1ueluHipHipUuGLAPGogPooPos (1iPrz

LuGLMGnssPrz (nGpnULGAssA ^ ssClGAPsaaeSLo ^ rl ^ e _J ^ GMMt (spnrH (snUuG

GogLLGPooAsnLLGClGeerPheValArH (1aValUAPAsrUMG (lGAsn (liSerAlA lle (1uAlieluLLuArHApnUeGAlnPooTAsLuGPozeuoAlaChr (1i (1iProSer

184 424

123

AGgHisProllellelleeysAlaAlyAspCGpClnGluPheArgUluUysUeuThGPhe τyGUevVaeAhreuvUluClnTlaAinUluUlnGln ^r y / rValGlvGlyGlyUlyGl: Pipe ProAlyCiuProSurClrProDlueurGhGlluAsnP: oorurProProSuoUyHUlvSur HisUrsSeGProTHnMutAlaHisUysTspPrIAsrsΆlallePhueeuSeGPhuGlnHns euueevTrgUl e: sValTGgPheeuvMuteevValGlyAlyeerAhGeuuT: HValTGg CluPhuUlyTsneίuGT.UaSurProΆlaPGIPGIClaCysTspeeuTrgaaleuueere: s euueuv.TrgTspeurHisaaleuuHnsSur.TGgLeuSerGlnCysProGluValHnsrro euurGoAhrPGoVaieeveeuPGoTiaaalTspPheSerLuuGlyGluTrpUysThGUln MuGGluGiuChrUrsAlaclsTspllueuvUnsTlaValThGeeuUeueuuGluUlyaal MuGAlaAlaAGgAiyUineeuUl: ProChrGrsLeuSuGruGUuvUuuAlyAln.euvSuG GlyAlnVai.CGgeuvUuveuvAlyTlaUuuGlnSerLeueuvGlyAhGAlseuvPGorGo GinClyTrgAhGThr (SEQ DD NO: 224)

ΡΜΟΝ28529

AlaAHsCyHeurDluMeGlluAHpAivllulluHisHisLuue · ysAGgProPGoTiaPGo eeueeuAHprGoT.ssTsneuuC.ssnHpClvTspValSeGllueuvMuGTspTGgTHneuu TrgUuvPGoTHneevUluSerPheVaiTrgTlaValLyHAsnLuvAiuTsnAlaeerUl: DluGluC.ialluUuuTrgTHrlLeuUlsPGOtysLeuProSerAlaThrAlaAlaProeuG nogHisPooDleDlulleUysAlaAlyTspTrpGlnGluPheAGgGluLysUuuAhrPhu ArreeuaalThreuuClvClnTlaUlsCluClnGl · n'tyrValGlvUlyClyClyUl: Pipe? RoClyUiurroeerClrProlleeerChGDluAΞnProrurPGoProSeGeysAlveur HiseyHrurPGoTHnMeGAspProTssLAlaDluPheLeuSerPheUlnKiseuueuuCrg clreysaaln.GgrhueuueIuteuuValClyClySerTłrreeuAys'aalTrgCluPhuUl: AsnMe tTlae UGPGoAiarroPGoAia7: ΉAHpeuuTGgValUuueuGUrHUuveuvlG · g TspSuGHnsVaieeuHisSeGTGgUuvSerUlnA: sProGluValHiHProeeuProAhr ProValeuuUevPGoAlaaalTspPhuSureuvCnrGlvCrpe: sAhrClnMeGUluUlu ThGeyHTlaAisLTHplleUevUl: TiaVaiThreeuLeuL · uuCluGlyVaiMuGTiaTea TrgCiyUlsιUuvUl: PrICrrAssUuuSurSeGeuuIleuClyCl] neeururCl: UlnVal AGgeuuUuvUevUi: TlaUeuCiseurUuueuuGlyThrGlnLuuProPGoUlsUl: TGg ΑΙοΑΗοΤΙιΗϊ? 1: ηO (SEQO No.

TlaAsnAyseeGDluMetDleTHpUlulluDluHisHisLuuLysAGgProProAlaPGo euveuuTsprooTssTsnUuuTHs.TspClvTspValSeGIleLuu! EuGAspTrgAsseuu TrgeuurGoTssLeuvUluruGPhuValTrgTlaValLysAHnLuuGluTsnAlaeuGUl: DleUlvTlailueuvTGgTHneuvUinrroCrsLeuP: oorurAiaAhGT | lAlarGoSur TogHnsPGollulleDluUysAlaUlyAspTroP-lnGluPheArgGluLysLeuAhrrhu Cyreuv'aalAhGUuvUlvAinTiaAesCiuAinClntyrValGiuAiyUlyUlyUi: EUG ProClyCluPrceuGCl · rrGOliuruGChGlleAsnProSerProrGorereysClurer HisUysSuGrGoTHnMuGTlaDlurhuUuuruGPheGlnHnseeveuvTogUlye: H'aal TrgPhueuueίuGUuuaalUlyCl: SeGChGeuvAisValArgCluPheUlyAsn.MutTla SurProTlaProPGoTlaArsTspeuvTGgaaleeuSeGLysLeuLuuTrgTspSurHis ValUuvHiseur.nGgUeueeGUlsG: HPGoUluValHisPGoLuuPGoAhGrGoaaleuu euuPGoTlaVaeTHpPheeureuvUiyCluTopeysThGGlnMuGUluAluThGUysTla ClnAspDleeeuAeyAlaValChreeueuueuuGluGlyVanMetAlaAlaArgCls'Cln euvClyrroChoC: seuuSuoSeGeeveevClyGlrnleuSurClyUlnaalAGgeevUev euuCl: AlaeeuClsSureeueeuClyAhrClnLeuPrΌPooClnUlyTrgAhGAhoAla HisLysTspProTsn (SEQ DD No: 226) pMON23533

124

184 424

Gla1ηnCysSerlltMtt1leGspGlu1lr1leHSsHisLeuLysArgProhooAeaPoo LeuLeuGspProGsnAsnLeLIASI ^ AspGluAspValSrrlerLeuMetAspAogApnLru 1.ogLeuPooG.snL EUC · · ^laSeυ0> PrValll'r AiaValnysAlpneuGlnlΛlpnGlaero'Clr 1leGluAla1leLr ^ IlrgAiηHJeuUlnPpr (AsPeuPhoOerAlaT (rrAH.laPooSro GogHSpPro1le1ltIltLysAl · aGlyAspTłr? GlnGluPheArgGluLysLu'uGroPhe T / ^ rLeuaalτrrLeuGluGlιn.1nGlnGluGlnnln hr0'alGluGlyGlyGlyll / SRO PooClyCluPooSerGlyProIleSe: 0lho1lrAsnProSerProProSerLypleuSrr HisLysSerProAsrmetGluValHiiPprOLu.PprTGhrhrValLeuL · euProAeaaal 1spPreSerLeuGlyG-ylTcpLysPGrOlnMeeGlnGluTGhOyΞAlaGlInisp1leLru GlyleaaaeτhrLellILeuLLuUlyGlyValMeUAltói ^ G7gGlyGlnLeuGeyPooGrr CysLeuSerSerLt'ιUl euGlnrl.nLeuSsuOlnrlnVaαll · _J · gLetU _J euLeuGlyAlaLeu ClnSeoLeuLeuGlyThrGlιn _J euPPoPpoClnGluycoTTr'ThrAlaHisLysAppPro lsn1lallrPreLeuSerPhrUlnHisPetUetUG 'oGCn / γsValaG7gPheLeuMrtyuu aαlClyGlySeoThrLeuIA / PalnsoGluPhrrlyrlnAsnnlyGlyAΞrtieetAeaSro PooAlaProProA (LACA / PipLeuAlrVaαneuSer0y / PeuLeιIG: gAspSeoHSpaal etulSηSeoAogLeuSeoGlnCysPoo (SEQ AND I No: 227) peON28534

Gla1sn.TssSer1leettIlrAspGlu1lu1luHisHisLeuLysArgProPoo1.laPro LeuLeu1spPoolpnAsnLruAsnApplluAppValeuoleuyrueutAppAogApnLuu GrgLe'uPooApnLeuGluSse0hrValll0AinValUysAsnLeuGluAΞrl AlaSuoGly 1ltGluAla1lrLrUlrgAiπPLuUlnPro · (A / PeυPPo0erAlaThrAH.laPooSeo 1oglisPoo1lrlee1ltLysAlaGlyAspTłO) GlnGlltPheC.rgGluLysLruGhrPhe TyoL RUV al thrL rul lull nAlallnGluClnlenG / oa allluCl / GlyGlyG / seo r ProGlyGluPooSrrGlyProIleSerTho1leAsnProSeoProProeroLypCluSer lSsLysStrProAsItfeetLLuPPoTGrrprValneυLeuPhrAlaVal AspPheSerLru ClyGluTrpLysThrGlιtfίetGlyGluTGh0e'sPA.ualιnlpIleLeuGlyAlaValτro LeuLeuLeuGiuClrVaHietAlaAlWAorGlyGlen.euGlyProThrCysLeuSroerr LruLeuGlyGlnLeuSerrlnrlyValnAgLeuLerLLuGlyAlaLeuGlnSeoLuuLuu ClyThrGlrϊL · · euProProOlllnlyAlΌTGh0Ge0leHlSp.ysAspProAsnAla1lrpre LeuSerPheGlnHisLeuULuAc oGlyrL'sPalll'rPhhUeŁIłetLeuValGlyGl / SRR ThoLeuCysValArgGluPPrUlnrlyAiPGlnrly / iηnίetAlaSerProAlaPooPro GlαCysAspLruΆrgVall _and euSsu0ysPeuLeŁL · ŁA'0g-ipSsrHlsValL euHspSeoArg L · · · EUS erClnArsProCluValHisPoo (SEQ II NO: 228 ) pMON28535

GlαAsnAsserr1lueet1leAηpGlu1luIlrHisHipLruLysArgFoohooAlaPoo LeuLeuGspPooGsnAsriLetIlsrnlspGluAspValSer1leLeuertAspAogApnyeu goggles euProGsnLeuGlιlSer0PrValy loAl.nValL · · ysP.snLeuG liuAsrLAlaSrrlly IleGluAlaIlrLeWirgAiPLLt.IGlnPpoCysPeuPprSsrAlaThrGldeaPooSro 'GogHisPoo1le1le1leLysAlaGlyAspTrpGlnGluPheArgGluLysLuuGrrPhr C / rLruValThrLuuGluG-nnA.nGlnnlnGlnGCnΊhr · ValGluGlyGlyGlyll / SRR PooGlyGluPrcιSerGlyProIleSerThr1luGsnProeerPooPooeeoy / pGluSeo iSpLysSerProAsInletValnee.ueuPPoAinValylpPheSerLeuG lyGluGopLrs ThoGl.ηΜεΡσίυΟίηΤίτΟ. / ΑΐηΟ lιAipZleUeuUlnAln, va InTaio LeuLeuLeullu ClyValMetAlaAHrogCurlnPeuGlnSprΊ'hr0AsPeuSerOerLeuLeuGl / Gln LeuSeoCl / GlnVanAogeeuLr ^ IyeuClyAlaLeuGlnSerLeuLeuGlyτroGlnLeu PooPooClnyl / GogGhoThoGlaHisLyρGspProAsnAlaelrPheŁruSuohhrlen / sauohhraluLLuohhrlen iSηLetuGuLLuLArguLerLLuArguLerLLuPalrgu

184 424

125

CogAlbPheUlyGlyCsGAlyUlyCsrlMetceαrerProAlaPrzOgoGlaCysCspLeb CrgValLuurerLysLuuUuuTggCspSeoHisValLeuHisSerTogLeurerUlnCys ProUluValHisPgzLeg: 22PzCLeg

OeON28536

TlaCsoCysSeglleMetIleGspAluIleeleHlsHl sL · · EUL ysCogPgzogzclaPrc UebUeuCspPrz1srAsnUeuC.snCspAlbCspVαlreolleLebeeLGspCggGsnyuu CggUuuPozGsnyeuGluregPheValCogGelValLysAsInJeuGybasnClαSurUly eluUluClaeluLuuCrgTsnLeuGlnPgo (G / sLeuPgoSerAlaThgAlaAlaPgzreg CggHisPoolleelelleLysAlaGlyAsp ^r ^ CgpGlnGlyιPheAggGluLysLe UChrPhe CyoLebVαlChlgLeuUluAlnGlaAlnAluUlnGln (CsgValGluUUyUlyAlyGlyreg PooUlyUlbPgoregUlyProeluSurChgeleAsnProSerPooOooSugUysGebrur HisLysSugOooGsnMetTlαVllCsoOheSureeuAlyAluCgoUysChrAl] GMutGlu UlbChoUysClaUlnGsoIleLeuAlyCllValGhgLelULeuLubUibA lyVaeMut.T.ea ClaArgAlyUlry _J euAlyOgzChrTysUeuSegSegLeuLeuGUyGlnLeurerGlyGln VαlCggLeuLuuLeuGlyTlαLeuAlnSegLeULeuGlyThrGlnLeuPgzPgoGlnGly GogChoChoClaHisLysCspPrzTsnClaeleeheLe ^ bSegPheGlnHiseeuyuuArg UlyLysValargOheLeuMet.LeuValΑlyGlyregThgLeuCysValGogΑluPhuUly AlyGsnGlyGlyGsrM [utClaregOgzCllPgzegoAla (CssAspLeuCogValyubSeg LysLeuLeuC. ogAsoSerHisValUuuHisSegAggLeuSegGlnCysPrzAluVllHis ProLeuOooChrOroValeeuLeuPrz (SEQ ID No: 230)

OeON28527

CllA.snCysSeoelueetIluGspAlulyeeleHisHisLeuLysAggPrzeroClαPrz LubLuuGspPoo> GsnCΞnLeuCsnCspAluCsoVllregIluLeuMeLGspCggGsnyeu .CrgLuuOroCsnyeuAluregPheValCggCllValLysAsnLeuGlbCsGAlaruoGly eluGluClaeluLuuCrgASIGLeuGlnPgo (T / sLeuProSegAlaThgAllAlaPooSer CggHisOrzleueleeleLysAlaAlyAsp'CgιpClnGluPheAggGluLysUeuChoOhe CyoLuuValChgLuuAluAlnGlαUlnAluUlnGln'G / gValGluGlyUlyUlyGlyreg PooGlyUluPooSugAlyProeluSegChglleAsnPgoSegPgoPrzSerLysGlbSer HisyysrugPgoT.sGe] etCSPPheSegLeuGeyGyUh gpLy s ^r ChgGlIKeetAlbGlbCho LysAeaUlnT.speleLuuAlyGlαValChgLu · ueelbLeuGluGlyVayHetClαAllTrg UlyUenLebUlyOozChrTysLebSerSegLuuLeuGlyGlyG _J euSeoUlyAlnVaeArg LubLeuLebGly.TlαLeuUlG-rerUeuUeuUly'hhgGlyGLeuPgoPooUlnAlyAogChr ChoGlaHisLysT.spOrzCsnClaeluPheLeuSegPłleGlnHisIJeuLeuCogUlyUys VaecggPheLuue [etUeuValUlyUlySegThgLeu (G / sValArgGluPheAlyGlyCsn UlyUeyCsGeetAlaregPrzClαProOgzCeα <G / sAspLeluAogVaeLuuSuryysyuu UebGggCsoSegHisValLebHisSerCrgUeuSegGlnCT / sPgoGluValHisPooLeu PooChgPooValLuuyubProGlaVal (SEQ ID NO: 231) pΜΟΝl8 538

ClaCsnCysSerlleeetlleTsoAluIleeluHisHisLeuLysArgPozPrzAlaPgo

UeuLe: uAso) PoΌggsnl ^ snLeba.znasp> Ay.bCsρVllreoeluLuuMetasoTggGsnLeu

CogLeuProCsnLeuAluSeoPheVllAogTlaValIL / ΞAŚnLeuGluAsnClaSerAly eluGlbGlalluLuuCogCsnLeuAlnPozCysLeuProSerAlaThgGeaAllOooSur

TrgHisOooIlelleeleUysAllGlyAspTlg ^ GlnGluPheArgGluLyseeuChrOhu

CyoLeuVαlChoyeuUluAlGClαAlGAluGlnGln ^Γ CsgValGluGUyUlyAlyUlySer

OgoUlyGlbPgorerUlyPrzeleSeo ChoeluAsnProSerProPooreoLysGlbrur

HisLysruoProGsGeutUlyAluCopUysThgGlrGletGluGluThoLysClaGlnAso

126

184 424 lluLeuGlyAlaValThAUuuUeuUuuyl'pUlrΊ'alMetAldAl <acogTlryι _{n eu} in · vein OhoTroyrsUuuSehSeoUuρUupU.lr> uanUuuSehU lrUlnVaaArgUuuUeuUeuy | y AlayuuylnSeoUeuUe ρTlyThruar.LU.uuPooProUlnUlrAogτrphrhAl _{and Hi-S} yy _{y n} AsoPhoAsnAlallePhuUuuSuIPhuylnHinLeuUuuArgUlyUyΞValA hot _U ^τ y _eu MetLeuValTlrTlrSuoτroUepC'yna alrngGluOhuUlrUlrAnnUlrUlrAΞnM _U t AlaSuohroAlaPhoPooAlayrsAnoLeugpgValLepSuoUrnUeuLeuAogAΞoS _Uh HinVαlyuuHiseuoCpgUuuSuhUanCysPooTlpaαlHinPhoLuuPhoτrhP _Oo v _a l UeuUuuhooAlaValAspPreSe; Uuu (SEQ lD Ni: 202)

OMOr28539

AlaAsn.yrsSureluMutlluAspGlpileiluHisiisLepLysArgOhoPooAl _l .h ₀₀ UepLuuAnpPhoAsnAnnLuuAsnAnpTluAsoValSeIeluUuuMutAspCpgAsnLuu AAgLuuhroAsnLeuTluSerhhuaalArgAlaValUysAsnLeuUluAsnAlαSuoyly lluTluAlailuLuuArgAsnLupTanhhoyrsLepOopSeoAlaThAAlaAlaPopSeo AogHishrollellelleUysAlaUlyAsohAoUlnUlporuAogUluLrsLuuThAhre TyoUuuValτrhLuuUluUlnealUlnUluTlnTanTrIaαlUluUlyUlyTlyUlyeeo PhoUlyylpPooeuhUlrPhoIleSerThrlluAsnOrpSerProProSurUysUlueuh HisLrneehProAsrLMutTlyPooTr.oTynLuuSuoSeiUuuUuuUlyTlnyeuSuryir UlnVllAhgLuuLeuUuuUlrAlaLuuylnSuoUuuUepUlyThrUlnLupProOhoyln UlyAAgThoThrAlaHisLysAnpProAsnelaileOhuLupSeoPruUlnHisLepyuu AAgUlyUrsVa | gpgPhuLeueIrtLuuValylyylrSeITrALepCysValApgUlphhe UlrUlyAsnTlrTlrAsnMutAlaerhhopAlaPAoPrpAlaCysAsoLeuAAgValyuu SurUysLuuLuuCgg.AsoSerHiΞValLuuHlsSurgA'gUeuSeoUlnyysProTlua'αl HlSpooLeuProThoPooa'alLuuLr ^l pPhoAUaValAsoPruSurLuuUlrUlPhoρLys ThoUlnMetTluUluThoUysAllTlΓ "AsoeluLupUlrAlaValTrIUuuUeuUeuylu UlyValMetAlaAlaAAgUlyTlnLuu (SEQ lD No: 233)

OMOr28500

AlaAsnCysSurilUleutilrAnpGlullullrHisHisLeuLysAAgPrphroAlahAo LupLuuenohrpAsnAnnLuuAnnAsoylPA · soValSuhelrLuuMutAnoAAgAsnLuu ArgLuuPooAnnLuuUluSurPheValA-PgcAaValL, ysAsnL'UuUluAsnAlaSeAyly llrUlpAlaelrLuuArgAnn.yupylnhooCrsLuuPopSuoAlαTroAlaAllPooSur ApgHishrpeluilreluLynAlaGlyAsohoo> TlnUluPhuAAgUlpLynLrphrphhu 'TroLuuVαlhhoLuuTluUlnAlαylnyluTlnUlnTyIaalUluUlyUlrUlrTlreeo pApTlrylPhPPeerylyhApeluSuAhroelrAnnPooSerProPrpSuALysy | safety update ^{iisLysSeoPrpAsnMetUlyhhrylnyruP>} ooProUlnUlygrgτrrThpAlαHisLrs AsoProAsnelalluPruLupSrohhuylnHinLuuLepArgUlyLrsValArgPruLuu ^ ίutUrpVllUlyTly'SerThoLupyrnValArgTlpPhuUlrUlr'-Cn: nUlyUlyAsnieet elaSuAhooAlaPhoPooAlαyrsAnoyuuApgValLepSuhLrsLup.yeueAgAsoSeo HisValLuuHisSuoArgLuueuoylnyrshhoTlpValiisOooLuuProThhPooVal UuuLeuPooΑlαVllΑspPreSuhyuuylrUluTooUrscroUlnMutUluTlpTrrLys AlaUlnC.soeluLuuTlrAlaValhhoyeuLeuLeuUluUlyaaUMutAlaAlaAogylr UlnUuuUlrhroTroyrsUuueuheurLuuyupUlyUlnUeuSeoTlrUlnValArgLup LeuLuuylyAlaLuuTlnSurLepLuu (SEQ lD No: 230)

OMOr28541

AlaAnnCynSehlIrMutlleAspGipelelluHisHisIjepLysArgPooProAlaPro

LeuyuuAsoPooAsnAsnyeuAsnesoylPAsρValSuIlleLeuMutAΞpgpgAsnU ₎ eu

ApgLuuPooAsn.UuuTluSeoPruValgpgAlaValUrsAsnUuuTluAsnAlaSurylr

184 424

127 l1uAlG (lilluUeGA.oH (pnLMuGlnPrzCypLeuPrzEerAlaThrAel_GliPozEuo GogHSpProl1ueeeeeLUAPAliGlyAspTrsGlnGluPheArgGl ^ GLypUMGGhrPhL CyrLMGai1ChreeuClGAlnAliGlnGluGenGln'TyrValGluGlyGeyAlyAlyEuo PooClACeuProSeoClyPozllLEMrChreeMGpnPrzEerProProSeoLAPAlGEMo HSsLypEuohoo AsnMetAlAArgT hrThrAlaHis LysAsp ProAsnAlallePhuLuu EMoPhLClnHSsLeGLeGAogClyLysVaeArgPheLeuMetLeuValGlyAlyEurCho LMGTypaalGrgGluPheClAClyApnG1yClyAPIileMtAlaSerProAlaPooPrzAli TAsAssLuG (rgValLLGEurLAPLuuL, uGAogGppSurHSsValLeuHinSLrArHLuG EMoClnΊAPPooGluaalHSpPozLMuPozChoProValLMl · GUeuProAliValAPsPhM EeoLuGAeyAluTrpLynGhoAenMetGluGeuThrLysAlaG] lnAspIeMULGAeyAea aalChoLUGLMuLUGClGClyVilMutAlaAeiGrgGlyGlnLeuGlyPozThrCypLMG EuoSuoLeGLMuGlyAlnUuGEurClyAlnailArgLMuL, uuLeuGlyAeaLeGAlnEeo LMGLMGClArhrAlsUeGPozhozAln (SEQ ID No: 235) pMON28542

GlaAsnTASEurelMMLtl1eAppGlulluleuHSpHSsLeGLysArgProPozAliPrz LeGLUGGPsProAs: ι ^ nsnLeGAsnAppGlGAPsailSuol1uL, MuMetAssAoHApnLuG (0HUUGPrzGpnLuGAeGEurPrMVilA0H (eiValLypApnL, euGllGAsnAlaSMrClA l1eAlG (lalleLeuArHAnsUMuClnPrzCysLuuPooSMrAla '] rnOCeaAeiPozSer GrgHSpPrzl1uelul1eLAPAli (1yAppTrpClnGluPheArgGlGLynUeGChoPhu ryoLeGaaerhrLeuAeGAenAliGlnGluGenGlnTyrValGluGlyG lyClyClASur PrzAlACeGProeerAeyProelMSurThoeeMCsnPozSuoProProSMoUypAlGSLr HipLypEeoPooAsriMeLAeaHSpLypAspPooGpnAlilluPhuLeGSLoPheClnHip ULGUeGAogClyLypVaeAogPhuLeuMetLLGValGeyGlySerTłnOeMGTAPValCrg AeGhheAeAClyAsnG1yA1yAp: nMetAlieLoProAlaProProAla <ΊypAPsUuGArH aaeuuGEuoLysLuGLeGAoHAPSEMoHisVilLMGHSpEMrArgLeuSeoAenTAPPrz ClGValHisProLeuPozChoPozValLeGL, MGProAliValAspPheSMO, UMGClA (lG CrpLysChoCl] ϋeutGlGClGChrLypAeiGlnAppIluLeuGlyAlaVaeτhoLuGLuG LuGAlGClyaalMetAliAla (oHGlyGenLeG (1yPrzThr ( ΊysLeuSeoeLrLuGLuG AeAAenUeGeurGlyGenVie (oHLuuLeuLMuAlyGlaLeuGlnSerLLGULGGlyThr cenLeGProPozAlnAey.1o HChoCho (SEQ ID No: 236) pMurA285nTys eleMetleMAPs (lGl1ueeeHSpHSsLMGLypArgPooPozAlaPoz LeGUMGApsProApnAsnULGApnAppGluAspVa1Sur1leLel GeetAnsAogApnUeG AogUeGPrzGpnLuGGlGEerPruaalArHAlaVilLypAsnL · · euGlGAsnAeiEMoClA elMAlG (lalleLeuArgAnsLuuGlnPro <TsnLuuProSerAlaThrAeaAUaPooSeo (OHHSpPozl1eelellLLAS (1i (1yAppTrpClnGluPheArgGlιGLAnULGThoPhM CyoULGValrhrϊeeuGeuGen (liAlnGluGenAlnTyoValGluGlyGeyAeAAlASur PooAlyCΊGProSerGlyPozllMSurThrl1eGpnhrzEMrP: ooProSLoUAsClGEMr HSsLAPEeoPooAsn.MetAssPoz (pnAlieeePhMUUGELrPheGlnHipUeGUMG (OH cnALAPVan (ogPheLeuMetLuuValGlyGlySerThrLeGCyΞValAoHAeGPhuCly Ala (snAlyGlyAsn] eLtAeaSMrPrzAeahrzProAlaΊysAspLeuAoHVaeUuGSeo LAsLMGUuGCrgAspEeoHipVilLuuHSpEuoGoHLLGSMrGlnCysPozAlGVilHSp ProLuGPrzThrProValLeGULGProAliValGppPhuEMrLeGGlyGlGGosLAPCho ClnMutceGGluThrLynAeaClnAspeleLLGClyAlaValThrLeuLMGUeGAUIlAlA aalMMt (poly (1aArHAlyAlnIJULGΤyAhrOłlrOTsLeGSerSeuL · eGLeGAlAAlnLuG EeoAlyAlsValArgLeuUMGUuuGlyAlaLLuGlnSeoLeuLeuGlyThoGUnLeGPos PozAlnCl \ 'GogThoChoAeaHSpLAS (SEQ ID No: 237)

128

184 424

PMON28544 .ClaTsnCy? SurDluMeGlleTspGl'uDluDeeHnsHi? EuvU:? ^ AGgProProTlaroo euueevTsppGoAHnA.HseuvAssTnpUlvc HpVal SerlluU uuMetAspArgAsne uu TogeeuProAsnLuuUluSerPheValArgAlaValLysAH] neuuUivTHsAlaruGUl: lleGluAlalleeuuTogAsnLeuGlnProęysLuuProSurAlaThGTlaTlarroreG TrgHisrGoDiuDiuDluLysAlaGlusT3pTrpGenAlurhuTrgAive: HUuvThGrhu TyreuuValThrLeuUluGlnΆlaGlnGluGlnGlnTyrValUluUerUl Cl Ul: ProGlyGluProSurAiyPooIluSer ^pipes, ThGDeeTHsPGoeuGrGorGoeuGU: HUlveuG HnseysSerProAHnMuGAlaIlePlleLeuSuGrhuAlsHnHeuueuvTGgAi e: HVALA AGgPhuLeιVluGLuuValGlyGlySe: GΓ} rrLuuCypaaiArgAevPheAl Ul: TssAU: ClrTsISeetAlaruGProAlaP: ooProAla (AssAHpUeuArgValUuveuGerHeevUev AGgAspSerHisVaeLuuHisSerOlrgLeuSerGinCysProAiuValHnsProUuvrro AhrProaalLeuLuuProAlaValeτspPheSurLuuGlyUluTrpU: sAhGUlseuGUiu CluChr: essAlaGinAspIleLeuGlyAlaValThrLuuLuuLuvCluAlyaaiMuGTla AlaArgGlyGlsUuuAl: PGoAhrAsseuueeGrurLeuLeuGlyGl: reJeuSerGSyeOn ValnrgLeuLeuLuuAiyAlaLeuGlnSerLuuLuuGly'ThGAinUuvrGoPGoAlsUiy TogGhGTeoTlaHisUysAspPronnn (SEQ DD NO: 238)

PMON28545

AlaTsnCysSerDiuMetDiuTspAiulluDiuHisHiseeuUysTogPGoProTlaPro UuuUeu Asp PGoAsnA? ΪsLe ^ vTsrsT3IP7luA? PValrerDlueuuMeGTHpTGgTsnU.eu .CGgeuuPGoASISeuuGiuSeGPheVa) UlGgAlaValLysAsseuuUluTHSLClaeuGAlr DieCluAlaDleUuuTogAsnLeuGinPGoęysLuurroSeGTiaThGTeaTlaProeeo TrgHisProD Ue Di uDiee:?. TlaUi: Background pTopAesU luPhuAGgAluiy sLeuThrPhe A: reuuValT: h.eeuAluGlenAiaGl: sGluGlΓ.GlnTyrValGevUlyAl: Street: Ulyrer ProGlyGluPGoSerAlyProDluSerThGDiuTHnrrorurPGorroeuGe: HUlveur HiHeysSeGPGoAsnMuGAsprroASIsTlaDluPhuUeuruGPhuAlsHiseuvUuvTGg UlyeysVaieTogrhuUuuMetLeuValGlyGlySeGThGLuvAyHa'aiTrgCluPheAlr Ul: nsIStetAiaSerPGoAlaPGoPGoAla (AysAppLeuAGgValeeveuGeyHUuveuu TGgnspSerHisVaiLeuHisSerAGgLeuSerGlnAs? ProGivValHn? PGoUeurro AhGPGoValLe'veeuProAlaValeA; pPheSerLeuGlyGluTrpey? ThrGlnMeGAlu UluCroLysAlaGlIsnHpIleLeuGlyAlaVaΓΓhrLe'vLeuLuvUluAeyaaiMuGTla TlaArgUlyU lsUuvAl: PGoAhrAr? ^ UuveureureevUuuUis GIS ruSurU Lyu et al Val.CrgLeuLeuLeuGlyAla] leuGlnSerLeuLeuGlyThrGisUly.TrgThGAhrTla HisU '(SEQ DD No: 239 )

PMON32132

SurPGoAlaPGoProAlatysAspLeluAogYaiLuurureyHUeueuuTrgTsprerHis aaleeuHisSeGArgLeuSerGlnSA sPGoGluValHi ^r? RGoLuvPGoThGPGoValUeu euvPGoAlaValAspPheSeGLeuGlyGluT: GpLysThGGl] SMuGUluAlvAhre: Loop GlnAspIleLeuGlyAlaValThrLeίV _J euLeuGluGlyValMutAlaAiaArgGl Aln UuuGlyP: roTłeo (A:? LuuSerSerLel.ΛeuGlyGllSeuueerGiynlnVaiTogUuveuu UuuClyAl alleuGlnrurLeuLeuGluSΓłroGinLeuPGorGoGisUlyTrgAhGAhrTia HiseysAspProA? SLTlaliuPheLeuSerPhuUln.Hi? UeueuvTogAi e:? ValTrg PheeuuMuGUuvVaini Ul: eeGThreuvAsHVaiTrg (SEQ DD No .: 252)

PMON32133

184 424

129 reohooAevhoohooalaGGpaPGUGuAoglalLeuSerLysLGuUeuArgAsprGoHSp laIUe'uHSprroGogUrureoyaGCGShos-luValHisProLeuProThrProVvlLeu L _{e O} uh ola _and lalApprrereo: Al _{a P} eGuGlGCluTopLysThrGlrGeetGluGluThrLG ylGaPGlIeUeuyaGalalalProUeuUeuLeuGluGlyValMetAlaAlVsogGlGya _G LeuGl / yPooτe.oGGGsUrureorGoUeuLruclyGlnL · cG (SerGlyG.lnVauSrge el ·. (L · L eu _{e 'U} GlGaI _a UeuGaGrroLeuL.GU- l GTrollnGlyArgThrThrAiaHSiLysA _P Gh ₀₀ lPGAlallGhreUeureorruyeGHSpUeuLruArgGlyLysValArHrheLeuleute.eu laIGlGyiGrroProUeuCypVaaAog (SEQ ID No: 253)

GMON32134 reohooalahooP'0slla _(P GGSAppUeuGrgValLeuSerLysLeuLeuArgA pSeoHip lalUruHSpreoaogLluSroylGGGsroslluValHisPrαLeuPrcThrProValLeu _L eu _h0 c _{G l} .la al _G .PG _h erSro _U euClGGluCopLysThrGlIGeetGluGluThrLy _{P and} al--lGapplleLeu lGliaValτroLeuLruLluGluGlyV _a lMetAlvGlvGrHylGylG LeullyhocPhoGGiUluSerSGoLeuLruGlyGlin. _J euSerGlyGinValArgLGίGLeu UeuGlGAlaUeuGlGreoLeuLuuylGP'roCln: eeuProProGlnGlyArgThrτroAla HSsLGPapGrosapGalallePheUeu.rerPheGliGSi LeuLeuArgGiyL _P · ySlaaGoH pheLe'uMrtUr uValGiyllGsreoPhoUeuΓGGiaalSgog (SEQ ID No: 254)

The following examples will illustrate the invention in more detail, although it will be understood that the invention is not limited to these specific examples.

Example 1

Construction of the parent BHK expression vector

A. Removal of the AflIII site from the mammalian expression plasmid.

A new mammalian expression vector was constructed to accept the NcoI-HindIII or AfIII-HindIII gene fragments in frame and 3 'to the hIL-3 receptor agonist gene pMON13146 (WO 94/12638) and the mouse IgG2b linker fragment. First, a single AflIII site was removed from pMON3934, which is a derivative of pMON3359. pMON3359 is a pUC18 based vector containing a mammalian expression cassette. The cassette includes the herpes virus IE110 primer (-800 to +120) followed by the modified human IL-3 signal peptide sequence and the SV40 late polyadenylation (poly-A) signal that has been subcloned into the pUC18 polylinker (see Hippenmeyer et al., Bio / Technology, 1993) , pages 1037-1041). The modified human IL-3 signal sequence, which facilitates secretion of the gene product outside the cell, flanks the BamHI site at the 5 'end and a unique NcoI site at the 3' end. The unique Hindin site is located 3 'of the NcoI site and 5' of the poly-A sequence. The sequence encoding the signal peptide is shown below (restriction sites indicated above). The ATG codon (methionine) inside the NcoI site is in-frame with the ATG initiator of the signal peptide (underlined);

BurSSI NCol

5 'TcncrrnrrsTTGTrrcrccccccicrccircrCTiCTCCGGrccrTGCcccGrrrcTrrncii (SEQ (D Nr: 255)

A single AflIII site was removed from pMON3934 by digesting AflIII followed by filling the overhangs by adding DNA polymerase and nucleotides. The digested DNA fragment was purified with the Magic pCr Clean up kit (Promega) and ligated with T4 DNA ligase. The ligation reaction was transformed into DH5a and the cells were plated on zLB agar plus ampicillin. Individual colonies were screened for loss of AflIII site by restriction analysis with AflIII and HindIII, resulting in a single fragment if the AflIII site was removed. The obtained plasmid was designated pMON30275.

B. Transfer of the pMON1341 / IgG2b cassette of the hIL-3 receptor agonist into pMON30275.

The NcoI-HindIII fragment (about 425 bp) from pMON30245 was ligated to the fragment

NcoI-HindIII (about 3800 bp) pMON30275. pMON302465 (WO 94/12638) contains the gene encoding the hIL-3 receptor agonist pMON13416 fused to the mouse IgG2b hinge. Directly 3 'to the IgG2b hinge and 5' to the HindIII site

130

184,424 is the site of AflIII. The genes can be cloned into AflIII-HindIII as well as NcoI-HindIII sites or AflIII-HindIII sites in the hinged hIL-3 variant pMON13416 / IgG2b to create new chimeras. The NcoI site and AflIII site have compatible overhangs and will ligate together but both recognition sites are lost. The plasmid pMON0304, containing the DNA sequences of (SEQ ID NO: 78) encoding the hIL-3 variant pMON13416 fused to the mouse IgG2b hinge region, was the result of this cloning.

Example 2

Construction of an intermediate plasmid containing one copy of the c-mpl (1-153) ligand gene of the dimer template

To generate plasmid DNA with the c-mpl (1-153) ligand coding sequence followed by a unique EcoRI restriction site, the gene is isolated by reverse transcriptase / polymerase chain reaction (RT / PCR). Human fetal liver (lot # 38130) and adult (lot # 46018) A + RnA are obtained from Clontech (Palo Alto, CA) as the source of the messenger RNA (mRNA) c-mpl ligand. The first chain of the cDNA reaction is performed using the cDNA Cycle ™ kit obtained from Invitrogen (San Diego, CA). In the RT reaction, random primers and an oligodT primer are used to generate cDNA from the amalgamation of fetal and adult liver mRNA. To amplify a fragment of the cmpl ligand gene encoding amino acids 1-153, the RT product serves as a template for PCR with a combination of primers, a forward primer: c-mplNcoI (SEO ID NO: 13) and a reverse primer: Ecompl. The c-mplNcoI primer hybridizes to the c-mpl ligand gene (Bases # 279-311 based on c-mpl ligand gene sequences from Gene Bank # L33410 or Sauvage et al., Nature 369: 533-538, (1994)) and codes for the restriction enzyme site NcoI immediately 5 'to the first codon (Ser + 1) of the c-mpl ligand. The restriction enzyme site NcoI encodes the methion and alanine codons upstream of Ser + 1 and includes the codons (Ser, Pro, Ala and Pro) of the c-mpl ligand. The EcoRI primer hybridizes to bases # 720-737 of the c-mpl ligand and encodes an EcoRI (GAATTC) site in frame with the c-mpl ligand gene immediately after Arg-153. The EcoRI site forms the Glu and Phe codons after Arg-153. The approximately 480 bp product was purified, digested with NcoI and EcoRI and ligated into the NcoI-EcoRI vector fragment pMON3993 (approximately 4550 bp). pMON3993 was a derivative of pMON3359 (described in Example 1). The human IL-3 signal peptide sequence that was subcloned as a BamHI fragment into the unique BamHI site between the IE110 primer and the poly-A signal contains an NcoI site at its 3 'end, followed by a unique EcoRI site. The plasmid pMON26458, containing the DNA sequence of (SEQ ID NO: 79) coding for amino acids 1-153 of the c-mpl ligand (SEQ ID NO: 161) was the result of this cloning.

Example 3

Construction of parental plasmids containing second genes for dimer matrices

To amplify fragments of the c-mpl ligand gene starting at amino acid 1 (Ser) with the codon ending after amino acid 153 (Arg), the RT reaction of Example 2 serves as a template for PCR by combining the following primers: c-mplNcoI (SEQ ID NO: 13) (forward primer) and c-mplHindIII (SEQ ID NO: 15) (reverse primer). The c-mplNcoI primer (SEQ ID NO: 13) is described in Example 2. The c-mplHindIII primer (SEQ ID NO: 15) which hybridizes to bases # 716-737 of the c-mpl ligand adds both a termination codon and a HindIII restriction enzyme site immediately after the end codon of Arg ¹ .

Two types of PCR products are generated from the RT cDNA samples, one with a codon deletion for amino acids 112-115 and one without deletion of these codons. The c-mpl ligand PCR products (approximately 480 bp) are digested with restriction enzymes NcoI and HindIII for transfer into the mammalian expression vector, pMON3934. pMON3934 is digested with NCoI and HindIII (about 380 bp) and accepts the PCR products.

The plasmid pMON32132 (SEQ ID NO: 249), encoding amino acids 1-153 of the c-mpl ligand (SEQ ID NO: 252) was the result of this cloning. The plasmid pMON32134 (SEQ ID NO: 250), encoding amino acids 1-153 of the c-mpl ligand (SEQ ID NO: 253) was the result of this cloning.

The plasmid pMON32133 (SEQ ID NO: 251), encoding amino acids 1-153 of the c-mpl ligand with codon 112-115 (A1 12-115) deletion (SEQ ID NO: 254) was the result of this cloning.

184 424

131

Example 4. ,

Generation of the dimer 5L PCR template with the ∆112-115 deletion in the second c-mpl ligand gene. .

A PCR template is constructed to generate novel forms of c-mpl ligand by ligating the 3.7 Kbp BstXI / EcoRI fragment of pMON26458 to the 1 Kbp NcoI / BstXI fragment from pMON32133 (containing amino acid 112-115 deletion) along a synthetic EcoRI / AflIII oligonucleotide linker 5L 5L-5 '(SEQ ID NO: 18) and 5L-5' (SEQ ID NO: 19).

The EcoRI end of the linker will be ligated to the EcoRI end of pMON26458. The AflIII end of the linker will be ligated to the NcoI site of pMON32133, and no restriction sites are retained in polygoning. The BstXI sites of pMON26458 and pMON32133 will also be ligated. The plasmid pMON28548 is the result of cloning and contains the DNA sequence o (SEQ ID NO: 80) which encodes amino acids 1-153 of the c-mpl ligand joined by a linker GlyPheGlyGlyAsnMetAla (SEQ ID NO: 222) with amino acids 1-153 of the c-mpl ligand which contains a deletion of amino acids 112-115 (SEQ ID NO: 162).

Example 5

Preparation of the dimer 4L PCR matrix

A PCR template is constructed to generate novel forms of c-mpl ligand by ligating the 3.7 Kbp BstXL / EcoRI fragment of pMON26458 to the 1 Kbp NcoI / BstXI fragment of pMON32132 along the 4L-5 'linker; EcoRI / AflIII synthetic oligonucleotide 5L (SEQ ID NO: 16) and 4L-3 '(SEQ ID NO: 17).

The EcoRI end of the linker will be ligated to the EcoRI end of pMON26458. The AflIII end of the linker will be ligated to the NcoI site of pMON32132, and no restriction sites will be retained after ligation. The BstXI sites of pMON26458 and pMON32132 will also be ligated. The plasmid pMON28500 is the result of cloning and contains a DNA sequence of (SEQ ID NO: 82) which encodes amino acids 1-153 of the c-mpl ligand joined by a linker (4L) GlyPheGlyAsnMetAla (SEQ ID NO: 223) with amino acids 1-153 of the ligand c- mpl (SEQ ID NO: 163).

Example 6

Preparation of the 5L dimer PCR template

A PCR template is constructed to generate novel forms of c-mpl ligand by ligating the 3.7 Kbp BstXI / EcoRI fragment of pMON26458 to the 1 Kbp NcoI / BstXI fragment of pMON32132 along the 5L-5 'linker; EcoRI / AflIII synthetic oligonucleotide 4L (SEQ ID NO: 18) and 5L-3 '(SEQ ID NO: 19).

The EcoRI end of the linker will be ligated to the EcoRI end of pMON26458. The AflIII end of the linker will be ligated to the NcoI site of pMON3,2132, and none of the restriction sites will be retained after ligation. The BstXI sites of pMON26458 and pMON32132 will also be ligated. The plasmid pMON28501 is the result of cloning and contains the DNA sequence o (SEQ ID NO: 82) which encodes amino acids 1-153 of the c-mpl ligand joined by a linker (5L) GlyPheGlyGlyAsnMetAla (SEQ ID NO: 222) with amino acids 1-153 of the c-ligand mpl (SEQ ID NO: 164).

Example 7

Preparation of the 8L dimer PCR template

A PCR template is constructed for generating new forms of c-mpl ligand by ligating the 3.7 Kbp BstXI / EcoRI fragment of pMON26458 to the 1 Kbp NcoI / BstXI fragment of pMON32134 along the 8L-5 'linker; EcoRI / AflIII synthetic oligonucleotide 4L (SEQ ID NO: 20) and 8L-3 '(SEQ ID NO: 21).

The EcoRI end of the linker will be ligated to the EcoRI end of pMON26458. The AflIII end of the linker will be ligated to the NcoI site of pMON32134, and no restriction sites will be retained after ligation. The BstXI sites of pMON26458 and pMON32134 will also be ligated. The plasmid pMON28502 is the result of cloning and contains the DNA sequence of (SEQ ID NO: 83) which encodes amino acids 1-153 of the c-mpl ligand linked by the linker (8L) GlyPheGlyGlyAsnGlyGlyAsnMetAla (SEQ ID NO: 224) with amino acids 1-153 of the ligand c -mpl (SEQ ED No .: 165).

132

184 424

Examples 8-44

Generation of new c-mpl ligand receptor agonist genes

Genes encoding novel c-mpl ligand receptor agonists were generated using method III (Horlick et al., Prot. Eng. 5: 427-433,1992). PCR reactions were performed using the dimer templates pMON28500, 28501, 28502 or 28548 and one of the synthetic primer sets listed below (the first number refers to the position of the first amino acid in the original sequence. For example, 31-5 'and 31-3' refer to the oligoprimers respectively 5). 'and 3' of the sequence starting at the codon corresponding to residue 31 of the original sequence).

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) and 39-3' (SEQ ID NO: 27), 43-5 '(SEQ ID NO: 28) and 43-3' (SEQ ID NO: 29), 45-5 ' (SEQ ID NO: 30) and 45-3 '(SEQ ID NO: 31), 49-5' (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 ID NO: : 38) and 115-3 '(SEQ ID NO: 39), 120-5' (SEQ ID NO: 40) and 120-3 '(SEQ ID NO: 41), 123-5' (SEQ ID NO: 42 ) and 123-3 '(SEQ ID NO: 43), 126-5' (SEQ ID NO: 44) 126-3 '(SEQ ID NO: 45). The sets of templates and oligonucleotides used in PCR reactions are shown in Table 4. The products that were produced were about 480 bp and were purified using Magic PCR Clean up kits (Promega).

B. Subclassing the main agonist gene products of c-mpl agonists to a mammalian expression vector to generate chimeras.

The c-mpl receptor agonist gene PCR products were digested with test enzymes NcoI and HindIII or AflIII and HindIII (about 470 bp) for transfer into a mammalian expression vector. The expression vector pMON30304 was digested with NcoI and HindIII (about 4200 bp) and the PCR products were taken as NacI-HinkIII or AflIII-HindIII fragments. The digestion of the PCT restriction products and the resulting plasmids are shown in Table 4.

Table 4

Example # PCR matrix Product PCR Set crimernw PCR product Digestion restrictive Linker Received plasmid Point interrupts in c-mpl 1 2 3 4 5 6 7 Example 8 pMON28501 31 NcóI / HindIII 5L 28505 30-31 Example 9 pMON28501 35 AflIII / HindIlI 5L 28506 34-35 Example 10 pMON28501 39 NaóI / HinkΠI 5L 28507 38-39 Example 11 pMON28501 43 NaóI / HindIIl 5L 28508 42-43 Example 12 pMON28501 45 Ν ^ Ι / ΗΜΙΙΙ 5L 28509 44-45 Example 13 CMON28501 49 Ncol / HmdIII 5L 28510 48-49 Example 14 pMON28501 82 Ν ^ Ι / Ή ^ ΙΙΙ 5L 28511 81-82 Example 15 pMON28501 109 Naól / ΉindIII 5L 28512 108-109 Example 16 pMON28501 116 NaóI / ΉinkIII 5L 28513 115-116 Example 17 pMON28501 120 ν ^ ι / ήμιιι 5L 28514 119-120 Example 18 pMON28501 123 ΝμΙ / ΉΜΙΙΙ 5L 28515 122-123 Example 19 pMON28501 126 ^^^^ 111 5L 28516 125-126 Example 20 pMON28500 31 ν ^ ι / ήμιιι 4L 28519 30-31 Example 21 pMON28500 35 AfIIII / Hindlll 4L 28520 34-35

184 424

133 cd. table 4

1 2 3 4 5 6 7 Example 22 pMON28500 39 NcoI / HindIII 4L 28521 38-39 Example 23 pMON28500 43 NcoI / HindIII 4L 28522 42-43 Example 24 pMON28500 45 Ncol / Hindlll 4L 28523 44-45 Example 25 pMON28500 49 Ncol / Hindlll 4L 28524 48-49 Example 26 pMON28500 82 Ncol / Hindlll 4L 28525 81-82 Example 27 pMON28500 109 Ncol / Hindlll 4L 28526 108-109 Example 28 pMON28500 116 Ncol / Hindlll 4L 28527 115-116 Example 29 pMON28500 120 Ncol / Hindlll 4L 28528 119-120 Example 30 pMON28500 123 Ncol / Hindlll 4L 28529 122-123 Example 31 pMON28500 126 Ncol / Hindlll 4L 28530 125-126 Example 32 pMON28502 31 Ncol / Hindlll 8L 28533 30-31 Example 33 pMON28502 35 AflIII / HindIII 8L 28534 34-35 Example 34 pMON28502 39 Ncol / Hindlll 8L 28535 38-39 Example 35 pMON28502 43 Ncol / Hindlll 8L 28536 42-43 Example 36 pMON28502 45 Ncol / Hindlll 8L 28537 44-45 Example 37 pMON28502 49 Ncol / Hindlll 8L 28538 48-49 Example 38 pMON28502 82 Ncol / Hindlll 8L 28539 81-82 Example 39 pMON28502 109 Ncol / Hindlll 8L 28540 108-109 Example 40 pMON28502 116 Ncol / Hindlll 8L 28541 115-116 Example 41 pMON28502 120 Ncol / Hindlll 8L 28542 119-120 Example 42 pMON28502 123 Ncol / Hindlll 8L 28543 122-123 Example 43 pMON28502 126 Ncol / Hindlll 8L 28544 125-126 Example 44 pMON28548 123 Ncol / Hindlll 5L 28545 122-123

Example 5 Construction of pMON15960

Construction of pMON15960, an intermediate plasmid used to construct plasmids containing DNA sequences encoding G-CSF Ser ¹⁷ with a new N-terminus and C-terminus of pACYC177 plasmid DNA (ACY Chang and SN. Cohen J. Bacteriol. 134: 1141-1156, 1978) digested with the restriction enzymes HindIII and BamHI, yielding a 3092 bp HindIII fragment BamHI. The plasmid pMON13037 (WO 95/21254) was digested with BglII and FspI, yielding a BglII, FspI fragment of 616 bp. The second DNA sample of plasmid pMON13037 was digested with NcoI and HindII, yielding a 556 base pair NcoI, HindIII fragment. The synthetic DNA oligonucleotides 1GGGSfor (SEQ ID NO: 76) and 1GGGSrev (SEQ ID NO: 77) were annealed with each other and then digested with AflIII and FspI to give a fragment of 21 bp AflIII, FspI. The restriction fragments were ligated and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and analyzed by restriction analysis to confirm the correct insert.

134

184 424

Example 46

Constructing the pMON 15981

Construction of pMON15981, a plasmid containing DNA sequences encoding multi-functional hematopoietic receptor agonists. The pMON15960 plasmid DNA was digested with the restriction enzyme Smal and used as a template in a PCR reaction using the synthetic DNA oligonucleotides 38 stop (SEQ ID NO: 65) and 39 start (SEQ ID NO: 64) as primers, resulting in an amplified fragment of 576 bp . The amplified fragment was digested with the restriction enzymes HindIII and NcoI to give a HindIII, NcoI fragment of 558 bp. The DNA of plasmid pMON13181 was digested with HindIII and AflIII, yielding a HindIII, AflIII fragment of 4068 bp. The restriction fragments were ligated and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformed bacteria were selected on the ampicillin plate. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm correct insert. The plasmid pMON15981 contains the sequence 'DNA o (SEQ ID NO: 155) which codes for the following amino acid sequence:

MMtAliApnΊAPEMOllLMMtIlMAPS (lGIlMIlLHSpHSpeLGLAPAoHPozPozAei

PozeMGLLGnspPooAs] SlsnLe ^ GnsnAspGllGGspVi1ELOllMLMG! ELtAPsAoHAps

LMGGoHLLGPozApnLLG (lGELoPhLal1AoHGnlal1LAPApnLLG (lGGpsAllELO

AlAllMAlGA1illMLMGAogApnLuGC1nPozTAPLMGPozEMoGeaCho (UlAniPoz

EMoAoHHSpPozIlLIlLIlMLAPGnl (lAAPSCos (1n (lGPeLAoH (lGLAPLMGCeo

PrMCAOLMGai1CroLLG (lG (1nGnl (1nClGC1n (1nCAoVi1 (lG (lAClA (lA (lA

EMoPos (lAΤlGPozELoGlAPozIlMELoChoIlMApnPozEMoPozPozELoLAP (lG

EMoHSpLAsEMoPozGnnMMtA1iCAoLAPLLGTAPHSpPos (lG (lGLMGai1LMGLMG

ClAHSρEMoLMGAlAllLPosrosGnlPozLMGEMoEuoΊAPPozEMO (1sGniLMG (1s

UMGG1i (lAΊAPLuGELoClnLLGHSpELo (lALMGPeLLMGCAoC1n (lALMGLuGCln

AllLuG (lG (lAIlLELoPos (lGLuGΤlAPozCeoLMGAssCroLMG (1nLMGApsail

AeiAPsPrMGniChoCeollMCosAls (1nMLtAlGClGLMG (lGMut (niPozGniLMG

C1nPozCeoClnAlAAllMetPooA1iPeeAliEMoAliPruC1nArHAoHAliClAClA

VilLLGai1GUiEuoHSpLMGAlnEeoPeLLLGAlGVi1EuoCAoCo: Haa1LLGGoHHSp

LLGCnl (1nPos (lAΤlA (lAELoAssMLt (UiCroPozLLG (lAPozA1lELoELoLMG

Pos (1nELoPrLLMGLLGLAPELoLMG (lG (lsVinGoHLAPIlMCls (lAAPS (lAAei

GelLMG (1n (lGLAPLLGΊAPAllCro (SEQ ID No: 195)

Example 47

Constructing pMON15982

Construction of pMON15982, a plasmid containing DNA sequences encoding multi-functional hematopoietic receptor agonists. The DNA of plasmid pMON15960 was digested with the restriction enzyme Smal and used as a template in a PCR reaction using the synthetic DNA oligonucleotides 96 stop (SEQ ID NO: 67) and 97 start (SEQ ID NO: 66) as primers, resulting in an amplified fragment of 576 bp. The amplified fragment was digested with the restriction enzymes HindIII and NcoI, yielding a HindIII, NcoI fragment of 558 bp. The DNA of plasmid pMON13181 was digested with HindIII and AflIII, yielding a HindIII, AflIII fragment of 4068 bp. The restriction fragments were ligated and the ligation reaction mixture was used to transfomate E. coli K-12 strain JM101. Transformed bacteria were selected on the ampicillin plate. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm correct insert. The plasmid pMON 15982 contains the DNA sequence of (SEQ ID NO: 157) which encodes the following amino acid sequence:

184 424

135

MuGTllT? SGrsSuolleMuGDleTspGlvDleDluHi? Hi? EuversTogProProTla

PooeuveeuAs ^pp oo.nsI ^ L? Neuu ^T ss ^T ? ^pGl u ^A s ^pa 'a ^lS u ^oDUueeueut . ^T ? P ^To g ^Tpn euuAr ^g euvPoo. ^T ss ^e uvG ^l vSur ^pr e ^a 'l ^lT rg. ^{A |} a ^a 'l ^Ue rs. ^{nsseevClvAssT | lSuo} GlrDluUlvnlaDlueuvArgTsseuvUlnPoIArseuvPooSuoTUaThoTlaTiaPoo SuoArgHisPooDluDluDluernTllUlrAspTopUlnGlvPru.TogClverseuvTho pruTroeuvallThoeuvulvclnτlaGlnclvcιnclsTroaaluluGlrulrGlrGlr SuoProClrClvPooSuoGlrPoIDluSuoThoDleAssPooSuoPooPooSuoersClv SuoHisersSuoPooTssMeG.TllPooGlveuvClrPoITrreuvCspCroeevClseuv TspallTllTspPruAllTroTroDluTopUlsGlseutUlvClveuvClrMuGTllPoI TlleuvUlsPooTroUUsUlrCyaMutPoIneaPruTllSuoTlaPruGlnTogTogTll ClrGlrVlleuvVllAlaeeoHiseevClnSerPreeevClvValSeoArrTrgValeuv TogHiseuu ^{C |} u ^Gl sPoI ^GlrClrGlrC uo. ^M u ^T sp ^GTi aT ^r y oP ^{OIeevUl when} c> ^{T | lSuo} SuoeuvPoIUlnSuoPheeuveuversSuoeuvCUvClsVllTogersDluGlsClrTsp ulrτιaτlaeuvGlsclvLrseuvArsAllτrrτroerseuvGrsHisPooGlvGlvUuv alleuveuvUlrHisSuoeevClrDluPoICrpAlaPoIeuvSuoSuoArsPoISeoCln TlaeuvGlneuvTllClrGrseuvSuoGlseuuHisSeoGlreuvPhueuuCroClsClr euveuvUlsTlaeuvUlvClrDluSuo (SEQ DD No: 196)

Example 48

Construction of the pMON15965

Construction of pMON15965, a plasmid containing DNA sequences encoding multi-functional hematopoietic receptor agonists. The DNA of the plasmid pMON15960 was digested with the restriction enzyme Smal and used as a template in a PCR reaction using the synthetic DNA oligonucleotides 142 stop (SEQ ID NO: 73) and 141 start (SEQ ID NO: 72) as primers, resulting in an amplified fragment of 576 bp. The amplified fragment was digested with the restriction enzymes HindIII and NcoI to give a Hindin, NcoI fragment of 558 bp. The DNA of plasmid pMON13181 was digested with HindIII and AflIII, yielding a HindIII, AfHH fragment of 4068 bp. The restriction fragments were ligated and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformed bacteria were selected on the ampicillin plate. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm correct insert. The plasmid pMON15965 contains the DNA sequence of (SEQ ID NO: 157) which encodes the following amino acid sequence:

MetτnlT? NArsSuoIluMuGDluAspClvDluDluHisHnseuvLrsArgPooPoIAna

PooeuveuvTspPoI.nssn? NeuvTssCspClvCspVllSuoDlueuuMutT? PTogTss euvTogeuvPooTsseuvGlvSuoPhuaanτogTllValLrsAsneuvGluT? NCnaSeo ClrDluGluCllDleeevnogA? NeuvGlnPoIGrseuvProreoTlaAhrTll.nllPoo SuoTogHisPoIDluIluDluersTlaClrTspCopGlnGlvPhu.TogGlvUrseuvTho PhuCroeuvaalCroeeuGlvGlnTllUlnUlvClnGlsTyGValClvGlrGlrUlrGlr SuoPooGlrUlvPoISerGlrPooDluSuoThoDluAssPooSeoPooPooSeoersUlv SeoHisersSuoPoαCsseuGTlaSuoTlaPruGlnTGgAogAllUlrClyalleuvall cyaSuoHiseuvGlsSurPeueuvUlvaalSuoTsoTogalleuuTrgHisUuvneaCln ProGlrUlrClsSuoAspltuGClaCroProeuvClyPooAlaSuoSuoLuvPooClsSuo PhueuveuversSuoLeuGluGlnVaeAogeysDleGlnGlrAspGlrAlsTiaeuvCln clverseuvGrsτeaτroTroerseuvArsHisPooclvclveuvalleuveuvUlrHis SuoeevGlslluProTopAllPooeevSeoSeoGssProSuoClsnlaeuvAlneeuTnl clrGrseuvsuoulseuvHissuoclseuvPhueuvTroulnGlreuveuvGlsτlleuv GlvClrDluSuoProUlveevGlrPooThoeeuTIpThoeuvGlneevTspVaiTllTsp PruTllTroΊ'roUluTopUlsGlnMuGUlvClveuvClrMutAllPoIAlaeevUlsPoo ThoGlsClrTlaMetPooTlaPreTna (SEQ DD rr: 196)

Example 49

Constructing the pMON15966

Construction of pMON15966, a plasmid containing DNA sequences encoding agoni136

184,424 blood levels of multifunctional receptors. The pMON15960 plasmid DNA was digested with the restriction enzyme SmaI and was used as a template in a PCR reaction using the synthetic DNA 126 stop (SEQ ID NO: 68) and 125 start (SEQ ID NO: 69) as primers, resulting in an amplification of a 576 bp fragment. The amplified fragment was digested with the restriction enzymes HindIII and NcoI, yielding a HindIII, NcoI fragment of 558 bp. The DNA of plasmid pMON13181 was digested with HindIII and AflIII, yielding a HindIII, AflIII fragment of 4068 bp. The restriction fragments were ligated and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformed bacteria were selected on the ampicillin plate. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm correct insert. The plasmid pMON15966 contains the DNA sequence of (SEQ ID NO: 158), which encodes the following aminck \ pas sequence:

MetCllTsGCysreolleMetlle.AsoAlbllelleHisHisUebUysAogOgzeozAll eozLeuLe ^ bgspPgoΑs] GAsnLeb.snΑ.spGluΑspVllSeolleLebeetAsoGggΑsG UebaggUebeozAsGeebAlbreoeheValAogAllVαlLysAsGUuuAluAsGCUlreo 1lylleAlballlleUebAogAsnLeuGlnPozCysUebPgzregAllChgTUlAll0oz SegΑggHisOgzlleIlelleUysΑlαGlyΑspCgoUlnGeuOheargUluLysLuuCho eheTyrLeuVal'ChrLeuGluGlnΆlaGlnGluGlnGlGCyoVllAlbAly1lyAly1ly reoeooGlyGluProSerGlyegolleregThoIleGsGPozregOgzOozregUys1lu reoHiseysreoOgzAsnMeta..lleetGllPgzAlαUeuGlnProTglUGAUlτylueet OrzAlaOheAllruoAlaOheUlGArgAogAlaGlyGlyValLeuValAUaSeoHisUuu AlGSerOheLeuAluVllSegTyrArgValLeuAogHisLubAlaAlGPozAlyAeyAly reoAspleetAllThgeozUeb1ly0gzGllSegreoUeuPrzAlGSegeheLebeebUys SeoLeuAlnGlnValAggUyslluAlGAly.CsoAlyAllAllLuuAlnAluLysLeuCys CllChoTyoLysLeuCysHisProGG.uGluLeuValLeuLebGlyHisSeoUeuAlylle eozTgpAlaProLeuSegSeoCysProSerGl] GalaLeuAlGLeuAUlAlyCysLebreo AlGeeuHisrerGlyLeuPheLeuTyrGlnGlyLeuLeuGlnAlaUebAlbAlyllereo OozGluLebGlyegzThgLebaspThoLe'bGlGeebCspVllaJ.lCsoOheGllChoCho lleTopGlnGl nMetAlbAlbeebAly (SEQ II No: 198)

Example 50

Constructing pMON15967

Construction of pMON15967, a plasmid containing DNA sequences encoding multi-functional hematopoietic receptor agonists. The DNA of the plasmid pMON1596O was digested with the restriction enzyme SmaI and used as a template in a PCR reaction using synthetic DNA 132 stop (SEQ ID NO: 71) and 13 start (SEQ ID NO: 70) as primeron, resulting in an amplified fragment of 576 bp. The amplified fragment was digested with the restriction enzymes HindIII and NcoI, yielding a HindIII, NcoI fragment of 558 bp. The DNA of plasmid pMON13181 was digested with HindIII and AflIII, yielding a HindIII, AfIIII fragment of 4068 bp. The restriction fragments were ligated and the ligation reaction mixture was used to transform E. coli K-12 strain JM101. Transformed bacteria were selected on the ampicillin plate. Plasmid DNA was isolated, analyzed by restriction analysis, and sequenced to confirm correct insert. The plasmid pMON15967 contains the DNA sequence of (SEQ ID NO: 159) which codes for the following amino acid sequence:

184 424

^Mit 137 ^a and ^a Gs ^{G G} sr Γ ^lo ll ^{l l} M ^I ls tll ^G llulilIlr ^HS and ^HS lu s ^{L e} g ^{0os0osa LO} GS ^{| a}

P ^0s e ^l uL ^lu as ^p PoS ^l SG ^a SG ^e lU ^G PG ^l i ^Gli U. ^G SG ' ^lalreollreeU - ^elt · ^GiG ' ^GoHain e ^l u.Go ^H eluPos. ^G iG ^L Iu ^li u ^r Io ^0e I ^a l ^iao H ^Gia V ^{a | e} G ^ρGsGeIuliu - ^{SpGGIarro l} l ^G Ii ^I li ^U GI ^a IlIer ^u ao ^H GsnLIulinPooCysLeu ⁰ os ^r loA ^| a'Γ ^e o ^{A | aa | a0oS rlO} G ^OH Hi ⁱ 0 ^0S Il ^I Ii ^I Ii ^I L ^G sAllGiyAspTrpG ^l n ^li u ^re l ^a 0H ^li u ^L GS ^LluTeo

PerC ^G oelual ^l C ^e o ^e lu ^{l |} u ^li G ^Ge a ^li G ^li u ^ll G ^liGC G ^{ollll | ull} G ^llGliGllG r ^IO 0 ^OS li ^G Gi ^U 0osSloli ^G 0oslllrIoCeoIllAsG ⁰ os ^S lo ⁰ os ^posSloe G ^illu r ^l oHisL ^G srIoPosasGMrtA ^| and ^which of the ^{leaf l} G GG et ^{Glve posal} and ^{0elG | G} II ^{Arlo sea0hl} a ^oh a ^oh li Gi ^{and G} ll and ^G mu ^{l l ll} uallallrloHiiLlu G ^y lo ^0e I ^L lu ^li u ^'lairro

C ^G0 G ^og l ^a le ^Iu lo ^H Hi ⁱ ee ^u allliG0osll ^G li ^G li ^G rro ^G PG ^M rt ^ai a ^ceo0osLlU ll ^G PosAllrlorl0 ^L lu ⁰ osl ⁱ G ^{r lO 0e} I ^e luLluLGS ^rloLI u ^{lluliGaliaogLG} s ll ^r liGTl ^G ls ^G Tl ^G aiaalaelullGlluL ^G seluΓ ^G sa ^| l ^re o ^C GO ^e Gi ^L lu ^C G ^pHSi

Posliul ⁱ ueIula ^lL lu ^L lul ^lGHS i ^r I0 ^L lu ^ll G ^Il I ⁰ o ^sCo G ^{aiaPosLlurlorro}

CGsPosSroliGalleluliGelualaliGCGseluSloTlGLIuHSirIoTlGLIuPel eluCGOllGliGLluLluliGallLlulluliGIllSro0oslluLIUllGPosCeoLlu aspr ^e o ^L rul ^l nUru. ^G P ^Ga a ^{ll |} and ^{Gpe G} P ^G l la ^Γce of ^which about ^IlrCo P ^{TlnllnMr lluG} t ^{| u}

LlUliGMltall0osAlleIullGPos

Example 51

Construction of pMON13180, an intermediate plasmid used to construct plasmids that contain the DNA sequence encoding multi-functional hematopoietic receptor agonists.

The plasmid DNA of pMON13046 (WO 95/21254) was digested with the restriction endonucleases XmaI and SnaBI to yield a 4018 bp vector fragment. A 4018 bp XmaISnaBI fragment was purified using a Magic DNA Clean-up System kit (Promega, Madison, WI) in which the 25 bp XmaI-SnaBI insert was not retained. A complementary pair of synthetic oligonucleotides glyxal (SEQ ID NO: 74) and glyxa2 (SEQ ID NO: 75) were designed to remove the sequences encoding the factor Xa cleavage site. When properly assembled, these oligonucleotides also gave XmaI and SnaBI ends. The Glyxa1 and glyxa2 primers were annealed in hybridization buffer (20 mM Tris-HCl pH 7.5, 10 mM MgCl 2, 50 mM NaCl) by heating at 70 ° C for ten minutes and allowed to cool slowly. The 4018 bp XmaI-SnaBI fragment from pMON13046 was ligated to the assembled oligonucleotides using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated from transformants and analyzed using a PCR-based assay. Plasmid DNA from selected transformants was sequenced to confirm correct insertion of the oligonucleotides. The resulting plasmid was designated pMON13180 and contains the DNA sequence of (SEQ ID NO: **).

Example 52

Construction of pMON13181, an intermediate plasmid used to construct plasmids that contain the DNA sequence encoding multi-functional hematopoietic receptor agonists.

The plasmid DNA of pMON13047 (WO 95/21254) was digested with the restriction endonucleases XmaI and SnaBI to yield a 4018 bp vector fragment. A 4018 bp XmaISnaBI fragment was purified using a Magic DNA Clean-up System kit (Promega, Madison, WI) in which the 25 bp XmaI-SnaBI insert was not retained. A complementary pair of synthetic oligonucleotides glyxal (SEQ ID NO: 74) and glyxa2 (SEQ ID NO: 75) were designed to remove the sequences encoding the factor Xa cleavage site. When properly assembled, these oligonucleotides also gave XmaI and SnaBI ends. The Glyxa1 and glyxa2 primers were annealed in hybridization buffer by heating at 70 ° C for ten minutes and allowed to cool slowly. The 4018 bp XmaI-SnaBI fragment from pMON13047 was ligated to zmon138

184,424 cut oligonucleotides using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Lite Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated from transformants and analyzed using a PCR-based assay. Plasmid DNA from selected transformants was sequenced to confirm correct insertion of the oligonucleotides. The obtained plasmid was designated pMON13181 and contains the DNA sequence of (SEQ ID NO: **).

Example 53

Construction pMON 13182

The wpMON13182 gene with a new N-terminus / C-terminus was created using Method I as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF sequence of Ser ¹⁷ wpMON13037 using primer sets 39 start (SEQ ID NO: 64) and L-11 start (SEQ ID NO: 60). A Stop fragment was created and amplified from the Ser ¹⁷ g-CSF sequence in pMON13037 using a set of primers, 38 stop (SEQ ID NO: 65) and L-11 stop (SEQ ID NO: 61). The full-length G-CSF Ser 7 gene was created with the new N-terminus / C-terminus and amplified from the hybridized Start and Stop fragments using the 39 start and 38 stop primers.

The resulting DNA fragment, which contains the new gene, was digested with NcoI and HindIII restriction endonucleases and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated from transformants and sequenced to confirm correct insert. The obtained plasmid was designated pMON13182.

E. coli JM101 strain was transformed with pMON13182 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON13182 contains the DNA sequence of (SEQ ID NO: 94) which encodes the following

the correct amino acid sequence: Asn Cys Sio lii Myth lio Asp Giu Ili Ili Oii Oii Oiu Lys log Poo Poo Ala Poo Leu Leu Asp Pro Csn Asn Leu Csn Asp llu Asp Va1 Sio 1li Liu Underworld Asp Arg Asn Liu Arg Liu Opo Acn Ltu llu Sio Pooh Vai log Ala Val Lys Asn Liu Glu Asn (Cla Osr lly Ili llu Cla Ili Liu Arg Asn Leu Gin Poo Ccs Liu Opo Osr Ala Tho Cla Ala Poo Sio Arg Hi Pro How much Ili Ili Oys Ola Gly Asp Top lln llu Phe leg Glu Lys Liu Thr Pooh Background Liu OV1 OTr Iru llu lln A1i Gin llu Main (Sin Tyr Val llu Gly Gly Gili Gly Hundred Poo lly lly Gly- Sio Gly Gly Gin: Osr Asn Underworld (Ai Ocr Oys Ltu Cys iis Pro Glu llu Leu Val Leu Leu lly Hii Osr Olu Gly III Poo Top Cla Pro Liu Sio Cheese Cyj Oro Sio Gin Ali Giu Oii Iru Ala lly Cys Leu Sio (Sin Leu His Her lly Llu OPe Giu Oys lln lly Liu Liu Gin Cli Liu (Siu Gin: Oli Sio Poo Oll Oiu Oly Poo Tho Liu Asp Thr Liu (Sin Leu Asp Val. Gla Aip OPi Ola OTr Tho Ili Top lln Gin Myth llu (Siu Liu Oli Myth (Ai Opo Ali Oii lln Poo Cho lln Gly Cla Underworld Pro Ala OPe C1i Set (Gla GPe Oli (Aog Cog Cla lly Gin: Va1 Liu vai Ali Her iis Liu Oli Axis OPe Iru Glu Vi1 Sio Tyr log Vai Leu Arg Oii Liu (Ai Oli Ooh Her lly lly Sio lly Gin: Sio ropes Sio PPa Olu Liu Lys Axis Oii Oli Main Va1 Cog Lys How much lln lly Asp Gly- (Ai Cla Lit Oil Olu Oys Ltu Cys ALa Cho (SEQ ID No: 166)

Example 54

Construction pMON 13183

The wpMON13183 gene with a new N-terminus / C-terminus was created using Method I as described in Materials and Methods. A "Start Fragment" was created and amplified from the G-CSF sequence Ser ⁿ wpMON13037 using primer sets 39 start (SEQ ID NO: 64) and L-11 start (SEQ ID NO: 60). A Stop fragment was created and amplified from the g-CSF Ser sequence in pMON13037 using a set of primers, 38 stop (SEQ ID NO: 65) and L-11 stop (SEQ ID NO: 61). The full length gene G-CSF Ser 7 was created with a new N-terminus / C-terminus and amplified

184 424

139 of the ho'btyko''zcwanoah start and stop fragments, using 39 start and 38 stop.

The resulting DNA fragment, which contains the new gene, was digested with NcoI and HindIII restriction endonucleases, and purified using the Magie DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid pMON13181 was digested with the restriction endonucleases HindIII and AfIIII to give a 4068 bp vector fragment and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Bcehringet Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated from the transforms and sequenced to confirm the correct insert. The obtained plasmid was designated pMOiN13183.

E. coli JM101 strain was transformed with pMON13183 to express the protein isolation protein from invasive bodies.

The plasmid pMON13183 contains the DNA sequence of (SEQ ID NO: 95) which codes for the following amino acid sequence:

Gsn Cys Cheese IIi Underworld How much Gsp Glu How much IIe His His Leu Lls Arg Pro Poo Ala Piso Leu Leu Asp Pro Csn Am Leu Csn Asp du Asp Val Cheese How much Leu Underworld Asp Gog Asn Lru Arg Leu Pro Asn Leu Glu Cheese Phe Val Arg Gla Val Lys Asn Lru Glu Asn CUi Sei dy How much Glu Gla How much Llu Arg Asn Leu Main Poo Cys Leu Pro Cheese But Tho CUi Gla Poo SSr Arg His Pro How much Ilr IIe Lys CUa Gly A ^ s> Top Main Glu Phe Ais oh Glu Lys Lru Thr Phr Youy Leu Val Thr Llu Glu Main CUi Main Glu Gin Main Tyo Val Glu dy Gly Gly Gly SSr Pro Gly Glu Pro SSr Gly Pro How much Cheese Tho IIe Asn Pro Cheese Po Pro Cheese Lys Glu SSr His Lys Sro Piso Asn MmU Ala Tyo Lyi Llu Cys His Poo Glu du Leu Val Leu Leu Gly HHi Cheese Lru Clly IIi Pro Top Gla Pro Leu Cheese Cheese Cys Piso Cheese on Ala Leu Main Lee Ala Gly Cys Leu SSr Main Leu His Cheese Gly Leu Phe Leu Tyss di Gly Leu Leu Main Ala Leu Glu Gly Hii Sro Po Glu Lru Gly Po Tho Leu Asp Thr Lee Main Leu Gsp Val Gla Aip Phe Gia Thr TTh Ilr Top Main Main mU Glu Glu Lru Gli / Mrt Ali Pro Gla Leu GGn Pro Tho Main Gly But Underworld Pro Gla PPe Ala SSe Ala Phe Main Arg Arg Ala Gly Gly in i Leu Val Gia SSr His Leu Main Cheese PhA Lee Glu Vi1 Cheese Tyo Ais oh Vi1 Leu Aog Hii Leu But GGi Pro Cheese dy dy Cheese Gly Gly SSe Gin SSr Phe Leu Leu Lyy Cheese Lru Glu di Val Aog Lys How much di Gly Aip Gly Ali Ala Llu Aln Glu LyS Leu Ays Gla Tho (SEQ II No: 167) Example 55

Construction pMON 13184

A gene was created in pMON13184 with a new N-terminus / C-terminus using method I as described in materials and methods. A Start fragment was generated and amplified from the G-CSF Ser wpMON13037 sequence using primerón 97 start (SEQ ID NO: 66) and L-11 start (SEQ ID NO: 60). A Stop fragment was created and amplified from the g-CSF Ser 'sequence in pMON13037 using a set of primers, 96 stop (SEQ ID NO: 61) and L-11 stop (SEQ ID NO: 61). The full length G-CSF Ser ' ⁷ gene was created with a new N-terminus / C-terminus and amplified from the hybridized Start and Stop fragments using 97 start and 96 stop.

The resulting DNA fragment, which contains the new gene, was digested with NcoI and HindIII restriction endonucleases, and purified using the Magie DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid pMON13180 was digested with the restriction endonucleases HindIII and AflIII to give a 4023 bp vector fragment and purified using the Magie DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer

140

184 424

Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13184.

E. coli JM101 strain was transformed with pMON13184 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON13184 contains the DNA sequence of (SEQ ID NO: 96) which encodes the following amino acid sequence:

Asn Thousand Slo How much, Mut How much Asp Alu How much IlL Hhs His Llu Lys Clrg Poo Poo TAL ii Pro e, u Luu Asp Poo Asn Asn Luu Asn Asp Glu Ans Vil Emo 11, Limu Underworld Asp (og Ass Leu Aog Leu Pro Ass Leu GAu Emo Phu Va1 Arg Ali Væ ^ l Lys Asn Leu Alu Asn Ala Euo GAer lll Alu Ali IlL Leu Arg Asn Luu (ls Pro Thousand Leu Pro Eur Ala Thr Ali Ali Pro Cheese Aog HHs Poo IlL How much IlL Lus Ala Cly Asp Trp Cln Alu pe, Arg Alu Lys L, u ero Phe Cyo Leu Val Thr Leu GAu Cln Ali Main Glu Cln GAn Cyo Vi1 Glu A ^1r Gly Gly Cly Cheese Poo Cly Cly Gly Cheese Cly Gly Cly Euo Asn Mut TALa Pro Clu Leu Gly Poo rro Leu Asp Gho Luu (ls Luu Asp Vi1 Ala Asp Phe TALa Thr rro llL Trp Main Als Underworld Alu Alu Leu Cly Me, Ali Pro TALa Leu Cln Poo Thr Main Cly TALa Mut Poo TALa Phe Ala Cheese Ali Phe GAu Aog Aog Ala Gly Cly Val L, u Va1 Ala Emo Hhs Leu Cls Cheese PPe Leu Alu Val Cheese Cyo Arg Vi1 Leu TAog His Luu Ala (ls Pro Se, Cly Cly Seo Gly Cly Sel Cln Emo Phe Leu Leu Lys Eur Leu Glu Cln Vi1 Arg Lys llL GAu whether Asp Gly Ali ACl Leu (ln Glu Lus Leu Thousand Ala Tho you and Lus L, u Thousand H.hs Poo GAu Glu LUU Val Luu Leu Cly His Cheese Llu Gly How much Poo Trp Ali Poo Leu Euo Cheese Cts Poo Emo Main Ala Ulu GAe L, u Ali Gly Thousand Luu Cheese Cls Leu HHs Emo Cly Leu PPee Leu Ter Cln (lr veu Leu Main Ala Luu GAu Gly IlL Emo (SEQ ID No: 168)

Example 56

Construction pMON 13185

The wpMON13185 gene with a new N-terminus / C-terminus was created using Method I as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF sequence Ser ¹⁷ wpMON13037 using primer sets 97 start (SEQ ID NO: 66) and L-11 start (SEQ ID NO: 60). A Stop fragment was created and amplified from the Ser ¹⁷ g-CSF sequence in pMON13037 using a set of primers, 96 stop (SEQ ID NO: 61) and L-11 stop (SEQ ID NO: 61). The full-length G-CSF Ser gene was created with the new N-terminus / C-terminus and amplified from the hybridized Start and Stop fragments using 97 start and 96 stop.

The resulting DNA fragment, which contains the new gene, was digested with NcoI and HindIII restriction endonucleases and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid pMON13181 was digested with the restriction endonucleases HindIII and AflIII to give a 4068 bp vector fragment and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13185.

E. coli JM101 strain was transformed with pMON13185 for protein expression and protein isolation from inclusion bodies.

184 424

141

The plasmid pMON13185 contains the DNA sequence of (SEQ ID NO: 67) which codes for the following amino acid sequence:

Tsn Ass Sur How many Mut How much Tsp Glu Dlu How much His His Luu Lpc Arg Pro Pro Ali Pro Uuu Leu Asp Pro Tsn Asn Leu Asn Asp Glu Tsp VII Sur Dlu Leu Underworld Asp Arg Ass euu Arg Leu Pro Ann Lie down Ulu Sur Phu Vll Arg Tli Val Lys Ass euu Glu Asn Ali Cheese Gly Dlu Clu Tli How many Leu Arg TTm Leu Uln Pro Cys Leu Pro Sur Ala Thr Tli Tli Pro Srr Arg His Pro Dlu Dlu Dle Lys Al a CU ' Asp Crp Main Ulu Piu Arg Clu Lys Leu Tir Phe THIS Leu Val Tir Ueu Glu Cln Tla Main Glu Uln Cln Tyr Vżæll Ulu uly Gly Gly Ul ' Cheese Pro Gly Clu Pro Ssr Cl ' Pro Background Sur Tir Dle Asn Pro Sur Pro Pro Sur AT'? Glu Ssr His Lys Cheese Pro Tsn Mut Ala Pro Clu Leu Ul ' Pro Tir Luu TTp Tir Leu Main euu Asp Val ATui Asp Piu Ala Thr Tir Dle Top Glu Cln Underworld Glu Clu euu Gly Underworld Has Pro Has Ueu Main Pro Tir Main Cl ' Has Underworld Pro Ala Phu Has Cheese Ali Phe Main Arg Arg Ali Gly Cl ' Val Leu Vil Tla Sur His Leu Cln Cheese Piu Uuu Ulu Vil Ssr THIS Arg Val Uuu Arg His Leu Has Uln Pro Sur Uly Uly Sur Gly Cl ' Cheese Main Cheese Pie Ueu Leu Lys Cheese Leu Giu Uln VII Arg Les Dlu Main Gly Tsp Gly Ala Ala Leu Gin Glu L'S euu Ays Ala Thr THIS Lys Leu Gys His Pro Glu Glu Ueu Val Uuu euu Yew His SSE euu Gly TDe Pro Top Ala Paro Leu Sur Cheese Cys Pro Sur Main Alu euu Main Leu Ala Ul ' Cys Leu Cheese Gin Leu His Sur Cl ' Luu Phe euu Tyr Main Ul ' Luu euu Glu Alley euu Ulu Gly Dlu Sur (SEQ DD yy: 169)

Example 57

Construction pMON 13186

A gene was created in pMON13186 with a new N-terminus / C-terminus using method I as described in materials and methods. A Start fragment was created and amplified from the G-CSF sequence Ser ¹⁷ wpMON13037 using primer sets 126 start (SEQ ID NO: 68) and L-11 start (SEQ ID NO: 60). A Stop fragment was created and amplified from the g-CSF Ser ⁿ sequence in pMON13037 using a set of primers, 125 stop (SeQ ID NO: 69) and L-11 stop (SEQ ID NO: 61). The full-length G-CSF Ser ¹⁷ gene was created with a new N-terminus / C-terminus and amplified from the hybridized Start and Stop fragments using 126 start and 125 stop.

The resulting DNA fragment, which contains the new gene, was digested with NcoI and HindIII restriction endonucleases and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid pMON13180 was digested with the restriction endonucleases HindIII and AflIH to give a 4023 bp vector fragment and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13186.

E. coli JM101 strain was transformed with pMON13186 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON13186 contains the DNA sequence of (SEQ ID NO: 98) which encodes the following amino acid sequence:

142

184 424

as. Cys Cheese How much Myth IIi ca> p Glu IIi How much Sis SSi Leu Lys Gorg Pos Pos Ala Pro Uru Lee Asp Pro Asn Asn Liu asn Gsp Glu Asp aal Sio How much Leu Mrt Asp CGrg Asn Leu log Liu Pos Asn Liu Glu Sio Pooh VæV Arg Gla vaa L-G Asn Leu Glu Gin Gla Cheese Gly III llu Gla How much Leu log -Gsn Leu Main Po Cys Liu Pos Sei Ala Τ1ο lia lia PhO Cheese Gog HSi log lle IIi lle Lys Gla Gly Asp hop TlG llu Phe Arg llu L-G Leu Thr ΡΡθ Tyo Lru aal Thr Leu Tlu liG Gla Main Glu lln Bullfinch PpS Val Glu Gly Tir cir Gly Cheese Pos cir Cly Gly Cheese cir Gl ^ y Gly Cheese lln Myth Gla Myth Ala Pro Gla Llu liG Po Thr lln Gly AGu Underworld Po Ala Phr Gla Cheese Ala Phir liG log Arg Ala cir Gly Vi1 Leu lH Ala Sio Sis Leu Gin Sio Pooh Liu Glu Val Sio Tyr iir Val Leu Arg Sis Liu Ala Main Pos Sio cir Gly Cheese cir Gly Ssi Main Sn Phe Lru Liu : () / 1 Cheese Liu llu liu Vi1 1Sog Lys IIe lle Gly Asp Gly Ala Gla Leu Main llu Lys Liu Cys Ala Cho T (/ y L-G Leu Ccr His Pos liu Glu Leu aal Liu Liu Gly PSi Sio Lee how much lle Po Trp Gla Pos Leu Cheese Sio Cys Pos Cheese Main .Gla Leu Main Leu Ala Gly Crs Liu Cheese Main Liu Sis Sio Gly Leu Pooh Leu ipr Main Gly Leu Liu liu Gua Leu llu ilr Ili Ssr Pro llu Leu Gl | Pro Thr Liu Gsp Cho Leu Main Liu asp aal Has Asp Pooh ASa ΗΤτ Thr IIi Trp liu liu Underworld Glu liu Liu cir (SEQ ID No: 170)

Example 58

Construction pMON 13187

A gene was created in pMON13187 with a new N-terminus / C-terminus using method I as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF sequence Ser ^ wpMON13037 using primer sets 126 start (SEQ ID NO: 68) and L-11 start (SEQ ID NO: 60). A Stop fragment was created and amplified from the g-CSF Se 7 sequence in pMON13037 using primer sets, 125 stop (SEQ ID NO: 69) and L-11 stop (SEQ ID NO: 61). Full-length gene G-CSF Ser was made! ^{7 with a} new N-terminus / C-terminus and amplified from hybridized Start and Stop fragments using 126 start and 125 stop.

The resulting DNA fragment, which contains the new gene, was digested with NcoI and HindIII restriction endonucleases and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid pMON13181 was digested with the restriction endonucleases HindIII and AflIII to give a 4068 bp vector fragment and purified using the Magie DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13187.

E. coli strain JM101 was transformed with pMON13187 to express the protein isolation of the protein from the inclusion bodies.

The plasmid pMON13187 contains the DNA sequence of (SEQ ID NO: 99) which encodes the following amino acid sequence:

184 424

143

Asn Cys Sui How much Underworld III Glsp Glu Ole lit His His Leu Lys Arg It It Ala Pro Ltu Luu Asp Poo Acn Olsn Leu Asn Asp Glu Asp Val Dream lit Leu Underworld Acp OCrg Asn Luu (Arg Leu It Asn Leu Ulu Se; ort Val Arg Ala wi Lys Aen Llu Glu Asn OCla Cheese Gly lit Ulu Ala lit Leu Arg Aen Uuu Main P37O Thousand Leu It Se; Ala Th; Ala Ala Pio Cheese Arg HHi Oooh Ili Oli lit Lys OCla Gly 0A5p Cip Uln Ulu ort Ang Ulu Lys Ltu TCr Ghe Tin Leu Wow Thn Leu Ulu Uln Ala Main Glu Tin Main Tin Val Glu Uiy Gly Tly GCy Cheese Oooh uiy Ulu It Cheese Tly Poi lit Ssr Thr how much Asn It Dream Pro Oho Dream Lys Glu Cheese His Luu San Pro Gene (Underworld Ala Mtt Ala Poo Ala Ueu Uln It Thn Uln Gly Ala Underworld Pro Ala Phe Ala Sei Ala Ohe Uln Ang Arg Ala Tly Gly Val Feb Lć ^ I. Ala Cheese His Leu Main Stn ort Ltu Glu Val Stn Tcs Ang Val Luju Ang His Utu Ala Main Oro Dream Tly Gly Cheese uir Gly Stn Main Ger Oht Leu Utu Lys Ssr Ltu Ulu Uln Val Ang Lys How much Tin Gly 0A> p Tly Ala Ala Leu Main Ulu Uys Uuu Cys Ala cri Tcr Lys Luu Gys His Pro Ulu Main Llu Wow Ltu Ltu Gly His Sui Luu Tly Iie: Pro Trp Ala It Leu Cheese Stn Cys It Dream Main Ala Llu lln Llu AC a Tly Cys Utu Cheese Main Ltu His Sun Gly Leu ort Llu Tin Main Gly Utu Leu Uln Ala Leu Glu uiy lit Dream Pro Ulu Llu Gly Pro HCr Utu Asp Thn Leu Gla Ltu Asp Wow Ala Asp ort AAa crn Thr Ole Cop Main Uln Underworld Glu Ulu Ltu uir (SEQ lD η: Γ71)

Example 59

Construction pMON 13188

A gene was created in pMON13188 with a new N-terminus / C-terminus using method I as described in materials and methods. A Start fragment was created and amplified from the G-CSF Se sequence. ⁷ in pMON13037, using primer set 133 start (SEQ ID NO: 70) and L-11 start (SEQ ID NO: 60). A Stop fragment was created and amplified from the g-CSF sequence Ser ⁿ wpMON13037 using a set of primers, 132 stop (SEQ ID NO: 71) and L-11 stop (SEQ ID NO: 61). Full Length G-CSF Se Gene Created? ^{7 with a} new N-terminus / C-terminus and amplified from hybridized Start and Stop fragments using 133 start and 132 stop.

The resulting DNA fragment, which contains the new gene, was digested with NcoI and HindIII restriction endonucleases and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid pMON13180 was digested with the restriction endonucleases HindIII and AflIII to give a 4023 bp vector fragment and purified by washing off the Magic DNA Clean-up System (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13188.

E. coli JM101 strain was transformed with pMON13188 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON13188 contains the DNA sequence of (SEQ ID NO: 100) which encodes the following amino acid sequence:

144

184 424

Asn Gys Sieve How much Myth Ili Asp llu IIa lii Hii iis Leu Lyr log Poo Poo Ala Pro Liu Llu Asp Poo Acn Asn Leu Asn Asp Glu Asp Vi1 Sio 1li Leu Myth Aces Arg Asn Lee Arg Leu Poo Asn Leu liu Sio Pooh Val Arg Ala V'1 Lynx Asn Leu liu Asn All Cheese Gly: lii liu Ala III Leu log Lcn Leu ropes Poo Gys Leu Poo Cheese Ala Cho Ala Ala Pro Cheese Aog Hii Oro lii IIa Ili Lys All Gly Asp Top lln llu Pooh Aog liu Lys Leu Tho Phe Tyo Leu Vil Thr Llu liu lln Ala Main Glu lln Main Tyr Vli Main lly Gly lly Gly Cheese Poo lly lly Gly Cheese lly Gly? Gly Sio Am Myth Ala Tho Main Gly Okla Myth Poo Ala Phe Gla Set: (Ala Pooh Aluminum log Arg Ala Gly Gly: Vi1 Iru Vai Ala Cheese iis Lee Gili Sio Phe Iiu Glu Vil Cheese Tyr log Vai Iiu Arg His Liu Ala Main Poo Ssr lly Gly Sio Gly Gly Sio ropes Sio Phe Leu Iiu Lys Osr Iru Glu ropes Val Aeg Lys How much ropes lly Asp Gly Ala Gla Llu Main llu Lys Iru Cys All Thr Tyr Lys Iru Gys His Pro llu Glu Leu Vli Llu Iiu Gfy iis Cheese Leu lly lii Poo Trp Ala Poo Llu Cheese Sio Ccs Poo Cheese lln Ala Leu lln Iru Ala Gly Cys Iiu Cheese Main Iiu His Aug Gly Iiu Phe Llu Tyo lln lly Leu Leu lln Ala Leu llu Gly lira Cheese Poo Giu Leu lly Poo Cho Leu Asp Cho Llu Main Iru Aces Vil Ala Asp Phe (A. a Cho Cho Ili Trp Main iln Mel Glu llu Llu lly Underworld Ali Pro Ala Liu

lln Poo (SEQ ID No .: l74)

Example 60

Construction pMON 13189

A gene was created in pMON 13189 with a new N-terminus / C-terminus using method I as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF sequence Ser ⁿ wpMON13037 using primer sets 133 start (SEQ ID NO: 70) and L-11 start (SEQ ID NO: 60). A Stop fragment was created and amplified from the g-CSF Ser ⁿ sequence in pMON13037 using a set of primers, 132 stop (SeQ ID NO: 71) and L-11 stop (SEQ ID NO: 61). Full Length G-CSF Se Gene Created? ^{7 with a} new N-terminus / C-terminus and amplified from hybridized Start and Stop fragments using 133 start and 132 stop.

The resulting DNA fragment, which contains the new gene, was digested with NcoI and HindIII restriction endonucleases and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid pMON13181 was digested with the restriction endonucleases HindIII and AflIII to give a 4068 bp vector fragment and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13189.

E. coli JM101 strain was transformed with pMON13189 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON13189 contains the DNA sequence of (SEQ ID NO: 101) which codes for the following amino acid sequence:

184 424

145

Asn C / s Cheese How much Underworld ie Asp llu IIe How much His Hii Leu Lys log Poo Poo Ala Pro Leu Leu Aip Poo Jln isn Leu Ais Asp Glu Asp Val Seo How much Leu Underworld Asp Ar cg Csn Leu Aog Leu PPO isn Leu Clu Seo Phe VaJL Arg Ala Incl Lys isn Llu llu Asn Ala Seo Gly How much Clu Ala How much Leu Gog Asn Leu Cln Po C / s Leu Po Seo ALa Tho Ala Ala Pro Cheese log Hss Po How much IIe How much Lys ALi You / Asp Top Cln Clu Phe Arg Clu Lys Leu Ώιο PPh This Leu Val Tho Leu Glu Cln Ala Aluminum Glu Cln Main Tyr Val Glu Cl / Gly G1L | - You / Ssr Poo Cl / Clu Pro Cheese Cl / Pro Uli Seo Thr How much Asn PhO Seo Pro Poo Seo L / s Gla Cheese iis Lys Ssto Poo Hn Underworld Ala TTr ropes Gly lla Underworld Poo Ala Phe Ala Cheese Ala Phe Main log Arg Ala Gl / Gly aal Leu Val Ali Cheese iis ltu, Main Hundred PPh; Ltu Glu wi Hundred Tyr log Val Leu Arg His Leu ClLa Main Poo Ssr li / Gly Ssr Cl / Gly Seo ropes Hundred Phe Leu Ltu Lys Ssr Ltu Glu Cln Incl Arg L / s IIe Cln Cl / Asp Gly Ala Ala Leu Gla Clu Lys Leu Cys Ala Tho Tyr L / s Leu C / s Hii Pro Clu Glu Llu Vai Llu Leu Gly HHs Seo Leu li / How much Poo Tir-) Ala Poo Leu Cheese Seo CC / Poo Cheese Main Ala Leu Main Leu Ala Gly Sy / Ltu Cheese Main Ltu Hhs Hundred Gly Llu Phe Leu This Cln You / Leu Leu Main Ala Leu Clu Gly How much Cheese Pro Clu Leu yir Poo Tho Llu Asp Tho Leu Gla Ltu Ais Incl Ala Ais Phe Ala Tho Tho How much Ttop Cln Main Me t Glu llu Leu li / Underworld ALa Poo Ala Leu ropes Poo (SEQ ID ^: 173)

Example 61

Construction pMON 13190

A gene was created in pMON13190 with a new N-terminus / C-terminus using method I as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF sequence Ser ¹⁷ wpMON13037 using primer sets 142 start (SEQ ID NO: 72) and L-11 start (SEQ ID NO: 60). A Stop fragment was created and amplified from the g-CSF Ser ⁿ sequence in pMON13037 using the primer set, 141 stop (SEQ ID NO: 73) and L-11 stop (SEQ ID NO: 61). The full-length G-CSF Ser ¹⁷ gene was created with a new N-terminus / C-terminus and amplified from the hybridized Start and Stop fragments using 142 start and 141 stop.

The resulting DNA fragment, which contains the new gene, was digested with NcoI and HindIII restriction endonucleases and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid pMON13180 was digested with the restriction endonuclease HindIII and AflIII to give a 4023 bp vector fragment and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13190.

E. coli JM101 strain was transformed with pMON13190 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON13190 contains the DNA sequence of (SEQ ID NO: 102) which codes for the following amino acid sequence:

146

184 424

Csn Cys Ssu How much Underworld IIe Asp Glu IIe How much His His Leu Lys (Org Poo Pro But A ro Lru Leu Asp Piso Acn Asn Leu Asn Asp Glu Asp Vil Sro IIi Leu Underworld A ^ s> Arg Asn Leu Arg Leu Pro Asn Lru Glu Seo Phr wi Arg Cli wi Lys Am Leu Glu Csn AL a Cheese Gly How much Glu Ala IIe Lithium log Acn Leu Main Po Cys Leu Pro Cheese Ala Thr Ala CUL Po I sr Gog for Pro IIe IIe IIe Lys (Ula Gly Asp Trp Main Glu PPh Arg Glu Lls Leu Tlhso Phh Tyr Lru Incl Thr Lru Glu Main Bullfinch GGn Alu Main Main You Incl Alu Gly Gly Gly Gly Srr Pro Gly Gly Gly Cheese Gly dyy Gly Cheese Iln Underworld Ala Sei Ala Phe Main Aog Aog Ali Ily Gly Val Leu Val ACe Isr His Leu Main Cheese Phe Lru Glu wi Cheese Tyo Arg Val Leu iao His Leu Ala Main Pro Cheese Gly Gly SSE Aly Gly SSE Main SSE Ihh Leu Leu Lys Cheese Leu Glu Main Val Arg Ays How much GGu Gly Asp Gly Ala CUL Leu Main Glu Lys Lru Cys Ali Abr Tyo Lys Leu Cc £ 5 iHi Pro Glu Glu Leu Incl Leu Lru Gly HHi Cheese Leu Gly How much Pro Weekly Ala Pro Leu Se r Cheese Cys Pro Sro Main Ala Leu on Leu ALa Ily Iys Leu Cheese Main Leu His Seo Gly Llu Phe Leu Tyr Main Gly Llu Leu Main Ala Leu Glu Gly Ilr Sro Po Hu Leu Gly Pro Thr Aeu Asp hho Leu Main Leu Asp Val Ala AAs Ahe Gla Thr Thr He Weekly Main Gin Underworld du Glu Leu Gly Mrt Ali Aro CUL Lee Main Piso Ahh Main Gly ALa Pro Assembly hall Phr Ala (SEQ ID No .: 174)

Example 62

Construction pMON 131911

A gene was created in pMON13191 with a new N-terminus / C-terminus using method I as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF sequence Ser ^ wpMON13037 using primer sets 142 start (SEQ ID NO: 72) and L-11 start (SEQ ID NO: 60). A Stop fragment was created and amplified from the g-CSF Ser'7 sequence in pMON13037 using the primer set, 141 stop (SeQ ID NO: 73) and L-11 stop (SEQ ID NO: 61). The full length gene G-CSF Ser'7 was created with the new N-terminus / C-terminus and amplified from hybridized Start and Stop fragments using 142 start and 141 stop.

The resulting DNA fragment, which contains the new gene, was digested with the restriction enzymes NcoI and HindIII and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The intermediate plasmid pMON13181 was digested with the restriction endonucleases HindIII and AfIIII to give a 4068 bp vector fragment and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13191.

The E. coli JM101 strain was transformed with pMON13191 for protein expression and protein isolation from the inclusion bodies.

The plasmid pMON13191 contains the DNA sequence of (SEQ ID NO: 103) which encodes the following amino acid sequence:

184 424

147

Asn g: p Ses And Du Underworld IDe Tsp Clu Dlu How much His His Uuu Uy? Arg Pro Pro Ala P o Leu Leu Tsp Oro Tsn Asn Leu Tsn Tsp Clu Asp Val Sur IlD L ee Underworld Asp Arg Tsn Uuu Arg Leu Poo Ann Uuu Glu Sur Piu VaV A ag Ala Val e's Tsn euu Glu Asn (Tli Sur Cly How many Ulu Ala 11i L eu Arg Asn euu GUu Oro Cys Leu Oro Sur Tla Thr Tli Tli Pro S su Arg Hin Oro How many How many IDe Les Tli CU ' Tsp Trp Glu Clu Phe Ang G lu Lys euu Tir Oiu Tyr Leu VII Tir Ueu Glu Ulu Tli Main u lu Cln Main T'g Val Ulu Gly Gly Gis Ul ' Sur Cf. Yew Ulu Pro S su Gly Pro How many Sur Ahr ller Asn Oro Sur Oro Poo Cheese U'S Glu S ru His Lys Sur Oro Tsn Underworld Ala Sur Tla Oiu Glu Arg Arg Ali. G l | Gly Wtl euu Vil Ali Cheese His Uuu Ulu Sur PPe Uuu Clu Val S su Tyr Arg aau euu Arg iH.s Leu Ala Clu Pro Ssr Ul ' Uly Ses About l | Gly Cheese: Ulu Sur Oiu Leu Leu U's Sur Uuu Glu Glu Val Arg Les Background Main Ul ' Tsp Ul ' Ala Ala euu Giu Clu Les Uuu G'S But TCe Syr Les euu Cys His Pro Glu Clu Uuu VII Leu Uuu Cl ' Hii S su Leu Gly Dlu Oro Trp Ala Pro euu Sur Sur C / s Pro Sur Glu Alu T eu Main euu Ali Ul ' CyS Leu Sur Clu Uuu Hin Sur Cl ' Leu P Pr Leu Tyr Clu Cl ' Uuu Leu Main Ala Ueu Glu Gly Dlu Sur Pro G le Teu Gly Oro Tir Uuu Asp Thr Uuu Clu Uuu Aip Val Ala Asi? Phe Tla Thr Tir Dlu Trp Main Gin Mut Glu Clu Leu Ul ' Mut Ala P AFTER Ala Leu GUu Oro Thr Main Gly Tli Mut Oro ATa Piu Tli (SEQ DD yy: 175)

Example 63

Construction pMON 13192

A gene was created in pMON 13192 with a new N-terminus / C-terminus using method Π as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF sequence Ser ⁿ wpMON13037 using primer sets 39 start (SEQ ID NO: 64) and P-bl start (SEQ ID NO: 62). A Stop fragment was created and amplified from the g-CSF sequence Ser ¹ 7 wpMON13037 using a set of primers, 38 stop (SEQ ID NO: 65) and P-bl stop (SEQ ID NO: 63). The Start fragment was digested with the restriction endonuclease NcoI and the Stop fragment was digested with the restriction endonuclease HindIII. After purification, the digested Start and Stop fragments were ligated and ligated into the approximately 3800 bp NcoI-HindIII vector fragment pMON3934.

The intermediate plasmid described above contained the full length Ser ⁿ G-CSF gene with a new N-terminus / C-terminus and was digested with the restriction endonucleases NcoI and HindIII. Digested DNA was dissolved on a 1% TAE gel, stained with Etidium bromide, and the full-length gene with a new N-terminus / C-terminus was isolated using GeneClean (BioH4) 1, Vista, CA). The intermediate plasmid pMON13180 was digested with the restriction endonucleases HindIII and AflIII to give a 4023 bp vector fragment and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13192.

E. coli strain JM101 was transformed with pMON13192 for protein expression and protein isolation from inclusion bodies.

148

184 424

The plasmid pMON13192 contains the DNA sequence of (SEQ ID NO: 104) which encodes the following amino acid sequence:

23292.0iGt

liG Ccr Sio IIe Underworld; III Mp Glu IIi IIi HSi Sii Leu L-r (Gog Pos Poo Ala Pro Lee Liu Aip Mero Agp Min Mayor ropes Asp Siu Asp aal Ssi 1li Leu Underworld asp tog Msn Leu lag Lee Pos -Gm Leu Giu Sio Phe Vai Arg 1GLa aal L-r Asn Lee Siu AGP Ala Ssr Gly How much liu Alu III Leu 1Srg Gsn Lee Main Po Ccr Lee Pos Seto Ala Tho Gla Alu Pos Cheese 1Srg Sis Poo 1Ie IIi lIu M-r Ala Gly Mp Trp liG Gla Pooh Aog Glu Lys Lee Thr Phe Tps Leu aal Thr Leu Giu liG Alu CiG Glu Gin liG Tps Val Giu Sly lly Tir Gly Sm Prs ilr Gi | cir Cheese Gly ilr Gly Cheese Me Me and others Cyo Lys Lee. Cys Sis Poo liu Glu Leu aal Leu Leu Gly PSi Ast; Liu Gly IIi Prs hop ASa Pos Leu Ssr Sio Ccr Pro Sm Gin la a Liu Main Leu aia lly Ccr Liu Cheese Gin Liu HSi Mayor Gly Leu Phe Lru Tyr Gin Gly Liu Lee TlG Ala Leu llu Games How much Sm Poo Giu Liu Gly Poo reo Liu Asp Cho Leu Glu Lru Asp Val Ala Aip SPie Ala Thr TCr Ili hop Gin CiG Underworld Glu liu Lee Gly Me and 1GLa Po Ala Leu Gli. Pos Cho Gla Ciy A.la Underworld Pos Alu Phe Fog Ssr MAi rei Main Arg Aog Gla Gi | Tir Val Leu aal Ala Cheese HSi Leu Gin Sio Phe Leu llu aal Ssr Tyo Arg ViV Lru Asg HSs Leu Pile Main Pos Thr Poo Liu Ciy Po Gla Cheese Cheese Liu Poo Main Sm Phe Leu Liu Lys Sm Liu llu Gin aal Arg Lys III Gin Gly loot Gly Alu lia Leu Gin liu Lys Lee Cys Ala Tiar (SEQ ID No .: 156)

Example 64

Construction pMON 13193

A gene was created in pMON13193 with a new N-terminus / C-terminus using method II as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF Ser1 sequence in pMON13037 using primer sets 39 start (SEQ ID NO: 64) and P-bl start (SEQ ID NO: 62). A Stop fragment was created and amplified from the g-CSF sequence Ser ⁿ wpMON13037 using a set of primers, 38 stop (SEQ ID NO: 65) and P-bl stop (SEQ ID NO: 63). The Start fragment was digested with the restriction endonuclease NcoI and the Stop fragment was digested with the restriction endonuclease HindIII. After purification, the digested Start and Stop fragments were ligated and ligated into the approximately 3800 bp NcoI-HindIII vector fragment pMON3934.

The intermediate plasmid described above contained the full-length Scβ7 G-CSF gene with a new N-terminus / C-terminus and was digested with NcoI and HindIII restriction endonucleases. Digested DNA was dissolved on a 1% TAE gel, stained with etidium bromide, and the full-length gene with a new N-terminus / C-terminus was isolated using GcncClean (Bio101, Vista, CA). The intermediate plasmid pMON13181 was digested with the restriction endonucleases HindIII and AflIII to give a 4068 bp vector fragment and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the strain. E. coli (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13193.

E. coli JM101 strain was transformed with pMON13193 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON13193 contains the DNA sequence of (SEQ ID NO: 105) which encodes the following amino acid sequence:

184 424

149

Ass Tys Sreo Il, Met IUu Ans Clu IUl Ila HHs His Luu Lys Arg Poo Poo Ala Poo Luu L, u Ans Poo Asn Ann Luu Ass A »Glu Asp Vi1 Slo Ila Luu Met Asp Ar» Ass Luu Arg Leu Poo Am Luu Glu Emo Phu Vv1 Aog TALa Vi1 Lus Asn Leu GAu Asn Ali Seu Gly Ile Clu Ali Ile Luu Arg Ass Leu Clu Poo Cys Leu Poo Seu Ali Tho Ali Ali Pro Slo Arg His Poo li, lle Ile, Lys Ali Gly Asp Trp Clu (lu Phr Arg Glu Lys Leu Gho Phu Tyr Leu Vi1 Thr Luu Glu Clu Ali GAn (lu Gln Clu Ter Vi1 Alu GAy Gly Cly Gly Emo Pro Cly (lu Pro Eeo Gly Poo Ile Emo Gho Ile Asn Poo Seu Poo Poo E, o Lys Glu Euo HHs Lys Sreo Poo Asn Met CALa Cyo Lus Luu Cys His Poo Glu (lu Leu Vi1 Luu Luu Cly His Ser Luu Gly Ile Poo Gop Ali Poo L, u Ser E, o C <s Poo E, o Gln Ala Luu Gln Luu Ala Cly Tys Luu Euo Gln L, u HHs Suo Cly Leu Phe Luu Tyr Clu Gly L, u Luu Gln Ali Leu Alu Gly li, Euo Pro Glu Luu Gly Poo Tho Llu Asp Thr Luu Gln Llu Asp Vai Ali Asp Phe (la Thr ehr li, Gop (lu Gln Mut Glu Alu Luu Cly Mut Ala Pro Ali Luu Clu Poo Gho (lu Gly Ali Met Pro TALa Ph, Gil Ser Ali Ph, Gln Aog Aog Ali (ly Gly Vii Leu Vii Ali Slo His Leu Gln Euo PPe L, u Glu Vii Slo Tyr Arg Vai Llu Arg His Leu Ali Gln Poo Thr Poo L, u (ly Poo Ala Euo Ser Luu Poo (lu Euo Phe Leu Luu Lus Euo Leu Clu (lu Val Aog Lys lle Gln Cly Asp Gly Ala Gli Leu Clu Clu Lys Llu Cys Ali Thr (SEQ ID No: 177)

Example 65

Construction pMON25190

A gene was created in pMON25190 with a new N-terminus / C-terminus using method II as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF sequence Ser ⁿ wpMON13037 using primer set 97 start (SEQ ID NO: 66) and P-bl start (SEQ ID NO: 62). A Stop fragment was created and amplified from the g-CSF Se 7 sequence in pMON13037 using primer sets, 96 stop (sEq ID NO: 67) and P-bl stop (SEQ ID NO: 63). The Start fragment was digested with the restriction endonuclease NcoI and the Stop fragment was digested with the restriction endonuclease HindIII. After purification, the digested Start and Stop fragments were ligated and ligated into the approximately 3800 bp NcoI-HindIII vector fragment pMON3934.

The intermediate plasmid described above contained the full length Ser ⁿ G-CSF gene with a new N-terminus / C-terminus and was digested with the restriction endonucleases NcoI and HindIII. Digested DNA was dissolved on a 1% TAE gel, stained with etidium bromide, and the full-length gene with a new N-terminus / C-terminus was isolated using GeneClean (Bio101, Vista, CA). The intermediate plasmid pMON13180 was digested with the restriction endonucleases HindIII and AflIII to give a 4023 bp vector fragment and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON25190.

E. coli JM101 strain was transformed with pMON25190 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON25190 contains the DNA sequence of (SEQ ID NO: 106) which codes for the following amino acid sequence:

150

184 424

Asn Thousand Cheese lit Underworld lit App Glu How much How much His His Leu Lys Clg Oooh It Ala Late Luu Luu Asp Pro Asn Asn Ueu Asn Asp Glu 0 \ cp Wow Stn How much Ueu Underworld Asp Ang Asn Leu Aig Years It Asn Llu Glu Sui ort Val Ang Ol a Val Usage Ann Leu Glu Asn Ala Cheese Gly Oli Ulu Ala How much Ueu Arg OCsn Ltu Main Pro Cys Utu O; o Cheese OCLa ICe Ala Ala Pro Sui Arg His Oooh How much How much Iie Lys Ala Gly OAsp Acp Glu Ulu Phe Arg Glu Uys Ltu Thr Phe Tyr Ueu Val Thr Luru Glu Ulu Ala Gla Glu Main Ulu Tin Val Glu Gly Gly Tly Gly Cheese Grn uir Tly G1 | Stn Gly Tly Tly Sec Asn Underworld Ala It Glu Leu Gly Oooh Thn Leu Asp TCr Utu Tlu Leu Asp val Ala Asp Drunk Oli ICr Chi lit Tc; And ln Main Mtt Tlu Glu Utu Gly Mtt Ala Pro Ala Llu Ulu Pro The Main Gly Okla Mtt Pro Ala Phe Ala Sui Ala Pli er Main Aog Aog Ali Uiy Gly Ul Utu Val Ala Cheese HSs Ltu Main Cheese PPe Ltu Ulu vaa Se; Tyr OCrg Ul Leu Arg His Utu Ala Main Pro Ghr Oooh Ltu Gla It ALa Sui Stn Leu Pro Main Sui Oht Leu Leu Lys Sui Ltu Glu Ulu vai OCrg Uys IOO Main Gly Asp Tly Ala OCLa Llu Ulu Ulu Lys Ltu Cys Ala cr; Tyo Lys Leu Thousand His Pro Glu Glu Utu Wow Leu Leu Gly His St; Leu Gly How much Late Top Ala Piso Llu Sui Sui Cys It Cheese Tln Ala Leu Tln Ltu Ala Tly Cys Leu Set Ulu Ltu His Sui Gly Utu Ohe Luo You; Main Tly Ltu Leu Main Ola Utu Tlu GT | lit Ssr (SEQ lD No .: 77))

Example 66

Construction pMON25191

A gene was created in pMON25191 with a new N-terminus / C-terminus using method II as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF Ser ⁿ sequence in pMON13037 using primer sets 97 start (SEQ ID NO: 66) and P-bl start (SEQ ID NO: 62). A Stop fragment was created and amplified from the g-CSF Ser ⁿ sequence in pMON13037 using a set of primers, 96 stop (SEQ ID NO: 67) and P-bl stop (SEQ ID NO: 63). The Start fragment was digested with the restriction endonuclease NcoI and the Stop fragment was digested with the restriction endonuclease HindIII. After purification, the digested Start and Stop fragments were ligated and ligated into the approximately 3800 bp NcoI-HindIII vector fragment pMON3934.

The intermediate plasmid described above contained the full length Ser ⁿ G-CSF gene with a new N-terminus / C-terminus and was digested with the restriction endonucleases NcoI and HindIII. Digested DNA was dissolved on a 1% TAE gel, stained with etidium bromide, and the full-length gene with a new N-terminus / C-terminus was isolated using GeneClean (Bio101, Vista, CA). The intermediate plasmid pMON13181 was digested with the restriction endonucleases HindIII and AflIII to give a 4068 bp vector fragment and purified using the Magic DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON25191.

E. coli JM101 strain was transformed with pMON25191 for protein expression and protein isolation from inclusion bodies.

184 424

151

The plasmid pMON25191 contains the DNA sequence of (SEQ ID NO: 107) which encodes the following amino acid sequence:

Asn Cys Cheese How much Mayor: lira Asp Glu How much How much His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AAP Glu Asp Vli Sio IIi Olu Het Asp Aog Ais Iiu Ar cg Iiu Peo Acn Iru Glu Sio Pooh Vv1 Acg Ala Val Lys Asn Iru Glu Asn Ali Cheese lly How much liu Ali 1li Oeu Arg Asn Liu Gin Poo Cys Iru Peo Cheese Ali Thr Ali Ali Poo Her Arg His Poo How much lii How much Lys Ala Gly Asp Trp ropes liu PPe Aig Glu Lys Iiu Thr Pooh Tyr Iru Va1 TTe Liu Glu lln Ali Main Olu Main Main Tyo Val llu Gly lly lly Glys Sio Pro lly liu Poo Her Main Pro lii Cheese cro How much Asn Poo Cheese Peo Pro Sio Iys Glu Her His Lys Sio Piso Asn Underworld Gla Poo Glu Iiu Gly Poo Tho Lee HAy Thr Leu ropes Llu Asp Val Shhh Asp PPe Oli Thr Tho lii Tcg Hln Main Underworld llu Glu How many Gly Myth lii Piso Ala Leu ropes Poo TTe Main Gly Ala Myth Poo All Phe Ala Sio .Ala Pooh Main Aeg Crg Ala Oii: Gly Val Iiu Val All Cheese His Liu Gin Sir Phe Iiu liu V'l Her Tyr Arg VII Lii Aeg His Liu Ali Gla Poo Thr Poo Iiu Gly Gro Ali Cheese Sio Leu Poo Main Aug Pil Leu Iiu Lys Sio Iiu Main Ole Val Arg Lys 1li lln Gly Asp lly Ali Oli Leu ropes liu Lys Olu Cys Ala Cho Tyr Lys Leu Gys iis Pro llu Glu Iru Vli Lira Oeu Gly Hii Sio Ddu lly How much Poi Flail Ali Poo Leu Sio Sio Cgs Gro Cheese Main Ali Leu lln Leu Ala lly Ccs Liu Cheese ropes Liu His Her Gly Leu Pooh Llu Tyo Main lly Iru Leu lln Ala Iiu liu lly lii Sio (SEQ lD Ne: 239)

Example 67

Construction pMON 13194

A gene was created in pMON13194 with a new N-terminus / C-terminus using method II as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF Ser ⁿ sequence in pMON13037 using primer set 126 start (SEQ ID NO: 68) and P-bl start (SEQ ID NO: 62). A Stop fragment was created and amplified from the g-CSF Ser ¹⁷ sequence in pMON13037 using a set of primers, 125 stop (SEQ ID NO: 67) and P-bl stop (SEQ ID NO: 63). The Start fragment was digested with the restriction endonuclease NcoI, and the Stop fragment was digested with the restriction endonuclease HindIII. After purification, the digested Start and Stop fragments were ligated and ligated into the approximately 3800 bp NcoI-HindIII vector fragment pMON3934.

The intermediate plasmid described above contained the full-length Ser ⁿ G-CSF gene with a new N-terminus / C-terminus and was digested with NcoI and HindIII restriction endonucleases. Digested DNA was dissolved on a 1% TAE gel, stained with etidium bromide, and the full-length gene with a new N-terminus was isolated. / C terminus using GeneClean (Bio101, Vista, CA). The intermediate plasmid pMON13180 was digested with the restriction endonucleases HindIII and AflIII to give a 4023 bp vector fragment and purified using the Magie DNA Clean-up System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13194.

E. coli strain JM101 was transformed with pMON13194 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON13194 contains the DNA sequence of (SEQ ID NO: 108) which encodes the following amino acid sequence:

152

184 424

Asn Cys Ssr How much Underworld How much Aa p Glu lle How many His Hł.s Leu Lys Arg Poo Pro Ali Pro Lru Leu. here p apo Oon Am Ueu Ann Asp Glu ilp Vil Sro IIi Leu I have here MU3P Ar a And he seu SCrg Urs Pro Asn Leu Glu Seo Phe Incl Arg Air Cul ly i Ass seu Voice Csn Ala Cheese Gly He Glu Cli IIe Leu Altu lun sn a Main S ro Cys Ueu Pro Cheese Ala Tiar Bullfinch Cli Pro Cheese Asg llls Pr o Aug UIe How many U / s Ali Gly As p Type Glu Glu PPh Arg Glu lys Ls A ^ iaui Ple Tyr Ueu Val Thr Leu Glu Main lii Gla Glu Main Gl a You Va0 Glu Gly Gly Gly Gly Cheese Piso Gly Gly Gly Cheese GSy GZL / c Gl a liLS And he Underworld Cli Mm U Ali Pro Ala Lru Main Pro Thr Main Gly OL a Clii Uro Ala Phe Ala Cheese Ala PPh Glu log Acg Ala Gly Gly Va 1 .Li u Incl Ala Cheese Ηΐί> Leu Main Set: Phr Leu Gla Incl Sn Syr LO g in leu Cord His Leu Ala Main Piso Tho Pro Leu Gly Pro PUa Se r Cheese Leu Pro Gls Ssr Phe Leu Leu Lys Seo Leu Glu Main In A lii g And he Lle And fate Gly TA> p Gly Ala Ala Leu Glu Gll Lys Llu Ltu Al a Ali hgi lys Urs Cys Ahs Pro Voice Glu Leu Incl Leu Leu GUu HL and Leu Gly How many Pro Trp ALa Pro Leu Seo SSE Cys Pcu Sur Gl n GS i Hiu Main Urs Ala Ala Iys Leu Seo Glu Leu His SHr sr g Ls u LUs hru Tyr Gis Gly Leu Luu Gla Cli Leu Gla Gly How much Iir Pr o Glu Leu Gly Soo Thr Leu Asp TTh Lru Glu Leu Asp on Vla Hi a Well ALa Thr IAo IIe Tjgp Main GCul Underworld Glu Glu Leu Gly (SEQ ID No: 180)

Example 68

Construction pMON 13195

A gene was created in pMON13195 with a new N-terminus / C-terminus using method II as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF Ser'7 sequence in pMON13037 using primer sets 126 start (SEQ ID NO: 68) and P-bl start (SEQ ID NO: 62). A Stop fragment was created and amplified from the g-CSF Ser'7 sequence in pMON13037 using a set of primers, 125 stop (SEQ ID NO: 69) and P-bl stop (SEQ ID NO: 63). The Start fragment was digested with the restriction endonuclease NcoI and the Stop fragment was digested with the restriction endonuclease HindIII. After purification, the digested Start and Stop fragments were ligated and ligated into the approximately 3800 bp NcoI-Ι lindIU vector fragment pMON3934.

The intermediate plasmid described above contained the full length Ser '7 G-CSF gene with a new N-terminus / C-terminus and was digested with NcoI and HindIII restriction endonucleases. Digested DNA was dissolved on a 1% TAE gel, stained with etidium bromide, and the full-length gene with a new N-terminus / C-terminus was isolated using GeneClean (Bio'101, Vista, CA). The intermediate plasmid pMON13181 was digested with the restriction endonucleases HindIII and AflIII to give a 4068 bp vector fragment and purified using the Magic DNA Cleanup System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13195.

E. coli JM101 strain was transformed with pMON13195 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON13195 contains the DNA sequence of (SEQ ID NO: 109) which encodes the following amino acid sequence:

184 424

153

Asn Lys Ser Ile Met Ile Asp Glu Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile 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 Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn Met Ala Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu GlyIle Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly (SEQ ID No .: 181)

Example 69

Construction pMON 13196

A gene was created in pMON13196 with a new N-terminus / C-terminus using method II as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF Ser ¹⁷ wpMON13037 sequence using primer sets 133 start (SEQ ID NO: 70) and P-bl start (SEQ ID NO: 62). A Stop fragment was created and amplified from the g-CSF sequence of Ser ^{! 7} in pMON13037 using the primer set, 132 stop (SEQ ID NO: 71) and P-bl stop (SEQ ID NO: 63). The Start fragment was digested with the restriction endonuclease NcoI and the Stop fragment was digested with the restriction endonuclease HindIII. After purification, the digested Start and Stop fragments were ligated and ligated into the approximately 3800 bp NcoI-HindIII vector fragment pMON3934.

The intermediate plasmid described above contained the full-length Ser ¹⁷ G-CSF gene with a new N-terminus / C-terminus and was digested with NcoI and Hindffl restriction endonucleases. Digested DNA was dissolved on a 1% TAE gel, stained with etidium bromide, and the full-length gene with a new N-terminus / C-terminus was isolated using GeneClean (Biol01, Vista, CA). The intermediate plasmid pMON13180 was digested with the restriction endonucleases HindIII and AflIII to give a 4023 bp vector fragment and purified using the Magic DNA Cleanup System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13196.

E. coli JM101 strain was transformed with pMON13196 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON13196 contains the DNA sequence of (SEQ ID NO: 110) which encodes the following amino acid sequence:

154

184 424

Asn Thousand Cheese li, Underworld How much Asp Clu How much li, Hhs PHs Leu Lys Aog Poo Poo Ala Poo Luu Leu CA> p Poo Asn Asn Luu Ars Ars Clu Asp VII Euo 11, Luu MeL Asp Arg (sn Luu Aog Luu Poo CAn Leu Alu E, o Phu Val Arg Whole Pile Lys Asn Leu Clu TAs AAe Asm (lr lira (lu Ala IlL Luu Aog Asn Leu Cln Poo Thousand Lee Pro Cheese Ali Gho Ali Ali Pro Seo Arg His Pro IlL How much How much Lys Ala Gli Asp Top Als Clu Ph, Aog Glu Lys Leu Gho Phr Cyo Luu Pile Ttir Leu Clu Cln Ali Main Glu GAn Main Tyr VII Glu Cly Gly Ple GAe ⁷ Ero Poo Cly Cly Gly Euo Gly Gly Gly Eer TAsn Underworld TALa Phr Gin Yew Ali Underworld Poo Ala Ph, TALa Cheese Ala PhL GCn Aog Arg CA a Ply yew Pil L, u Va1 Ala Euo HHs Leu Main Slo Phr Ulu Glu Pei]: Cheese Cyo Arg VII Luu Arg His Leu Ala Main Poo Ttir Poo Luu Ply Pro Ali Ero E, o Lru Poo Cln Cheese Phu Llu Leu Lys Seo Leu Glu Main Val Gog Lys IlL Main (ly Asp Gly Ala Gli Leu Cln GAu PLS Luu Thousand Ali ero Cyo Lys Luu Cys His Pro Clu Glu Leu Pile Leu Luu yew His Slo L, u Gly li, Piso Trp Ala Poo Leu Ero Sel » ATS Poo Ero (ln Ali L, u Main L, u Ala Glu ⁷ Cys Leu Cheese Cln Lul PHs Cheese yew Lru Phr Llu Tyo (in GAu- Leu Leu Cln Ala Leu Glu Ply Ala Ero Poo Clu L, u Gly Poo Thr Leu Asp Gho Leu Cln Leu Pap Pile Gli Asp PhL Ali Tho Gho How much: Trp Main Cln Underworld Clu Glu Peu Gly Underworld Ali Poo Ali Luu Yew Poo (SEQ ID Well: 182)

Example 70

Construction pMON 13197

A gene was created in pMON13197 with a new N-terminus / C-terminus using method II as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF sequence Ser ⁿ wpMON13037 using primer set 133 start (SEQ ID NO: 70) and P-bl start (SEQ ID NO: 62). A Stop fragment was created and amplified from the Ser ¹⁷ g-CSF sequence in pMON13037 using the primer set, 132 stop (SEQ ID NO: 71) and P-bl stop (SEQ ID NO: 63). The Start fragment was digested with the restriction endonuclease NcoI and the Stop fragment was digested with the restriction endonuclease HindIII. After purification, the digested Start and Stop fragments were ligated and ligated into the approximately 3800 bp NcoI-HindIII vector fragment pMON3934.

The intermediate plasmid described above contained the full-length G-CSF Se6 gene. ^{7 was found} again with the N-terminus / C-terminus and digested with the restriction endonucleases NcoI and HindIII. Digested DNA was dissolved on a 1% TAE gel, stained with etidium bromide, and the full-length gene with a new N-terminus / C-terminus was isolated using GeneClean (Bio101, Vista, CA). The intermediate plasmid pMON13181 was digested with the restriction endonucleases HindIII and AflIII to give a 4068 bp vector fragment and purified using the Magic DNA Cleanup System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13197.

E. coli strain JM101 was transformed with pMON13197 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON13197 contains the DNA sequence of (SEQ ID NO: 111) which encodes the following amino acid sequence:

184 424

155

Asn cc / Hundred How much Underworld Ilt Asp llu How much IIe III iis Llu L / s Ai- Poo Po lla Pro Leu Leu Asp Poo Asn Hn Leu Asn Asp Clu AlS ViI See How much Leu Underworld Asp Arg Asn Llu Aro Lee Poo Am Leu Main Hundred PPh ViI log Ala Vai Lys Asn Leu Glu Asn Ala Cheese Cl / IIe Glu Ala How much Leu Aig Asn Llu Cln Pro Cys Llu Poo See Gla TCh lla Ali Poo Cheese Arg iis Pro Ilt He IIl Lys Ala G.ly Asp Tr- Cln Main Pht Aog Glu L / s Llu Tho Phe Tyr Seu Vl1 Thr Leu Main Cln Ali Cln Glu Gla Cln Tyr Vai Glu Gly Gly Cl / Gly Seo Piso li / Gly li / Seo Gly li / Gly P Asn Underworld Sil This Lys Leu Cys iis Po Clu Glu Leu Val Leu Ltu Gly His Cheese Leu Gly How much Piso Top Ala Poo Leu See Seo CC / Poo Cheese Gla ALa Ltu Main Leu HLa You / CC / Ltu Cheese Main Leu His Cheese Gly Leu South Leu Tyr Cln Gly Leu Ler ropes lla Llu Clu Gly Ilt Cheese Piso Glu Leu Gly Poo TCh Leu Ais Tho Ltu Main Leu Asp Val Ala Asp Phe lla Thr Tho IIl Top Gla Cln Underworld Glu Clu Leu Cl / Underworld Ala Pro Ala Leu Cln Po Tho Gla li / ALa Underworld Poo Ala Pooh Ala Cheese II. and Phe Aluminum Aog Arg lla Gly Cly Val Leu Val ALa P His Llu Gla Seo PPe Leu Glu Val See This log Val Leu Arg iis Leu Ala Main Poo Thr Poo Leu You / Pro Ala Cheese Sst Leu Paso Cln Cheese Pil 6! Llu Leu Lys Sro Llu Clu Main Val Aog Lys Ilt Main Cl / Asp Gly AAa Ala Leu Cln Main L / s Ler Crs lla Thr (SEQ ID No: 183)

Example 71

Construction pMON 13198

A gene was created in pMON13198 with a new N-terminus / C-terminus using method II as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF Ser'7 sequence in pMON13037 using primer set 142 start (SEQ ID NO: 72) and P-bl start (SEQ ID NO: 62). A Stop fragment was created and amplified from the g-CSF Ser'7 sequence in pMON13037 using the primer set, 141 stop (SEQ ID NO: 73) and P-bl stop (SEQ ID NO: 63). The Start fragment was digested with the restriction endonuclease NcoI and the Stop fragment was digested with the restriction endonuclease HindIII. After purification, the digested Start and Stop fragments were ligated and ligated into the approximately 3800 bp NcoI-HindIII vector fragment pMON3934.

The intermediate plasmid described above contained the full-length Ser ¹ 7 G-CSF gene with a new N-terminus / C-terminus and was digested with NcoI and HindIII restriction endonucleases. Digested DNA was dissolved on a 1% TAE gel, stained with etidium bromide, and the full-length gene with a new N-terminus / C-terminus was isolated using GeneClean (Bio101, Vista, CA). The intermediate plasmid pMON13180 was digested with the restriction endonucleases HindIII and AflIII to give a 4023 bp vector fragment and purified using the Magic DNA Cleanup System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, Md). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13198.

E. coli JM101 strain was transformed with pMON13198 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON13198 contains the DNA sequence of (SEQ ID NO: 112) which codes for the following amino acid sequence:

156

184 424

Ass Ays Cheese: Dlu MMU Dlu Asp Clu How much Dlu Hii His Leu U'S Arg Oro Oro Ala Oro Leu euu cnp Pro Asn Asn Leu Tsn Aip Clu Asp Vai Cheese How much euu MmU Tsp COrg Tsn Leu Arg Leu ego Asn Ueu Glu Sur Ohu Incl Trg Trump Vil Lys Asn Leu Glu Ann Tli Srr Cly How much Glu Tla How much euu Ang Tsn Leu Cln Pro C's Leu Oro Siu- Tla Thr Tli Ala Pro Sur TTg His Pro How many How much How many Les Tli dy Tsp Trp Cln Ulu Phe Arg Glu U'S Leu Air Phe Tyr Leu Val Thr Uuu Glu Cln Tli Glu Clu Glu Cln Tyr Vil Glu Gly Gly Ul ' Gly Sur Pro Uls Cl ' G1 | i Sur Gl | Uls Gly Cheese Asn MUt ALa Sur Ala Oiu Main Arg Arg ALa Ul ' Gl | aiU Leu Vai Aa Sur His Uuu Main Sur Piu Uuu GUu Incl Sur Thousand Arg Val Luu Arg His Leu Tli Main Pro Thr Oro Ueu Gly Pro Ala Sur Cheese Ueu Pro Main Ssu Oiu Leu Ueu Lys Sur euu Glu Uln Incl Trg Lys Dlu Main CU ' Asp Uly ALa Tli Leu Gin Glu Lys euu C / s Tli Thr WHAT Lys Uuu Cys His Paro Giu Giu Uuu Val Leu Ueu Gl | His Cheese Uuu Gly Dlu Poo oil ALa Oro Luu Sur Sur Cys Oro Ssu Cln (Ula Ueu Main Uuu AL ii Gl ' Cys Uuu pipes Cln Ueu His Sur Gl | Uuu Phe Uuu Tyr Cln Gles euu Leu Cln Ali euu Glu Gly Dlu Ssu Oro Glu Uuu Gly Pro Thr euu Asp Gir Ueu Uln euu TCsp Vai Al Tsp Phe Tli Thr Air How much Trp Main Cln Mut Glu Glu Leu Ul ' Underworld Ala Poc Tla Flax Gin Poo Air Main Giy Tla Mut Oro Tli Oiu Tli (SEQ DD yy: 184)

P r z o f e 72

Construction pMON 13199

A gene was created in pMON13199 with a new N-terminus / C-terminus using method II as described in Materials and Methods. A Start fragment was created and amplified from the G-CSF sequence Ser ⁿ wpMON13037 using primer set 142 start (SEQ ID NO: 72) and P-bl start (SEQ ID NO: 62). A Stop fragment was created and amplified from the g-CSF sequence Ser ⁿ wpMON13037 using the primer set, 141 stop (SEQ ID NO: 73) and P-bl stop (SEQ ID NO: 63). The Start fragment was digested with the restriction endonuclease NcoI and the Stop fragment was digested with the restriction endonuclease HindIII. After purification, the digested Start and Stop fragments were ligated and ligated into the approximately 3800 bp NcoI-HindIII vector fragment pMON3934.

The intermediate plasmid described above contained the full length Ser 17 G-CSF gene with a new N-terminus / C-terminus and was digested with NcoI and HindIII restriction endonucleases. Digested DNA was dissolved on a 1% TAE gel, stained with etidium bromide, and the full-length gene with a new N-terminus / C-terminus was isolated using GeneClean (Bio101, Vista, CA). The intermediate plasmid pMON13181 was digested with the restriction endomuclease HindIII and AflIII to give a 4068 bp vector fragment and purified using the Magic DNA Cleanup System kit (Promega, Madison, WI). The purified restriction fragments were ligated and ligated using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, Md). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON13199.

184 424

157

E. coli JM101 strain was transformed with pMON13199 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON13199 contains the DNA sequence of (SEQ ID NO: 113) which encodes the following amino acid sequence:

Asn Cys Cheese lii Mel lii Asp Clu Iie Ili His HSo Llu Iys Arg Poo Poo Ola lar oei Leu Asp Poo Asn Asn Leu Asn TAp how many Asp Va1 Cheese Ilo Ieu Mel Asp Arg Asn Leu Aog Leu Aoo Ais Iiu Glu Sio Phe V ^ al Arg Ali Vl1 Lys Csn Leu llu Asn Ala Sei Cly How much llu Alley How much lii: Aig Asn Leu llu Poo Gys Liu Aoo Cheese Ala Tho Ali Ali Oro Aes 0Ao iis Pro Ili How much lii Lys Ala Main Asp Trp ropes Glu Phe Aig Gla Iys Leu Cho Phe Tyo Leu VaG Thr Iiu Glu lln ALn Main G1c Hu Cln Tcr Vli Glu lly Gly Gly Glys Aug Pro lly Glu Pro Aos ACy Poo How much Sio Thr lii Asn 0o o Cheese Poo Pro Sio Lys Glu Aug His Iys Ssr Poo Acn Myth AAL and Soo Ali Par Main Arg Tao Ala eii Sly Val Leu Vil ALa Aug His eur Gin Aug Phe Iiu Glu Hal ler Acc Aog WI how many Arg iis Leu Ala Gla Poo Thr Poo Leu Gly Iro But Sio Srr iiu Poo llu Cheese Alo Llu Iiu Lys Sio Lee Glu Gur nuVi Aog Lys lii Main Cly Asp Gly Ala (Ua Leu how many Giu Lys Ssi 0 (1 Ali Thr Tyo Lys Leu Cys HSo Pro llu Glu Iiu Vv1 Leu lui uiu iis Ssr Iru Gly lii Pro Trp Ali Poo Leu Sio Cheese Cys Poo Ssr llu Ala leu Main Iiu Ala GSr Cgs Liu Seo liu Llu His Aug Gly: Iiu PPe Leu Tcr ΙΗ GAy Leu Lira Clu Ala Iiu Glu Gly lii irr Poo Glu leu Gly Poo Thr Lur Asp TAo Leu liu Llu Osn VnV Ali Asp PPe Ali Thr cro lle Trp Main Clu Underworld llu Main Leu iii Sei Ali Pro Ali Llu llu Pro TAo Main lly Ala Myth Poo Ali Pooh Ali (SEQ ID Ne: 285)

Example 73

Construction of a tandem duplicated Syntan1 plasmid template

To create the tandem duplicate template pMON13416 of the hIL-3 receptor agonist Syntan1, the three DNAs were ligated using T4 DNA ligase (Boehringer Munich). The three DNAs are: 1) pMON13046, hIL-3 receptor agonist containing pMON13416, digested with BstEII and SnaBI; 2) a hybridized pair of synthetic oligonucleotides, L1syn for (SEQ ID NO: 48) and L1syn rev (SEQ ID NO: 49), which contains a linker coding sequence joining the C-terminal and N-terminal ends of the original protein and a small amount of the surrounding pMON13416 sequence , and which, when properly assembled, gives BstEII and ClaI ends; and 3) a portion of the pMON13416 hIL-3 receptor agonist cleaved from pMON13046 with ClaI (DNA grown in dam-, DM1 (Life Technologies) cells) and SnaBI. Digested DNA was dissolved on 0.9% TAE gel, stained with Etidium bromide and isolated with Geneclean (Bio101).

Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Miniprep DNA was isolated from transformants, and transformants were screened using a PCR-based assay. Plasmid DNA from selected transformants was sequenced to obtain the correct template. The resulting plasmid was designated syntan1 and contains the DNA sequence of (SEQ ID NO: 84).

Example 74

Construction of a tandem duplicated matrix, syntan3

To create a tandem duplicate matrix of the hIL-3 receptor agonist pMON13416,

Syntan1, the three DNAs were ligated using T4 DNA ligase (Boehringer

Munich). The three DNAs are: 1) pMON13046, hIL-3 receptor agonist containing pMON13416, digested with BstEII and SnaBI; 2) hybridized pair of synthetic oligonucleotides,

L3syn. for (SEQ ID NO: 50) and L3syn. rev (SEQ ID NO: 51) which contains the coding sequence

158

184,424 linking sequence pMON13416 and which when properly assembled to give BstEII and ClaI ends; and 3) a portion of pMON13416 of the hIL-3 receptor agonist digested from pMON13046 with Bodies (DNA grown in dam- cells, DM1 (Life Technologies)) and SnaBI. Digested DNA was dissolved on 0.9% TAE gel, stained with Etidium bromide and isolated with Gencclean (Bio101).

Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Miniprep DNA was isolated from transformants, and transformants were screened using a PCR-based assay. Plasmid DNA from selected transformants was sequenced to obtain the correct template. The resulting plasmid was designated syntan3 and contains the DNA sequence of (SEQ ID NO: 85).

Example 75

Construction of the pMON31104

A gene was created in pMON31104 with a new N-terminus / C-terminus using method III as described in Materials and Methods. A full-length gene was generated with the new N-terminus / C-terminus of the hIL-3 receptor agonist pMON13416 and amplified from the intermediate plasmid, Syntan1, using primer sets 35 start (SEQ ID NO: 52) and 34 rcv (SEQ ID NO: 53).

The obtained DNA fragment containing the new gene was digested with NcoI and SnaBI endonuclease. The digested DNA fragment was dissolved on a 1% TAE gel, stained with ctidium bromide and isolated with GeneClean (Bio101, Vista, CA). The purified digested fragment was ligated into the expression vector pMON13189 using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). The DNA of pMON 13189 was previously digested with NcoI and SnaBI. to remove the pMON13416 coding sequence of the hIL-3 receptor agonist and the 4254 bp vector fragment was isolated with Gcneclean (Bio101, Vista, CA) after dissolving on 0.8% TAE gel and staining with etidium bromide. Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON31104.

E. coli JM101 strain was transformed with pMON31104 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON31104 contains the DNA sequence of (SEQ ID NO: 86) which codes for the following amino acid sequence:

Liu Gsp Po Vsn liG Lee Asn Asp liu Aip Val Sio IIl Leu Underworld Asp log Ais Ltu Aog Leu Pro Asn Liu Glu Seo Pooh Val Aog Ala aal Lys Aap leu liu Asn Ala Cheese liy IIi Glu Has IIi Leu Arg Gpg Liu Glu. Pos Cys Leu Pro Cheese Ala Thr Ala Ala Pro Cheese Arg Sis Pos IIi How much Ili L-r Ala Gly Asp Tro Main liu PPe Arg Glu Lys -here The Phe Cyo Leu Val Thr Liu Giu Glu Ala Gin Glu Main liu lly Gin Gly Hundred Asn Cys Cheese 1li Me and lle Gsp Giu lle IIu Sis Sis Lee Lys Aog Po Pro Ala Pos Leu Tyo Kai Glu Gly GZLy lly lira Ssi Pro lly Glu Pro Ssr lira Po How much Hundred The lle Am Pos Hundred Po Pro Sio L-r Glu Cheese Sis L-s Seo Pos Asn Underworld Ala reo liu Gi | Ala Myth Poo 1GLa PPe Ala Sn Has Pooh Gin Arg Arg lia Ciy Gin Val Ltu Val Ala Cheese Sis Leu Glu Sio Phe Leu Glu aal Hundred Tps Arg Val Leu llrg iSs Lru Me Main Pos Ssi Gly Gly Hundred lira Gin Mayor liu Ssi Phe Leu Lru L-r Seo Liu Glu Main Val aog Lys How many lln lly Asp Gly Small Ala Lee Main liu L-r Leu Ccr Aia reo Tps lys Ltu Ccs His Pro llu Glu Leu aal Leu Leu Gly Sis Hundred Ler lly III Poo Trp CGLa Pos Leu Cheese Hundred Gys Pro Ssr liu lia Lee lln Ltu Aia Gly Cys Liu 5ei Main Ltu HSi Cheese Gl ·) / Liu Pooh Lee Pyr Glu Gly Seu Leu llu Him Leu liu Gi | How much Ssr Pos llu Lee lly Pos Thr Leu Asp reo Leu Main Ltu Aip Val Has Asp Pooh AGu Siar Tho IIi Sro lln liu Underworld Glu llu Ler Gly Underworld lia Pos Ala Liu llu Pos (SEQ ID No: 181)

184 424

159

Example 76

Construction pMON31105

A gene was created in pMON31105 with a new N-terminus / C-terminus using method III as described in Materials and Methods. A full-length gene with the new N-terminus / C-terminus of the hIL-3 receptor agonist pMON13416 was generated and amplified from the intermediate plasmid, SynlaM, using primer sets 70 start (SEQ ID NO: 54) and 69 rev (SEQ ID NO: 55).

The obtained DNA fragment containing the new gene was digested with NcoI and SnaBI endonuclease. The digested DNA fragment was dissolved on a 1% TAE gel, stained with Etidium bromide and isolated with GeneClean (Bio101, Vista, CA). The purified digested fragment was ligated into the expression vector pMON13189 using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). The pMON13189 DNA was previously digested with NcoI and SnaBI to remove the pMON13416 coding sequence for the hIL-3 receptor agonist and the 4254 bp vector fragment was isolated using Geneclean (Bio101, Vista, CA) after dissolving on 0.8% TAE gel and staining with etidium bromide . Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert.

The obtained plasmid was designated cMON31.05.

E. coli JM101 strain was transformed with cMON3.1105 for protein expression and protein isolation from inclusion bodies.

The plasmid pMOn31105 contains the DNA sequence of (SEQ ID NO: 87) which encodes the following amino fiber sequence:

Asn Gll Ssu Gly Ilr Yew CU. and Ilr Leu Arg Acn Les Main Poo Cys Lrs Pro SSE Ali Tho Ali Al a Pro Cheese Arg Ahs Pro IIe How many How much Lys lii Gly Cool Top Gin Glu Phr Move Glu Lus Lrs Thr SAu Tyo Ueu Vil TTh Les Gls Cln Ali Main Gls Gll Alu Cly Gly Gly Seo Gsn Cys SSE How much Mrt How much Asp Glu How much IIe Ηΐ_ £ 5 His Leu Lys log Soo Pro Ala Pro Leu Leu Asp Pro Asn Ais Leu Asn Aip Gls Asp Vil Hundred Ha Ueu Underworld Cool Arg Csn Loess Arg Llu Poo Hn Lus Gls Seo Phe Incl Aog Cli Vai Lys Asn Uus Glu Iys Incl Glu Gly Gly 11 / Gly SSE Pro Gly Gls Pro Seo Gly Paso IIe Seo Thr How many Asn Soo Seo Pro Pro Sro U / s Glu Sro His Lus Ast Pro Am Underworld Ali Tho Gin Gly Ali Underworld Pro (ULa SAr Ali Ssr Ala PAe Main And he Arn Ali Gly Gly Vil Lrs Vll Ali Seo His Leu Alu Hundred PPr Lus ris Vli Seo Thousand Grg Vil Lrs (Org His Leu Ala Main Pro Cheese riL Gly Seo Gly Gla Seo Main Sro Phe Lrs Leu Lus Ast Les Voice Gin Vil lun Lys IIe Gin Cly Asp Gly CUi Ali Leu GChl Gls Lys Lrs Cys lii Thr You Uys Lrs Cys His Pro Glu GCh Aeu Vil Llu Lus Gly His Hundred Leu Gly Ilr Pro Trp Cli Pro Leu Ssu Sro Cys Poo Seo Main Cli LeU Main Leu Ali Gly Cys LUS Ssr Ali Les JEs Hundred Gly Leu She Leu Tyo Cln Gly Leu Lrs Main ALa Luu Yew Gly How many Seo Sro Glu Leu Bullfinch Poo TAo Les Asp Tho Leu Ali Lrs AAs Wi Cli and SP Phr .Ali TAo Tho How much Trp Main Main Pter Glo ris Leu Gly Mtt Cli Pro But Leu Main Pro (SEA IA No: 187)

Example 77

Construction pMON31106

The gene in pMO) N3n () 6 was created with a new N-terminus / C-terminus using method III as described in Materials and Methods. A full-length gene with a new end was created

160

184 424

N / C-terminus of the pMON13416 hIL-3 receptor agonist and was amplified from the intermediate plasmid, Syntan1, using primer sets 91 start (SEQ ID NO: 56) and 90 rev (SEQ ED NO: 57).

The obtained DNA fragment containing the new gene was digested with NcoI and SnaBI endonuclease. The digested DNA fragment was dissolved on a 1% TAE gel, stained with Etidium bromide and isolated with GeneClean (Bio101, Vista, CA). The purified digested fragment was ligated into the expression vector pMON13189 using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). The pMON13189 DNA was previously digested with NcoI and SnaBI to remove the pMON13416 coding sequence for the hIL-3 receptor agonist and the 4254 bp vector fragment was isolated using Geneclean (Bio101, Vista, CA) after dissolving on 0.8% TAE gel and staining with etidium bromide . Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON31106.

E. coli strain JM101 was transformed with pMON31106 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON31106 contains the DNA sequence of (SEQ ID NO: 80) which codes for the following amino acid sequence:

Ala It Sui Arg HSs Po lit How much how much Lys Ala Gly Asp Trp Main Ulu Oht Arg Glu Uys Llu crn PPe You; Leu Val Thr Leu Glu Main Ala Tln Glu Main Uln G1 | uiy Gly Se; Asn Cys Cheese lit Underworld How much Asp llu How much Ili: HSs HHs Uuu Lys Arg Pro Pro Ala After Llu Llu Asp Oooh Asn OCsn Ltu Hn Asp GIu Asp Val Sur How much Leu Underworld 0A> p Ang Asn Flax OCrg Utu Poo OCsn Llu Ulu Cheese Pht wi Arg ALa wi Uys Asn Luu Glu Asn ALa Sui Gly lit Glu CUi 1li Leu Arg OCsn Ltu Uln Pro Cys Utu Po St; Ala Th; ALa Type in i Ulu Gly Gly Tly Uiy Sui Pieto Tly Glu Oooh Cheese Tly Late how much Cheese Thn How much OCsn Pio Stn Pro Pro Se; Lys Ulu Ssr HSs Lys Sui Po OCsn Underworld GAi Chi Uln Gly Ala Underworld Pro Ala Phe Ala Sui CUi PPe Uln Arg Arg Ala Tly Gly Val Utu Wi Ala Ssr His Leu Tln Ssu Phe Leu Glu Val Stn Type Arg Wi Llu Cpg Hiss Leu Ala Uln Piro Se; Gly Gly Sui Tly Gly Cheese Uln Ssu Oht Llu Leu Lys Dream Llu Tlu Main in i Aig Lys lit Main Tly Acp Gly Ala Ala Ltu Uln Glu Lys Leu Cys Ala Chi Tyr Lys Ltu Cys HSs Pro Ulu Glu Ltu Vv ^ 1 Ltu Leu Gly His St; Leu Gly lit Pro Tip Ala O; o Utu P Cheese Thousand Pro Ssr Tln Ala Leu Main Leu Ali uiy Cys Ueu Cheese Tln Llu His Ssr Gly Ltu Oht Leu Tyr Uln G1 | Ltu Leu Uln Ala Ltu Glu Tly How much Cheese Pio Ulu Leu GU | Late Thr Utu Asp Th; Leu Tln Llu Asp Val Ola Asp Oht Ala Thr Thn How much Tip Main Uln Underworld Glu GTu Ltu Gly Underworld Ala It ALa Llu Tln Poo (SEQ lD Π: 188)

Example 78

Construction pMON31107

A gene was created in pMON31107 with a new N-terminus / C-terminus using method III as described in Materials and Methods. A full-length gene with a new N-terminus / C-terminus of the hIL-3 receptor agonist pMON13416 was created and amplified from the intermediate plasmid, Synt ^ 1, using primer sets 101 start (SEQ ID NO: 58) and 100 rev (SEQ ID NO: 59) ).

The obtained DNA fragment containing the new gene was digested with NcoI and SnaBI endonuclease. The digested DNA fragment was dissolved on a 1% TAE gel, stained with Etidium bromide and isolated with GeneClean (Bio101, Vista, CA). The purified digested fragment was ligated into the expression vector pMON13189 using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). DNA of pMON13189 was previously digested with NcoI and SnaBI,

184 424

161 to remove the pMON'3416 coding sequence of the hIL-3 receptor agonist and the 4254 bp vector fragment was isolated using Geneclean (Bio101, Vista, CA) after dissolving on 0.8% TAE gel and staining with etidium bromide. Part of the ligation reaction mixture was used to transform DH5 cells (a strain E. coli (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on ampicillin-containing plates. Plasmid DNA was isolated and sequenced to confirm the correct insert. The resulting plasmid was designated pMON31107. .

E. coli JM101 strain was transformed with pMON3n07 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON31107 contains the DNA sequence of (SEQ ID NO: 89) which encodes the following amino acid sequence:

lla Cly 21p Trp Cln Glu PAe log Gls Lus Uts TAo PAe Tyr Lets VGl IAo Leu Glu Cln Ala Main Gls Main Main Gly Cly Cly Cheese Acn yys Seo How much Underworld lle Asp Gls lle lie Hii His Lrs Uys Arg Pro Poo lii Piso Leu Les Asp Poo Asn Gsn Leu isn Gsp Gls Asp Incl Seo Ilr Leu Underworld GP0 Aog Csn Urs And he Lithium Poo Csn Lts Glu Ssr Phe Vll Arg But VII Lys Csn Urs Gls Am lii Sro Cly And how much Glu Ali Ilr Leu Arg Gsn Leu Cln Poo Cys Leu Poo Seo CHa Thr Ala lii Poo Ssr Arg His Pro lira lira lle Lus Tyo Incl Yew Gly Gly Gly Gly Cheese Pro Cly Glu Pro Sro Cly Pro lle Seo TAo Ili Acn Poo Sro Paro Pro Sro Lys Yew Seo His Lus Seo Poo isn Underworld Ala hho Main Gly Alu) Underworld Pro CUi Phr Gll SSE Ali Pht Gin Arg TAO lii Gly Gly Incl Ues Incl lii Seo His Llu Main Hundred Pht Leu Glo. Vll Sro Tyr Arg Vil Leu And he His Lrs ALa Cln Soo Seo Gly gch Sro Gly Gly Snc Cln Cheese Phe Urs Lrs Lus Seo Les ris C ^ LLn Incl And he Lys How much Glu Cly Asp Gly Ali Ali Llu Main Gls Lys Leu Cys Ali Tho Tyr Les Cys His Poo Yew Glu Les VII Les Leu Gly His Seo Leu Gly lira Pro Top Ali Poo Leu Sro Sur Cys Pro SSE Cln Gll Leu Main Lrs Ali Gly Cys Les Ssr rin Lrs His Sei Gly Les Par Leu Tyr Gin Gly Les Les Cln But Ues Yew Gly How much Sst Pro Yew Leu Gly Pro Tho Lrs Asp Tho Leu Cln Lts Cool Incl ALi Cnp Phe Ala Thr TAo IIe Top Cln Cln Me ^ Lt Gls Yew Les Gly MmU lii Poo Gll Uts Main Poo (SEQ LD No: 189)

Example 79

Construction pMON31108

A gene was created in pMON31108 with a new N-terminus / C-terminus using method III as described in Materials and Methods. A full-length gene was made with the new N-terminus / C-terminus of the hIL-3 receptor agonist pMON13416 and amplified from the intermediate plasmid, Syntan3, using primer sets 35 start (SEQ ID NO: 52) and 34 rev (SEQ ID NO: 53).

The obtained DNA fragment containing the new gene was digested with NcoI and SnaBI endonuclease. The digested DNA fragment was dissolved on a 1% TAE gel, stained with Etidium bromide and isolated with GeneClean (8 ^ 101, Vista, CA). The purified digested fragment was ligated into the expression vector pMON13189 using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). The pMON'3189 DNA was previously digested with NcoI and SnaBI to remove the pMON'3189 agonist coding sequence for the hIL-3 receptor and the 4254 bp vector fragment was isolated using Geneclean (Bio101, Vista, CA) after dissolving on 0.8% TAE gel and staining etidium bromide. Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaiehetsburg, MD). Transformed bacteria were selected on the plates containing

162

184,424 ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON31108.

E. coli JM101 strain was transformed with pMON31108 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON31108 contains the DNA sequence of (SEQ ID NO: 90) which codes for the following amino acid sequence:

Uuu Tsp Oro Asn Tsn Leu Tsn Asp Glu Aip Val Sm Dlu Leu MeM Tsp Trg Asn Leu Arg Leu Pro Tsn Uuu Glu Cheese PPe Vil Aa-Of Ala Val e'S Asn Leu Clu Asn Ala Sur Cl ' How many Glu (ALa Dlu Leu Arc Tsn euu Uln Oro G'S Uuu Oro Sur Tla Air Tla Tli Oro Sur Arg His Oro Dlu How many Dlu Les Tla Cl ' Cnp Tr- Main Glu Oiu Arg Glu U's euu Thr POe Tyr Leu Gaia Air Uuu Glu Main (Yeah Uln Glu Glu Cln Cl ' Gly Gly Cheese Gly Gl ' Cl ' Sur Gly Gly Gly Sur Asn Cyc Sur Dlu Mut How many Asp Glu Dlu Dlu His His Leu Les Arg Poo Pro Tla Oro euu tyr Val Glu Gl ' Cl ' Gly Gly Cheese Poo Ul ' Glu Pro Cheese Uly Pro 1ll Sur Thr How many Tsn Oro Ssu Pro Poo Sur Les Glu Cheese His U'S Ssu Oro Asn Mut Ala Air Main Gly TAL ii Mut Peo Ala Phu Tli Sur Tli Piu Main Arg Arg Tla Gl ' Al ' Vai Uuu Vai Tla Cheese His euu Glu Sur POe Uuu Clu Val Srr Tyr (Arg Val Leu Arg His Uuu Ala Glu Pro Sru Gl ' Cl ' Sur Gly Gly Ssu Uln Cheese The Uuu euu U's Ssu Uuu Glu Main aai Trg Les Cle Gin Cl ' Asp Gly Tli Tla Luu Glu Glu Les Leu G'S Tli TAr Tyr Les euu C / s Shhh Oro Clu Clu Leu Val Leu Uuu Cl ' His Sru Leu Gly How many Poo Try Tla Oro Luu Ssu Sur C / s Pro Sur Cln Ala Leu Main euu ALa Clu G'S Uuu Sur Main Ueu His Cheese Gl ' Uuu PPe Leu Tyr Cln Gly Leu Ueu Main Ala Leu Ulu Gl | How many Sur Pro Glu Leu Gly Oro Background: Teu Cnp Air Uuu Main Uuu Ace?) Val Ala Tsp Phe (Tla Thr Ahr How many Tiy> Main Uln Underworld Glu Glu Leu Gl ' Mut Tli Cf. TCLa Leu Uln Cf. (SEQ DD No: 190)

Example 80

Construction pMON31109

The wpMON31109 gene was created with a new N-terminus / C-terminus using the method. III as described in materials and methods. A full-length gene was made with the new N-terminus / C-terminus of the hIL-3 receptor agonist pMON13416 and amplified from the intermediate plasmid, Syntan3, using primer sets 70 start (SEQ ID NO: 54) and 69 rev (SEQ ID NO: 55).

The obtained DNA fragment, which contains the new gene, was digested with NcoI and SnaBI endonuclease. The digested DNA fragment was dissolved on a 1% TAE gel, stained with Etidium bromide and isolated with Geneclean (Bio101, Vista, CA). The purified digested fragment was ligated into the expression vector pMON13189 using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). The dNa of pMON13189 was previously digested with NcoI and SnaBI to remove the pMON13416 coding sequence of the hIL-3 receptor agonist and a 4254 bp vector fragment was isolated using Geneclean (Bio101, Vista, CA) after dissolving on 0.8% TAE gel and staining with etidium bromide . Part of the ligation reaction mixture was used to transform DH5c cells of the E. coli strain (Life Technolpgies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON31109.

E. coli JM101 strain was transformed with pMON31109 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON31109 contains the DNA sequence of (SEQ ID NO: 91) which codes for the following amino acid sequence:

184 424

163

Asn Ali See A ^ l- lira Glu Ali Iie Iiu Arg Hapi Iiu Cln Pro Cys Liu Poo Sei Ola Cho Ala Ali Paro Sio Arg His Poo lii lle lle Iys Ali Giy Oc p Top Main Clu Phe Gog Glu Lys Iiu TAo Phe Tyr Iiu Vi1 TTh Oeu 1 ^ Gla. Ali Gin Clu Main Main Cly lly Giy Cheese lly lly Giy 0 rt, lly Gly: Cly Ssr olsn Cys Cheese lii Myth How much Asp llu Ili Ili Hii (Nov Leu Iys Arg Poo Paro Alu Poo How many Leu Asp Poo Asn Agp 0 eu Asn Asp Clu JAP Vi1 Cheese Iie Iiu Myth Asp Arg Asn Iiu Al] 0 Li Poo Asn Iru Giu Sio PPh Incl Aog Ali Val Iys Asn leu Main Ocr Vli Glu lly Giy lly Gly Axis Poo Gly Clu Poo Sio lly Poo OIe Sio Tina, III Ais Poo Cheese Pro Poo Sio Lys llu Sio iis Lys Her Poo Asn Myth Me TAo Main Oly? (Gla Myth Peo Ali Pooh Ali Srr Ala Par Main Aog Ai ^ g Ali Gly Cln Hal Iiu Vi1 AU a Sio iis Ler Olu Sio PPh Iiu Gla Vi1 Cheese Ots Arg Va1 Iru Aog iis Iru Ali Ole Poo Ssr lly Gly Sio Gly Giy Sio Cln Aug Phe Iiu leu Lys Her Iiu Main lln Incl Aeg Lys (In Main lly Asp lly Ali Ali Nov Main llu Lys Iiu Cgs Ali Thr Tcr Iys Iiu Gys His Poo Cil Main Oeu Vli Leu Iiu Gly iis Cheese Clu Giy Ili Poo Flail All Poo Lii Her Sio Cgs Poo Cheese ropes Ala Leu Cln Iru Ala lly Gys Iiu Cheese G ln Liu His Sio Gly Iiu PPe Cee Tyo Gin Cly Iiu How many lln Ala Oeu how many Gly lii Cheese Poo Glu Llu lly Poo TAo Leu Asp TAo Lira 0 Shh Iiu Asp Vi1 I and Asp PPe HAn Tho TAo lii Top Cln ropes Myth liu Clu Iiu Cly Myth Ali Poo Ali Iiu Cln Poo (SEQ

ID 10: 1915

Example 81

Construction of the pMON31110

A gene was created in pMON31110 with a new N-terminus / C-terminus using method III as described in Materials and Methods. A full-length gene with the new N-terminus / C-terminus of the hIL-3 receptor agonist pMON13416 was generated and amplified from the intermediate plasmid, Syntan3, using primer sets 91 start (SEQ ID NO: 56) and 90 rev (SEQ ID NO: 57).

The obtained DNA fragment, which contains the new gene, was digested with NcoI and SnaBI endonuclease. The digested DNA fragment was dissolved on a 1% TAE gel, stained with Etidium bromide and isolated with Geneclean (Bio101, Vista, CA). The purified digested fragment was ligated into the expression vector pMON13189 using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). The pMON13189 DNA was previously digested with NcoI and SnaBI to remove the pMON13416 coding sequence of the hIL-3 receptor agonist and the 4254 bp vector fragment was isolated using Geneclean (Bio101, Vista, CA) after dissolving on 0.8% tAe gel and staining with etidium bromide . Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON31110.

E. coli JM101 strain was transformed with pMON31110 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON31110 contains the DNA sequence of (SEQ ID NO: 92) which encodes the following amino acid sequence:

164

184 424

Ali Poo Cheese Arg His Piso lle How much lle Lus (li Gly Aup Gop Main CUu Phe Arg (lu Lys Luu Tho PPe rig Luu VII Thr Leu (lu Glu Ali Cln Glu. (ln Cln Gly Yew Gly Eto Gly Air Gly Ero Yew Gly yew Ero TAn Thousand Emo How many Pet How many Asp Glu lira How much His His Leu Lys Aog Pro Poo lii Piso Leu Leu Asp Piso Asn Asn Leu Asn Asp Clu Asp ViU Eto Ilr Lru Underworld Asp Aog Asn Lru Aog Lru Poo Ass Lru (lu Cheese pet TTiil Arg Ali Val Lys TAn Lru Glu Asn Ali Cheese Aly IlL GAu Ali Ilr Llu Aog Am Lru Main Poo Cys Lru Poo Cheese Ali Gho ALa rig VaU Glu Air Gly (lr Gly Eeo Pro Yew (lu Pro Ero (lS Piso IUr Eto Ttir How much Ais. Poo Cheese Poo Pro - Eto Lys Glu Ero His Lys Ero Pro Asn Mrt Ala ero Main Air Ala Underworld Poo Ala Phe Ali Eeo Gli Phr (ln Gog Aog Ali (lr Yew VII Lru Vil Ali Ero His Leu Aln Eto PPe Uru Glu VII Cheese Cyo Arg ViU Lru Arg His Leu Ala (ln Piso Cheese Cly Gly Eeo Gly Air Cheese (in Ero Phi: Uru Leu Lys Eto Ltu Glu Aln Val Gog Lys IlL Main Yew Asp Gly Ali Ali Luu Aln (lu Lus Eru Ces Ali Thr Cyo Lys Lru Thousand ΗΪΗ! Poo Clu Glu Lru Vai Luu Lru Gly His Cheese Lru Gly lie Poo Trp Ali Poo Ler Eto Eto Ces Poo Cheese (ls TALa Lru Main Leu Gli Gly Thousand Lru Cheese (ln Ltu HHi Ero Gly Ltu Phe Ltu Tyr Cln Yew Leu Leu (ln TALa Ltu Glu Gly lira Cheese Poo Glu Utu Gly Poo Gho Leu (sp Gho Luu Aln Ltu Asp Vi1 TALa Asp Phe Ali Thr Gho lie Trp Aln Cln Underworld (lu Clu Luu Yew Underworld Ali Pro Ali Leu (in Poo (SSQ

ID No: 192)

Example 82

Construction pMON31111

A gene was created in pMON31111 with a new N-terminus / C-terminus using method III as described in Materials and Methods. A full-length gene with a new N-terminus / C-terminus of the hIL-3 receptor agonist pMON13416 was generated and amplified from the intermediate plasmid, Syntan3, using primer sets 101 start (SEQ ID NO: 58) and 100 rev (SEQ ID NO: 59).

The obtained DNA fragment, which contains the new gene, was digested with NcoI and SnaBI endonuclease. The digested DNA fragment was dissolved on a 1% TAE gel, stained with Etidium bromide and isolated using Geneclean (Bio101, Vista, CA). The purified digested fragment was ligated into the expression vector pMON13189 using T4 DNA ligase (Boehringer Munich, Indianapolis, IN). The DNA of pMON13189 was digested, previously with NcoI and SnaBI, to remove the pMON13416 coding sequence of the hIL-3 receptor agonist and the 4254 bp vector fragment was isolated using Geneclean (Bio101, Vista, CA) after dissolving on 0.8% TAE gel and staining with bromide etidium. Part of the ligation reaction mixture was used to transform DH5? Cells of the E. coli strain (Life Technologies, Gaithersburg, MD). Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated and sequenced to confirm the correct insert. The obtained plasmid was designated pMON31111.

E. coli JM101 strain was transformed with pMON31111 for protein expression and protein isolation from inclusion bodies.

The plasmid pMON31111 contains the DNA sequence of (SEQ ID NO: 93) which encodes the following amino acid sequence:

184 424

165

Ali Vil Hy Aap Trp Gln Glu Gln Glu Ala Phe Arg Glu Lys Liu Thr Phe gsc Tyr Cheese Lei Gly Phr Llu Gin du Main on dy dy Gly Gly Sei Gly Gly dy Cheese Asn Cys Sir How much Underworld Iie Asp Glu How much How much His His Leu Lys Arg Drank Pro Ali Pro Liu Leu Asp Pro Asn Asn Liu Asn Asp Glu Asp Val Sir How much Liu Underworld Asp Arg Asn Liu Arg Liu Pro Asn Leu Glu Cheese Phe Val Arg Ali Val Lys Asn Liu du Aap ALa Ser Gly How much du Yep How much Liu Arg Asn Leu Main Pro Cys Liu Pro Ser Al ai Thr Ala Aa Pro Sir Arg His Pro How much How much How much Lys Tyr Vil du dy Gly Gly dy Sir Pro Gly Glu Pro Sir Gly Po 1li Ser Thr 11i Asn Paro Sir Pro Pro Cheese Lys Glu Sir His Lys Sir Pro Asn Underworld Ali Phr Main Gly Ali Underworld Pro Ali Pooh Ali Sei Ali Phe on Arg Arg Ala Gly Gly Val Leu VaS Ala Sir His Lii Gln Sir Phe Leu du Val Sir Tyr Arg Val Leu Arg His Liu AAl Gln Pro GGr Gly Gly Cheese Gly Gly Sir Main Cheese Phe Liu Liu Lls Leu cheese du Main Val Arg Lys How much Main Gly Asp Gly Ali Ali Liu Gln Glu Lys Leu Cys ALa Thr Tyr Lys Leu Cys Hii Pro Glu du Leu Vil Leu Leu Gly Kis Sir Liu dy lie Poo Trp Ali Pro Lii Cheese Cheese Ccs Pro Cheese Main Ali Liu Ha Leu Ala Gly Cys Liu Sei Gln Leu His Cheese Gly Leu Pooh Liu Tyr Main Gly Leu Liu Main AAa Leu Glu dl ^ 11i Cheese Pro Glu Liu Gly Pro Thr Leu Asp Thr Lii Gln Leu Asp Vai Yep Asp Pooh ALi Thr Thr Iie Tut » Main Main Underworld Glu Glu Leu Gly Me and Aa Pro ALi Liu Main Pro (SEQ ID No: 193)

Example 83

Construction of the pMON31112

Construction of pMON31112, a plasmid containing a DNA sequence encoding a multi-functional hematopoietic receptor agonist that activates the hIL-3 receptor and the G-CSF receptor. The plasmid DNA of pMON13189 was digested with the restriction enzymes NcoI and XmaI to give the NcoI, XmaI vector fragment, which was isolated and purified from a 0.8% agarose gel. DNA from the second plasmid pMON13222 (WO 94/12639), US serial number 08/411 796) was digested with NcoI and EcoRI to yield an NcoI, EcoRI fragment of 281 bp. This fragment was isolated and purified from a 1.0% agarose gel. Two oligonucleotides SYNNOXA1.REQ (SEQ ID NO: 240) and SYNNOXA2.REQ (SEQ ID NO: 241) were hybridized and ligated to the 281 bp DNA fragment from pMON13222 into the zpMON13189 DNA vector fragment. Part of the ligation mixture was then transformed into E. coli K-12 strain JM101. Transformed bacteria were selected in plates containing ampicillin. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of the EcoRV fragment and sequenced to confirm the correct inserts.

The plasmid pMON31112 contains the DNA sequence of (SEQ ID NO: 114) which encodes the following amino acid sequence:

MetAlaAsnCysSerAsnMetlleAspGluIlelleThrHisLeuLysGlnProProLeu

ProLeuLeuAspPheAsnHnLemAnGlyGluAspGlnAspI IclerMe LAspAsnAsn

LeuArgArgProAsnLeuGGcAAaPheAssArgAlaValLysSerLeuGlnAsinA-aSer

AlalleGluSerlleLeuLysAsnLeuLeuProCysLeuProLeŁUAaThrAlaAlaPro

ThrArAHisProIlHHSsIleLrsAspGlySppTrrAsnGluPheArgArALysLeuThr

PPeTyryluLysThrLeuduUArlAradnAradndnApsValdudydyGlydy

SirProGlyGluProSerGlyProIleSerThrIiAPsnProSirProProSirLysdu

SlrHisLysSerPooSSmMetAllThrGlnGlynlMetProMlPheZrLlSlrAlaPhl

GlnArAArgAA.aGlyGlyValLiuValAliSirHisLiuGlnSirPhiLeuGluValSir

TyrArAV ^: iLiuAc <^ I ^ i £ ^] ^ c ^ Lu ^ e ^ l3li ^ I? 3: (^ i5Sii: C ^ li ^ C ^ l; ^ i ^ ei: G] -yGl.ySirGl ^ nSir ^ I? Hi

LiuLeuLysSerLeuGluGlnValArgLysIleGlnGlyAspGlyAliAlaLeuGlnGlu

LysLiuCysAliThrTyrLysLiuCysHisProGluGluLeuValLeuLeuGlyHisSir

LiuG.lyll ^^ I ^ r ^ oPrrpAlaPrroI ^ euSirSii ^ CysPi ^ oSirGlnAliLiudnLiu.Ał.iGLy

CysLiuSerGlnLiuHisSirGlyLeuPhiLiuPyrGlnGlyLiuLiuGlnAliLiuGlu dyIleSerPruGluleudyPrτPhileAPspThrLeudnLeuAρpValAl; A.spPPl AlaTPrPdelIluLuPrAlAprPrudIlUlPro:

166

184 424

Construction pMON31113

Construction of pMON31113, a plasmid containing a DNA sequence encoding a multi-functional hematopoietic receptor agonist that activates the hIL-3 receptor and the GCSF receptor. The plasmid DNA of pMON1397 was digested with the restriction enzymes NcoI and XmaI to give the NcoI, XmaI vector fragment, which was isolated and purified from a 0.8% agate gel. DNA from the second plasmid pMON'3239 (WO 94/12639), US serial number 08/411 796) was digested with NcoI and EcoRI, yielding a NcoI, EcoRI fragment of 281 bp. This fragment was isolated and purified from a 1.0% agarose gel. The two oligonucleotics SYNNOXA1.REQ (SEQ ID NO: 240) and SYNNOXA2.REQ (SEQ ID NO: 241) were browned and ligated to the 281 bp DNA fragment from pMON'3239 into the zpMON13197 DNA vector fragment. Part of the ligation mixture was then transformed into E. coli K-12 strain JM101. Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of the EcoRV fragment and sequenced to confirm the correct inserts.

The plasmid pMON31113 contains the DNA sequence of (SEQ ID NO: 115) which codes for the following amino acid sequence:

MrPAllApnyypreoAsnMetllrAsoGlsllelluhhoHSpLrsLysGlnrorrorLes rorLusLruAsprheAseGρnLrsAsnrlyGlsAspGlnCnpllrLrseetGlsCpelρn LrsAugAonrorAsnLrsGlsAlGrAuAsnArnGlGallLypreoLrsGln.CρeCHGreo CUlllerlsSeollrLrsLysAsnUesLrsPorCysLesrorLrs1llTAo1lGAlGrrr hhoArnHiprurlluIlulluGonGsprlu1sphrp1serlsrhe1rn1unUysI · ushAu ^SreΊ, LoLruLyshhoLrsGlsAsnAllrlnAlGGlnGlnhyoallGlsGlyGlLrlyrlL SrorrrrlyGlsProSeoGlLroolluSeohArIluGpeProreoPorrroSurLLPrls eeoHSsLysruorrrGprieePCllhAorlerlyAlaMetrorGllPheGllrrr1llrAe GleCrn1on1 (GGHLrlyVαlLesVαHalαSurHrsLusGlnreoPAuLesGlsVαlSuu hyoAugallLes1onHSsLesAllGlePorhAoPrrLrsrlyror1llruorroLusror rlnrurrAuUusLusULsSuoUesGlsrleVal1rnLLPllerlnGlLlsprlyAll1la LesrlnGlsLysLrsyysAllThoTLoLLsLrsyLsHSsrorGlsGlsLesaGlUusLes rluHSseroLesrlyllurorTopAlGrorUesSuoruoCyprorrrorlnGlGLusGln LesCllGlyCLsLrsreorlnLrsH. ^ SSerClLLtsPhrLesTyorinriLLesUesrin GllLesGlsGlyllereororGlsLrsGlyrorhAoUusAsohAoLrsGlnLesCppaGl GlaasprhrAlGhAohArllrhopGlnGl: neetrlsrlsLrsrluertAlαPorAllLrs Gleror (SEQ ID No: 200)

Example 85

Construction pMON31114

Construction of pMON3U 14, a plasmid containing a DNA sequence encoding a multi-functional hematopoietic receptor agonist that activates the hIL-3 receptor and the GCSF receptor. The plasmid DNA of pMON13989 was digested with the restriction enzymes NcoI and XmaI to give the NcoI, XmaI vector fragment, which was isolated and purified from 0.8% agatose gel. DNA from the second plasmid pMON'3239 (WO 94/12639), US serial number 08/411 796) was digested with NcoI and EcoRI, yielding a NcoI, EcoRJ fragment of 281 bp. This fragment was isolated and purified from 1.0% agatose gel. Two SYNNOXA1.REQ oligonucleotides (SEQ ID NO: 240) and SYNNOXA2. REQ (SEQ ID NO: 241) was homegrown and ligated with the 281 bp DNA fragment from pMON13239 into the vector DNA fragment from pMON1389. Part of the ligation mixture was then transformed into E. coli K-12 strain JM101. Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of the EcoRV fragment and sequenced to confirm the correct inserts.

The plasmid pMON3n14 contains the DNA sequence of (SEQ ID NO: 116) which encodes the following amino acid sequence:

184 424

167

MePrHGAsnCysruoAseMePIlrAPoGlsllellehAoHSsLesLysrlnSorrorLes

PorLrsLes1ρprAe1snAsnLrsasnGlyGls1soGlnGspllrUesMrtGlsGseAsn

Les1onAogror1snLesrlsGllrheCpnAog1lαVllLyserrLesrlnCpn1lαruo

CHlllerlseeolleLesLysAsnLruLrurorCysLesrorLrsAllhhoCUlCUlPor hAoAonHSsrorllrllelleAogAspGlyAspTrpAsnrlsrAe1ogAunLypUeshAo PrrhyrLesLysTAoLrsrls1seGlarleCHGGlnGlnTyoallrlsrlyrlyGlLrly ruoProrlyGlsPorruorlLrrrllererTAoIl <uapnrorSuororPurSerUypGls SeoHSpULsSeoPrrApeeuPAllThrGlnGlyAlaeetrrrCHlPAuAlGS.ur1lαrnu GlnAog1ogCHarlyGlyaalLrsaalCHaSeoHSsLesGleeeorheUrsrlsValreo hyoGogaGlLesAogHipLesCHlGlnPoreroGlyrlyeeorlyrlyrrorleSeorAu LesLesLyprroLesGlsGleaGl1onLysllrGleGlyCPoGlyaHaClGLrsrleGls LLsLrsCysCHlhhohyoLysUesCysHSprorGlsGlsLesallLrsLesrlyHSsreo LesrlyllrrorhooAlαrorLeseeorerCypS: loruoGlnAlGLesrlnLesAlαrly CysLrsreoGlnLrsHiseroGluLrsrAeLrslLorlnrlyLrsLrsGlnGllLesGls GlylleruororGlsLesGlyrorTAoLrs1solArUusrleLrsCnoVGlCHlAsorAe 1llhhohAollrToprleGlnMutGlsGlsLesGlLertCHlror.CllLesrlnPor (SEQ ID NO: 201)

Example 86

Construction of the pMON31115

Construction of pMON3łł5, a plasmid containing a DNA sequence encoding a multi-functional hematopoietic receptor agonist that activates the hIL-3 receptor and the G-CSF receptor. The plasmid DNA of pMON13197 was digested with the restriction enzymes NcoI and XmaI to give the NcoI, XmaI vector fragment, which was isolated and purified from a 0.8% agarose gel. DNA from the second plasmid, pMON'3222, was digested with NcoI and EcoRI, yielding a 281 bp NcoI, EcoRI fragment. This fragment was isolated and purified from 1.0% agatose gel. Two oligonucleotics SYNNOXA1.REQ (SEQ ID NO: 240) and SYNNOXA2.REQ (SEQ ID NO: 241) were hybridized and ligated to the 281 bp DNA fragment from pMON'3222 to the zpMON13197 DNA vector fragment. Part of the ligation mixture was then transformed into E. coli K-12 strain JM101. Transformed bacteria were selected on plates containing ampicillin. Plasmid DNA was isolated, analyzed by restriction analysis to show the presence of the EcoRV fragment and sequenced to confirm the correct inserts.

The pMON3n 15 plasmid contains the DNA sequence of (SEQ ID NO: 117) which codes for the following amino acid sequence:

eutAllCpeCysSurApneetIle.apoGlsIlullehAoHSsLesLyρGlnrroPrrLus rorLrsUes1sprAe1peGsnUrs1serlyGlsGsoGleGsolleLrseutGsp1sn1sn

LusAonGogror1snLrsGlsAllSheAseAonaHlallLypreoLesGlnCpn1Uleeo

AlGIlerlsrerlluUesULPCpeLusUusProyysUesPorLus1lGhAoAll1lGPrr hhr1ogHSprorllrHislleLysGρorlylPoTooCnnGlsrhr.ConAonLysLeshho rAehyoLrsLyshAoLrsGlsAse1lGGleAllGlerlehyoallrlsGlLrlyGlyrly ruororGlyrlsrrrreorlLrorlleSeoTholleAserorerororrorreoUyρGls reoHisLypee: lPrrAs] neetAllThoGlnGlyAlaerProrAllPheAllrro1llPAe GleAogAonAllGlyGlyVllLrsallAllrroHSpLrurlerrorArLusGlsallrro hLo1rnVαlLusAunHSsLes1lGGlePrrhAoPorLusrlLrrrAlarurSurLusPro rlneroPhrLrsLesLysrroLesrlsGlnalUCogLysllrGlnrlLAnpGlyAlGlll LrsGlnGlsLLSLusyLsAlαhAohyoLysLruCyρHSsrorGlsGlsUusaGlUusLrs GluHSsSroLeuGlyllerorhooGllPrrLrserorroCysPorreoGle1lGLusrln LusGllrlyCysLesreorleLusHSsruorluLeu.PheLesTLrGlnrlyLesUusGln CHlLrsrlsGlyIleeeororrlsLesrlyrorhhoLruAspThoLusGlnUesAppall .ClaanorAeAlαhAohAolleToorlnGleMetGluGlsLesGlyIeePTHarorAlaLrs GlnPor (SEQ ID N0: 202)

168

184 424

Example 87

Determination of the in vivo activity of the multifunctional hematopoietic receptor agonist proteins

The concentration of the multifunctional hematopoietic receptor agonist protein can be determined using a sandwich ELISA based on the affinity of the purified polyclonal antibody. Alternatively, protein concentrations can be determined by amino acid composition analysis. The bioactivity of a multi-functional hematopoietic receptor agonist can be determined in a number of in vitro assays. For example, a multi-functional hematopoietic receptor agonist that binds the hIL-3 receptor and the G-CSF receptor can be assayed in cell proliferation assays using cell lines expressing hIL-3 and / or G-CSF receptors. One such assay is the AML-193 cell proliferation assay. AML-193 cells respond to IL-3 and G-CSF which allow the determination of the combined bioactivity of the agonist at the multifunctional IL-3 / G-CSF receptor. Another such assay is the TF1 cell proliferation assay.

In addition, other factor dependent cell lines such as M-NFS-60 (ATCC.CRL 1838) or 32D which are an IL-3 dependent murine cell line can be used. IL-3 activity is species dependent while G-CSF is not, so the bioactivity of the G-CSF component of the IL-3 / G-CSF multifunctional hematopoietic receptor agonist can be determined independently. Cell lines, such as BHK or murine Baf / 3, that do not express the receptor for a given ligand can be transfected with a plasmid containing the gene encoding the desired receptor. An example of such a cell line is BaF3 transfected with the hG-CSF receptor (BaF3 / hG-CSF). The multifunctional hematopoietic receptor agonist activity in these cell lines can be compared to hIL-3 or G-CSF singly or together. The bioactivity of examples of the multi-functional hematopoietic receptor agonists of the present invention as determined in the BaF3 / hG-CSF cell proliferation and 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 to the pMON13056 standard protein (WO 95 / 21254). The bioactivity of examples of the multi-functional hematopoietic receptor agonists of the present invention as determined by the BaF3 / c-mpl cell proliferation and TF1 cell proliferation assays are shown in Table 7 and Table 8.

Table 5

Cell proliferation activity of IL-3 / G-CSF double agonists

pMON BaF3 receptor / hG-CSF receptor cell proliferation assay Relative activity * TF1 cell proliferation assay Relative activity * 1 2 3 13182 0.015 1.1 13183 0.02 n / a 13184 0.01 0.3 13185 0.023 0.36 13186 0.36 0.45 13187 0.07 0.26 13188 0.64 1.3 13189 0.58 1.37 13190 0.045 1.2 13191 0.14 2.7 13192 0.09 2.2

184 424

169 cd. table 5

1 2 3 13193 0.06 3.0 25190 n / a n / a 25191 0.43 1.2 13194 n / a n / a 13195 1.3 4.3 13196 0.66 0.5 13197 0.6 0.77 13198 0.6 0.5 13199 n / a n / a 15982 0.7 1.9 15981 0.068 12 15965 0, 0.82 15966 0.36 148 15967 0.62 1.37

nd = oii determined * The igoniSy bioactivity of the hematopoietic reIester is expressed by sii (iko relitic activity in comparison to Oilkiim otylldredeym slMON13056. o = (uo iięSzaa.

Table 6

Cell proliferation activity of 1L-3 / G-CSF double agonists

pMON BaF3 receptor cell proliferation assay / hG-CSF relative activity TF1 cell proliferation assay Relative activity 31104 + + 31105 + + 31106 + + 31107 n / a n / a 31108 + + 31109 + + 31110 n / a n / a 31111 n / a n / a 31112 + + 31113 + + 31114 + + 31115 + + 31116 n / a n / a 31117 n / a n / a

170

184 424 nd = not specified + Birιkpwność Al = I lob 2) ιsrLisp kowiopiso reeepton wieloszz / carriersweso w / nża n ii i jko act / relittuna versus n pilkin npιLdιldzν'm nMON 13056.

"+" Indicates that Al npartetzki I / li norówe / wilni n pMON 13006.

Table 7

pMON BaF3 receptor cell proliferation assay / hG-CSF activity * Assay of TF1 cell proliferation activity 28505 - + 28506 - + 28507 - + 28508 - + 28509 - + 28510 - + 28511 + + 28512 + + 28513 + + 28514 + + 28519 - + 28520 - + 28521 - + 28522 - + 28523 - + 28524 - + 28525 + + 28526 + + 28533 - + 28534 - + 28535 - + 28536 - + 28537 + 28538 - + 28539 + + 28540 + + 28541 + + 28542 + + 28543 + + 28544 + + 28545 + +

* Activity measured in I and II cellular Bif3 PoιLSeLkwιnLj uLepterlm c-mpl, in stsssks to l inindi c-mpl (1-103).

+ Activity measured in ntessnks to p ^ MON ^ O ..

184 424

171

Other factor-dependent cell lines known to those skilled in the art can similarly be used to measure the bioactivity of a desired multifunctional hematopoietic receptor agonist. The methylcellulose assay can be used to determine the effect of multifunctional hematopoietic receptor agonists on the expansion of hematopoietic parental cells and the pattern of different types of hematopoietic colonies in vitro. A methylcellulose assay can provide an estimate of the precursor frequency as the frequency of parental cells is measured per 100,000 input cells. Long-term stromal dependent cultures were used to identify primary hematopoietic parental cells and / or stem cells. Additionally, limited dilution of the culture may be performed, which will indicate the frequency of primary parental cells stimulated by the multi-functional hematopoietic receptor agonists.

Table 8

pMON # 1L-3 agonist activity (AML cell proliferation assay) C-mpl receptor agonist activity (Baf / 3-c-mpl cell proliferation assay) 28505 + - 28506 + - 28507 + - 28508 + - 28509 + - 28510 + - 28511 + + 28512 + + 28513 + + 28514 + + 28515 + + 28519 + - 28520 + - 28521 + - 28522 + - 28523 + - 28524 + - 28525 + + 28526 + + 28527 + + 28528 + + 28529 + + 28535 + - 28539 + + 28540 + + 28541 + + 28542 + + 28545 + + 28551 + + 28571 + +

Example 88

G-CSF variants that contain single or multiple amino acid substitutions have been generated using PCR mutagenesis techniques as described in WO 94/12639 and WO 94/12638. Tc and other variants (i.e., amino acid substitutions, insertions or dclections, and N-terminal or C-terminal extensions) also can be made by one skilled in the art using a variety of other methods, including assembly of a synthetic gene or site-directed mutagenesis (see Taylor et al. , Nucl. Acids Res. 13: 7864-8785 [1995]; Kunkel et al., Proc. Natl. Acad. Sci. USA, 82: 488-492 [1985]; Sambrook et al., Molecular Cloning:

172

184,424 a Laboratory Manual, 2nd edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, [1989], (WO 94/12639) and (WO 94/12638)). These substitutions may be made at one time or in combination with other amino acid substitutions and / or deletions and / or insertions and / or extensions. After the sequence is verified for changes, the plasmid DNA can be transferred into an appropriate mammalian cell, insect cell, or bacterial strain such as E. coli for production. Known G-CSF variants that are active include substitutions at position 1 (Thr to Ser, Arg or Gly, 2 (Pro to Leu), 3 (Leu to Arg or Ser), and 17 (Cys to Ser), and amino acid deletions 1-11 (Kuga et al., Biochemical and Biophysical Research Comm. 159: 103-111 (1989)). These amino acid substitutions can be used as a template for the formation of G-CSF receptor agonists in which a new N-terminus and terminus are formed. C. Examples of G-CSF amino acid substitution variants are shown in Table 9.

Example 89

Determination of the bioactivity of G-CSF amino acid substitution variants

G-CSF amino acid substitution variants can be assayed for proliferative activity using the Baf / 3 cell line transfected with the human GCSF receptor. The bioactivities of exemplary variants of G-CSF amino acid substitutions are shown in Table 9 relative to native human G-CSF. "+" Indicates comparable activity to the native one and indicates a significantly reduced or no measurable activity.

Table 9

Cell proliferation activity of G-CSF variants in the Baf3 cell line transfected with human G-CSF receptor

Item aa Native aa Mutant aa Activity * 1 2 3 4 13 Phe Cheese + 13 Phe His + 13 Phe Thr + 13 Phe Pro + 16 Oys Pro + 16 Lys Cheese + 16 Lys Thr + 16 Lys His + 18 Leu Pro + 18 Leu Thr + 18 Leu His + 18 Leu Cys + 18 Leu How much + 19 Glu Ala - 19 Glu Thr - 19 Glu Arg - 19 Glu Pro - 19 Glu Leu - 19 Glu Cheese -

184 424

173 cd. tbul 9

1 2 3 4 22 Arg Tyr + 22 Arg Cheese + 22 Arg Ala + 22 Arg Thr + 24 How much Pro + 24 How much Leu + 24 How much Tyr + 27 Asp Gly + thirty Ala How much + thirty Ala Elu + 34 Lys Cheese + 43 His Gly + 43 His Thr + 43 His Val + 43 His Lys + 43 His Trp + 43 His Ala + 43 His Arg + 43 His Cys + 43 His Leu + 44 Pro Arg + 44 Pro Asp + 44 Pro Val + 44 Pro Ala + 44 Pro His + 44 Pro Main + 44 Pro Trp + 44 Pro Gly + 44 Pro Thr + 46 Glu Ala + 46 Glu Arg + 47 Leu Thr + 49 Leu Phe + 49 Leu Arg + 49 Leu Cheese +

174

184 424 cd. table 9

1 2 3 4 50 Leu His + 54 Leu His + 67 Main Lys + 67 Main Leu + 67 Main Cys + 70 Main Pro + 70 Main Leu + 70 Main Arg + 70 Main Cheese + 104 Asp Gly + 104 Asp Val + 108 Leu Ala + 108 Leu Val + 108 Leu Arg + 108 Leu Gly + 108 Leu Trp + 108 Leu Main + 115 Thr His + 115 Thr Leu + 115 Thr Ala + 144 Phe His + 144 Phe Arg + 144 Phe Pro + 144 Phe Leu 4- 144 Phe Glu + 146 Arg Main + 147 Arg Main + 156 His Asp - 156 His Cheese + 156 His Gly + 159 Cheese Arg + 159 Cheese Thr + 159 Cheese Tyr + 159 Cheese Val + 159 Cheese Gly +

184 424

175 cd. table 9

1 2 3 4 162 Glu Gly - 162 Glu Trp + 162 Glu Leu + 163 Val Arg + 163 Val Ala + 163 Val Gly + 165 Tyr Cys n / a 169 Cheese Leu + 169 Cheese Cys + 169 Cheese Arg + 170 His Arg + 170 His Cheese +

* Activity in nesssks after n it / wieno I G-CSF nd = n s underlining

Without further processing, 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, intended to be illustrative only, and not intended to limit the remainder of the description in any way.

More details regarding the technique of molecular biology, protein purification, and biological assays can be found in WO 94/12639, WO 94/12638, WO 95/20976, WO 95/21197, WO 95/20977, WO 95/21254, which are incorporated herein by reference. the whole as a reference.

All references, patents, or applications cited herein are included in their entirety as written herein.

Various other examples will be apparent to those skilled in the art upon reading this specification, without departing from the spirit and scope of the invention. It is intended that all such other examples are included within the scope of the appended claims.

176

184 424

SEQUENCE (1) GENERAL INFORMATION:

(i) APPLICANT (1) NAME: & Co.

(B) STREET: POBox 5110 (y) Mlmo: enscino (D) STATE: lllSerSp (E) COUNTRY: Stin / United States ΑβΟ / 'ή (F) ZIP CODE (ZlP): 60580 (G) PHONE: (^^ ^) 470-6501 (H) 1ELEF1X: (708)470-6881 (I) NAME: MrnsaePr Company (B) STREET: 800 Nonte Liedunbuun Bosluvand (C) MlAnO: SP. Losis (D) ΠΙΠ: MSpprsuS (E) COUNTRY: United States of America Amur / ki (F) ZIP CODE (ZIP): 63167 (G) PHONE: (314)647-3131 (H) 1EUEFCX: (314)694-5435 ( SS) TITLE OF THE INVENTION: hematopoietic anesthetic / cn uucupPrn multifunctional / cn (iSS) NUMBER OF SEQUENCES: 258 (iv) COMPUTER READABLE FORM:

(A) MEDIA TYPE: D / skrutka (B) COMPUTER: krmoaPLbSle / z IBM PC (C) OPERATING SYSTEM: Py-DOr / Mr-DOS (D) PROGRAM: ΡιΡμΡΙι Ruluasu # 1.0, VurpSrn # 1.30 (EPO)

184 424

177 (2) INFORMATION ABOUT rEQ ID No: 1:

(i) SEQUENCE FEATURES:

(A) LENGTH: 174 amino acids (B) CYP: amino acid (C) NUMBER OF THREADS: unknown (D) TOPOLOGY: unknown (ii) TYPE OF PARTICLE: protein (ii) FEATURE:

(A) NAME / KIT: Modified site (B) LOCATION: 1 (D) OTHER INFO: / note = “Xaa in position 1 is CAr, See, Aog, Tyr or Cly;

(ii) FEATURE:

(A) NAME / KEY: Modified site (B) LOCATION: 2 (D) OTHER INFO: / note = "Xaa in position i 2 is Pro or Leu;

(hH) FEATURE:

(A) NAME / KEY: Modified site (B) LOCATION: 3 (D) OTHER INFO: / note- “Xaa in position 3 means Liu, Gog, Cyr or Sir;

(ii) FEATURE:

(A) NAME / KEY: Modified site (B) LOCATION: 13 (D) OTHER INFORMATION: / Notes ^ "aii in position 13 means Ple, Siog His, TAo or Ρο ';

(Hi) FEATURE:

178

184 424 (A) NAME / KUU / Z: Site modified (B) LOCATION: 16 (D) DNNE INFORMATION: / note = "Xaa at position 16 is Uys, Oro, Sur, Thr or Hi ?;

(ii) TETHT:

(A) NAME / KUU / Z: Site modified (B) LOCATION: 17 (D) DNNE INFORMATION: / note = "Xaa at position 17 is Cyn, Sur, Uly, Tla, Ilu, Tyr or Tog;

(ii) FEATURE:

(A) NAME / KUU / Z: Site modified (B) LOCATION: 18 (D) OTHER INFORMATION: / note = "Xaa in ppzycci 18 means Uru, Tir, Pro, His, Dlu or Ay ?;

(ii) / ECHA:

(A) NAME / KUU / Z: Site modified (B) LOCATION: 22 (D) I1 OTHER INFORMATION: / note = "Xaa in ppsycCi 22 is Arg, Tyr, Sur, Thr or Ala;

(ii) TETHT:

(A) NAME / KEY: Site modified (B) LOCATION: 24 (D) OTHER INFORMATION: / note = "Xaa in ppsy'Ci 24 means lira, pro, tyr or ueu;

(ii) / ECHA:

(A) NAME / KUU / FROM: Site modified (B) LOCATION: 27

184 424

179 (D) OTHER INFORMATION: "Xaa at position 27 is Asp or Tly;

(SS) GE.GSIA:

(l) NAME / KEY: Modified site (B) POSITION: 30 (D) ΙΜΓΕ INFORMATION: / note = “Xaa at position 30 is Ala, Ile, Leu or Gly;

(SS) CECSA:

(G) NAME / KLUGZ: MSejscr modified · (B) LOCATION: 34 (D) HNN INFORMATION: / note = "Xaa at position 34 is Lys or Seo;

(SS) CEGSSA:

(A) NAME / KLUGZ: Modified site (B) POSITION: 33 (D) OTHER INFO: / note = "Xaa in item 36 is Cys or Ser;

(SS) CECSA:

(l) NAME / KEY: Modified site (B) LOCATION: 42 (D) IHNE INFO: / uuaaa = “Xaa at position 42 is Cys or Ser;

(Si) CECSA:

(A) NAME / KEY: Modified location (B) LOCATION: 43 (D) OTHER INFORMATION: // note ,, Xxa in posy ^ j 413 means SSs, Cho, Gly, aal, Lys, hop, Ala, Arg, Cys or

Ueu;

180

184 442 (ii) FEATURE:

(1) NAME / KEY: Modified MStjsct (B) POSITION: 44 (D) OTHER INFORMATION: Ouwaca ^ ·. Wan w po zycjW po means Pro, Glu, Pieg, Asp, Val, Ala, His, Trpn Gin lsjb ino;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) LOCATION: 46 (D) OTHER INFORMATION: OuMAga = ..Wan in po life means Gis, Arn, Phe, lun, lit or Ala;

(ii) FEATURE:

(1) NAME / KEY: modified eSujpcu (B) LOCATION: 47 (D) OTHER INFORMATION: / note- “Xaa in item 44 means Lus lsb IAo;

(ii) FEATURE:

(A) NAME / KEY: Modified order (B) LOCATION: 49 (D) OTHER INFO: / note— “Xaa w poruji 49 means Uts, PAu, lun lsb Stu; ' (SS) CECili:

(C) NAME / KEY: Modified MSujscu (B) POSITION: 50 (D) ILNiE IeNFί ^: ReACaE: / uswvin = ,, Xaa w poruji 55) means Uus, Ilt, His, Poo lsb I / o;

(ii) FEATURE:

(A) NAME / KEY: Site modified

184 424

181 (B) LOCATION: 54 (D) OTHER INFO: / note = "Xaa at position i 54 is Luu or HSs;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) LOCATION: 64 (D) OTHER INFORMATION: u note a-o, Xaa in item i 64 means Tys or Su ;;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) LOCATION; 67 (D) NO INFO: / Note = "Xaa at position 66 is Gln, Uys, Lru or Tys;

(ii) FEATURE ::

(A) NAME / KEY: Site modified (B) POSITION: 07 (D) IlNiE INFORMATION: / Note = “Xaa at position 70 is Tln, hro, Lru, Arg or Ser;

(ii) TECHA:

(A) NAME / KEY: Site modified (B) LOCATION: 74 (D) line INFORMATION: / note = "Xaa in item 67 means Cys or Se ;;

(ii) TETHA:

(A) NAME / KEY: Site modified (B) LOCATION: 104 (D) OTHER INFORMATION: / note = “Xaa at position 104 is Asp, Tly or Val;

182

184 424 (ii) GEGiA:

(A) NAME / KEY: Site modified (B) POSITION: 108 (D) OTHER INFORMATION: / uwiGa = "aia at position 108 is Iru, Ala, Val, Arg, Trp, Cln or lly;

(Hi) FEATURE:

(A) NAME / KEY: Modified site (B) LOCATION: 115 (D) OTHER INFORMATION: / operating- "aai at position 115 is TAr, iis, Leu or Ala;

(ii) GEGiA:

(A) NAME / KEY: Modified site (B) LOCATION: 120 (D) OTHER INFORMATION: / Rig ^ "Xao at position i 1 ^ 0 is Glu. Glys OA ^ g, Lys Oiu Hiss (ii) GEGiA:

(Α) NAME / KEY: Modified site (B) LOCATION: 123 (D) OTHER INFORMATION: / laaGa = "Xaa in item i 1) 4) 3 is Glu, Aog, PAi or TAr;

(ii) FEATURE:

(A) NAME / KEY: Site Modified (B) LOCATION: 144 (D) OTHER INFORMATION: / the Xaa at position 144 means Phi, Hii, Aig, Pro, Lite, Glu Oiu Olu; and (ii) FEATURE:

(A) NAME / KEY: Modified location (B) POSITION: 146

184 424

183 (D) IINJE DNFORMT / JE: / note = and "Xaa at position 116 is Trg or Ain;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) LOCATION: 147 (D) OTHER INFORMATION: / note = “Xaa at entry 144 is Trg or Uln;

(ii) TETHT:

(A) NTZWT / KUU / Z: Place msdrfSkowasu (B) LOCATION: 156 (D) IITTE INFORMATION: / note = "Xaa at position 156 is His, Aly or Sro;

(ii) AE / HA:

(A) NAME / KUU / Z: Site modified (B) LOCATION: 159 (D) IITTE INFORMATION: / note = “itm w po zycj i 159 means Sur, Arg, Aho ', Tyr, Val or Gly;

(ii) / ECHA:

(A) NAME / KUU / Z: -Μί ^ Ξοβ modified (B) LOCATION: 162 (D) IINJE INFORMATION: / note = 'Xaa at position 162 is Ulu, Uuu, Uly or Trp;' (ii) FEATURE:

(A) NAME / KUU / Z: Site modified (B) LOCATION: 163 (D) OTHER INFORMATION: / note = "Xaa in position 1 ^ 23 is Val, Uly, Trg or Tla;

(ii) TETHT:

184

184 424 (A) NAME / KEY: Modified site (B) LOCATION: 169 (D) OTHER INFORMATION: / GWiHa = "Xaa at position 169 is Arg, Seo, Ueu, Aog or Ty-s;

(ii) FEATURE:

(A) NAME / KEY: Modified site (B) POSITION: 170 (D) OTHER INFORMATION: / GwaHa = "Xaa at position 170 is His, Arg or Euo;

(ix) SEQUENCE DESCRIPTION: EEQ ID No: 1:

Xii Xii Xxi Ply Pro Backdrop by Cli Lem Pro G1n Ueu XaaLeu Le, Xaa 15 1P 15

Xii Xii GAu Pin Vri AaV ips Xai GUs Ply Xaa Cln AlaXaa ii, Gln twenty 255 230 Clu Xli Luu Xaa Ala Tho Tyr Lys Leu Xaa Xaa Xaa Ginu Xa ^ a XXa Val 35 40 45 Xii Xii GAy His Cheese Xii Gly lie Pro Trp Ala Pop Leu Cheese Cheese Xaa 50 5A 60 Poo Ero Xaa Ala Flax Aau Uv u To me Gly Yeah Le u Aur Main Leu Nov About vr 65 7 A. 75 80 Aly Leu PPe Leu Tur But OP y Aus Leu Aln Al a Ueu Glu G Ay how much U, r 85 900 935 Poo Clu Luu Gly Pro Thr op u Tao Thr Leu G1 n Aro Asp Upl ASx Acp 100 105 110 Phe Ala Xia Tho How much Top Cln Cln Underworld Alu Xii Xia Aly Underworld (la Pro 115 12Ń 125 Ali Lru Cln Poo Tho Aln Cly Ala Underworld Poo Ali Phe Ali Eeo Ala Xia 130 135 140 Aln Xia Xii Ali Yew Cly VII Utu Vil Ali Emo Xia Uru Cln Xaa Phe 145 150 155 160

Ueu Xia Xaa Eer Tyg Aog VaU Lru Xai Xia Ueu (la Aln Poo

184 424

185

165

170 (2) INFORMATION ABOUT SEQ ID NO: 2:

(S) SEQUENCE FEATURES:

(A) LENGTH: 133 amino acid / (B) TYPE: amino acid (C) QUANTITY of NlCl: single / n (D) TOPOLOGY .: linS (ii) TYPE OF PARTICLE: biikko (ii) FEATURE:

(1) NAME / KEY: Site modified (B) LOCATION: 17 (D) OTHER INFORMATION: / swani = "Xll in item 17 means Stu, L / s, Gl /, Asp, MuP, Gln lsb Aog;

(ii) FEATURE:

(A) NAME / KEY: Modified site (B) POOOOENIII: P8 (D) OTHER INFORMATION: Suwaaa- "Xil at position 18 is Asn, His, Lus, lithium, PAu, Ann Isb Gin;

(ii) FEATURE:

(A) NAME / KEY: Modified MiuiPju (B) LOCATION: 19 (D) ILNiE INFORMATION: / swia <aa = “Xaa at position 19 oznicza Met, PAu, Ilt, Aon, Gly, Ala lsb C / s;

(ii) FEATURE:

(A) NAME / KEY: Place mod / fictitious (B) LOCATION: 20 (D) OTHER INFORMATION: / note- ,, Xaa at position 20 characters lle, Cys, Gin, Gls, Ars, Poo or Ala;

186

184 424 (ii) GNASl:

(A) NAME / KEY: Modified location (B) LOCATION: 21 (D) OTHER INFORMATION: / note = "Xaa in position 21 means Asp, Phe, Lys, Arg, Ala, Gly, Glu, Tln, Asg, Ceo,

Seo or aal;

(ii) CECSA:

(A) NAME / KEY: Modified site (B) LOCATION: 22 (D) OTHER INFORMATION: / note ^ "Xaa at position 22 means Glu, Top, Poo, Ser, Ala, SSs, Asp, Asn, Gln, Leu, aal or Tly;

(ii) CECSA:

(A) NAME / KLUGZ: Modified site (B) LOCATION: 23 (D) I ^ NEE I INFORMATION: / note = "Xxa in position 23 is Ile, aal, Ala, Gly, Top, Lys, Phe, Ueu, Seo or

Aog;

(SS) CECSA:

(A) NAME / KEY: Modified site (B) LOCATION: 24 (D) IlNN INNFRMMCCE: / note ^ ,, Xxa at position 24 is lle, Gly, Ul, Aog, Seo, Phe, Ueu;

(ii) CNCSA:

(l) NAME / KEY: Modified site (B) LOCATION: 25 (D) HNN INFORMATION / NOTE = "Xxa at position 25 is peo, Sis, Tly, Tln, Crg, Poo or Ala;

184 424

187 (ii) TETiA:

(A) NAME / KIT: Modified site (B) LOCATION: 26 (D) OTHER INFORMATION: / uwigi ^ "Xii at position 26 means iis, · Thr, PAr, Cly ?, log, Ali, Trp;

(Hi) TETiA:

(C) NAME / KEY: Modified site (B) LOCATION: 27 (D) OTHER INFORMATION: / aia at position 27 is Iru, Gly, Aog, Thr, Sie or Ala;

(ii) FEATURE:

(A) NAME / KEY: Modified site (B) LOCATION: 28 (D) OTHER INFORMATION: / note = "Xaa at position 28 is Lys, ArG, Leu, Clu, Cly ?, Pro, Val or Top;

(ii) TECiA:

(A) NAME / KEY: Modified site (B) LOCATION: 29 (D) OTHER INFORMATION: / note = "Xaa at position 29 means Glu, Asn, Leu, Pro, Arg and Val;

(li) FEATURE:

(A) NAME / KEY: MedyfSkewanu site (B) LOCATION: 30 (D) OTHER INFORMATION: / note = "Xaa at position 30 means Pro, iis, TAe, Cly ?, Asp, Ceu Srr, Leu or I ... ;

(li) GEGiA:

(A) NAME / KEY: Site modified (B) LOCATION: 31

188

(D) ANOTHER INFORMATION "Xxa at position 31 is Poo, Asp, Tly, Ala, Arg, Lru or Tln;

(ii) FEATURE ::

(A) NAME / KEY: Mirjncu modified (B) LOCATION: 32 (D) OTHER INFORMATION o / Note = “Xxa at position 32 is Leu, Val, A; g, Tln, Asn, Tly, Ala or Tlu;

(ii) TE CHA:

(A) NAME / KEY: Site modified (B) LOCATION: 33 (D) OTHER INFORMATION o / note “Xxa at position 33 means Pro, Luu, Tln, Ala, Th; or Tlu;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) LOCATION: 34 (D) OTHER INFORMATION o / note = "Xaa at position 34 means Lru, Val, Tly, Sur, Uyn, Glu, Tln, Thr, Arg, Ala,

Phu, lir or Mrt;

(ii) CECHA .:

(A) NAME / KEY: Site modified (B) POSITION: 35 (D) IiNŁ INFORMATION o / note = "Xxa at position 35 is Luu, Ala, Tly, Asn, Pro, Tln or Val;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) POSITION: 36 (D) IlNŁ INFORMATION o / note = "Xxa at position 36 means lnpi, Uru or Val;

184 424

189 (ii) TE / HA:

(A) NAME / KEY: Site modified (B) LOCATION: 37 (D) IDTE INFO: / note = “Xaa w means Phu, Sur, Pro, Trp or Ilu;

(ii) TEAHA:

(A) NTZWT / KUCZ: Modified site (B) LOCATION: 38 (D) OTHER II ^] ^ O1RM ^ (GJE: / note = “Xaa w is Tsn or Tla;

(ii) FEATURE:

(A) NTZWT / KUU / Z: Modified site (B) LOCATION: 40 (D) IINJE INFORMATION: / note = “Xaa w is Uuu, Trp or Arg;

(ii) FEATURE:

(A) NAME / KUU / Z: Modified site (B) LOCATION: 41 (D) Iirr INFORMATION: // Lwaga = "Xaa w means Tsn, Ty ?, Arg, Uru, His, Met or Pro;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) LOCATION: 42 (D) IDNo DNFORMT / JE: // note- "Xaa w means Aly, T? P, Sur, Cys, Asn, Uys, Chr, Uuu,

Piu, Tyr, Dlu, Mut or Tla;

(ii) FEATURE:

(T) NAZWA / KUU / Z: Miejsce Modyyikswasr position 37 position 38 position 40 position 41 position 4 (2

Val, Alu,

190

184 424 (B) LOCATION: 43 (D) OTHER INFORMATION: / uwini = "Xil w means Glu, Asn, Tyr, Leu, PAe, Asp, Ala, Cys

IAo ^, GI / Isb run;

(ii) FEATURE:

(1) NAME / KEY: Modified site (B) LOCATION: 44 (D) OTHER INFORMATION: / swana = "Xll in the tag Asp, Sen, Leu, Arg, U / s, mr, Met, Type

Gln, Ala lsb Ppo;

(ii) FEATURE:

(A) NAME / KEY: modified eSuipcu (B) LOCATION: 45 (D) OTHER INFORMATION: / note- "Xaa w means Gln, Piso, Phe, Val, MuP, Lus, Th, Lys

Asn, Arn, Sur, Ala, Ilt, Gls Isb His;

(ii) FEATURE:

(1) NAME / KEY: Modified site (B) LOCATION: 46 (D) OTHER INFORMATION: / note- "Xii w means Asp), Phe, Set :, Thr, C / s, Gls, Asn, Glu

Ali, T / u, lit, Val lsb Gl /;

(ii) FEATURE:

(1) NAME / KEY: Site modified (B) LOCATION: 47 (D) ILNiE INFORMATION: / note- “Xia wi lle, Gly, Vil, Sei ^, Ann, Por lsb His;

item 43

Gle, Aon, position 44

Glu, Asn, position 45

Tup ,, Asp, 46 position Lys, His, 47 position (ii) FEATURE:

184 424

191 (l) NAME / KEY: Modified site (B) POSITION: 48 (D) OTHER INFORMATION: / uaaHa = "Xaa at position 48 is Leu, Seo, Cys, Arg, Ile, Sis, Phe, Glu, Uys, Geo ,

Cla, Met, aal or Asn;

(SS) ANCna:

(A) NAME / KEY: Aiejscrowani (B) LOCATION: 49 (D) OTHER INFORMATION: / Note ^ “Xaa in entry 49 means Met, Aog, Cla, —ly, Poo, Asg, Sis or Csp;

(SS) CECSA:

(A) NAZWC / KUUGZ: Aiejscr modified (B) PHOŁENIE: 55 (D) OTHER INFORMATION: / mwa-tga ^ ,, Xaa in position 50 means Tlu, Leu, Tho, Asp, Tyo, Lys, Asn, Ser, Ala , Ille, aal, Sis, Per, Aet or Iln;

(ii) CECSA:

(l) NAME / KUUAZ: Modified ASRjsce (B) CURRENT: 51 (D) IHNE INFORRAGCJN: / uuaga = "Xaa in po zyc j i 51 means Asg, Arg, Aet, Pos, Sro, Cho or Sis;

(ii) CNCSA:

(A) NAME / KEY: Modified site (B) LOCATION: 52 (D) IHNE INFORRAATIONS: // uraga = "Xxa in item 552 means Asn, Sis, Aog, Leu, Gir, Seo or Tho;

(SS) CECSA:

(A) NAME / KEY: Site modified

192

18-4 422 (B) LOCATION: 53 (D) OTHER INFORMATION: / Xai at position 53 is Liu, TAe, Ala, Cly ?, Clu, Pro, Lys, Sir or M.

(ii) GEGiA:

(A) NAME / KEY: Site modified (B) LOCATION: 54 (D) OTHER INFORMATION: / Xii in position 54 means Aog, Asp, Ili, Ser, Val, Thr, lln, Asn, Lys, iis,

Ali or Luu;

(li) FEATURE:

(A) NAME / KEY: Modified site (B) LOCATION: 55 (D) OTHER INFORMATION: UnalGl = "Xaa at position 55 is Arg, Cho, Val, Sie ?, Ln or Cly;

(li) FEATURE:

(A) NAME / KIT: Location medyflkeaa.nu (B) LOCATION: 56 (D) OTHER INFORMATION: / Notes- ,, Xaa at position 56 is Poo, Cly, Cys, Ser, Cln, Glu, Gog, iis, Thr , Ala, Tyr, Ple, Leu, Va1 or Lys;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) LOCATION: 57 (D) OTHER INFORMATION: / the Xaa at position 57 is Asn or Cly;

(ii) FEATURE:

(A) NAME / KEY: Modified location (B) POSITION: 58

184 424

193 (D) NNE INFORMATION: / note- "Xaa at position 58 is Uru, Sur, Tsp, Arg, lin, Val or Ty ?;

(ii) AE / HA:

(A) NAME / KEY: Site modified (B) LOCATION: 59 (D) OTHER INFORMATION: / note- "Xaa at position 59 is Ulu, Tyr, His, Uuu, Pro or Arg;

(ii) AE / HA:

(A) NAME / KEY: Modified site (B) LOCATION: 60 (D) IINJE INFORMATION: / uuw ^ cg <n ^ "Xaa at position 60 is Tla, Sur, hro, Tyr Ann or Thr;

(ii) AEAHA:

(A) NAME / KEY: Site modified (B) LOCATION: 61 (D) IINJE INFORMATION: / note- “Xaa at position 61 is Phu, Ann, Ulu, Pro, Uys, Trg or Sro;

(ii) AE / HA:

(A) NAME / KEY: Site modified (B) LOCATION: 62 (D) IUNE INFORMATION: / note- at position 662 is Ann, His, Val, Trg, Pro, Thr, Tsp or Ilu;

(ii) AE / HA:

(A) NAME / KUU / Z: Modified site (B) LOCATION: 63 (D) OTHER INFORMATION: ,, Xaa in 6 (3 is Arg, Tyr, Top, Lys, Sur, Hin, Pro or Vai;

(ii) TE / HA:

194

184 424 (A) NAME / KEY: Site modified (B) LOCATION: 64 (D) OTHER INFORMATION: / notea "x _aa at position 64 is Ala, Asn, Pro, Sur or Lys;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) POSITION: 65 (D) IlNE INFORMATION: / note = "Xaa in ρσζγσΜίΐ 65 means Val, Thr, Pro, Hin, Lru, hhr or Ser;

(ii) FEATURE ::

(A) NAME / KEY: Site modified (B) LOCATION: 66 (D) OTHER INFORMATION: / note = "Xaa at position 66 is Lys, Li, Arg, Val, Ann, Tlu or Sur;

(ii) FEATURE:

(A) NAME / KEY: Mirjscr modified (B) LOCATION: 67 (D) IlNNE INFORMATION: // Lwaga = "Xaa in ppo zyc ci 67 means Ser, Ala, Phu, Val, Tly, Asn, ilu, Pro or Hin ;

(ii) FEATURE:

(A) NAME / KEY: Mirjscr modified (B) POSITION: 68 (D) NO. INFORMATION: - / weighting ¹ : “Xxa in position 68 means Luu, Val, Top, Ser, ilu, Phr, Tir or HSs;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) POSITION: 69

184 424

195 (D) ILNiE INFORMATION: / Note- "Wxi at position 69 is Gle, Ali, Por, TAo ?, Glu, lun, iop, Gly lsb L ...;

(ii) FEATURE:

(A) NAME / KEY: e [SeiPCU modified (B) POSITION: 70 (D) OTHER INFORMATION: / note- "Wxa in position 7 A means ise, Lts, Vil, iop), Pro lsb lla;

(ii) FEATURE:

(A) NAME / KEY: Modified location (B) POSITION: 71 (D) OTHER INFORMATION: / note- ,, Wxi at position 71 on Ali, MuP, Les, Poo, Ann, Gls, ino, Gln, Iop lsb ise ;

(ii) FEATURE:

(A) NAME / KEY: Modified site (B) POSITION: 72 (D) OTHER INFORMATION: / swana = "Xaa at position i Ί2 is Ser, Gls, MuP, Ala, His, Asn, Aon lsb Asp;

(ii) FEATURE:

(1) NAME / KEY: Site modified (B) PPOŁOENIEe 73 (D) OTHER INFORMATION: / swani = "Xaa in item 7 3 means Ala, Glu, Asp, Leu, Stu, Gly, 1An lsb lun;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) LOCATION: 74 (D) INNN INFORMATION: / i ^ T ^^^ a = ,, Xai in ρoryLji 77 means Ilt, MtP, ino, Poo, lun, Gly, Ala ;

196

184 424 (ii) FEATURE:

(A) NAME / KEY: Place modified (B) LOCATION: 75 (D) OTHER INFORMATION: / note = "Xaa in pp ^ 2 ^ z ^ s ^ jj- 0 5 means 1ln, Iys, Gly, Asp ^, Peo , Trp, Aog, Ser, Cln or

Iiu;

(ii) GEGiA:

(A) NAME / KIT: Modified site (B) LOCATION: 76 (D) IlNNE INFORMATION: Note = "Xaa in ppeysji 76 means Sir, Va1, Gla, Asn, Tep, Glu, Peo, Gly or A ...;

(Hl) CEGiA:

(A) NAME / KEY: Modified site (B) LOCATION: 77 (D) IlNNE INFORMATION: / Note: - ", Xaa in psysia 77 means Ile, Ser, Gag, Thr or Leu;

(li) TECiA:

(A) NAME / KEY: Modified site (B) LOCATION: 78 (D) IlNNE INFORMATION: / ubiquitous- "Xaa in pseity 78 is leu, Ala, Ser, Clu, PAi, Gly or Gog;

(ii) TETiA:

(C) NAME / KIT: Modifier location (B) LOCATION: 79 (D) OTHER INFORMATION: / uwggg- "Xxa in pseition 7 9 is Iys, TAo, Asn, Mit, log, lii, Cly or Asp;

(li) GEGiA:

(G) NAME / KEY: Site modified

184 424

197 (B) LOCATION: 80 (D) OTHER INFOiACCCCEi / uaaga = "Xaa at position 80 is Asg, hop, aal, Gly, Gho, Leu, Tlu or Arg;

(SS) CECSA:

(G) NAME / KEY: ASujscr modified (B) LOCATION: 81 (D) OTHER INFORMATION: / note = "Xaa at position 81 is Leu, TlG, Tly, Ala, Top, Aog, aal or Lys;

(SS) CECSA:

(l) NAME / KEY: Have / cr modified (B) TREATED: M2 (D) OTHER INFORMATION: / uaaga = "Xaa at position 882 is Leu, Giny Lyc, Trp, Arn, Asp, Gln, Asn, HA Sp Thr ,

Seo, Ala, Ty, i Ph, i lle, Aut or Vnl;

(ii) CNCSA:

(l) NAME / KEY: Modified Aiej / ce (B) LOCATION: 83 (D) IHN INFORMATION: / uaaHa = "Xaa a position 88 is Poo, Ala, Tho, Top), Aog or Aet;

(ii) CECSA:

(G) NAME / KEY: Modified site (B) LOCATION: 84 (D) OTHER INFORMATION: / note = “Xaa in position 88 is Cys, Tlu, Tir, Arg, Aet or yal;

(ii) CECSA:

(A) NAME / KEY: ASejscr modified (B) POSITION: 85

198

184 424 (D) IMNS INFORMATION: / note = "Xaa in ppsy" and 85 is Ueu, Tsn, Val or lin;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) LOCATION: 86 (D) IITTE INFORMATION: / note = “Xaa in item 8 of 6 means Pro, Ty ?, Arg, Tla or Uy ?;

(ii) TETHT:

(A) NAMED.TUACHE: Modified position (B) LOCATION: 87 (D) IITTE DNFORMTC JE: / note = “Xaa in p ^ yc 87 means Uuu, Sur, Crp or Aly;

(ii) GE / HT:

(A) NAME / KEY: Modified property (B) LOCATION: 88 (D) IITTE INFORMATION: / note = "Xaa in ppsy'ji 88 means Tla, Uys, Arg, Val or Trp;

(ii) FEATURE:

(A) NAME / KEY: Modified site (B) LOCATION: 89 (D) IDN ^T E INFORMATION: / note ^ - ,, Xaa in ppsy'ji 89 means Chr, T? P, Gy ?, Uuu, Vai, Alu , His, Tsn or e ...;

(Si) FEATURE ::

(A) NAME / KUU / Z: Miujncu Modyowanu (B) LOCATION: 90 (D) I1TNS INFORMATION: / note- "Xaa in pρsy'ji 90 means Ala, Pro, eur, Thr, GUy, T? P, Ilu or Mut;

(Si) CE / HA:

184 424

119 (A) NAME / KEY: Modified site (B) POSITION: 91 (D) IlNiE ΙΝΕΟΙΜΜΑΓΓΕ: / note ^ "Xaa at position 91 is Ala, Pro, Sr ;, Ghr, Phe, Uuu, Asp or Hin;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) LOCATION: 92 (D) OTHER 11 ^ 01 ^ (^: "x _{aa at} position 92 means Pro, Phej Pcg o track o Lps o HSs o CHa o USy o Ilo or

Ueu;

(ii) FEATURES:

(A) NAME / KEY: Site modified (B) POSITION: 93 (D) IN1 ^ E O ίΜΜΑΤΕ: Uuaaga = "Xaa at position 93 is Thp, Asp, Sr ;, Asn, Pro, Ala, Leu or Arg;

(ii) FEATURES:

(A) NAME / KEY: Modified site (B) LOCATION: 94 (D) OTHER NEOiReATIONS: / note, Xxa at position 94 means Arg, ile, Ser, Tlu, Leu, Val, Tin, Uys, His, Ala or Oro;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) LOCATION: 95 (D) OTHER O / Notea "Kaa at position 95 means His, Tln, Pro, Arg, Val, Lru, Tly, Thr, Asn, Lys,

Ser, Ala, Top, PheOli or Tyr;

(HH) FEATURE:

200

184 424 (A) NAME / KEY: Modified site (B) LOCATION: 96 (D) OTHER INFORMATION: / GwaHa = "Xia at position 96 means Pro, Lys, Tyr, Gly, Ile or Chr;

(ii) FEATURE:

(A) NAME / KEY: Modified location (B) LOCATION: 97 (D) OTHER INFORMATION: / uwrć ^^ £ ^ = ,, Xaa in position 97 is Ile, Val, Uys, Ala or Asn;

(ii) FEATURE:

(A) NAME / KUCK: Modified site (B) POSITION: 98 (D) OTHER INFORMATION: / uwi »a =" Xaa at position 98 means His, Nie, Asn, Ueu, Asp, Ala, Ter, Glu, Gin, Seo,

Phe, Met, Vai, Lys, Aig, Tyo, or Poo;

(ii) FEATURE:

(A) NAME / KEY: Site modified (B) LOCATION: 99 (D) OTHER INFORMATION: 'Xai in position 99 says lle, Leu, Aog, Asp, Va1, Pro, Aln, Als, Ser, Phe

or His;

(ii) CETHA:

(A) NAME / KEY: Modified site (B) LOCATION: 100 (D) OTHER INFORMATION: / blinks ^ "Xia at 100 oz. Lys, Cyo, Leu, His, Arg, No, Ser, Gln or (ii) CETHA :

(A) NAME / KEY: Site modified

184 424

201 (B) LOCATION: 101 (D) BOTTOM INFORMATION: / note- "Xaa at position 101 is Tsp, Pro, Mut, Uys, His, Thr, Val, Tyr, Giu, Tsn, Sur, Tla, Aly, Ilu, Uuu or gin;

(ii) FEATURE:

(A) NAME / KUU / Z: Site modified (B) LOCATION: 102 (D) DNNE INFORMATION: / note- "Xaa in position 102 is Aly, Ueu, Alu, Uy ?, Ser, Tyr or Pro;

(Si) FEATURE:

(A) NAME / KEY: Modified site (B) PPOOZEETIE: 110 (D) DNNE INFO: / \ iwaga = "Xaa in position 103 means Tsp or pipes;

(SS) CE / HT:

(A) NAME / KEY: Modified site (B) LOCATION: 104 (D) OTHER INFO: / note— "Xaa at position 104 is Arp, Val, Ty ?, Tyr, Thr, Met, Pro, Uru, Gin, Uys ,

Tla, Piu or Gly;

(ii) FEATURE:

(A) NAME / KEY: Modified site (B) LOCATION: 105 (D) IITIE INIORRMAGJE: // usaa- "Xaa at position 105 means Tsn, Pro, Tla, Piu, Ser, Crp, Gin, Tyr, Uru, Uys , Lira, Tnp or His;

(SS) GEGHA:

(A) NAME / KUU / Z: Modified site

202

188 442 (B) LOCATION: 106

(D) OTHER INFORMATION: / in the 20th century position H. 106 means Clu, Cheese, Gla, Lys, Tho, Ile, lly or Pro; (Hl) TECiA: (Α) NAME / KEY: Site modified (B) LOCATION: 108 (D) OTHER INFORMATION i / attention = ,, Χίτ w gaoitia lpo means Arg, Lys, Asp, Iiu, TTr, lin, Gln. His- Ser- Alg or Pro; (Hl) CECiA: (AND) NAME / KEY: Place medyfikeagne (B) LOCATION: 109 (D) NNNH INFORMATION i ^ 1 (3 = "XlG w gioycj i lpo means Arg, Thr, Poo, IIlu, Tyr, Iiu, Ser or Ily; (Hl) FEATURE: (AND) NAME / KEY: Site modified (B) LOCATION: 110 (D) NNNH INFORMATION AND RECOMMENDATIONS ^^ lG - pooycj i and after stands for Iys, Ala, Asn, - TTr, Κιπ Aig, Gln. Hi ^ - Glu- Cheese or Top; (loam) GEGiA: (AND) NAME / KEY: Site modified (B) LOCATION: 111 (D) OTHER INFORMATION: / note- _{in the} 13th century position 111

is Liu, Ile, Arg, Asp or Met;

(ii) GEGiA:

(G) NAME / KEY: Site modified (B) POSITION: 112

184 424

203 (D) OTHER INFORMATION: / Note- "Xaa at position 112 is Thr, Val, Gin, Tyr, Glu, His, Ser or Phe;

(ii) FEATURE:

(A) NAME / KEY: Modified site (B) LOCATION: 113 (D) OTHER INFORMATION: / note- "Xaa at position 113 means Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu,

Ile, Val or Asn;

(ii) FEATURE:

(A) NAME / KEY: Modified site (B) LOCATION: 114 (D) OTHER INFORMATION: / note- "Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg or Leu;

(ii) FEATURE:

(A) NAME / KEY: Modified site (B) POSITION: 115 (D) OTHER INFORMATION: / note- "Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp or

Underworld;

(ii) FEATURE:

(A) NAME / KEY: Modified site (B) LOCATION: 116 (D) OTHER INFORMATION: / note- "Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp,

Ser, Asn, His, Ala, Tyr, Phe, Gln or Ile;

(ii) FEATURE:

(A) NAME / KEY: Modified location (B) POSITION: 117

204

118 442 (D) OTHER INFORMATION: / Note = "Xaa at position 117 is Cho, Sro, Asn, 11le, Top, Uys or Pro;

(ii) GECSA:

(A) NAME / KEY: Modified Aiujsce (B) LOCATION: 118 (D) OTHER INFORMATION: ^ ιηι = “Xaa at position 118 is Leu, Sro, Poo, Ala, Glu, Cys, Asp or Tyo;

(ii) CECSA:

(A) NAME / KEY: ASejscr modified (B) LOCATION: 119 (D) OTHER INFORMATION: / Note ^ "Xaa in entry 119 is Tlu, Sro, Uys, Poo, Ueu, Tho, Tyo or Aog;

(ii) GECSA:

(A) NAME / KEY: MSUsce modified (B) LOCATION: 120 (D) IIINS INFRRMACJJEi / note = "Xaa at HO means Asn, Ala, Poo, Ueu, SS /, aal or Tln;

(Si) CNCSA:

(A) NAME / KEY: M In-place modifying (B) LOCATION: 121 (D) other: INFOJAACJJEi / notee = "Xaa In the Ul position is Ala, Sro, lle, Asg, Poo, Lys, Asp or Tly;

(ii) CECSA:

(A) NAME / KEY: Modified location (B) LOCATION: 122 (D) OTHER INFO i / note = ,, Xaa wi / ji 122 means TlG, Seo, Aet, Top, Aog, Phe, Pro, 111, (11, Tyr or Crs;

184 424

205 (ii) TETiA:

(A) NAME / KEY: Modified site (B) LOCATION: 123 (Ό) OTHER INFORMATION: / note = “Xaa at position 123 is ila, Mrt, Glu, iis, Srr, Poo, Tyr or Lru;

(xi) SEQUENCE DESCRIPTION: SEQ II no .: 2:

Ala 2 Poo Underworld: ΊΉ Main AND Thr Thr Seo Lru Lys II Thr Cheese Trp Val Asn 15 Cys Xaa Xaa Xaa X aa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa xao Xaa Xaa Xaa twenty 25 thirty Xaa Xaa Xaa Xaa Xaa Xaa As n Xaa Xaa Xaa Xa a Xaa XXa XXa Xaa Xaa 35 4I 45 Xaa Xaa Xaa Xaa Xaa Xaa xao Xaa Xaa Xaa Xaa Xaa Xaa XXa Xaa Xaa 50 55 60 Xaa Xaa Xaa XXa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65 70 75 80 Xaa Xaa Xaa XXa Aaa Xaa Xaa Xaa Xaa Xaa Xaa X! A Xaa Xaa Xaa Xaa 85 90 95 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Phe Xaa Xaa Xaa Xaa Xaa 100 105 110 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Cln Glu ΤΑ Thr Leu

115 120 112

Sro Lru Ala Ile Phe 130 (2) INFORMATION ABOUT SEQ II No: 3:

(and) SEQUENCE TIMES: (AND) LOOSE: 332 amino acids (B) TYPE: amino acid (T) THREAD QUANTITY: unknown d) TOPOLOGY: unknown (ii) TYPE PARTICLES: protein

(ii) CeCHA:

206

184 424 (A) TAZWT / KUCH: Modified site (B) LOCATION: 112 (D) IITTE INFORMATION: / note = 112 deleted or Ueu, Tla, Vai, Ilu, Pro, Phr, Trp or M ...;

(ii) FEATURE ::

(A) NAME / KUU / Z: Site modified (B) LOCATION: 113 (D) IITTE INFORMATION: / note = ("p ^ c ^^ z ^ cczj j 113 are deleted or Pro, Phr, Tla, Leu, Dlu , Trp or Mut;

(ii) FEATURE:

(A) NAME / KEY: Modified Miujncu (B) POSITION: 114 (D) IITTE INFORMATION: / note- "and" life 114 is deleted either Pro, Phu, Tla, Vai, Uuu, Ilu, Trp or Mut;

(ii) FEATURE:

(A) NAME / KEY: Site Modified (B) LOCATION: 115 (D) IITTE INFORMATION: / note- "dycc j 1115 is removed either Gin, Uly, Ser, Thr, Tyr or T? S;

(xi) SEQUENCE OPDS: SEQ ID No .: 3:

Sur 1 Pro Ali Pro Pro 5 Tli Tin Tnp Uuu Arg 10 Vai Uuu Cheese Uy? Uuu 15 Ueu Arg Asp Ssu His twenty Val LeV U Cs Aig 2 V Teu Sc r COg Cyu eur thirty Glu VuS Hi? Pro Leu 35 Pro Thr Prr Oc 1 Leu 4C LVl Tro uu a Lul Asp 45 Shhh Cheese aau Giy Clu 50 Trg Lys Thr Main Oc t 55 Glu GMu Thr Ly p Alu 60 Main > Usp How much Tui

Giy Ala Vai Ahr Uuu Ueu Uuu Alu Aly Val Mut Tla Tla Trg Aly Gin

184 424

207

7Α 75 80

Les Cly Poo Thr Csi 85 Leu Cheese Set: Utu Leu 9I Gly Main Leu Cheese Gly 95 Main Vil Arg Les Leu Leu Gly Assembly hall Les Main P Leu Leu. Gly Tho Main Xaa 100 110 110 Xll Xii Xii Gly PCrg Thy OTr Il His Lys Asp Pro As Ala How much PPh 115 110 125 Les Cheese Phe Main His Leu Leu Arg Gly Lys Val Arg PPr Llu Underworld Leu 130 135 114 Val Cly Glj / Cheese Thr Leu Cys Val Arg Arg lila Pro Pro Tho Thr Aln 145 FL50 155 116 Vil Poo Seo COrg Thr Cheese Leu Val Uts Thr Leu Am riun Leu Pro An 165 170 175 Arg Thr Seo Gly Leu Leu Clsp Tho Asn PAu Thr cna Cheese Ali Arg TLm 180 115 190 TAr Gly Cheese Gly Leu Leu Lys Trp Main Main Gly Drunk Aig But. Ayr Ili 195 220 205 Pro Cly Ues Leu An Cln Thr Cheese Ann Cheese Leu Asp Glu Ili Aro Aly ’ 210 215 222 Type Ues Asn Ag How much His Gls Leu Uts Asn Gly Thr (Pg Gly Leu PPh 225 230 235 224 Pro Cly Pro Cheese CPg Aon TAr Leu Cly Ali Pro Asp lle Dream Seo Gll 245 250 22 ^ 0, TAr Sn AP0 Thr Gly Cheese Les Prr Pro Gsn Leu Main Pro Gly Back Αη 260 226 220 Pro Cheese Prr TTin His Poo Pro Thr Gly Cln Tyr Tho Leu APr Aro Llu 275 220 285 Cf. Poo TAo Luu Pro Ter Po Val Val Main. Leu iSLs Pro Llu Llu. Lpo 290 225 300 Asp Prr Set: Ala Pro Ter Poo Thr Prr TAo Cheese Pro Ues Lts isn TTr 305 310 315 332 Seo Type TTr His Seo Main Asn Llu Hundred Main Gls Gly

325 330 (2) INFORMATION ABOUT SEQ ID Nu: 4:

(i) SEQUENCE FEATURES:

(A) LENGTH: 1 amino acid

208

184 424 (B) CYP: amisoquiP (C) THREAD QUANTITY: single (D) TOPOLOGY: linear (ii) GYP PARTICLE: protein (ii) CETHA:

(AND) NAME / KEY: Protein (B) LOCATION: 1 (D) OTHER INFORMATION: / note = "where

x = (glygiAglysuo) n and where n is an integer (xi) SEQUENCE DESCRIPTION: EEQ ND no .: 4:

Xaa (2) INFORMATION ON EEQ ND No: 5:

(i) SEQUENCE TECHNIQUES:

(A) LENGTH: 1 amino acid (B) GYP: amino acid (C) QUANTITY NNCN: single (D) TOPOLOGY: linear (ii) GYP PARTICLE: protein (ii) TECBA:

(AND) NAME / KEY: Peptide (B) LOCATION: 1 (D) OTHER INFORMATION: / GwaHa = "where

x = (glyglyglyglyser) n and where n is an integer (xi) SEQUENCE OPlE: EEQ ND No .: 5:

Xia (2) INFORMATION ABOUT EEQ ND No: 6:

184 424

209 (i) SEQUENCE FEATURES:

(1) LENGTH: 1 amino acid (B) TYPE: amino acid (C) NUMBER OF THREADS: single (D) TOPOLOTY: linear (Hl) TYPE OF PARTICLE: protein (li) TECH ::

(A) NAME / KEY: Protein (B) LOCATION: 1 (D) OTHER INFO: / wig- ^ dzle x = (GnyGlwg1yGlyGlWseo) n i Where n is an integer (eH) SEQUENCE DESCRIPTION: SEQ ID no: 6:

Xia (2) INFORMATION ABOUT SEQ ID No: 7:

(H) SEQUENCE FEATURES:

(A) LENGTH: 1 amino acid (B) TYPE: amino acid (C) NUMBER OF THREADS: single (D) TOPOLOT: linear (il) TYPE OF PARTICLE: protein (ii) CHARACTER:

(A) NAME / KIT: Protein (B) LOCATION: 1 (D) OTHER INFORMATION / oumacj ,, - day g- (gGy n oer (G i where n is an integer (xl) SEQUENCE DESCRIPTION: SEQ ID no .: 7 :

210

184 424

Xaa (2) SEQ INFORMATION NA No: 8:

(i) SEQUENCE FEATURES:

(A) LENGTH: 1 amino acid (B) TYPE: amino acid (T) QUANTITY NITi: single (D) TOPOLOGY: linear (ii) TYO PARTICLES: protein (HH) CECHC:

(A) NAME / KEY: Protein (B) POSITION: 1 (D) OTHER INFOR ^ NEHi FOwagJ :: "g / uia i = (alagHuoea) n H where n jrst number, integer (xH) SEQUENCE DESCRIPTION: SEQ ND No. : 8:

Xaa (2) SEQ INFORMATION NA No: 9:

(i) SEQUENCE FEATURES:

(AND) LENGTH: 35 amino acids (B) TYPE: Amino Acid (C) THREAD QUANTITY: single (D) TOPOLOGY: linear HH) TYP PARTICLES: protein

(xi) SEQUENCE DESCRIPTION: SEQ ID No .: 9:

Gly Tly Tly Se; Tly Gly Tly Cheese Gly Gly Gly Sec Glu. Gly Tly Ser

10 15

Glu Uiy Uiy Tly Se; Glu Gly Gly Gly Cheese Glu Gly Tly Gly Sen Gly

184 424

211

25 30

Cly lir Sro (2) INFORMATION ON SNQ ND No: 10 (i) SEQUENCE CECSES:

(AND) LENGTH: 24 amino acids (B) TYPE: Amino Acid (G) QTY NlCl: single (D) CRPOURGY: linear (SS) TYPE PARTICLES: protein (xi) RhlS SEQUENCE: SNQ ID go: 10:

Ile Sro Tlu Pos Sro -ly Pos Ili Sro Cho llr Apg Pos Seo Pos Tho

10 15

Sro Uys Glu Sro Sis Uys Sio Pos (2) INFORMATION R SEQ ND No: 11:

(i) SEQUENCE CECSES:

(G) LENGTH: 28 amino acids (B) TYPE: Amino Acid (C) QTY OF NlCl: single (D) TOPOLOGY: line (ii) TYPE PARTICLES: protein

(xS) SEQUENCE DESCRIPTION: SNQ ID go: 11:

Ili Clu —Ir Arg llr Seo Tlu Pos Sro —Ly Pos Ilr Sro Gho llr Apg 1 5 10 15 Pos Sro Pos Pos Seo Uys Clu Sro Sis Uy / Cheese Pos twenty 25

(2) INFORMATION R SEQ ID No: 12:

212

184 424 (i) SEQUENCE FEATURES:

(A) LENGTH: 4 amino acids (B) CYP: amino acid (/) AND QUANTITY NI / I: single (D) TOPOLOGY: linear (ii) CYO FREQUENT / ZKl: protein (xi) RPDS SEQUENCE: SEQ DD No .: 12:

Uly Aly Uly rur (2) INFORMATION R SEQ ID Tr: 13:

(S) SEQUENCE FEATURES:

(A) LENGTH: 45 base pairs (B) TYPE: kwa? nucleic (T) INQUITY NI / I: single (D) TOPOLOGY: linear (ii) CYP PARTICLES: different acid? nucleic (A) DESCRIPTION: / description '- "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13:

TGATCCTCCU GNCCN / ANAC NTTNTCTGTC TGTGTTTTTT GAGTG (2) INFORMATION ABOUT SEQ ID NO .: 14:

(i) SEQUENCE FEATURES:

(A) LENGTH: 30 base pairs (B) CYP: nucleic acid (T) LARGE NITD: single (D) TOPOLOGY: UinS (iS) CYP PARTICLES: other acid? nucleic (A) DESCRIPTION: / opS? - "DNA (synthetic)

184 424

213 (el) SEQUENCE DESCRIPTION: SEQ NA No: 14:

ATCCACCCAT TTCCTCATCT ACACGGTCCA (2) SEQ INFORMATION NA No: 15:

(i) TECES OF SEQUENCES:

(A) LENGTH: 33 pairs of zisid (B) TYPE: nucleic acid (T) NUMBER OF THREADS: single (D) TOPOLOTS: linear (il) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description - "dna (synthetic) (el) SEQUENCE DESCRIPTION: SEQ NA no: 15:

TClCAlCCTT ATTTCATCTA GA111C1GAT CCT (2) INFORMATION ABOUT SEQ ID No: 16:

(i) SEQUENCE FEATURES:

(A) LENGTH: 10 pairs zisid (B) TYPE: nuk1ilneaw (T) QUANTITY OF THREAD: single (D) TOPOTHIA: linear (il) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description - "DNA (synthetic) (xl) SEQUENCE DESCRIPTION: SEQ NA No: 16:

AlTTCCGGAl (2) INFORMATION ON SEQ ID No: 17:

(i) SEQUENCE FEATURES:

(A) LENGTH: 10 rules

214

184 424 (B) TYPE: nucleic acid (C) QUANTITY of NITi: single (D) TOPOLOGY: linear (iH) TYPE C TANK TYPE: other Hwnr nukl eiuouu (A) DESCRIPTION: / description a, _Z DNA (synthetic) (xH) SEQ ID NO: 17: SEQ ID NO: 17:

cattgttcct (2) INFORMATION ABOUT SEQ ID No .: 18:

(i) SEQUENCE FEATURES:

(A) LENGTH: 13 base pairs (B) TYPE: wukluHnoay acid (C) NUMBER OF NiCI: single (D) TOPOLOGY: linear (Hi) TYPE OF PARTICLE: other wunarinoay acid (A) DESCRIPTION: / description a ,, 1 ^ 1 (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID wa: 18:

AeTTCTTCTT CAA (2) INFORMATION ABOUT SEQ ID NO .: 19:

(i) SEQUENCE FEATURES:

(A) LENGTH: 13 bases (B) TYPE: nbnlrinpwy acid (C) QUANTITY of NiCl: single (D) TOPOLOGY: linear (iH) THESE PARTICLES: Hnny acid wbnaeinpay (A) DESCRIPTION: / description aDNA (synthetic) ( xi) SEQUENCE DESCRIPTION: SEQ NA No: 19:

184 424

215

CATACrGCCA TTA (2) INFORMATION ON EEQ ND No: 20:

(i) SEQUENCE FEATURES:

(G) LENGTH: 22 base pairs (B) AYP: sukluisows acid (C) NUMBER OF THREADS: single (D) COPOLOAlA: linSic (II) CYP PARTICLES: inn sGkUMLnzws acid (A) DESCRIPTION: / description = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ NA no: 20:

AArrCGGCAA CAATAACAGC AA (2) INFORMATION ON EEQ ND No: 21:

(L) TETHY SEQUENCE:

(A) LENGTH: 22 pairs of bases (B) AYP: SGkleLnname (T) NUMBER OF THREADS: single (D) COPOLOVA: ULN (LL) AYP PARTICLES: inn nucleic acid (A) DESCRIPTION: / description = "DNA (synthetic) (xL) SEQUENCE DESCRIPTION: SEQ ID no: 21:

TAAACAATCA TCCACACCAT CA (2) INFORMATION ON EEQ ID No: 22:

(S) SEQUENCE FEATURES:

(A) LENGTH: 27 base pairs (B) CYP: nGkiuinzws acid

216

H8 424 (T) QUANTITY ND / I: single (D) TOPOLOGY: linear (ii) TYPE OF CUPPLE: Znny inn kwl? CSuoeu (A) OOIK: / description - "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: KEQ ID No. : 22:

/ GTTCCTTGG TGGTA / T / AG TTTGT / T (2) INFORMATION ABOUT KEQ ID Ng: 23:

(i) SEQUENCE FEATURES:

(A) LENGTH: 29 base pairs (B) TYPE: kwa? nucleic (/) IUITY NI / I: single (D) TOPOLOGY: linear (n) CYP PARTICLES: other nvirgnic acid (T) OPIK: / description - "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: KEQ ID NO .: 23:

GTTCATACAT TTGGGCTCTG G / TGAGTCT (2) INFORMATION R KEQ ID No .: 24:

(i) SEQUENCE FEATURES:

(A) LENGTH: 27 base pairs (B) TYPE: nucleic acid (/) 1LTHREAD: single (D) TOPOLOGY: linear (Si) TYPE OF PARTICLE: other nucleic acid (A) OPIK: / description - "DNA (synthetic) (xi) SEQUENCE OOIK: KEQ ID No .: 24:

CGATTCTTAC TGCGATATCC TATCCAG

184 424

217 (2) INFORMATION ON SNQ ND No: 25:

(i) SEQUENCE CECSES:

(A) LENGTH: 29 base pairs (B) TYPE: nucleic acid (C) NNCINESS: single (D) TOPOLOGY: linear (iS) TYPE OF PARTICLE: other acid / nucleic acid (A) DESCRIPTION: / description = "DNA (synthetic ) (xS) SEQUENCE DESCRIPTION: SEQ NA go: 25:

gatagagctt AayyyTTAac GTCpyyyGA (2) SEQ INFORMATION NA No: 26:

(i) SEQUENCE CECSES:

(A) LENGTH: 27 bases (B) TYPE: nucleic acid (G) QUANTITY of NlCl: single (D) TOPOLOGY: linear (iS) TYPE OF PARTICLE: other acid / nucleic acid (A) DESCRIPTION: / description = "DNA (synthetic ) (ii) SEQUENCE OPNS: SNQ ND go: 26:

CGAhCCAGGG TCCCGCGGCC TGCT — TC (2) INFORMATION R SEQ ND No: 27:

(i) SEQUENCE FEATURES:

(l) LENGTH: 29 bases (B) TYPE: nucleic acid (C) AND QUANTITY of NNCI: single

218

184 424 (ϋ) TOPOLOGY: linear (ii) TYPE OF PART (ΐη: τ nucleic acid (A) DESCRIPTION: / description = "SHE (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ II No .: 27:

catcaacctt AiyGTyrAyG ταααιιιτι (2) INFORMATION ABOUT SEQ II No .: 28:

(i) SEQUENCE TIMES:

(A) DEADLESS: 30 bases (B) TYPE: nucleic acid (C) QUANTITY OF THREADS: single d) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description = "ΡΠ (synthetic) ( xi) SEQUENCE DESCRIPTION: SEQ H no: 28:

CCATCCATCC CTCTCCACTT TACCTTCCCA (2) INFORMATION ON SEQ H No: 29:

(i) SEQUENCE TIMES:

(A) LENGTH: 29 bases (B) TYPE: nucleic acid (C) NUMBER OF THREADS: single (O) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description = "INA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ II no: 29:

CATCACCCCT AACCCACCAG CACACCTCT

184 424

219 (2) INFO - ABOUT SEQ NA No: 30:

(i) SEQUENCE FEATURES:

(A) LENGTH: 27 base pairs (B) TYPE: nucleic acid (T) NIGNNESS: single (D) TOPOIOGNA: linear (il) TYPE OF PARTICLE: other acid n "k1uSneww (A) DESCRIPTION: / description -" DNA ( synthetic) (xl) SEQUENCE DESCRIPTION: SEQ NA no _: 30:

TGATTTATCC ATTTTAGTTT CCCACAA (2) SEQ INFORMATION NA No: 31:

(i) SEQUENCE FEATURES:

(1) LENGTH: 29 bases (B) TYPE: n "k1ic acid (C) AMOUNT OF NNTN: single (D) TOPOLOGY ·. liner (li) MOLECULE CYP: other Kwisą nukIul e _{n o} n (A) DESCRIPTION: / doc - "DNA (synthetic) (xl) SEQUENCE _DESCRIPTION: SEQ ID NO: 31:

1ATTAACCTT ACATACTACC GAlGACCAC (2) IN / ORVATIONS ABOUT SEQ ID NO _: 32 _: (i) SEQUENCE FEATURES _: (A) LENGTH: 27 bases (B) TYPE: Nucleic acid (C) NNTN NONNESS: Single (D) TOPOLOGY: linear

220

184 424 (SS) TYPE OF CTRIPCTCLINK OTHER NUCLEAR LESS (A) DESCRIPTION: / description = "DNA (synthetic) (xS) SEQUENCE DESCRIPTION: EEQ ND no: 32:

CGACCCACAA AAGAAAUUAA AACCCAG (2) SEQ INFORMATION NA No.33:

(S) SEQUENCE FEATURES:

(A) LENGTH: 29 pairs of bases (B) CYP: nGniMisic acid (C) AND THREAD QUANTITY: single (D) TOPOLOGY: linear (iS) AYP PARTICLES: isnic acid nuclLisows (A) DESCRIPTION: / description = "DNA (synthetic) (xL) SEQUENCE DESCRIPTION: EEQ ID so: 33:

AACTAAUCCA ACAAACCAAA UACCACAAC (2) INFORMATION ABOUT SEQ ID No: 34:

(S) CETHY SEQUENCE:

(A) LENGTH: 27 pairs of bases (B) CYP: nukieisows acid (C) NITN AMOUNT: single (D) COPOUOAIA: linear (ii) CYP PARTICLES: insy sGnUMinows acid (A) DESCRIPTION: / description = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ NA no: 34:

TAACCTACUU UATTTATTTA TTATCTA (2) INFORMATION ON EEQ ND No: 35:

184 424

221 (S) SEQUENCE FEATURES:

(A) LENGTH: 29 base pairs (B) TYPE: Nucleic acid (T) NUMBER OF THREADS: single (D) COrOUOGIT: linear (s) SPOON TYPE: other kwa? nucleinow '(A) ROIK: / opS? - "DNA (synthetic) (xi) OODS SEQUENCE / JD: KEQ DD No: 35:

ATAGATGCTT T / TAATGTCC / CnAGTTGC (2) INFORMATION ON KEQ ID No .: 36:

(S) SEQUENCE FEATURES:

(A) LENGTH: 27 base pairs (B) TYPE: Nucleic acid (T) AND QUALITY riAI: single (D) TOPOLOGY: iSnSowa (ii) TYPE / TRIPPERS: Snny kwa? nunlrn new (A) OPIK: / description - "DNA (synthetic) (xi) SEQUENCE OODS: KEQ DD No: 36:

CTAC / CTTGA GATTTGAG / T TTTCCCT (2) INFORMATION ON KEQ ID No .: 37:

(S) SEQUENCE FEATURES:

(A) LENGTH: 29 base pairs (B) TYPE: nucleic acid (/) NI / I QUANTITY: single (D) TOPRUOADA: LSni (SS) CYP PARTICLES: other acid? nunirSowy

222

184 424 (A) DESCRIPTION: / description a ,, DN1 (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID No .: 37:

yeTceeyccT aaagtigtct cggcagttc (2) INFORMATION ABOUT SEQ ID NO .: 38:

(H) SEQUENCE FEATURES:

(A) LENGTH: 27 base pairs (B) TYh: nucleic acid (C) NUMBER OF THREADS: single (D) TOPOLOGY: linear (ii) THYO PARTICLE: Hny acid wuklrHnpay (A) OOlS: / description aDEe (synthetic) ( xH) SEQUENCE DESCRIPTION: SEQ NA No: 38:

CTATCC1TGT TceTGeccic eTCTcec (2) SEQ INFORMATION NA No: 39:

(i) SEQUENCE FEATURES:

(A) LENGTH: 30 base pairs (B) TYPE: nunluHnoay acid (C) NUMBER OF NiCI: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other acid wbkarinpay (A) DESCRIPTION: / opHs a ,, DN1 (synthetic ) (xH) SEQUENCE DESCRIPTION: SEQ NA No: 39:

TlTyCATCCT 1CTTTTT1TG AlTyTTGTTT (2) SEQ INFORMATION NA No: 40:

(i) SEQUENCE FEATURES:

184 424

223 (G) LENGTH: 30 pairs of bases (B) TYPE: nucleic acid (C) NICN LOOSE: single (D) TOPOLOGY: linear (SS) TYPE OF PARTICLE and other nucleic acid (A) RPlS: / opi / = "DNA ( synthetic) (xi) SEQUENCE OPNS: SNQ ND go: 40:

GGACCCAGGT CGCACAAGGA TCCCAATGGC (2) SNO INFORMATION ND No: 41:

(S) SEQUENCE CECSES:

(A) LENGTH: 29 bases (B) TYPE: acid / nucleic (C) NIGN NLQ: single (D) TOPOLOGY: linear (iS) PARTICLE TYPE: other nucleic acid (A) OPNS: / opS / = "DNA ( synthetic) (xi) SEQUENCE OPNS: SNQ ND no: 41:

TACCGAGCCh AGGhGGTGCh GCTGTGCGG (2) SNQ INFORMATION NA No: 42:

(i) SEQUENCE GNCS:

(G) LENGTH: 30 bases (B) TYPE: acid / nucleic (C) AMOUNT OF NNGN: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) OPNS: / description = "DNA (synthetic )

224

184 424 (xi) SEQUENCE DESCRIPTION: SEQ DD no .: 42:

CGTACCTTAG TTT / CCATGG TTTTTTC / CG (2) INFORMATION ON KEQ DD No .: 43:

(i) AEAHY SEQUENCE:

(A) LENGTH: 29 base pairs (B) CYP: nucleic acid (/) NDCI SIZE: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nvnUrgnic acid (T) OPDS: / description - "DNA (synthetic) (xi) SEQUENCE OODS: KEQ ID No .: 43:

nTACTTACAT T / TTGTGTGC TATAATC / T (2) INFORMATION ON KEQ ID No .: 44:

(i) AE / HY KEKWEN / JD:

(A) LENGTH: 30 base pairs (B) TYPE: nucleic acid (/) NUMBER OF THREADS: single (D) TOPOLOGY: linear (ni) TYPE OF PARTICLE: other nucleic acid (A) OPIK: / opSs - "DNA (synthetic) (xi) SEQUENCE OOIK: SEQ DD no: 44:

CATACCTAGA T / TTCTC // T ATACTAC / TA (2) INFORMATION ON SEQ ID Tr: 45:

(S) SEQUENCE FEATURES:

(A) LENGTH: 32 base pairs

184 424

225 (B) TYPE: nucleic acid (C) QUANTITY NlCl: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE n other nucleic acid (1) DESCRIPTION: / rpis = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 45:

gaicaigcti aiiigggiic ciigtgagci gt (2) INFORMATION ABOUT SEQ ID Nu: 46:

(i) SEQUENCE FEATURES:

(i) LENGTH: 83 bases (B) TYPE: nucleic acid (C) QUANTITY NICl: single (D) TOPOLOGY: lieirwi (ii) TYPE OF PARTICLE: other nskltSnrw / (A) DESCRIPTION: / description = "DNA (synthetic ) (xi) SEQUENCE DESCRIPTION: SEQ ID No .: 46:

AATTCCGTCG llCAChGACC TTCTATCTG1 AiACChTGGA GA1CGCGCAG

GCTClACAGT ACGTAGAGGG CGGTGGAGGC TCC (2) INFORMATION ON SEQ ID Nu: 47:

(i) SEQUENCE FEATURES:

(C) LENGTH: 83 pins of bases (B) TYPE: nucleic acid (C) QUANTITY of NlCl: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: ion nucleic acid

226

184 424 (A) DESCRIPTION: / description - "gout (synthetic) (xH) SEQUENCE DESCRIPTION: SEQ ID no: 47:

CGCCGGACCC TCCACCCCCC TCTACGTACT CTTCACCCTC CCCCTTCTCC

AC1CTTTTCG GATAGAACCT CA1TTTACCA CCC (2) 1N / OUGCJE ABOUT SEQ NA No: 48:

(i) SEQUENCE TIMES:

(A) LENGTH: 59 pio bases (B) TYPE: kwis n "kaulneaw (C) NICN DEFENSE: single (D) TOPOLOTS: linear (li) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description -" dna ( synthetic) (xl) SEQUENCE OPNS: SEQ ID no: 48:

1CTACCCTTC ACCAACCGCA GGAACAACAG CCTGGTCCCT CTAACTCCTC

TATAATCAT (2) IN / OUVATIONS ABOUT SEQ ID No: 49:

(i) SEQUENCE FEATURES:

(G) LENGTH: 56 pio zisid (B) TYPE: acid n "kaelneay (C) NNCI acidity: single (D) TOPOLOGY: linear (il) TYPE OF PARTICLE: other nukaulnoay kwis (G) DESCRIPTION: / description -" dna ( synthetic) (xi) SEQUENCE OPNS: SEQ ID no: 49:

184 424

227

CCATCATTAT ACACCACTTA CAGCCACCAC CCTCTTCTTC CTCCCCTTyC

TCAACC (2) INFORMATION ON SEQ II No .: 50:

(i) SEQUENCE TIMES:

(A) LOOSE: 80 base pairs (B) TYPE: nucleic acid (C) NUMBER OF THREADS: single (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description = "1INA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ II no .: 50:

CTTACCCTTC AyCAlCTCCA C-lAClACAC CCTCCTyCCT TTCyCCGGCC

CACCyCTCCC CCTTCGAACT yCTCTATAAT (2) INFORMATION ABOUT SEQ II No: 51:

(i) SEQUENCE TIMES:

(A) LENGTH: 80 bases (B) TYPE: nucleic acid (C) NUMBER OF THREADS: single (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description = "INA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ II no .: 51:

CCATCATTAT ACACCACTTA yiACCCCCCC CCCTCCCACC CCCACAyCCA

228

184 424

CTACTTCUTT ATCTCCGCUC AAATCCAAAA (2) INFORMATION ON EEQ ID No .: 52:

(S) CETHY SEQUENCE:

(() LENGTH: 30 base pairs (B) CYP: nukUMSnz-ws quis (C) NITN QUANTITY: single (D) TOPOLOGY: fox (LS) AYP PARTICLE: other SGnlMinic acid (A) DESCRIPTION: / description = "DNA ( syntutsczns) (xL) SEQUENCE DESCRIPTION: EEQ ND no .: 52:

AACTUACTAC GGTATCAAAC CTUACCAACC (2) INFORMATION ON EEQ ND No: 53:

(S) SEQUENCE FEATURES:

(A) LENGTH: 28 base pairs (B) TYPE: nucleSnows (C) NNCN QUANTITY: single (D) COPOLOAlA: ILsLic (SS) AYP PARTICLES: real nunleonic acid (A) DESCRIPTION: / description = "DNA (synthetic) (xL) SEQUENCE DESCRIPTION: EEQ ID No .: 53:

CATCAAAATU AATAAAGUAU TAUUAUAA (2) INFORMATION ON EEQ NA No: 54:

(S) SEQUENCE FEATURES:

(A) LENGTH: 32 base pars. (B) CYP: nucleic acid

184 424

229 (/) QUANTITY NDCI: single (D) G000U0A1T: linear (SS) TYPE CG / YSTGCZKI: other inn kukleSuoeu (A) OODK: / description - "DNA (synGttycsry) (xi) SEQUENCE OPDS: KEQ DD No .: 54:

GTTCGT / CTT GACTTATGCT A / TGACTATG TG (2) INFORMATION ABOUT SEQ DD Tr: 55:

(i) SEQUENCE FEATURES:

(A) LENGTH: 28 base pairs (B) CYP: nvnlrinohydrate (T) THREAD LENGTH: single (D) AOPOUOAIA: linear (ni) CYO / NUCLEAR KD: Snny nucleic acid (A) OPIK: / description - "DNA (synthetic ) (xi) SEQUENCE DESCRIPTION: SEQ DD No .: 55:

GT / ATATTCG TTTTCTATAT T / TTGTCT (2) SEQ INFORMATION DD Tr: 56:

(i) SEQUENCE FEATURES:

(A) LENGTH: 32 base pairs (B) CYP: Owi? Nucleic (T) QUANTITY NDCI: single (D) norOUOniA: USnial (ii) CYO MOLECULES: other Nucleic oat (A) OPDS: / description - "DNA (synthetic) (xi) SEQUENCE OOD: KEQ DD No.: 56:

ATTCATCCTT AGCTACAGCG CGCGGTTTTC CT

230

184 424 (2) SEQ INFORMATION NA Na: 57:

(i) SEQUENCE FEATURES:

(A) LENGTH: 28 base pairs (B) TYPE: WbkluHnic acid (C) NUMBER OF THREADS: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other vucarivic acid (A) DESCRIPTION: / description a ,, DNA (synthetic ) (xH) OONS SEQUENCE: SEQ NA No: 57:

yGCTlTTiyT TITGCyTTTT ClTlTTGC (2) INFORMATION ABOUT SEQ ID NO: 58:

(H) SEQUENCE FEATURES:

(A) LENGTH: 32 base pairs (B) TYPE: wpkauHnoay acid (C) THREAD QUANTITY: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: Hnny nuklrHnoa · y acid (A) DESCRIPTION: / description a ,, 1 ^ 1 (synthetic) (xi) OONS SEQUENCE: SEQ ID wa: 58:

G1TCT1CC1G GTCTTC1GGT T1CTTTCCAG 11 (2) SEQ INFORMATION NA No: 59:

(i) SEQUENCE FEATURES:

(A) LENGTH: 28 base pairs (B) TYO: nucleic acid (C) AMOUNT NNCN: single

184 424 231 (D) TOPOLOGY: linear (SS) PARTICLE TYPE and other nucleic acid (A) OPNS: / description = "DNA (synthetic) (xi) SEQUENCE OPNS: SNQ ID no: 59:

CTCGAhTACY GAChHCAhGA CGATCCGA (2) INFORMATION ON SNQ ID No: 60:

(i) SEQUENCE CECSES:

(A) LENGTH: 54 base pairs (B) TYPE: nucleic acid (G) QUANTITY NNCI: single (D) TOPOLOGY: linear (Si) TYPE OF PARTICLE: other acid / nucleic acid (A) RPNS: / description = "DNA (synthetic ) (xi) SEQUENCE OPNS: rNQ ND go: 60:

GGhCTGAGAG GGGCGAGAGC CGCCATAGGG CGGCGGAAGG hGGCGhATAA GGCG (2) SEQ INFORMATION ND No: 61:

(S) SEQUENCE CECSES:

(A) LENGTH: 54 base pairs (B) TYPE: GuklriGowr acid (C) NICN AMOUNT: single (D) GRPOLOGY: linear (iS) TYPE OF PARTICLE: other nucleic acid (L). RPNS: / description = "DNA (synthetic) (xi) SEQUENCE OPNS: SNQ ID go: 61:

CaGCCCTCCC TCGGCTCTGG CTGChCTCAG ATGPTCCTGC TCaayhCPPT ATAG

232

184 424 (2) INFORMATION ABOUT SEQ ID Nu: 62:

(i) SEQUENCE FEATURES:

(A) LENGTH: 18 bases (B) TYPE: nucleic acid (C) QUANTITY of NlCl: single (D) TOPOLOGY: OSnirwi (ii) TYPE OF PARTICLE: other nucleic acid (1) DESCRIPTION: / description = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID nu: 62:

GGGyTGCGCA AGGTGGCG (2) INFORMATION ON SEQ ID Nu: 63:

(i) SEQUENCE FEATURES:

(1) LENGTH: 21 bases (B) TYPE: nskluinrwy acid (C) THREAD QUANTITY: single / nczi (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (1) DESCRIPTION: / description = "DNA ( synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID nu: 63:

ACACCATTGG GCCCTGCCAG C (2) INFORMATION about SEQ ID Nu: 64:

(i) SEQUENCE FEATURES:

(i) LENGTH: 32 base pairs (B) TYPE: Nucleic acid (C) AMOUNT OF NlCl: single (D) TOPOLOGY: linear

184 424 233 (li) TYPE OF PARTICLE o other nucleic acid (A) DESCRIPTION: / description - "DNA (synthetic) (el) SEQUENCE DESCRIPTION: SEQ ID no: 44:

GATCGACTAT GGCTTACAAC CT1TCCCACC CC (2) INFORMATION ON SEQ ID No: 65:

(i) SEQUENCE TIMES:

(1) LENGTH: 36 base pairs (B) TYPE: nucleic acid (C) NICN NLQ: single (D) TOPOLOGY: linear (il) TYPE OF PARTICLE: other nucleic acid (1) DESCRIPTION: / description - "dna (synthetic) (xH) SEQUENCE DESCRIPTION: SEQ NA no: 65:

CCATCGAAGC TTATTA11TC CCACAGAGTT TCTCCT (2) SEQ INFORMATION NA No: 66:

(i) SEQUENCE FEATURES:

(Α) LENGTH: 32 pioy zisid (B) TYPE: nucleic acid (C) NNC1 NLQ: single (D) TOPOLOGY: linear (il) TYPE PARTICLES: another nucleic acid (AND) DESCRIPTION: / description - "DNA (synthetic)"

(xi) SEQUENCE DESCRIPTION: SEQ ID no::

CATC1AGCAT CCGTCCC1A1 TTCCCCCCCA CC (2) INFORMATION FOR SEQ ID No: 67:

234

184 424 (S) SEQUENCE FEATURES:

(A) LENGTH: 36 base pairs (B) TYPE: kwa? nucleic acid (T) STRING SIZE: single (D) TOPOLOGY: linear (ii) PARTICLE CYP: other nucleic acid (C) OOIK: / description - "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: KEQ DD no .: 67:

CGTTCATTGG TTTTTTGGTT TCT // CCCCT AAACCT (2) INFORMATION 0 KEQ ID Tr: 68:

(i) SEQUENCE FEATURES:

(A) LENGTH: 32 base pairs (B) TYPE: kwa? nuOiuSnoay (C) QUANTITY NI / I: single (D) TOPOLOGY: linear (iS) CYP PARTICLES: different acid? nucleic (A) OPIK: / opS? - "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: KEQ ID No .: 68:

ATTCGTCCTT nGGCTTGnT / CCGA / CCAGC TG (2) INFORMATION 0 KEQ ID Tr: 69:

(i) SEQUENCE FEATURES:

(A) LENGTH: 36 base pairs (B) TYPE: Nucleic acid (C) NDCD STRENGTH: Single (D) AOPOUOGY: Linear (ii) CYO FREQUENT / ZK1: Other acid? nuOirn new

184 424

235 (A) DESCRIPTION: / description = "DNA (synthetic) (xL) SEQUENCE DESCRIPTION: EEQ ND No .: 69:

TGAACGAAAC TTATAATCTC AACCTAGCTA CCAGCA (2) INFORMATION ON EEQ ND No: 70:

(S) SEQUENCE FEATURES:

(G) LENGTH: 32 bases (B) AYP: nGkiuinzwA acid (C) THREAD QUANTITY: single (D) TOPOLOGY: linear (LL) CYP PARTICLES: issy acid nGkIeLnname · (A) DESCRIPTION: / description = "DNA (synthetic ) (xL) SEQUENCE DESCRIPTION: EEQ ND no: 70:

AAATAATCAA AUTTACCTAG GArGCCATGC TA (2) INFORMATION ON EEQ ND No: 71:

(S) CETHY SEQUENCE:

(A) LENGTH: 36 base pairs (B) AYP: NNCN acid (C) NNCN QUALITY: single (D) TOPOLOGY: linear (Li) CYP PARTICLES: Linear nucleic acid (A) DESCRIPTION: / description = "DNA (synthetic) (xL) SEQUENCE DESCRIPTION: SEQ NA so: 71:

CUAACGAAAC TCAAAAAUUT CUTAGAATAA GGACCA (2) INFORMATION ON EEQ ND No: 72:

(i) SEQUENCE TECHNIQUES:

236

184 424 (A) LENGTH: 36 bp (B) TYPE: Owi? nucleic (/) LOT OF NICD: single (D) TOPOLOGY: linear (ii) TYPE OF CROBULLET: other inns kukleSukiy (A) OPIK: / opS? - "DTT (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID No .: 72:

CGTTGATTGG TTTTTTGGGG AGCTAUGCTG AGG // T (2) INFORMATION ON KEQ DD Tr: 73:

(i) SEQUENCE FEATURES:

(A) LENGTH: 36 base pairs (B) CYP: kwa? nucleic (/) SUMMARY NI / D: single (D) TOPOLOGY: linear (ii) KEQ TAPEZKI CYP: other nνklrgnoay acid (A) OPIK: / description - "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: KEQ DD No .: 73:

CGTACATTAG TTTTTTGGGG TTGUCCnn / T TGGGAG (2) DNFORMA / JE O KEQ ID No .: 74:

(i) SEQUENCE FEATURES:

(A) LENGTH: 21 base pairs (B) CYP: kwa? nucleic (T) QUANTITY. THREADS: single (D) TOPOLOGY: linear (Si) CYP PARTICLES: Snny nucleic acid (A) OPDK: / description - "DNA (synthetic)

184 424

237 (xi) SEQUENCE DESCRIPTION: SEQ II no: 74:

CTACACCCCC CTCCACCCTC C (2) INFORMATION ABOUT SEQ II No .: 75:

(i) SEQUENCE CECTS:

(A) LOOSE: 25 base pairs (B) TYPE: nucleic acid (C) NUMBER OF THREADS: single (I) TOPOLOGY: linear (ii) TYPE, other nucleic acid (A) DESCRIPTION: / description = "INA (synthetic) ( xi) SEQUENCE DESCRIPTION: SEQ II no: 75:

CCCCCCACCC TCCACCCCCC TCTAC (2) INFORMATION ABOUT SEQ II No: 76:

(i) SEQUENCE TIMES:

(A) LENGTH: 53 base pairs (B) TYPE: nucleic acid (C) NUMBER OF THREADS: single (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description = "INA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ II no: 76:

TTCTACCCCA CCGTCCCCAC CCCyCCCCCC yCGCTCACAT GTCGACACCA TGC (2) INFORMATION ABOUT SEQ II No: 77:

(i) SEQUENCE FEATURES:

(A) DEAL: 53 base pairs

238

184 424 (B) TYPE: nskluSnrw acid / (C) QUANTITY NlCl: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE Nucleic acid (1) DESCRIPTION: / description = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID nu: 77:

C11TGGTGTA GACATGTCAG AGCCGCCGCC GGGCTGCGCA AGGTGGCGTA GAA (2) INFORMATION ABOUT SEQ ID Nu: 78:

(i) SEQUENCE FEATURES:

(1) LENGTH: 439 base pins (B) TYPE: nucleic acid (C) QUANTITY of NlCl: single (D) TOPOLOGY: linirvah (ii) TYPE OF PARTICLE: other nucleic acid (C) DESCRIPTION: / roSp = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID nu: 78:

184 424

239

UCC1CCCUCC 60 CCCCCCTTCC CUCTUCCCCC CTCCCTCCCC CCCA1AUCCC ACCTTCACCC CGUCGUUCCC 120 CUAACAACCC CCATUCCUCC TCCTGCCCCC CCCGUCCUUC ccueicccTT CTCCCTCCCC 180 CCCGTTAUCU CTTCUCCATU TCCUCCAATA ACCCATACAC CUCATCAGTT CCCUAUTCAC 240 CGCCCCGTCC CCTCCCCCCC CUCCGUCCCC CCUCCACUUC CTCACCCTCC CUCCCCCC1C 300 CCCCClTCCC GGCCUUCUCC TUUCACUCCC CCCTTTACCA CCCGACTGTC CACCCTTCCA 360 CCCCTTATCC AUCUCAUTAC CCACCTCCCT TCTCUTGCUU CGTCTTCTCC CCUUTCU1CC CUTCTTGTCC AAGCGCCCCC ACCAACCCTC cccccccucc CACCG1AGCT

420

CCCCCCCCCC CCCCCCTTC

439 (2) SEQ INFORMATION NA No .: 79:

(i) SEQUENCE FEATURES:

(1) LENGTH: 465 base pairs (B) TYO: iunauiipay acid (C) QUANTITY NiCl: ppjras · icgn (D) TOPOLOGY: linear (SS) TYO PARTICLES: other nucleic acid (A) OONS: / description a _Z , DNA (synthetic) (xi) SEQUENCE OhiS: SEQ ID NO: 79:

ccccccuccc ycccTTychG TGcccTycuc tcccgcctgc cccctccgcu cgcctcccac 60

UGCCCTCCCC TCAUCCTUCU CCCTCTCCCA UCU1GCCCCC CCCGTCCCCC CCCTUTCCCU 120

CGTCCCTCCU TGTCCTTGCU CCGUUTCGCC TUTCAA1CCC CTCCUUCU1C UACCCAGTCC 180

CCGG1CACCC CTTUCTCCUC UACCCCCCCT CCU11UUUCT TUCTUUCCUC CCUUUTACCA 240

CCUUUCCCCC CCCUCCTCCC CTCCCCCCCT TUUCCUCCCC CCUTCCCTUC CCUTCTCCTC 300

240

184 424

yyrcGCirrr 360 ClCGlGirrr rcrriiCArr ccirccrrrr ΓΑΓΑ111ΓΑ1 iGrcnrnicr ΓΑΓΑΑ11ΑΤΓ 420 rCGACirCGC rcccrcciir ΤΤΓΓΑΑΓΑΓΓ CirTrCIGCl nisiiTiriT hCCrhlAClC cicnicnics ΤΤΓΓΑΓΓΓΤΓ ciricrciii AATCA

465 (2) SEQ INFORMATION NA No: 80:

(i) SEQUENCE CECSES:

(A) LENGTH: 927 base pairs (B) TYPE: GuklriGowr acid (C) STRENGTHNESS: Single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other GuklriGsay acid

(A) OPNS: / description = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ND go: 80: Tcrcrcircc 60 CGCCTirCPi rinrrcrriA ΤΤΓΓΤΓΑΙΤΑ AirTGCThri ΤΤΑΓΤΓΓΓΑΤ ΤΤΓΓΤΤΓΑΓΑ 120 ICAinrriAl rrAlCCCCGA CAiicccArr ccrrirrric nrcricrrri rrccccirci 180 Τ — 1ΑΓΡΤΤΑ1 rrriTGAiAA Ρ1 — ΑΑΑΑΓΓΓ AlAhTIGIGA 1ΑΓΓΑΑ1ΤΓΑ CGCCirATTC 240 TCilAirAlT lArrrrccrc rrCGATCiAl CGGTiCAGCr ΑΓΙ — iCACAG CTllCArcrA 300 ΓΤΤΙΓΓΤΓΤΓ ΙΤΓΓΓΤΓΓΤΤ iiiciiccrc crncACAi — c rciccccrrc crriiiircc 360 TiCAlAirrr rrCCGCAArr riiccrrcrr cArAiiiCAi ιαγγαγαιγτ CAriAllATC 420 rcssTircir rrccrrcAir ΤΤΓΓΑΑΓΑΓΓ CircrriAll AGAlCCirir yyrcr — ATic 480 rrTTAiCAic irccirrrrr τ — ricrAiGi Aarrciicii γααγατιτγι Tccrrrircc riccTirrri CGArrccriA ICrrCCAlCA AirCCCCrri ΤΤΑΓΤΓΓΓΑΤ

540

184 424

241

CTGTCCGCGA CTGCAGCCAC TGGlTCTGGA GGCCTTGATT TCTC1TTCCT IGTTCCGGTC 600

TCCTTCCGCC CCCATCTTAl TCCCGGACAl CC1AA1CTTT ACCCCCAC1A lAGGAACCCC 660

TAllATACTT CCCCACTAlC CATTTCTCC1 TTCCACCCAC ClACClTGCG CTC1C1AGGC 720

GTClGGTGTl TTTCTTCTCT ACTTTCCGTC CCCTACTCTT TCCCATCCCC GGlCTCGGTC 780

TTCCCCCGTT TCGACAlGTC TTTT11CATT GAClCTACCA TTATA1TCTA GAACCACTTT 840

1GC1CTATGT CTGC1A1GTC TTA1TCTGC1 GCTTCACCAC ACCCCTCCCC GGCCACCGTG 900

1CA11ACCCC TTlGTGTGTC TCCTACl 927 (2) SEQ INFORMATION NA No: 81:

(i) SEQUENCE FEATURES:

(A) LENGTH: 936 pairs of bases (B) TYPE: kwis nuklulneay (C) QUANTITY NNTN: single (D) TOPOPY: lnnlowi (li) TYPE OF PARTICLE: other acid n "kiiinoac (1) OPNS: / description -" DNA ( synthetic) (el) SEQUENCE OPNS: SEQ NA no: 81:

CTTTTACGCT GCGTCCTCTC CGCTTTCCGA CCGTCTACCA ClGClTCCGC TCAGCTTTAC 60

CCGTTCTCTA CCCCAGCGGl TTA1CGTTTC GGCCTTGATT TCCC1CTCCT CTTT1TTTC1 120

TCCTTTCGCC CCCATCTCAC GTTCCCACAC CCClCAATTT ICACClACCA CATTAAClTl 180

TAllATACTT CCCCACTAlC CATTTCCGTC GCCCllCCAC CCACClGACT CTllllATGC 240

GCCCCAGTTA CCCCTTCTCC ACTTTCGTCC CCCTAlTCCT TCClAClCCC TTCTTCTTCT 300

GCCCCCCGTT T1TA1A1TTC TTTTCCCGTG T11TCCGTCG ClGAClCTAC CCGGATGCGC 360

242

184 424

GTGCClUCrG AGCCTUGACT GTTGGTUCUG TTAACCAAAA TUGTGGATUC ATCUlTlAlT 420

TTAATCCTUA TCCrAGCCUU UTAAAGGATA TCGUTACUll ACTTAU1GAA gctucgutgc 480

AGAGATGAG / GTCCTTUTUC GGrGGCTCTG GTGCUTCCTG TlGTTGlTUT GTGGGCCUTG 540

GTTGCGCUGC UTGTGACGGC UTCGGGAUCl UTTGAGAGTT TUGGCTGTGG T1TAGTUTTG 600

GGTCGTCTCU TGryTCUGTT UUlCUCATUl CCCAGAACUC TlUTCUCCCG GCTCUGCGCG 660

GAGCTTATCU CC1GCUCUCG GGTTGCUTTC unuinnuTun tuu / augagu ucutgtagtg 720

CCCGGGCGTT CGATCCCATG GGTGCTGGCG GAUGCTTGTl ICGACCrCGU TGTGGTGGTT 780

UUllAGATCG AUClGCCGGT TCCCAGGGCC ATCAGrAGAA AGGGGAUGAG GCGCUGTATG 840

TAUUCrAAGC ATGAAAGGTT GATCAUGCTA GCAGCAGTGA TAACAClACA UUTUGUTTTG 900

ATlCTlATTC TCGCAGCCTA GCAGGCGTUA UTACll

936 (2) INFORMATION ON SEQ DD No .: 82:

(S) SEQUENCE FEATURES:

(T) LENGTH: 939 base pairs (B) CYO: nucluic acid (G) QUANTITY T1TD: single (D) TOPOLOGY: lSniowi (SS) TYPE OF PARTICLE: Snny acid snOlrinoay (A) OODS: / description - "DNA (synthetic) (xS) SEQUENCE OODS: SEQ DD No .: 82:

TGAAAClATG GCAATUGTTC TCCGGTGGlC ITAATAAlTC TlATUGrCGC TUAGCGAGAT 60 iCGATTACAC UACGTGCCCC AACUTUGGAC UCUUTTAAAA ATCCCAATAA CGGTCTGGTC 120

184 424

243 ciGCCTGCir TrGacTTiaG cttcggccic yGGcAccccc crayGcarra Gaccaacccc 180 caccacaTic irccaccaci cacccTTcic cyccacGcac icaicccacc accccccccc 240

CTGcrccccn ciicccicyc aiccyicciG ccccAGcyyi yycGccacci ccGiciccic 300 cttcccgccc TGccraGCcy ccyyGGCAcc ccccTicciy caciccccar GacccccccT 360 cacnacGaic cccaTCCCCi ciiccyGarc yTCcaacccc tcctcccccc aacGGiGCGT 420 yyccTcaicc iiGiAGcacc Giccccccic iGccicnccc rciTccrccr cacccicccG 480

TCTCCCGClC CCCCTGCiTG TACCTCCCA GiCCiCCCiC CaCTGCiTCC ICCCiCCCAT 540 ricciicaca ccccacTcac ccacTGccca cccGiicccc ciTTCccTac accyciccTC 600 cicccicciG TCGCciiTCG ciiCGGccca TCGCinaccc crcTCGarGa GacccncGcc 660 cAGcacATTC iCGCcrcaci cacccTicic ciCGaGcrac tcctggcccc acccggccac 720 cicrraccca cttgcctctc aicccTCciG CGCcacciii ciCGaccGGi ccgictcctc 780

CilCGCCCCC iCCCGAGCCl CCiTCGCCCC CACCITCCiC CaCCCGGCAC GaCCCCTCCT 840 cacaacGaic ccaahcccci cttcctccgc TTCcaacacc tcctccgccg nacrriGCGT 900 llCClcaiCC iTCiCCGCRCG

939 (2) INFORMATION ABOUT SEQ LD No .: 83:

(i) SEQUENCE FEATURES:

(AND) LENGTH: 948 base pairs (B) TYPE: nskluinrwy acid (C) NICl QUANTITY: single (D) TOPOLOGY: Linirva (ii) TYPE PARTICLES: ieey quickies (AND) DESCRIPTION: / description = "DNA (synthetic)

244

184 424 (xi) SEQUENCE DESCRIPTION: EEQ ID so: 83:

gtcttattat tttttttttt tcacccttta crTTGTacea acTCCTecTr tcatttttct 60 ττίίττίαία atatatctat ttagtcttta agccggcctt tgcccttggt attgtgtttt 120

ΊΤΤΊΊΤΤΊΤΤ TCCATTTTCA TGTAACACGA GCCAACGTTT ΑΤΑΤΑΤΑΤΤΑ (ΑΤΤΑΑΤΑΊΑ 180 ίατταίαττί gctacctcat catttcttcc cgccacagac ttagcctact atttaaatcc 240 ttcttcttta tttttttttt gttttctttc ccatgttcttcttccgttttctttc ccatgttcttt ttccgttttctttc ccatgttctttttccgttttctttc ccatgttctttttccgttttctttc ccatgttctttttccgttttctttc ccatgttctttttccgttttctttc ccatgttcttcttccgttttctttc ccatgttctttttccgttttctttc ccatgttcttcttccgttttctttc ccatgttcttct

TATACCCAGT TTACTCTTCT TCGTCCCACT GTCTAATATT GTTGTTTATT AAACCTATTT 420 ttttttattt CGTTATTATT (GTCACCTGT cctcttaccc aatgccctcc taatcttatt 480

ΑΑΊΑΤΤΤΊΤΤ ΤΤΊΊΑΤΤΤΊΊ (CTTGCCCGG CATCGCTCAC GTTGTATCAA ΑΊΤΑΊΤΤΊΤΤ 540 (ATTTTTAGC ttttttatct tatacccact taccctttac atacctcttt ggtctttata 600

TTTATTTTCT cctttttttt tcacttcact cgcctatagc ccaaaatttc tagccattat 660

ΑΊΤΑΑΤΤΊΑΤ ACTCTATTTT TCAAATACeT ATTTTATCTT TCCACTTATe CAGCCTAlTA 720

ΊΤΤΤΤΑΊΑΑΊ GCTCATTTCT GGGCCGTGTA GTTTGTTGCC ((TACTTGTC TTTATATTTT 780 tttttttttt gctttctttt ttatacttgc tccccaattt gttgtttgtt ataccctatt 840 cttacatttt ctactcattt tcatcttatt ttttccactc tttactattt tttttccata 900 ccattttttt ttttcacttt tctaccaact tttatttttt cttctctc 948 (2) INFORMATION EEQ ID NO: 84:

184 424

245 (i) SEQUENCE TIMES:

(A) LENGTH: 688 base pairs (B) TYPE: nucleic acid (C) NUMBER OF THREADS: single (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description = "INA (syntut / czn /) (xi) SEQUENCE DESCRIPTION: SEQ II no .: 84:

TcrcicriiT 60 rcGiTTiTic TCATTClTCA lATllCATlT CGGTTGAlll llTCATGTCT CTTTTGCGTC 120 llTTTllCCl ITGCGClCll TlAillTllT CTTCCTTlll TGlACGCAGs ttcttcgtcc 180 CTAAlTGTlC AllCTTTClC IClllTlllG CGCAlTlCAl 1C1CTCT1TT ciircTTCci 240 CCllTlTTTT ClGlCTTCTA CTGlTCCGTC TTATTlCTTl TC3CTCGGTT TTcrcccTiT 300 TTCllTCTTl CGlAlCTACl TllGlllTCl CACTCTTlll CilAlTCGCT CTTGTGTGTl 360 CTTlTTTTTl GCGAiCGCGC CCllGlCGlC cciyciciTi TlA1ThlGTT TcriiTGiTG 420 cciciciirc TATATGATCT CCllllCGGC GGCCTlTTlC TCTTCCATGT CClGCCCTTC 480 IClllTllll ATlTTTGClC GTTClTCClG CC1G1TTTTG llCTTGCCCl TTTlCGCllT 540 TTTlllllGl CCCCT1GGA1 TCTAlGillT CTCTTlllll TTCACCGGCl rTTTTCTiii 600 TCGGClTTAl CCGTCGGClG CCTTlTCCTT CTATTTlTTG llTATGTGlC TlCTlTGlAl 660 CTAlCTClAł CCCAlClllG TGCCCAllGl CTCCTlTTGl 1CTTCCCTAT TATTlAGTCl CGCTllllAG AATllTCT

688 (2) INFORMATION ABOUT SEQ II No .: 85:

(i) SEQUENCE FEATURES:

(C) LENGTH: 712 bases

246

184 424 (B) TYPE: nucleic acid (C) QUANTITY NICl: oriudrejzl (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / roip = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID en: 85:

caTcrciicc iccicicica icaicGCira aciTCiccci ccciiarcca cccccccigc 60 ccciihccic cacccccacc cccTCAciGa ccaAcacGic iciaiccicc tcgccccacc 120 cciiccccii ccnanccirr acarchicci accgcctcic cccraciicc accctcccic 180 acGiciiGaG ccAiiiciic cicaichccc accaiGiciG ccciciccca ccgccgctcc 240 ciciccacAi ccrciccicc iccnrrcarc iGCCicccac ccattcccgc acaccciGac 300 ciicTCiCTG ciiaccciiG acccaccccc cccacacccc cgiggiggci cicccggigc 360

CTGCGCCGGC CGhTCiTTCT GCiCiCTACl GCiCCaiCTC CTTaiTCTiC CCiTCACCaC 420 accacciGca cctticcicg ccccrccccc cctcctigcc racGacGici ciciccigct 480 cGaccraaac citcactcrtc 540 cGaccraaac citcactcrtc

AAciGCcica rcTaiiraGr ccattcttcc laciciccAr ccctctctcc ccicigcctc 600

CCCCGCTCCC IClCCCCCiC CCaTCCTCCl CACCCCCCri CCCTCCCaCG AgTTCCGGCC 660 aaaacTGCCG iiciricicr TTacccTTrc ccttgccccc rcrccacaci cc 712 (2) INFORMATION ABOUT SEQ ID No .: 86:

(i) FEATURES:

(A) (B) (C)

LENGTH: 975 base pairs TYPE: Nucleic Query NICl QUANTITY: Single

184 424

247 (D) COOOUOAIT: lSsSoaa (iS) CYO PARTICLES: other Owch nuOiuSnoar (A) OODK: / description - "DNA (synthetic) (xi) SEQUENCE OODS: KEQ DD No .: 86:

AGGUATUl 60 AAGAUCAGCC AGTGAACGAA CCAUAGCTGT GTCTGATGAT UUAAAUAAAG GCCAGCGTTA 120 ACAlGATClC lAUACCGCTC CGGCATGTAC ACCAATCAUA CAATGAATAA uGccrrucii 180 GCATCACCGl TCATATAAAA AACTUTCTUA AGTGTUAGCA UGGGCAAGGA CACAUCACTA 240 ACATGCCGCT ACCCUGACUG UCGTCUGCCC CATGAACUCA CCAAATGAGC CCGCCCGCCU 300 TTAAGCTTCA CACACAUGAC UCCACAGAlG UCUUriGGCG CATGTGGCGT ACTTTCACAl 360 ATUACCCCCT AAATGAGCTA CCUACAGAAA GTUACAGTTC GCAAUTACCC UGGliriCCU 420 UATAAAAUGU TCAAGGUCAC UCTAAACTAT ACAGTCCGAT AAAGCATGAT GGCCCriACU 480 AATGCGATAC ATATGAAAAA CTCCATAAAA AGGCTUAGAC CGGCUAACCG gggcatcgtc 540 CAGCGACAGC UGAAGGAGCC UTAATUCTTG ACAUAAACGC CAAGAUACTG ACUGCiiTir 600 AUTCAAGCCT CGTAAGGGAA ATTCAUACUA agtgtuugcg GCGTGCGCCG CGCAClCCAr 660 TAATGAGCCC UTGCCCACAU ACAlTGAUTA ACACAAAGUU AGAClGCGGA CGCATAAAUL 720 AUCAUATGTG CCTAAGGTAA AACATUTUAA AAAGAlCCUA CGCCCTCCCG GCGUCCAAAr 780 ArATUCGAAT GGGACGCCGT AAAATGAUGT GGTUAAAGCU GGAGUAGATG AACATlUCTl 840 UATUGrCUCU GGACGCCGAT ClAlCAGTCT CAACATAGAA UGGCGTAACG

GACGAAATlG TAlGGCCATA AAAGGAGCCU LUTAAGAAAT TlCCACGAGC UGAGGTCGAA 900

248

184 424

GTCGCCGACT TTGCCACCAC CATCTGGCAG CAGATGGAAG AACTGGGAAT GGCCCCTGCC 960

CTGCAGCCCT AATAA

975 (2) SEQ INFORMATION NA No: 87:

(H) SEQUENCE FEATURES:

(A) LENGTH: 975pa; bases (B) TYPE: npclrSnpay acid (C) QUANTITY NiCl: single (D) TOPOLOGY: linear (SS) PARTICLE TYPE: other nbnluSiPay acid (A) OONS: / opHs a aDE1 (synthetic) (xS) OhiS SEQUENCE: SEQ ID e.g. 87:

ATGGCTCTGG 60 ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGACCGAAAC CTTCGACTTC 120 CAAACCTGGA GACGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG 180 caattcttcg TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC 240 CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG TTCTATCTGG 300 TTACCCTTGA GCAAGCGCAG GAACAACAGG GTGGTGGCTC TAACTGCTCT ATAATGATCG 360 ATGAAATTAT ACATCACTTA AAGAGACCAC CTGCACCTTT GTACGTAGAG GGCGGTGGAG 420 GCTCCCCGGG TGAACCGTCT GGTCCAATCT CTACTATCAA CCCGTCTCCT CCGTCTAAAG 480 AATCTCATAA ATCTCCAAAC ATGGCTACCC AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT 540 TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG CTAGCCATCT GCAGAGCTTC CTGGAG3TGT 600 CGTACCGCGT TCTACGCCAC CTTGCGCAGC CCTCTGGCGG CTCTGGCGGC

184 424

249

ΤΓΤΓΑΤΑΙΓΤ ΤΓΓΤΤΓΤΓΑΑ ΙΤΑΡΤΤΑΙΑΙ ΓΙΑΙΤΙΑΙΑΑ Α11ΤΓΓΑ — 11 riACCGClGA 660 irCrrrrAGl ATlilCCiTl Τ1ΓΓΑΓΓΤΑΓ S11CTTTTCC ΑΓΓΓΓ1Α11Α 1ΓΤΤ1Τ1ΓΤ1 720 rrciiGCAcr rTCTGCGrAh γγγγτιιιγτ ccc — rg1 rt cccGrgg1 rt cccGrgg1

ΓΑϊΓτττΓΐτ τγττγτττατ γγααγτγγατ AircicrcTT τγγτγταγγα icciccrrci 840 rATirrCCTC AGiCCACACC CrrClAiTTi llTCCCGCCT TTTACArerT TCGCCTTGAr 900

TCCirCTArT TGTCCGCCAr CATCTiGCAi A11GTGCAG1 ΑΑΓΤΤΙΤΑΑΤ llCCCCCGCr 960

CCGrAICrrr AACAA

975 (2) INFORMATION ABOUT SEQ ID No: 88:

(i) SEQUENCE CECSES:

(A) LENGTH: 975 pairs per / ad (B) PYP: acid / nucleic (C) NLCL NlCl: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) RPNS: / list = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SNQ ND go: 88:

ArTicricAc 60 CCCCTCGACA rcrnATAirc ATGAGllCAl TTlAChllCG ATSaTTACTl llSGGACriA 120 ClCCCClCCC niTTGcrcrc iAiriAGCTC AllSICAArG TCCTTTTT1C hCCGACTTCC 180 CTATGATTGC ΓΤΑΤΙΑΑΑΤΤ ArGCGCCGCC TA1ATATACC ACCTCCACCr TCCCCCTACC 240 ClAGCGGCCr CliriGCiAG lACTCCrCCA rrCTCATill CCllAGCCCC C1ACCCCCAA 300 GCrriTATAl crcciCGGii 1CCGTC1A1A ICrrAlAGAG rccGCCACir AhClGCGGAA crccrccrAG TCTCrAACCA C1CCCGCCCC criccACiic ChlClCAGll

360

250

184 424

11T11T11A1 CTCTTTTlCC CCClGGCCGC ClCGGGCCTC TCATCACTCl TTGCCTCTTC 420

GGlCTTACll ACCTTGACAA ATTTGGAAAT ACCCTCATTT ACCCClTTAC CTGClTTTCT 480

CGTCTTCTTC TCTA1G1TTC ClCCCCClll CCTGTCCTTC TTA1TTACTC ITCCAlTCTC 540

GCillllCCC GCCATGlTlC CTCCTCTClT TCTCTCGAlG TTCTTGCTCC TTCC11T11T 600

CGCTllllTC TTTC1TTTAA 1TTTTTC1AC TAA1C1ACAA ACACGTllll TllCCCTCCC 660

CTITTTTlll ClGllTTCTl CCTTCGGCCT AA1TC1T1TT ATGTTCACCA CTTCCTlTCl 720

TCT111TATC TCTCCCCTCC TTTTTGCCTC TTTTC1A1TC TTClTTTTAl TTAC1TTTT1 780

TAlTTClTAC 1TTCTTT1A1 TGGCGTGC1C ACTCCTTCCC TTGCTCAGTA liilGCGGCl 840

GACCTTTTCi AAlllATCCG GTTT1A1CT1 C1TTTCGTTC CiCATAClGC CGCCGCClAG 900

ITClTTlATC TC1TTATT1T TACTTllCGl TAlCCCCAll GGTCClCAAC 11GTGTC1TT 960

TClCllTTTC CACAG

975 (2) SEQ INFORMATION NA No: 89:

(i) SEQUENCE FEATURES:

(Α) LENGTH: 975 pio bases (B) TYPE: nlkIeSneay acid (C) NNCN NLQ: single (D) TOPOLOTS: linear (li) TYPE OF PARTICLE: other acid n "k1einoas (A) DESCRIPTION: / description -" DNA synthetic?) (el) SEQUENCE OPNS: SEQ NA no: 89:

ACCCTTCTll CCCAGTCCTAo AlCATCCCCC CGiAGlATTll. T1CCTTACTC 1CTTACCTTC 60

184 424

251

cattactttt 120 atccatacta tttttttact gttaattttt ctatacgtag TCAGCCACTT ACATATTACT 180 GACACACATT attttccttt cgctgctatt TCACTCATTT taactattca CATATTTTGA 240 TTTTCATACA tttaaattat TCATTCTTCA attgctatat tcgtccaatt CTTATCAlCA 300 ATCTACACAC tttagtattt agttatttca gctgctttac TTGTTACTTA cctttttttt 360 tcattatctt tttatttttt TCATCTTCAA GTATTAGTAA tgatcgacct cctattttat 420 CTATTTTCCC ttcattcttt CAGTTCACTG TTATCAGTAA TTTCCTCTTG ttctttacat 480 AACTGTACAC ATTGTTAAAT (TATTGATTT acctgtttag CTTCCTTGGT tttttttttt 540 gttcttctta tctaccacct cgtttctggc tgatttagtg (TAAACTTTT tcttctctct 600 tcgattcttt tttattttat cccctttaat ttttcccttc tgtccctttt gttcctattt 660 gtttttgtaa tttcgcatat taatttacac acagttatcc ttacactcta tttttttact 720 (CAATTCCTC TCTTATTCAT aactttgctt ATTTTCACCA CTCCCCCTTC tgttcctatc 780 TGTTCACTAC TTTTCCCCTT TTTTTCACTT TTTCTTTTAC TTACATTTTC tatttcctat 840 CTTATCCCAC TCACTGTCAT actctttgtc GTTGTTATTA tccatctttt tattttttct 900 aactcagagt ttttcacttt ctttttattg GCCATATATG ttactcttat tgtttttatt CTCTTATTAT tatcccccat tacatttaat aatgcttaac tttttttgtt

960 ttttattttt aacac

975 (2) SEQ INFORMATION NA No: 90:

(i) TETHY SEQUENCES:

(A) LENGTH: 999 base pairs (B) TYPE: SINGNESS QUICK (T) AND SEQUENCE OF THREAD: single

252

184 424 (D) TOPOLOGY: linear (ii) THOUSAND PARTICLES: ieer nucleic acid (A) DESCRIPTION: / description = "DNA (synthetic) (xi) OSIS SEQUENCE: SEQ ID eo: 90:

aTGGCiCiGG ccccGaccaa CCiCCCiGCC Gaaccccici ciATCcTcai ccrcccaaac cTTCGaciic 120 caaaccircc GTGCTTCCiC ncGicirica aracciiaGa AcaTccaicc GiTTiiracc 180 cnAiiciicc laciCTCccc CCTTCiCiGC ccicicccac CCCCCCCCCC iCTCiaccic 240 cacTcricai CCTCGCCGCi GaciGCcacc acttccccct caracicccc iTCiaicTii 300 iTacccTTGa GcacGcrcac iiccaacacc riGGiCCClC ICCCCCiCGC aiciicircc 360 riiciaccir CTCTCTCCTC aicccTcrrc TTATTcaica cTTnaccccc ccaccicccc 420 CiTTCiCCll CCTCGCCCGi Gcaccciccc ccGCTGaacc cicTGcicca aTCicincTa 480 icacccccic TCCicccicT raacrcicic ciacaicicc acgcciccci acccaiccTi 540 ccaircccGC CiTCGCCTCi GClllCCCGC rcccGCcacc TGGCCICCTG iniciaccc 600 CICICCCCCC CllCCiCGCC GlllCGiaCC ccciiciacc ccrcciiccc caicccicii 660 CCCGCiCTCG CCCCiCiCAC acciTCCicc TCAcriCTTh ccrGcacciG airaacaicc 720 CCCGCGClGC CCCCGCCCTC caGCccrcGC icicicccnc circaccciG TCCCCCCCCl 780 CCCCGCTCCi CCTCCiCCGC cccTCiciri CCCTCCCClC GCCTCCCCTC riciccTGCc 840 ccaccccccc CCiCCCGCTC GCTCGCTCCl TGcrcccaci ccaicccccc

cTiiiccici cccccccrci cciccccgcc ciGCcarcca tcicccccgc riTGGGiccc 900

184 424

253

ATTClCGATl TAGClTllTT CllTCTTlTT llTTCCCGTl GTAGTAlTll 1T1CTCC1TG 960 yiiiciGCCi yciTiiTTTT tcttttgtii tttiiitii

999 (2) INFORMATION ABOUT SEQ II No: 91:

(i) SEQUENCE TIMES:

(A)] LOOSENESS: 999 bases (B) TYPE: nucleic acid (T) NUMBER OF THREADS: single (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description = "ΏΠ (synthetic ) (xi) SEQUENCE DESCRIPTION: SEQ II no .: 91:

ClGlTlCCCG 60 TGCTlGGCCl TGAGGTAAll TTCTlGAGTT CTTlATCllC ITlGATTGCG GTTCTGGTTl 120 TAGTTCGCTl AGGCTTAilT llTlTTllll TACCGGlTCl ITGlGClCTC TGGlCAAiCT 180 rccTiTTTrc TTlGCTTlTT ThłlllGlll TlTACllATA ITACCllCGG GGTCTCCCTl 240 GCGCTCGTGG TCGTGGlGTl AlTTGTTTGi lAATCllTll TlAAlTCAGG GllTlTTTCl 300 ICCllTGATT TGTCTGTTGl TTGllTTTll ITAlTTlTGi llATGClGCC GTTTTlCTTT 360 TGClGGCTTl 1GGTGTCTGA τττττιιιττ CGGCGAlTlC TllACGCGGG GTTiCGGlTC 420 CClAlTCTll CGAGGGTlGl GGllGTTTTT TGGGTG1ATT llTCCGTCTG ICyCTCATCl 480 ττΑίτττιιτ CTyCTTGlTl lAillllTTT ITCGATTlTT AlATChGITG ATTT1GGCCG 540 TGCTCTCGGT GTGTGGTlTC GTlTTATllT GTTGCCTAGG llGCCTTTTG ICllTTClTT ATTTGClGll TTGTGTGllG GTGTTlClTT ITGGCTlATl TTlTATTGCG

600

254

184 424

CC1CCCGCGT 660 UCT1CGCTGT CUTCTCTCC1 C1CCCCCC1C CCAAUGCCCC A1AUCCAUCG C11AA1AGCC 720 CUTTCTCCTU C1CATCTCCC CClUCGlAlC T1C1C1CCCC CGCCCC1CC1 CTCCACCCCU 780 CTUA1CTG1C UCCTCTCTTC ccccccccuu UCCCCCCCC1 G1CCCCCCCU CTCTCCGTCC 840 CCC1CCAU1C CCCTCAUCTG 1CCTTCCUCT CTAUCCAACC CCCCC1C1UC CCTCCCCCCC 900 ccceyTTTCT CCC1CCTGCC CTTUCCUGGA CCCCCCCC1A 1CCTTUCCCC ACCCGGTCCA 960 CCCG1CCTCC TTCC1TCTCC 1CCTCCUCCC CCACCCGCCl 1CCGCCGATT 1CA1AACC11 uccGGicccc TTCCCTUCCU CCCTCACCA

999 (2) SEQ INFORMATION NA Nn: 92:

(S) SEQUENCE FEATURES:

(A) LENGTH: 999pa; base (B) TYPE: iunluSipay acid (C) NUMBER OF NiCI: single (D) TOPOLOGY: lSiSoan (SS) THESE PARTICLES: other nukarSipay acid (A) OONS: / description a, ^ 1 (synthetic) (xi) OONS SEQUENCE: SEQ NA No: 92:

CG11CG1CAC 60 CCTChCTATA CCCACTCCCC CCCCCllCCU UCTCCGUTCA A1CCCTCC11 lAAieiCClC 120 ClCTCTACCC UTTTCCCCCT 1C1CCC1C1C CTGA1CAACC 11UTU1C1UC GCG11C11CU 180 1CATCUTCUU CUGTTCCCCC C1CCCGCCCC TUCCC1AC1A CACTACCCCG CCCGGAAC1A 240 UCCCCCCTUC CCCCTTUCCT 1ACCC1CACC CCCCCACGGl CGCAUCC1CC CCCCGCCTTA 300 CTUCCCGCAC CCTGCTACCT CCCCACCG1T CUAGCTGC1C AC111CCUCC CClAACCCAl 360 ACAACUCCCC C11TACC1CU UTAACCCCTC UTACCCGCCC ACCCCUCCC1

184 424

255

CCClCTGCCT CGGCCiCCCl CCaCGGCCCl CGaGCClCCC CGGCiCTTCC ClCTGCTCCC 420 ciciCTccia TcaccccGic Tccicccici aaaiacicic TTAacicicc accccTGGCi 480

CCCCTGGGlC CCClCCCGCC CTlCCCCiCl CCTTTCCCCC CCCGCCCCGG CCGGGTCCTG 540

CllGCTTCCC TiCTGCGGCC CTTCCTGGCG CTGlCGiaCC CCCIiClCCC CCACCTTGCC 600 caicccicic ccggctctcc cggctcictc ggcttccigc TcaAGiciTi acaccciGic 660 ccarcccicc cgccccctgg ccccgcgcic cccccgaicc TGTcicccac ciacatgctg 720 iCCCTCCCCC TGGTCCiCGi CCiCCTCCGa CTCiCTCiCC CCCTCCCClC CCCTCCCClG 780

CCC1CCTGCC CCCCCCCCCC CClGCTCClC CCaGCCTCCI TGaGCCTCCl CCTTTGCGGC 840

ClThlCCiCT TCCaCGGGCl CCTCCTCCCC CTCGirCCCa ICiCCCCCCC CilGCGTCCC 900 ccciiGcaca cccircAGCi rraccTCccc ccciTTGCca cccccaicic gctgctgttg 960 cncGcachcccaG cccicaCiCi

999 (2) INFORMATION ABOUT SEQ ID Nu: 93:

(i) SEQUENCE FEATURES:

(A) LENGTH: 999 bases (B) TYPE: nucleic acid (C) QUANTITY OF THREAD: single (D) TOPOLOGY: linirva (ii) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / rpis = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID No .: 93:

aiGGCiccac ciGcciccca ccgcttcccg ccarcaciGa cgttcicici ccitccccti 60

256

184 424

GClTAAlTlC S11GSTCGTA C1CT11T11T CTClCCllCl CTAlTlGCll TCCCTTTAAT 120

CCTCTCATCC C1STTGAC1A ACCTCTCTAC TATGTAAAlA CATCATTC1T STTCTC1TC1 180

1STTTCSSTS STTTCAATCA GlCAlCGCCT CTCACTTC1A ClClTTlACl TTCCTCSTTT 240

GTAGATTTll 11A1CCCT1C AGCiCTTCTC GllCGTCCAl AC1CT1TCCT S11CACC1A1 300

CCAACTCTTC ICATCTTTA CCGCT1TTTC TTCTCClTCG T1CTT1TATT TCTCTlSCGC 360

TCSACTATTS CTSS1CATCC A1AC11GCCC 1CA1CTTTTT TlllTlSATT 1CTC1CCTTA 420

ATTCTCSTTS CTCCTTTlCT TCTTTGCCTT SSACSATTCT ATSSCTTTTT GCATATCCTC 480

ATTTSCClTl TCST1CT11G TTCTCGCCCT CTTCCGGAlG CTT111TA11 A1C11CTTCC 540

1TC1TCA1TT STTG1CS111 TTCTGT11C1 CC1CT1TSCT 1T1TTCCAT1 TTATTCT1T1 600

CllTTGTGTl ICllTCTCCC TllGTGTGCC CCCCCTTC1T CTAA1TTTCC A1A1TSA1CC 660

SlSSClSTTT SlilTlSCCi GlTCCGCTCT CS11ACSA1T C1T1T1TTST TCATASCTC1 720

C1TT1TTTT1 SllSCCCilC 1TC1TCC11A CGTTGTGCll 1TSCTTTTT1 CCCCTTCTCC 780

S1TCTTTCCT TCS1TTAG1T TTCCGClTCl- CTS1CCC1TC C1S1TTSCTC TTATA1TC1T 840

TCCCCTTTCC ACCSiGGiGC TTT1GC11TT TCCiSSCGCG CACTTTTT1A CCCCClCTTT 900

SCTCC11SCS TSTTGTAGTC ICAGCTTCTT CACCTC1TTA TTCTCATTCC 1TS1TS1AC1 960

CSAlAACTCl ISSTClTGGT CCTGTCGTAl TTTTASTGA 999 (2) INFORMATION ABOUT SEQ ID No: 94:

(i) SEQUENCE FEATURES:

(1) LENGTH: 918 pio zisid (B) TYPE: kwis nukauSneay (C) THREAD CHARACTER: single

184 424

257 (D) COOOUOAIA: linear (SS) CYO TCĄrCECCK1: Snny acid nuOluSsoar (A) OPIK: / description - "DTA (synthetic) (xS) SEQUENCE OODS: SEQ ID NO: 94:

ATGGATACGT GACACATTAC GATAUATUCC 60

AGATrUATGC AAGAUAACAA GGTATATGCA 120

ACCAlCGTTG CAAAGGCUCA CAUGTCGlTC 180

UGCCTTGCUC CCACCGCCAC CCATGTAACC 240

TGCAUCACCG AAACAATAAC ATlCGCCIUr 300

TCGTCTATGC CTAAAGCCCA GAAlUAUTil 360

TGAAAUClTC CTCCTCCTGC ACUAUGArAA 420

UCUATlUTGG CGGTGUCAAA GGATGTCCUA 480

CUGAAlGAAG CGATGATUGG ACUATCATTl 540

AAGCCCATGA CCGCCCAAGT GGCACUCCTC 600

ATUAClArUG AAUTGUAACA GCCTGGAAAA 660

CCUCGAAATG GAATCAAUGG AAAAAAUUUr 720

AUAAUllACG CAGCUUTGGT GUTTUATClA 780

AUGlTTATAG GGGAAGTTUG GAAUGGARAT 840

ATGCClTATT CACACGAACC GACCCCUCTA 900

ACTCTATTTA AACrCCCUAC AGGAGATGAA

GCAUCGCTAT GrATAATGAT GGAAAGTTAG

ACUlGTlTGC ClCCGTCAGA ATTCUGATGA

AGATUTArUA AATATUAAAG GGAACGAAAA

GCGTGGAATU AAGTAAGGGA TTATGTCAAC

GCAATAACUC AAUrCIAlGG AGAGUGACUA

AAACTUlATT AACCUATGTU GAAGGGGCCC

ACGAAGTUlU GTAAGATUAU GCGCTCGGAG

AUAAAAATAA ATClClUGGT TTCAATGCAA

CGAAGGlTUT TCGCTAGAAA ACCGCCGCAC

AGTTTGTUUA CUTTCCCCGC AGCAGTGGUC

CAACTGAAGl AGTTGlGGCA TCACCTAGCU

AATATUACCA CATTGAGUAC lUCGTACTCA

GCAGUATATU UAUUATGTGC CACACCGGTU

AAlllGlCTC UAUAAlGUGr GAAGCCCCAC

258

184 424

CCiGITICCA CCT1STGA

918 (2) SEQ INFORMATION NA No: 95:

(i) SEQUENCE CECSES:

(A) LENGTH: 963 pioS bases (B) TYPE: nucleic acid (C) NNCI NUMBER: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) RPIS: / list = "DNA (synthetic) (xi) SEQUENCE OPNS: SEQ ID go: 95:

ATCiCTGGCC 60 irrcTATAAr TATCTGT — lG ATClCGCATC GCCT1G1CA1 GCCACCTTCA CCGPCTCTil 120 ACCCGGGCAA CCCCSaTGAC TlGCAClTCT CTATCCCTAT ITGCCiAASC crTCiGCThr 180 CSAlCCTTCG IGlChPGTTG A111CTTCCG GllGCrCG — 1 AAAC1CACCA liCAPClGll 240 ciacTCTTCi CAGTCTCCAA CC1T1CCTCC CCTCCTCCGC llCCiCGCCC rcrciscirr 300 CSSCClTCAC CAAlGCATGT TlCClCCAlT G1TTCC1GTA lAlACTTACl TTCTATCGll 360 ttacccttcg GCGlCCTCAT 1AACAGCGCT GCiTATATTl CliTTiCliC TCCCCillTl 420 AGCC1TCT1T TCCAlTCTCC ACTGCCAACC C1TCTCCTCC TTCCAAATGA CCCCATAlAT 480 crcc.aasciT iicrcicisi CT1TCCCACC CCiATTATCT ilTiCTlCTC liACGCTCTC 540 T1GGCGTCCC crTTCcrccc CTT11CTCCT GCCCCATCCA iTCCCTicsi CTClClllCT 600 ICTTClTCCA Gccccirnic ITCCCTCTCC TCTGCCGT1C 1CTCCT1CGT

TCCCT — iAll iiiriCCCCC CTACTTT1TC CCCACCCPTl ICnCGCTTCG TCCTTGCTTC 660

184 424

259

GCCGACTTTG 720 CCACCACCAT CTGCCAGCAG ATGGAAGAAC TGGGAATGGC CCCTGCCCTG CAGCCCACCC 780 AGGGTGCCAT GCCGGCCTTC GCCTCTGCTT TCCAGCGCCG GGCAGGAGGG GTCCTGGTTG 840 CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCAC CTTGCGCAGC 900 CCTCTGGCGG CTCTGGCGGC TCTCAGAGCT TCCTGCTCAA GSTCTTTAGAS CAAGTGAGAA AGATCCAGGG CGATGGCGCA GCGCTCCAGG AGAAGCTGTG TGCCACCTAA

960

TAA

963 (2) INFORMATION ON EEQ ND No .: 96:

(S) CETHY SEQUENCE:

(A) LENGTH: 918 pairs zisid (B) AYP: nuclLLsows acid (T) IUQUE NNCN: single (D) TOPOLOGY: linear (LL) AYP PARTICLE: other nGnlLLnic acid (A) DESCRIPTION: / description = "DNA (synthetic) (xL) SEQUENCE DESCRIPTION: EEQ NA no: 96:

ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60

CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGAOGTCT CTATCCTGAT GGACCGAAAC 120

CTTCGACTTC CAAACCTGGA GACCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180

GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240

TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300

TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360

TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC CCGAGTTGGG TCCCACCTTG 420

260

184 424

cacrcrciGC 480 acciGCccii CGCCGTCiii CCCGCCCCCC icicccacca cciccaacic ClGCCTCiCG 540 CCCCiGCCCl CCCGCCCCCC CCGCCTCCCC TGCCCCCCli CCCCiCiCCi iiccaiCGCc 600 CCCCCCGGGG GC1CCTGG11 CCiGGCCaiC TCciraccTT CCiCGGCGiC iccirccccc 660 iiciacrcca ccTiicGcar CCC1C1GCCC GCiCTGGCCC CICiCGGCGC iiccTccica 720 acicihhaic ccaaGicccc cccaiccaGG CCCA1GGCCC aCCCCTCCGG raccAicici 780 CTCCCCCC1C caaccTGiGC cacccccacG TCCTGCTCCl ccicrcacAc iciCTccrcc 840 1CCCC1GCCC iCCCCTGCCC hccTCcccca cccaccccci GcacciGGca ccciGCTira 900 Gccaaciccc TTGCGGCCTT TiccTciacc CGGGGCiCCl CCGGCCCCTC caaccGniai cciaaicn

918 (2) INFORMATION ABOUT SEQ LD No .: 97:

(i) SEQUENCE FEATURES:

(A) LENGTH: 963 pioy zisid (B) TYPE: nskluinrwy acid (C) NLCL QUANTITY: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other eucluretic acid (T) OSLS: / description = "DNA (synthetic) (xi) SEQUENCE OSLS: SEQ LD er: 97:

aiCGciraci cciciaiaaT igtcgatgcc ciTCiccaic ACTTCiAGai accccciGcr 60

CCTTTCCTGC accccaccnc cciciaiGac caacacGiCT cicicciGai crcccccccc 120

CTTCiACTTC caacccTcca caccTTcric arcGCirica cccccTicra acaiGCCica 180

184 424

261

GGTCTTGAUl ACATTGCTAl ΤΑΤΤΑΤΑΑΤΤ AACTlCCTlA AATGTGGGCA UGTAlACAGG 240

CGTAUAAATA GAATGATGAT AACUCACUCT GAATlAGAAU AATTGACUlA TlATATCAGU 300

TTATCTGTUC TTAAGGTTGC lACClACACU CCAACAAACT AGUCACAUlG GCGTlUAUAG 360

TGGAAG7ATG AAGAUTGCUU TGAAATGTCT AGTCTGCAGA AlTCCAAGAA CT / TCCACAC 420

TATTTTCCAT ATAATACGCT lUATGAACCC TTlGlTAGAA AATCGCAAAA AGTGACCATU 480

GAAlTAUAAU AATCTUAACA ACAACTATCC AAUAAGATGC CCCAAGTGGG CATGUAGAGT 540

CGGATUGAlA AGAAAACGGl TlAACTGAAC GGATTGGGGT ATCGTCCTGC GAUGAlGGTC 600

UGAlIGUTAA TGUTCGGCAC AACTATGGAU ACATCGACCU CUGCGTTCTC GGCAlTCTTA 660

AUGACAGTTU ACGAUAGATG TClAUCGTAT GUAUCAT / CG CUACACTGAT UAT / CACTGT 720

TTCUClAACU TGACACAGAT AACUCUGUAT UAAlAAUACA TACAGCAUTA CGTCTUTCAA 780

AGGTCAAAlA TUTAAAAGAA AlCGGACATG GTCATGGCGC UCGACTTTGT UGAGATGAAA 840

CCGlATGAAA TGCUATGGTU AAAAAlAAAU GGAATGAACG TGGCAlAGTU ACTCAUGGCA 900

ATTACTCUAU CAGTTCTAAT ATCAGACCCC ATCATCAAlG AGATCUCAlA CACATAGTAC 960

CAA

963 (2) INFORMATION ON KEQ DD No .: 98:

(S) AE / HY KEKWEN / JD:

(T) LENGTH: 918 base pairs (B) TYPE: nucleic acid (A) QUANTITY ri / D: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nuclunne wine (A) OPIC: / opinion - "DNT (synthetic)

262

184 424 (xi) SEQUENCE OPlE: SEQ atttttaatt ttgtgagcct tagttagcaa 60

TTTGTCTGAT ACTTCAGClA TTTCAAGCAT 120

TTGTCATTGT TCACTTTCCA CATTGATCCA 180 tttcggcatt taagctagtt gaatttttca 240

TTTTCATATT TCATTAGTAT TAATTTACCC 300 ttttagtttc gaatttttca ctaaccctac 360 tttttttttt cgtcccttct tttttatctt 420

ATTTACCCTC ttatcttatt tcgttttctt 480 atgttgattt agttctatat tcgttaccac 540 tcttttgttc cttctttttt ttttttttac 600

AACAACATTT ACCCTTATCT TTTATTTTTT 660 ttttattttt actacttctt cttttctcta 720

CATTTTGATT ΤΤΑΤΤΤΑΤΤΊ TTGATACTTC 780

TTGTGTTTTG ATTACCCCTT ΤΤΤΤΤΑΤΤΤΤ 840

ATTTTCCATA TATTCTAGTC TTATTTTCTT 900 tcctaattct tataagac

918 (2) INFORMATION ABOUT SEQ ID No .:

Sun Sat: 98:

ACCAGATATT ACTTAAACAT ATTATTGTTA taacattgtg taacttacag ccatttacat

ACCCTGCGTA AAAATTTACA CAATCTCATA ttattcttct tttttcctat ccttttattt cattgatagt aaacttaaaa cacattcatc taataatatt acacacacca ttttttattt

AATAGACTTA TACTTTCGGT TTTATATTTT ctcgcccatt accacctact atcctttttt tccgtttatt atacgcaatc ttatttgctt

ACTTTTTTCT TTAACCTGCG ATATTACTTC taccaccatt taggccttat ttataatttc tatgtgttct ctacctttga tttgtttttt

CTACCTTCTT TCACTTAATG ΤΊΑΤΑΤΤΤΤΤ tgtaaatcta caccttttca tggccccttt catgcgttta ttattagtgt ctattacatt

99:

184 424

263 (i) SEQUENCE FEATURES:

(1) LENGTH: 963 bases (B) TYPE: nucleic acid (C) NLCL LOOSE: single (D) TOSOIOGIG ..: linear (ii) TYPE OF PARTICLE: non-nucleic acid (T) DESCRIPTION »: / description =" DNA (synthetic) (xi) SEQUENCE OSLS: SEQ ID NO: 99:

CTcrciacci rcTciaiaai rcicrcTCia ATTaicccic ccihacaccG gcccccigcc 60 cciTTCCTGC accciaccca cctctctcac GaiccccTci citicctgci Gcacccaacc 120

CTTCGaciTc cAciccTCGa GccchiCGTc AcGCCicicc CGccciTcrn acaTCcaTCT 180

GCiaTiCCCC CCCilCiTCG iCCTCTCCTT CCCTCTC1GC CCTCTGCCAC CGCCCCGCCC 240 icicGaccic cacicaicai cgccgccggi gccicccccc ACTTCCGCGr aaaccTcccc 300 ihciniciGr TTccccacccTcag cgtgcccgcgccgccccggccgc

TCCCCGCGiC GCCCGiClGC TCCCTTCTCT ACiCiCACCC CCiCiCCiCC CTCTTlCGAC 420 icicaiacai ciccaaccci cgctctcgcc cctgcccigc ccccccccca gcctcccttc 480

CCCCCCiTCC CCTCiGCTTT CCCGCCCCGG GCCCGGCCGG TCCTGCiiCC iCCCCTiCTC 540

CCCGlCiTCC ICGCCClClC CiCCCCCCTT CiACCCCCCC TTCCCCCCCC C1CTCGCCGC 600

TC1CGCCGC1 cTcacaccTT cctgcicatc Tcihiaracc tccigcgcgc gciccacggc 660 cciccccccc ccciccaccc rcacciGiGi gccccciccg ccctgtcccc cccccccgcc 720

CiGClGCTCC ICCGaCaCiC TCTCCCCaTC CCCTGGGCTC CCC1CCCC1C CTCCCCCCCC 780

264

184 424

TACCTTTClT ACTTCCCCll TTCCTTCCCC TSATCTCSCS 1T1CTTTCTC TTCTCSTTA1 840

CClTCTTTlT AllTTTTGCA C111ACATTC TTTlllCCll CCTTTCTTCC 11ATATSTCC 900

CllTCllSTC CTCTT1STTC CCTCSCCAGC CCTCllTAlT A1ACC11C1A ATCCCCSCAl 960

Tli

963 (2) NNFOUVATIONS ABOUT SEQ ID No: 100:

(i) TECES OF SEQUENCES:

(A) LENGTH: 918 pio bases (B) TYPE: n "kiiSnic acid (C) NNCN NLACITY: single (D) TOPOLOCN: linear (il) TYPE OF PARTICLE: other nucleic acid (A) OPNS: / description -" DNA ( synthetic) (xl) SEQUENCE OPNS: rEQ ND no: 100:

SClCGTSSGT 60 CTCTTlTCCC 1CTCGATGCC CCTlCCTlCG ATCTAAS1S1 ATTATTC1TA TCTTClTCll 120 1GTT1SSTS1 TTTGCSTlCG IGCllTlCGC TCATTTTCSC 11ATT1ASAT TTCTlSTCCT 180 GACGTGTllA 1ACCTTCGTG llCCTCCTTl A1ASTTCA1S ASACCTCCTA C1CCCC1S1C 240 TCACTGTCTl CCSTCTCCAC TTlCCCGCCT TTCTTCTTCT 1CTT1TATTT CTCG1ST1CT 300 CACCTATCAC TAAGGCAG1T lATCCCCGSl AATTGT111A ASSATCCATC TTTCGTTTCi 360 CTATTTTT1A ICGAGCGGAl ISlTllTAiC ST1CA1A111 T11CC1AC1T TCTTT1C1CC 420 1C11TCGT1C TCGCGGTTCT GCTSTiCTCA TTTA1C1C1T TACCTC11TT CCTCTTCTC1 480 GTTGTCGlTl TTGGGCAGGC llCiCTTCll CTCTCSlTCC CGT1TS1A1T TTTGTlGGCC CCCT1TATT1 TCCTCTAGCG TSTTCC1T1T S1TTTTTC11 TG1TCGTC1T

540

184 424

265

11CTCTCG — 1 ICCCCCTiCT ASS1TCCCCG IGlCAAiriA 11AA1ATCCG lilClGCGiC 600

CCGlCiCTCC GTTATGATCC 1TCT1CCGCC TzACAATCCTC 1CCGCCCC1A 1CG1CTTCT1 660

CTCCTCClAC ACTCTCTlii CATCCCCTTi TCTCCCCTTA TCTCCT1CCC CA1CCGGCCC 720

CCTCGTCT11 CAllCTlCTT CG1CCGGCTC CGCGlCCCCC TTTTCCTCCA CC1TC1GCCC 780

CTCCAT — CCC TTTGGGCTlT ATCCCCCTG1 CCTTlTCCCG CCTCllGCGC GCCCCGlChl 840

IGCiCCTCCl ACTTTTCCAC CGCCGTCril CAlCGCITGi G1CAG..CTCT1 AACTGCCCCC 900

1CCCTTCATC CCTGSTGS

918 (2) INFORMATION ABOUT SNQ ID No: 101:

(S) SEQUENCE GNGS:

(1) LENGTH: 963 pairs per / ad (B) TYPE: nucleic acid (G) NLGI NLITY: single (D) TOPOLOGY: linear (ii) TYPE PARTICLES: other acid / nucleic acid (AND) DESCRIPTION: / description = "DNA (synthetic)

(xi) SEQUENCE DESCRIPTION: SEQ NA no: 101:

GTliCTGGCT 60 1CCCTGTAAT TATCTATllS ATCGTGCGCC GCTCGAGlAi GCCGCCCGCA CCCCCTCCTT 120 ACCCiGSCAl CCCCGGCTGC GAGlACTCCC CTGTCCCilT 11GCCTGA1C CTTC1GCTTC 180 CGGACCTTlA 1A1CTTCTTG GCCGCTGTCG GCGlCTCGiA AGGTGCGTCG ilTGTTlGTl 240 CGGCCCTTC1 TGGCCTCCGA CCGCGTCTGC CCCCCTCCAC TTCCTC1CCC TCTCiGCATC C1GTCATCGT CAGlTCAlTT iGCCGGClGl GlTTCClliG AAAACTTGCT

300

266

184 424

CCTllCGlll TCAGGTTTG1 GTilGGlTll llAClATClC lAGCllCCCG TGGClGAGGT 360

TTTTTlllll AATTlCTCGG ITTAllTlTl ITlACGAlTT TGCGCTTTTT ICGTlGAGAi 420

TTlTACGAAC TlTTAClTll GGGTATTCil GGClTGCllT TGGGTTTGGT TTCTlTCThy 480

GAlTGGTClG TCGGlGGCll TTTGCTClTl llTTATTTGT AGCCTCGCTC GCAGlTCCTl 540

ClTTlTlllT TlTlTTlTTl CGTCCAlTTT ITTGGGGGTC TCGGAllTlT CTlGAlGTGT 600

TClTCTAllC TTThiGAGCl AlCGClllll ATTClGCGTl ITGCTGTGlT GGTGTAGGAl 660

AlGTTClGTC TT1TGT1T1A ITTGTGTTAT TTTGlCGAlT TCGTGTTGTC TlGATAGTTC 720

TCGllTACTT TTllGGCTGT TTTGClAłTT TGTACTGlTT AlGTTTCGCl ITTGCTCCGT 780

CGTlCCAlTT 1GT1TT1C1G TGGGTThłCT TCTTATTlll 1GCTGTTGTC GGCGT1GGA1 840

GGGACGCTTT TTllGlTGGC 1TTGATT11G llTATAGCGT AlGlGGAClT TlGGGlTTTG 900

GTTlTTATTl CGlGlTilTA GACGGllllA TTGGGG1CGG TTTTIGTGTr GTAGTTTTAl 960

111

963 (2) INFORMATION ABOUT SEQ II No: 102:

(i) SEQUENCE TIMES:

(A) LENGTH: 918 bases (3) TYPE: nucleic acid (G) NUMBER OF THREADS: single (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description = "INA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ II no: 102:

GlllTClCTC GTCTTGCAlT lATTlATGGi ATGCTCTiCT ATGGlCAGAG ATGGTTTGTA 60

184 424

267

CCCGT1CCUU CCCCGACCAC CCTCCCT1CC UCAUCCUTCC CCCCCCCUCC TUCCCTACCC 120

CTCC11CCCC CACCCCTUUC lATCTCyiCC CUTUCCTCCC AUAACCGCTC AAATUCCTCC 180

UUCAGGG111 CCACCCCTC1 CCAGCCCCCC CCAC1CCCGC CCCCCTCCCC UUCTTCCTCC 240

CCCC11CCCC CCAGCCCCCC CAATGCAlUG G1CTTUCCA1 CACGCCUGUC CCCCCTTACU 300

CCCC1GCCUU CTCCCCCT1C icecucucci ICCCACCClC CClCAlCUTG cugtutcggc 360

TTCCC111C1 1CTTTGCTTT CTUT1UCCCC ACCCClGyTT CCUCCCTCCC UCUCCTUGTC 420

1TC1111CCC GGTCCTCGll CCCTCCUCC1 AUTTCCCTTU C11T1TCUG1 CCUCUTTCTC 480

CGCCACCCCT C1CCTCCCCC CGTCU1CCCT TUCUTCTCTC AlCUCCTTCC 1CTCA11TTC 540

CTC111CACU G1C1ACCUCC CCCTT1C1CC TUCUCATCTC CCCCUTCUCC UCTGCyTGCC 600

CCCCACCAlC C1T1CCCCCC CTCTUCUCCT 1CTCC1CCCU UCCACCCTCC TTTCATCCTC 660

TUTTCGCCCC CUC1CTCCCU CCCCC1CCC1 1CCCC1CCUC CUUCCUUCCT CCGTC1CCCA 720

CTCC1G1UCU '1CCGTGTCCC CTACCCT1UT CGCCC1CCTU CCCC11CC1T 1CTACCCCCC 780

UC1GTUU1CC CCACCTT11C CCCACCTCC1 CCUUAC1CCU CCTCCCTC1C CCCTCCCCTC 840

TTTCA1CC1C CTUCCTCCCT UTGCCCUTCC CCTTCCCCTC CUCCCCCCCC UTTCUCCATG 900

CC11CCCGC1 CCGCCC1A 918 (2) INFORMATION ON SEQ ID Na: 103:

(i) SEQUENCE FEATURES:

(A) LENGTH: 939 alkaline membranes (B) TYO: acid in polyurethane (C) NUTTY NiCl: single (D) TOPOLOGY: linear

268

184 424 (ii) 1YP PARTICLES: ieey nucleic acid (C) DESCRIPTION: / description = "DNA (synthetic) (xi) OSLS SEQUENCE: SEQ LD NO .: 103:

ciccciaaci 60 cciciciaai rchCGCicca CTTATCCA1C acianacac accccciGca CClilCCTlG 120 acccGaacaa CCiCGCIGCC Gccrcccici ciciccicai CGGCCCACCC ciTCGnciic 180 canacciGGa GCCC1TCC1C AGGCCTGTCC acacchiacc Aiciccaica GGTaiicgGG 240 cnaiiCTTCG icchchccac CCATGTC1GC ccicicccac CGCCCCGCCC TCTCGncaic 300 caaicaicci caAcccccci GCCTGGCCCC gATTccGGGa cacaciGCcc Ticiaicicc 360 TTGCCCTTGa ccaccccccc GCACCCCCGi ccriaGacrr ccciccacrc 1CCCCGCCTC 420 aacccicicc iCCCCTCiCl cchchccacc CGTCTCCTCC Gicicaacaa icicaingai 480 ciccaaacci CGCTTCiGCi hhccTGcrcc GGGCaGGaGC CG1CC1CC11 CCTGGCCniC 540 yccGGaccii CCTCCCCCiC TCG1CCCCCC ilCiCCGCCC CCTTCCGCGG CCCiCilCCG 600 CCTCTGCCCC Wanticccarc iicciccica cGiciiicia ccaciiraca aaiaiccnGC 660 GCGGiCGCCC CGCGC1CCCG CAGlAGCTCi circcaccia CAGGCiriGC cncccciaci 720 CGCTCCTCCT CCiCGGCCAC iCTCTCGCCC 1CCCCTGGGC icccciracc icciGCccca 303 Gccaccccci CCCGChGCCT GCCTGCT1CC Gcccacicca laGCCCcchi TTCClCTGCC 840 acGCccicci rccccccciG GCTCGGAiay CCCCCGGCii rrcicccacc

Tiicacaccc iccncciccn ccicgcccgc ittgcccccc ccaicrccca cccGaiGGca 900

184 424

269

GAAATGCGAA GGCAAGAGlA AATUACCAAA CAAAAUUUTG AACTUAAUUA ATTGUAATAC 960

TAA

963 (2) INFORMATION ON KEQ DD No .: 104:

(S) SEQUENCE FEATURES:

(A) LENGTH: 927 base pairs (B) TYPE: nnnluSsoay acid (C) TlCD DURABILITY: single (D) GOOOUOADT: linear (SS) PARTICLE TYPE: Siny kwa? nuclunne (A) OODK: / opSn - "DTA (synthetic)

(xi) CCI SEQUENCE: SEQ ID no: 104: ATACAGAAGA 60 GCGGTATCAT UCTAUATGCA CTTCTAAATG CATTCACCAC CGAAAGTCGA ggtcgaatgc 120 AAGACAAACA GGTGACCCCA UATLAGUTAT ATATGATGAT UCCAACCCAA GTGGCAATTA 180 ACAAGGCUCA UCUCCTAGTC AlllATUTAC AUCCATTAGA CCATUACTGC CUTCTGCCCn 240 AAATTATTGC TTATATCACC AACTUTATlA AATACGGAAA CCAAUACGAA AGTCUAGAGG 300 ATATGATGAT GCCUUTCCUT UCATUGACAU CATTGCCGCA CCCAATUCGl GTATCGGTCC 360 TTAAAGCTGA UAAAUGCCAC LATAACGCIT AAUTACAGCC AUCTlUAAIA TGGAACCUTA 420 GGGlTTGTGl GCCAUUCCGA CCAATGGATC AACAUCTGTG GACGAAACAU GACATGUCUG 480 CGATAUCCGC ATGTATGClA CTAAAGTGUU ATGCACTGAG GTGGTCAAAA AUAAAGGGGG 540 AACACAGUCA AlGATCGTTU ClAAACATAG ATCCAGGAAC TCGGATGTAA GCUGGGCCGG 600 GGAAUCAAGT ULATUGGATA TGAAAACClT TGACTCGGAG GTCAlAGAGA GTUGAGGCCC ACCTGUGACC GTCTCAGAAA CAACTATGGA AlAAUAAAGA ACAAATGGGC

660

270

184 424

ATGATTTTCC 720 tttgctattt TATTCAACAC cttagttttt tttttttttt tttattttat ttttttacaa 780 ccttatgttt tctgctgatt tattgctctc ttcgtttttc ttcacttgat tttttttgat 840 CTTATTCCCT (TACCTCATA TClGGCATTT tgcttatttt TTCATTTCCC attggtttac 900 CTCACGTCCG atactacctc atacatcttt atatttatct tctactttgt TACCAGlACT ttttgtttat TTAACAA

927 (2) INFORMATION ON EEQ ID No .: 105:

(L) SEQUENCE FEATURES:

(A) LENGTH: 972 pior zisid (B) TYPE: nucleSowr (C) NUMBER OF THREADS: single (D) TOPOLOGY: linear (Si) CYP PARTICLES: issy kwis suclLSnname (A) DESCRIPTION: / description = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: EEQ ND so: 105:

ATACTGCATT tttttagaat cattcagcaa agcagctagt atataaacaa attatttata 60

TTCCTCTTAG ATTTCACTAC TTTCACTCAT CAAAATATTT TGAATTCCCT (CATTGAGAT 120 ttttcattct tacattctta tacctctcga actctcatta acaatggata aaccctagta 180 ttgaggtaca taagttcctt gacctctttaa ttatctttaa tctatctttcat 240

GTGTCATATT TAAGTACTAG TAACATACAC CATTTTTCAT CACTTTTCTC AAACTGCATC 300

TGTGATTGAA CGATTTTCCC TTAACTCTAC CAATAATATT ΑΤΑΤΑΤΑΤΤΑ TCCCATACCT 360 tttttaaccu aattattgtt tttaactttt attattcatt ttgtcttttt tttgccacac 420

184 424

271

CTCTCCSAAC GCTTSACTSC llGTTATCll TC1C1TTSTC CT1AGGA1TT 11C1TC1TTT 480

C1ATSTCTTC T1C1TATTTT TG111TCGTT TCCAlTCTTC CTTTTACCTC llGTGClGCl 540

TTCCCAC1TT CGCTlACTTC ATTCCACAlT 11TTTTTCTT CTCATCA1C1 CTTTTTCTCC 600

CTTTTG1GA1 11ACACTTCT TlAlCTCClC TTCGCTCTCC STATATTCTC 1TT11CC1CC 660

1CTCSTTTC1 TTACCCTTSC TC11TACCAC ATClGClAGT CC11AST1CT TTCC1TCTCC 720

TC1CCTGTTT CC1CC1TTCT CTT1CTTCCT 1TTCTC1CCC CTTClTCTTl CCTAlCACCC 780

1CTTC1CCCC CCClCTGCTC 1TA1S1TCTT TCC1A11T1C T1CATT1T1T CTCAT1CTCT 840

TTCCC1CA1T TTCTSTTGCT 1CCTTTT1TT ACTCTTTTCC TTTACA1CCT TTCCTTTGCl 900

CCTTCA1A1C AliClAlCAS 1ACCTAG11T CAC11T1CA1 TlTTCTAlll lACCTTlTlC 960

ITTCCTTSAC CA

972 (2) rEQ INFORMATION ND No: 106:

(H) SEQUENCE FEATURES:

(A) LENGTH: 927 pio bases (B) TYPE: nucleic acid (C) THREAD QUANTITY: single (D) TOPOIOGNA: linear (ii) TYPE OF PARTICLE: other i-nucleic acid (A) OhNS: / description - "dna ( Synthetic) (eH) SEQUENCE DESCRIPTION: SEQ ID no: 106:

ICCCCCllTC 60 iCTTCCCAGC 1GTT1CC1S1 ACTACATSCT ITCGCAClll CTTATTTlCC TTCCTCTC1C 1GTT1C1TAG TTTCSlTCST CSAlAClCTC TCATTTTCCC ICCTTCCAAT 120 TCCT11GCTT TACSCTTlCA CAlTCCTlCA A111TT1TT1 ACAATTTGCS ASGTCTCTTA

180

272

184 424

llTATT — Ali 240 CS1TTCTTC1 TGGTCTCCGl CCAT1TCTGC CCTCTTCCAC llCCiCGCCC TCTCiGCATC 300 CAATCATCST C1SGGCAT1T 1GCTT1CG11 AATTCCIGiA AlAACTTACi TTCTGTCT1T 360 TTACCCTTGA TCGAGCCCAC TSlCGGCGlT ACTTACAT11 CiiTTiAlCC Tcccciiirc 420 TTilTTCGGC CiGCGGCTCC AGCGTCCCTC CCIATTTiT— TCCCACCTT1 iSCGCACTlC 480 GlCTiGACiT C1CCGACTTT TCCGCCACC1 TCT1TCA1CA iATilAAlGA CTTlGAGTTl 540 CCCCT1CCCT 1CA1CCCACC CA11CTTCCG TTCCTGCCTT CiCCTCTCCT TTCCAlClCC 600 lliCllTGll TiTCCGClTT iCTATCCATC TCCAT1TCTT CCTlCAilTl TCTTACClCl 660 TTCTAC1CCG CCTTGCTC11 CCCAC1CCAT TTTTCCCTTC CA1CTCCCTT CCCCGiAiCT 720 TCCTTCTCG1 TTCTPT1TAT CGAiTlGTlG liATCCATiG C1ATTTC1CA 1C1CTCCGTT 780 ATSATCTiTl TiCCACCTlC gaicttttcc ACCCCCA1TA ICTiTTTCTT CTCiTGCGCT 840 CTCTiTTCAT CCCCTGCTCT CCCCTTA1CT CCT1CCCCA1 CCAiCCCCTT CS1CT11CGT 900 ICTiCTTiGl CCGGCTCC1T llCiTCCTTT TCCTCTACCA TiliCTCCTi CGClCCCTli GG1CCGTATC CT1GTG1

927 (2) INFORMATION about SNQ ID No: 107:

(S) SEQUENCE ANASES:

(A) LENGTH: 972 pairs per / ad (B) TYPE: acid / nucleic (A) NOMINAL THREAD: G ^o iGdyncya (D) GOPOUOLA: linear (ii) TYPE OF PARTICLE: other acid / nucleic (1) DESCRIPTION: / description = "DNA (synthetic)

184 424

273 (xi) SEQUENCE DESCRIPTION: SEQ ID e.g. 107:

CC11CCCACC 60 ICCCCAGACT TCCC1CTTCC CCCCCCCCCC ACTCCCA111 cccccccucc CCGCC1CCU1 120 CCCC1CCCCC TCTCCCTTCC 1CA1CC1CCG CCCCCCGGAG 1TCCCUAAAC CCGC1ACCTC 180 CCCCCCCTUC TCUCTTCUCC AUUUCCUCCA C1CCCCCA1A ClCGTCATTC 11GCCCUCU1 240 CCCCCCCTCT TCATCCCCAA CC1CUCCCUC CCTCC1CCAC U1CCUCCCCC CCGC1ACCCC 300 CCCCCCTCCT TACTUCATTC 1CCC11CA11 CCCCCC1T1A CACCCCTCCT CCCCCCCCT1 360 CTCCCCTT1C TCACUCUCCU 1CCCCCCC1C CCUCC1AGT1 C1TCUTATTC CCCCC1U1C1 420 CCCC1CCTUU TCCCCTCTCC ACCCCCAACC CUCCCCCCCC UCCTCA1T1A CTcciccecc 480 CTCCCCCCCT TUCTCCCUC1 CCGTTTCCCC CCTTUUCC1C CCTTCCTTCG 1AC1TC1CC1 540 ACTCC1CCCC TACCCTCTTU CC1CCUCCT1 Acucecciii CATUTCCCCT 1CCCG1CCUC 600 CCACCCCTTT TTCCCCUCC1 1CCCTCTCCG CC1CCCGCCA UC1CC1UUCC TTlllGlCCC 660 CUGCT1CG1G CCACCCGCCl A1CCTCCCU1 CTUCUCC1CA CCUCTCCCCA CUCC1CCCT1 720 CUCC1CCCCC CTCCCCTTUC CCC1CCC1CG CCCC1CCCC1 UCUCTCCCCU CCCCC1CCTT 780 GATC1CAAUT GATCCCGCCC CCG11C1CC1 1C1CC1C1CC CCCTGCTA1U CC1C1GTCCC 840 CCTCCACUCT TTTCCCCCCC 1C11CTTTUU CUCC1CCC11 CCCCTCTCCT 11CCGCCCCC 900 UUUCCCCCCT UCTCTTCCUC CCCC1CCC11 CCCTUCATCC 11CCU1CTTC CC1C1CC1AC CCCCCA1CTT TCTCTTCCTC CCCCCGUUCUC CCCC1CA11C CCTTUCCTUT

960

CCACCCCA1C CA

972 (2) LEFT ROLLINGS IN SEQ NA Na: 108:

274

184 424 (i) SEQUENCE FEATURES:

(A) LENGTH: 927 base pairs (B) TYPE: nucleic acid (C) QUANTITY NICL: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: ieey nucleic acid (A) DESCRIPTION: / description = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID er: 108:

GTGCCiCCCi 60 ccicic Tags ccicGAirca CTTCicccic cciicaaiai nccacciGCc CC11TGC1CC 120 ccccGcccca CCTCGAlGCC ccncAccici CTCTCCTGai cracccacac CTTCCCCTiC 180 caaaccircc GaccTTCcia aCGCClGiCC ccacciinGa aaaTCcaicc CGiaThcacc 240 CiCTTCTiCC iacTCTCCca CCGTCICiCC ccicicccrc CGCCCCGCCC iciCGCcaic 300 caniccicci CGCCGCCGCl caciGCccac ccTiccciGa ancnciGacc 1TC1C1C1CC 360 iiacccThcc CCCCCCCCCG Gaaccccaci CCGiaGGCGC CCGlCGAGCC 1CCCCCCC1G 420 ClCCiTCTCG CCCCGGC1CC TnccTCGciT TCGCCCCTGC cciGcacccc ccccacGCic 480 CCGTCCCGCC CTTCGCC1C1 Gciiiccacc CCCGCGCGCC GGCGClCCiC CTTCCiCCCC 540 aiciccAcac CTTCCTGGTC G1G1CC1CCC rCGTTClGCG ccacciiGcc caccccccac 600 CCTTGCCCCC TCCCACCTCC C1CCCCCCCC CCTiCCllCi ccrciciiic GAcccarica 660 ccnaccicca GGCCGCTCGC CCCCCCC1CC CGGCCGilCl G1G1CCCCCC lacacccici 720 Gccaccccca CGCGCTGG1C C1GC1CCGCC ACTClCllGl CG1CCCC1GG

Gciccccira ccicctgccc ctgccaggcc cigcagctcg ctggcigctt Grcccaachc 780

184 424

275

AATClGUCAA 840 TTCCGATATA AAACUGUATA ATUGCCCAAG TUGACIGGAT ATAAGAAGAC GTGlUTCAAA 900 AGTTClAGAA AGTGGAUGTl CAAITAlAAC CATGCUAACA GAGGACGTGC ACUACCAT GL AAlCAGTCCU ATAATAA

927 (2) INFORMATION ON KEQ DD Tr: 109:

(i) AEAHY SEQUENCE:

(A) LENGTH: 972 base pairs (B) CYO: kwa? nnnluSnowr (A) QUANTITY TICl: single (D) ΑΟΟΟΙΟΑΙΤ: lnsSoaa (iS) TYPE OF PARTICLE: Ssny nuOluSnoay acid

(xS) OODS (A) OODK: / description - SEQUENCE: KEQ DD "DTT (synthetic) no: 109: yy ATUGACAAAT 60 CGTATATAAT CAT / CATGCC ATGCTAAATA AGAGACAUnC AACAAGCGGA GATATUE 120 AAAAlACACA GACCTATGCA UCAlAGUTAT ATACAATGAT UCAAGCCATG GTTAUAGTGA 180 GCCCAGTGGA CACACCAGTC CUCUACGTAC AUCAATTACA CCTGGGAGTA UATATACAUG 240 GCATTGTTGC TTCGACGGCC GACA7CATUA GATGTCATCA UAGCGCAAGA CATALAGACA 300 GCCTAATAAT GCAGCGCCCT UAAA7UACAU TTTGAAlGCA CATAGACAGU TCGTCTCTGl 360 TTCGCCTCGA CACACACACl CCCGCAGClT AGUTAlAlGU ACAAGGAGGA TAAAGCGCCU 420 CCAAUTACCU GAGATGATAT AATCTGACAA AUTGTAAGAA UTGCCTCGTC TATAACACAT 480 GTAATTCGAC UGATAGCGAA SPECIES ACGGACAAAA UGACUGGACU AAlGAACCGU 540 AGTACGGCCG GGACAGAAlU UAAGlACGCl TAGTCUTGUG TAGAGACACC GAUCCACTAA TUlCUGCUTG utagagautA ATCAUAACAG TGUGUACUAA GAGAGAAGGC

600

276

184 424

GGTTTTGTT1 1T1TTTCGGT TTllAGTClT TlGCTTCClC TCCCllllCl llClCGAlCl 660

ACTTllllTl 1TGGT1T1GT GTlTTAllll iGlTCGTGTG TT1TT11TG1 ITllCGTTCT 720

TTTlllGllT TGlCGTTGTC TlllTGGlTl TGGGGCGCTT TTCGGlTCTT TTTGCGTrGT 780 llTTTCllTT 1GGTTTCGT1 GTllGGGGlT TGTTTGGlTT llTlTrllG TGGT40

TlTTlTTlll GGTlTThGTl GGTTTTGGAA GCG1T1TTTT TTlllCllll 1CGGCCGTTG 900 llTiTlTllT IGTllllTGC TGCTGGG1GC ITTACCCTTA TGCllCilCl GlCGGlAGAi 960GlAGAi

TllGGAlCil 11

972 (2) INFORMATION ABOUT SEQ II No: 110:

(i) SEQUENCE GEGES:

(C) BLINK: 927 base pairs (B) TYPE: nucleic acid (C) QUANTITY OF NITI: single (U) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (C) DESCRIPTION: / description = "INA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ II no: 110 ':

1TGGTC11TC 60 iThciicici llCTGGCGll ITClClGlCT 1T1111CG1G ITTlTTCGGl TTTTlGTlll 120 1TTTG1CT11 yTCTCCTGlT llClCGGCTC TllCTTlllC GG1TGG1G1T TCTTllTllT 180 TACATTCGGA GlGTTGClll llGGTTGCTl IGlATTClll AlACGCGTGl GlClllGllG 240 TAllCTCCGG 1A1CGGGAA1 TT11GTCTGT TT1T1GTT1T GGTTGGCGTT CTTTllTlTG TGllTlCTll TAillTllll llTCGGClAG AlCCTTllll CGAGGTG1GG

300

184 424

277 ggttatttta ggatttgtca ctaattttat caataatatg atcgatatcc tttgccacct 360

GTCTTACATA TTTCGCTCTT TCCTTTTGTT GATATGATTA TTTATTTTTT TAGATTCCTT 420 ggttttttti tggcttactc ttatctacca ctccgttgcc cgctgattta ttcctacact 480 ggttttccti tcgttcattt ttggtcattt tattggcttt acttcccctt atcccttttc 540 tttatttttt ttttttatat tgcttcctgt aacctgacac actactttat caacatttac 600 ctttatcttt tactctgtta ttataactgc gctatccttg ataacttcct ttattttaac 660 ccttgtcttt cccctctata tttttatctt atttttcccc ttttttgcac tgttatttct 720 atttatcttt gctattcctt atatgctgct acttaatgtt atattttttc gctttttcat 780 tattttttct gctacatttt ccaatcaaga ttttttaatc gccctttcct tgtcuatata 840 tttcaatgta atcgtcttta tgcgcttatt attagtgcct attatatcca ctaatgatca 900 attactttta tttgttactt tgaagaa 927 (2) INFORMATION ABOUT EEQ ND No .: 111:

(S) TETHY SEQUENCE:

(() LENGTH: 972 base pars (B) TYPE: nGkiLLnzws acid (C) NUMBER OF THREADS: single (D) TOPOLOGY: Siberian (SS) CYP PARTICLES: Sens nGklLishvic acid (A) DESCRIPTION: / description = "DNA (synthetic) (xS) SEQUENCE OPlE: EEQ ID so: 111:

attattcatt ttttcacaac cagtcaccac atgagatagt atgtaaccac attattccta 60 tttttttttt atttcaatac ttgtaagcat taacatcgtg tcagttgcac ccattcaaat 120

278

184 424

CTCC11CTCC TCGSTCTCll ICCTTTTlCA AlllGClCCl ACSATCTAlA AAATCCATCA 180

C1TACC1S11 CGGTCTTTC1 GlATGCCCGA CTCT1CCC1T TTCCCCTTCC C1TT1CATCT 240

CTTClSCCTC TAATCCTTAC TlSClGCllT 1ATT11CSSC SCTTGTlllA GCGGCTllCl 300

TTCCACTT11 CTACTCCC1A ITCACClCll lAATCCTAlC ITCCllliil TCCCillllC 360

CTCCT111T1 SATC1TTC1C TTTACTTCCT ACTCTTSACT T1TTCTTTTC CCTCASAGCS 420

CTCTSCSSST TCTCSACTAC 11TTCCTTAC C1C1TT1C1C TC1TTCTTCC TCTC1CCTTT 480

TC1T1CTC11 CAlllGCllC TTGClTGGTT AlTTGCCClT CCCCTCTTTC CCSClTCTCl 540

CCCCCT1TCC CAC1CTCTCC TlGlGClTTT ATATTCTTlC 1TTTC1TCC1 TTCCTTCCCC 600

TA1A1CTTCC CCTCTACCCT TCTliCiCGC ITCAlASAlA CCCCiilTlA CC1T1TA1C1 660

TCCTS1CA11 S1TT1C1CCT TlGTTGTCAl CC1TCTTATT TT1ACCACTT CCC1TCCCTT 720

CCSCGCTCTC CCC1CATTTT GCCllGCTTT CC1A1TTCCC CTTTCA1TTS ClCTTTlTAl 780

TT11CC11CT ICCGCllTTA CTTTTGTCCC llTTTCTTTT CTCACTCCll CTCTTTCTA1 840

1TCTTC1GA1 1GGTATTTTC GlCCCTClCC CCTCTTTTll ATCTSCCCTS ITCCCATlTT 900

CTClACCTTl TTACCSTTAC CCCCGllGCC ACGCCAlGGC ClliSlCilT CTCCCTTCTC 960

GllCTCTCCT 11 972 (2) INFORMATION ABOUT SEQ ID No: 112:

(i) SEQUENCE FEATURES:

(A) LENGTH: 927 pio zisid (B) TYPE: acid n "k1uSneay (C) NNTN FLUIDITY: single (D) TOPOLOC: linear

184 424

279 (iS) GYO PARTICLES: Snny kwan nnOluSsoa '(A) OODS: / opSn - "DTT (synthetic) (xi) SEQUENCE OPDS: SEQ ID NO: 112:

ATCGCTCAAT 60 UATGTCTCCT UATCGAGUAT ACTACACATA AACCACAlAC AA / CAAAGCA GTTGC1AGGU 120 ACGTGTAGTA GATGAACGAG GCACAGCCAT ATACGATGCT UUCGAUCCAG TTGGGCAGCC 180 AACAGATUUA UCUATTAGTA AGGUATAGAC AUTTGTTACC CCCCUTTCTA UGACCACAUG 240 GAATTATTAU TCCTATGAAC GGATGACAGA AGCTCCGAAA UGAGUACGAT TTTTGCGATA 300 GAACGATGCT AACGlTAGCC CAAGCGTTCU AACATGAGUC CCCAAClAGC OGATATAGGU 360 AGAGAATGUA UTATUAUTAG GAAACTTACT AGUCACCinU GUUGAAAUGT TAAAAllGTU 420 UTUGGAGTLA AUUCAAGATG CAACCCGTCG AGGGCGTAAC UAUGAUCGGA UlAlGlGTGA 480 TUACTUATAC AGATACUGAG ACATTAACCU AUGGUTAUGA GAUGUTAGT GlATCT / TAG 540 ACGAUAAACG CAAATCCUUA GTTlGGAU / G GATTCAAAAC UCCGTGAATG ATAAClAGTC 600 CAGAUACAUT UClCAACATG AAUUCACATU CAAGAUAUAA AAAUGClAAC GTlTlTlAGA 660 AATAGCAUAT ITUACTGGTA CCCUACTCCC GGCGGAGACU AGCGGArGGG UGGAAG / AAC 720 UAGGCGAGAC UCAATTTTGG GGGAUGGACU AAGCGAACAT UCACAGATCG TCGAACTACG 780 TTAAGAA / GA GAGTGGTACA TAGGACAGUA CTTCGAAUUA AGGGUCAUGG ATCTAGAAAC 840 ACGGCGCGTA ACAGTCCUAG AGAACGTTUA AAAATUTAlC GUATACTUAA AAACT7CGTG GCAACGCUAT UUCCUCAATU CCCATGCAGA GAUCTAClAC UGAGAAAAAC

900

280

184 424

GGTGCCTTGC CClCCTTClC ClAGICC 927 (2) INFORMATION ABOUT SEQ LD Nu: 113:

(i) SEQUENCE FEATURES:

(A) LENGTH: 972 pioy zisid (3) TYS: nucleic acid (C) QUANTITY of NlCl: single (D) TOPOLOGY: linear (ii) THOUSAND PARTICLES: nscytioic acid (A) OPLS: / description = "DNA (synthetic)

(xi) OPLS SEQUENCE: SEQ ID er: 113: ClCCCTCCCT 60 ccTCTAiagi caTccATcca CTTCTaccic CCTTAiCGCG TCCCCCTCCT CCTT1GC1CC 120 ccccGcccaa CC1CAGTCCC caacccGici CTCTCC1GT1 ccacccnccc CTTCGCCTTC 180 caaaccTGcg CGGCTTCCiG GCCCC1C1CC CGaCCTiCGC caciGcaiyc GllGTTGCCC 240 cagTTCThci iaaichccca CCGTCTClGC CCICICCCAC rcccGcaccc ICICGACCIC 300 caGTCATcni caacGCAGGi cacicccaar CCTTCCCGGC caaTCiGacG ilClAiCiCC 360 TTacccThca ccacccccAc Gancnccaci ccriaracrc CGGICGaCGC 1CCCCGGC1G 420 caccGiCTCi 1CCAC1C1C1 aciaicarcc cctcicctcc rTCTcncrac icycATAcci 480 ciccacacGT CGC11CTGC1 TTCCCGCGCC CCGCCGCTCC GCiCClGCTT cciaccccic 540 iccgcaccTi CC1GGTCC1C iCGiCCCGCG TTCTACCCCC cciiGCcccr cccacAccci 600 TGCGCCC1CC CGGCiCCCTC CCCCCGAGC1 iCCTCCiCAG CiCTiTAGCC CCGCTGTCCC 660 CGC1CCCGCG CGATGCCCCC GCGC1CCCCC aracccirTr iGccaccTcc

CniCiCiCCC CCCCCCGCGC GCIGCTCCTC CICGrGCGCT CTClCCCCAi CCCCiGCCCl 720

184 424

281

CCCCTCA1CT CCTlCCCGAT CCA11CCCT1 CGlCTCCCAT TCTiCTTCAi CCA1CTCC1T 780

GTCTTCCTTT TCCTCTACCA TCCTCTCCTT CAiiCCCTiG A1TTCAT1TC CCCCCA1TTG 840 iCTCCCGCCT TC1ACACACT TC11CTCTAC iTCiCClACT TTCCCACCAC ClTCCilCli 900

CAllTTCAGl A1CTTCCAAT liCCCCTCCC CTiCGTCCCI CCCAT11TTC C1TTCC11GC 960

TTCCCCTAAT Gl

972 (2) INFORMATION ABOUT SEQ ID No: 114:

(i) SEQUENCE CECSES:

(A) LENGTH: 963 base pairs (B) TYPE: Guk1riGsar acid (C) NlCl acidity: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (1) DESCRIPTION: / description = "DNA (synthetic) ^^ i) SEQUENCE OPNS: SNQ ND go: 114:

GTTCCTAACT 1CTCTAACAT 1ATCTATGAA GTCGTCACCC ACCTCAATCA 1CC1CCTCTG 60

CClCTCCTTT ACTTC1ACA1 CCTCAATTiT iAGiGCCAAC AT1TCCTAAT T — ACAAT1GC 120

CTTCTTCiTC CAAACCTCTA TCCATTCAAC CTT1CTGTCA ACTCTCTTC1 TA1TCC1TC1 180 iCAGTTTATI TCGTTCTTA1 IGATCTCCTC CAAT1TCT1C CCCTATCClC TGCCTClCCC 240

GCTCT1CATC C1ATCCAT1T CAGTGACiTT iACTTCGATT AlTTCCiTCT T1AACTGACC 300

TTCT1TCT1A A1ACCTTGT1 TlGCTCCCAT 1CTCi.AC1TT ACTTllAlTT CCCTGC1T — C 360

TCCCCTTCTT A1CC1TCT1T TCCAATCTCT ACTATCGACC CCTCTCCTCC iTCTAGAlll 420

282

184 424

GTTTCTCCCT 480 TGTTlAlTAT ttctacctaa cctcttagtt tttttttttt TTTCCTCTCT ΤΑΑΤΑΤΊΤΤΤ 540 TAAACACCAT TTTGGTTCTC atttatttct ACACTGGTTT ttaccgcctc gattttittt 600 GATATTATTT tttgcacttt gtgcctcttt ttactctttt GCCCAGTCCT tgttttactg 660 ttttctccta AACCAAAAAC agttaccttt (GACTCTATT ATGTTACAAC aaattttttt 720 TTCTTTCTCA (TTGTGTTAT ttttcccatt ttttattttt TCCATATCTC tgatctattt 780 tttttatctt TTCAACTCTT gcttttattt atattttttc (TTACTAACT GATTGCCATT 840 aatgttctct TGATCTATTT TCTGATTACC ACTGCTTCTA tutttgtuaa (CAATATTTT 900 TTAruTecAC ttttattttt catatatgtt ((TGCCATAT ttttcatctc ΤΤΤ1ΊΤΑΤΤΑ gtttttctta cccaaaaaaa TGCACAATCC tttttttttt ttattttgac

960

CAA

963 (2) INFORMATION ON EEQ ND No: 115:

(S) CETHY SEQUENCE:

(() LENGTH: 972 paos zisid (B) CYP: quickt sGniMSsowr (C) QUANTITY OF THREADS: single (D) TOPOLOGY: iSsiowa (Si) GYP PARTICLES: Less eukiussian quark (A) OPlE: / description = "DNA (synthetic) (xS) SEQUENCE OPlE: EEQ NA so: 115:

ATTTTTACTC ATTCTAlTAT (ACCGATCAC ATTAGTATTT ATTTGACCTA TTTATTTTTT 60 ttattcttct cttttactca tttcaacaac tactattcat acatttgcct ctaaaagaat 120 tttttttttt tcacttttta tctatataat tacttaat 180

184 424

283

1CCCCCTCU1 1CCGCCCCCA CCCTCTCCCG CCCC1TCC1C CCCTTGCCCC UTCClCACCC 240

CC1CUCCCCC CACGCACCCC CC1CUCCU1T 1CCCGT11TT CCTCCC1CC1 CAACCCG1CC 300

TCCGCCCCGC CCCCCCTUTC UCCCTCUTAG TCTCCCCC1C CC1TCUCUTT CG1CUUC11C 360

TCCCC1UGT1 1CCC1GCCTU GTCCACTCCG CCCCCCACCC C1CCCCCTCC ICCCCCCGlC 420

CCCCCCCCCG CCCCCACTGC 1TCTCCCCAG UTCUCCCCTC CU1CCTCCUC CCCC1CCTGC 480

CCUCTCT1T1 CCTUClUlUG CCCGUTTTCT C1CCCTCTTC CTCUCTTCCC UTCTTC1TC1 540

CCCC1CUCTC CCC1CCCCCC CGCUCCUCCC CCACCATTTU GCCCTUCCC1 ccccccuccc 600

CC1A1CTTCC CTCCCCC1CC CTTC1CUCCA 1CGG1ACCUC TCCA1GUCUC CTUCUCC1C1 660

CCCCCTGCUC AUCCUGTGTC CACCCAClCT CGUCUCCCCC CCUC1TCUCC 1TCTCC1CGC 720

UUCCCCTCTC CTUGCCTCCC CCTTTCCCCC CCTC1CTCCC UCCCCAUCCC G1CCCC1CC1 780

CTUUCCU1CC 1CCCUCUCCC ACGCTlCCTC 11CCCTTTCC CCCCCCCUU1 1CCCCT1CA1 840

UCCCCGGCll 11CGCCCCCC CGAlCCGUTT CCCCCCCTGT CCCCCCCUCC UCCTUCCTGC 900

1CC1CCTTCT CCCCCCCCCC CCTGCCGCGT CCU1CCTCCC CUGUlCClUC CCCTTCCCC1 960

CCTCCCTCCC cc

972 (2) SEQ INFORMATION NA Nh: 116:

(i) SEQUENCE FEATURES:

(A) LENGTH: 963 base pairs (B) TYPE: iunleSiPay acid (C) QUANTITY OF NITi: single (D) TOPOLOGY: MaSowi (SS) TYO PARTICLES: Siny acid nunluSipay (A) DESCRIPTION: / description ⁼ aDEA (synthetic)

284

184 424 (xl) SEQUENCE OPNS: SEQ NA no: 116:

STClTCACTT CTCTTAATCC lACTlCClSA ACTCCTCTTT CTTCCAllCC CTCCTTlCTC 60

CTCTTGTTCC ATCCCClCAS TTCTACCC1C lAACATTAAC CCCCCTTlCC CCAAASCAAT 120

TCCTCCT1CT TACATTCTCA CCTCTTGCST CCC1TCCCCA llCGTTTCCS CSCTCTACTA 180

CClACTllll 1TCCTTTCAS ASATTCTTTC CTACCTTC1T TCTClCCTCT CCTTlCCCTT 240

ATlTCCTCCT TAACTACCCC TT1C1AT11C lATCillSCl ACCTCT1CC1 TAASTCCCTC 300

CCTCCCTT1A SAATTTTCll 1SAT1T1TS1 1TCCACTA1C ATlTAClllC TC1TG1SC1C 360

CTTTTC11C1 AGTTCCGCll TTCACCTCCT ATCCCTAATT T1CTTCCCCT ICTCAASlGC 420

CCCCACAAAC TCTCCSACAC 11TTCTCCC1 11CCTTAC1T T11TTTCT1T TCTC1CCCTT 480

TA1T1TT111 TllCAlCGlC TTC1CCTCCT A1TTACTC1T ACA1TTCTCT C1A11C1CT1 540

CATT1TCTTT CATCTCACTC C1T1TC1TTC CTCC1TC1TC TC11T1CTCT CGllllCTGC 600

TT1TCTACCC TTCCS1A1TA AlTCACCCSC ACTTACilTl ACCCT1TA1T ICTCTSSCAC 660

CllTTCClCl TTATCTACAA 1TT1T1TCAT TTC1C11A1T TCiCCCTCCT TCG1TCTCTC 720

TTC11TCCTT TTT111TTTT CCClliCGCT CCTTTTAlTT AC1TTTTCTC CTC11TA11T 780

C1TCT1ACTT ICTTCCCTAl C1CTTTCTCT TCCCCTTACl CCTCCCTCCC ICTTCTlCSC 840

CC1ACACTTT TTCAlCCCll CTTTCTCCC1 yearsATATCTTlT A1TT11ST1C TCTT1STCTT 900

1TTATC1TTC TTTC1TA1TA ISCiCASlSl CCCClGlTGl TTTTT1CTTC 1TS1TCTCAA 960

184 424

285 cci

963 (2) INFORMATION ABOUT SEQ II No: 117:

(i) SEQUENCE TIMES:

(A) LENGTH: 972 base pairs (B) TYPE: nucleic acid (C) NUMBER OF THREADS: single d TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (C) DESCRIPTION: / description = "INA (synthetic) (xi SEQUENCE DESCRIPTION: SEQ H no: 117:

SlGGCTSATC 60 GGCTCCGGGC GACTGCTGGi AlGlTCiGGT CTTTG1SGC1 GTT1TTGCGG TGlGTGTTCl 120 CGCCGllGAl GTlTACClGl GliGlTCiSl ClllTTGiCT GGCGlATASG TTTCGTTllT 180 TAS1TGTTG1 GlTCTTTSlT TlllTlGCTi AlCTCTClTC GAATGTAGGC ICGlCCGlll 240 GCATTCGT1G AliTTCTTlG TTllllGlGT TlTCAlTTlG GGTTGTACCC 1CGGG1TCTT 300 TAllTTGCCT CSCGGCTlCT GlTlllllll AilCTTllTG TlAlTTGGGG TGTCCTGTG1 360 AiGTTGGGGS GlCTGTGTll ITCTClClll ATlCAllllG TGGGGGCGGC ITTTTlllll 420 ClTTlCGCGG TTT1CTTCT1 1T1SCCS1TT TllTiTTiyy ICCTGClGCC CClCClllGl 480 TCTTlAlTAT GlTCSTTCil llTGTTSTGT TllTTCCGGT TCCTGTGGGT TClGlTTllG 540 TlllSGGGGT GTTGGTTlTl llTTATTTGT SlllThlTTT GGCGGCGGCG IGTTGTllGT 600 ICTlTTCTTC TGTGTClCTT IClTTSCCGG GTTTTGTTCG TCCCC1GCTC ClGllTTTCT 660 CGGTTCAG1G TTGCGGGT11 GTGlllSlGl 1TC1GGGTGG CGGTGCGGCG TTTTCGGlll AGTCGCGClT GATTCCTiGl TllllTTlGT TTllGGllTT GGTGT1GCCT

720

286

184 424

1TACACTCTC TTilCATCCC CTCT1CTCCC CT111CTCCT iCCCCCiCCG 11CCCTTCAT 780

CTGGCGlTCh CCCTiACCCA ACTCCATA1C 1TCCTTTTCC TCTACCAC11 ICTCCTCCAT 840 iCCCTiCAAl 1CATATCCCC CT1TTTTCGT CCCACChT — G 1CACACTCCA ICTTilCGTC 900

1CCTACTTTT CCACCSCC1T CTCCCliAll AT1GAAT1SC TiliGAT — CC CCCT1CCCTT 960

CG1CCCTGGT AS

972 (2) INFORMATION ON SNQ ND No: 118:

(i) SEQUENCE CECSES:

(1) LENGTH: 918 base pairs (B) TYPE: Guk1eiGoar acid (C) QUANTITY OF NICN: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (1) DESCRIPTION: / list = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID no: 118:

iCTAGCTiCT 60 CTATGATTAT CC1TTAAATT ATAA1TCGCT TAGATA11CC ACChlCACCT TTCCT11ACC 120 CTSlCGlCCT C1AT1AC1S1 11C1TCTCTA TCCTGGTGG1 CCTAlACCTT C1ACTTCCAA 180 ICAPTlllGl CTTCITAATi ICTTTCAGlA 1CTTA1A1AA TGCITCAi — T ATT1G1CCAG 240 TTCTTCGTAA TCTCC1GCCA TChChCCCCT CT1CCACCCC CCAGCCCTCT C1ACATCCAG 300 TC1TC1TCAA TTCAliraAC TlTCG11.A1T TCCC1 — GACA IChllCiTTC ΤΑΤΑΤ — ΤΤΤΑ 360 CCCTTT1TCA 1TC1CA1—11 CGACA1TGCT TGTGiCTCCT hlTllTCCCC CCTiCTTGAC C1TCT1TTCC AATCTCTACT GTCS1CCCTT CTCCTCCTTC TA1ACAGTCT

420

184 424

287

cATTinhCTC 480 CGriCATCGA GGTTCACCCT TTGCCTTCTC ClGTCCTGCT GCCTGCTGTG GGC1TTTGCT 540 TGCGlCGGlG GAcrAyccAG GTGGGGGTGC cyAAGGyACG GGTCGTTCTG GGaGCCCiGA 600 CCCTlCllCl ccacccAciG 1TGCCACCCC ccGcAcAaci CCCCCCCAC1 TGCCTClCAT 660 CCCTCCTGGG ccacciTTCT GGCCGGC1CC C1C1CCTCC1 TGCGGCCCTG CCGGlCCiCC 720 1TCCGCCCCG CCilCCTCCC CGGCGCCCGG ccacrccica CGCCGT1CCC CCTGCCahCO 780 TCCTCCGCii cccccaccTG CTCCGCGGAC aCGiGCCTTT CClCATCCTT CTCCCTCGGT 840 cceicciCTG CClCaGGGCC TTyCCCGGCG ayATGGcric ICCCGCiCCC CCTGCTTGTC 900 accciccGacT CCiCAGTAin CTGCTTCClC CCTCCC11G1 CC1TCACAGC AGachGaGcy GGPCCCCn

918 (2) INFORMATION about SEQ II No ?: 119:

(i) SEQUENCE FEATURES:

(T) LENGTH: 918 pau zisid (B) TYS: nskluic acid (C) LOOSE OF NlCl: single (D) TOPOLOGY: lieirwi (ii) TYPE OF PARTICLE: eucluirin acid (A) OSLS: / description = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ id no .: 119:

GCTGaCiGCT CTCTAiTrAi CCTICCCTTT TTTCTTCaCI iaaAGCCCCC GCCTGCCCC1 60

1TGC1GGACC CGGACACCCi CCC1CACGCC CACCiCiCia TCC1GT1GGC CCCCiiCCTT 120 cicciiccaa aycTccai-ac cttcctcacc gctgtcaigc TCTiAcrGic iccatccgci 180 aTTCCTCCCCCC1 CACIGCCCCC1 CTC1CTCCCCCC1

288

184 424

AUCAACAGCC 300 AACAAAAAAC AUAAUGCKAA GUUAAAlAAA TAAUCGAATA AATUCAUTTA ACAGAGGAAA 360 GGAGAUAlAA aiACCAAUTT ACAAAGACAU AACACllGll AlUCCCATAA AAlCCAGCCG 420 TUGAAGlTAA CCAATGACG AAGCAAGAUA AAAAAAA1AA GACACTTATT TATACATCAT 480 GACAGACCAT 1GATAA7TAAA GTCCTGCTGC GAUAACACUA GGCGACCTAC UUCUCATUCA 540 CCAAGGCCCA AGA <U <UAATA <A CACCAAACll ATAGGAAUAU AUAAGAACAA ATAGACATUA 600 AAGGTGTAAA 1UAAGAAG1G C1AACAGAGU CAAAAAAAGC AGAAAAAAGA GAAGGUGAAG 660 ACAAAACAGU CACUGAAAAG GAGGTCCTłG GGUCCCtGAA UACAGTCAAG ATTAGAACL 720 GAGAGACAGA AAGCAGlTAA AAACAAACAC AUAAACGACA AUGAAAAAAA GAAAUGAAGG 780 CAGCAAAGGA AAGTGGTAAr GAGGCAAGAA AGAAGGAAUA CUGCUCCAAA CAAAAGAUAC 840 GACUUAAATG AUUGGG / AAA AAUUCGTCAA AAUAACCGAA AUGAAGAAAA GAAACC1AAG GATlTACCAT 1 / AGAGCAATC GAAGAAUAAA AAAAACUACU CAACAUAACU

900

A1AAACUCUG ΤΤΑΤΑΑΑΑ

918 (2) INFORMATION ON KEQ ID No .: 120:

(S) SEQUENCE FEATURES:

(A) LENGTH: 918 base pairs (B) CYO: nucleic acid ^, y (A) QUANTITY NITD: single (D) TOPOLOGY: linear (SS) GYO PARTICLES: other nucleic acid (A) OODS: / description - "DTT (synthetic) (zS) SEQUENCE OODS: KEQ DD No .: 120:

184 424

289

(TTCATGCTT 60 tcctaatcAt ttagaaacgt AGATCGTATT GCGCCACGTT attgttattg TGATTCCATT 120 TCCATCCCTC tacgaattca (ATATTTTTA cttttatuta TTCCAGTTCC TTCTGTCCAA 180 ATTGUlATCll tgttccaatt ctttttccta GTTGACAGAC gctggtatcc cgttaactaa 240 TTCTTTAtAl TTTTTAATTC GCTTTATTTT tttttatctt TCTATTTGTC TCCTCGCCAA 300 TTATTACTAl tctatggtat tautactact gttttaagaa atcaattgct TAACTACTGA 360 TTTTTAAATA attttaagca taatattact gatacaatcc tccatttgtt ttactgcaat 420 TCGTTAlGTT AAGTATTATG AGTACTTTIT TTTTCTTCCT gaaataagtc TATACATTTT 480 TAAACACCAT TTGCCTATTG (TGATAAATC GGACTGACCC ccaggtcaaa attcccattc 540 ACAAAATTAl ACTATACCAT atctttcact tacgtatttg gtcattccat tccttcactc 600 caatattaca ATlATCAAAA TTClTTGCTT TTTTATTTTT TTTCCCUCCC TTTTTGCAAT 660 ACCGTTCrCT TTATTTCACU cttttttata ACTGTTTCCC aatttattct tttttacact 720 CTGCGACTAC attctatcat (AGTTTAlTT TTAGTCTTTT tactggttaa TCTTTCTGTT 780 AACAAlACTG CTCCTATTCA atcttatgct CACCACTTGT ttgtcttttt AAAAAATGTT 840 CTCUTAATAT CCTCGTTTTT tttttttttt TTTATCGTTG tttacgttct CATAAATTCT GCTCAGlT TC TTAGACTTGT ΤΑΊΑΑΊΑΑΑΤ GCACTTGCCC TTTACACCCC

900 tctttttctt tcacacct 918 (2) INFORMATION ABOUT EEQ ND No .: 121:

Sequence techniques:

(A) LENGTH: 918 pio zisid (B) CYP: eucluSeowr acid (T) NUMBER OF THREADS: single

290

184 424 (D) TOPOLOGY: linear (SS) THESE PARTICLES: Gray nucleic acid (A) DESCRIPTION: / description a "DNA (synthetic) (xS) SEQUENCE DESCRIPTION: SEQ ND no .: 121:

ICGAlCTTCT CCCTGACGAC CUCTGieCTT CCACCTCCCT TCGAGC1CCC ACCC1CCCCC 60

CT1CC1UCCC CG1ACCACCG CCATTCCTCC UCC1TTTCCC CCCCGCCU11 CC1CA1CCCC 120

CGCCTTCCCA CCCCUUC1A1 CCTCUTACTU UCCTCCCC1C CCTCC1CC1C GUT1GTCT1C 180

CGG1C11CCA TCCTTCTTAA CCCCCACCCC CTCCGTCCCT CCTCCAC1GC CTCACCCTCC 240

CGlClCCCCC TCCTTCCTlA UUCAGTT1CC TUUCCC1CAC TCC1UUACC1 ACCTACUTTC 300

CAGCCU1TCA CCCTC1CUCA CGCTCAUUCC CCCCCUCACT TCUCUU1C11 GTTCTUTTCC 360

CCGUlClACC C1CCC1UTCC CCTCTChCCC CCClACCClC CGCCTCC1CC GAACUCCTCC 420

CCG1ACCCCC CAAATCClTC CUCGGCTCTC C1CCGU11CT AAT1UC1CAC CCA1CTUUCU 480

UC1ACCCCUU TACCTTCCAC CCTTGTA1CC UC1CCCCCCC T1CCTUC111 11CTCCTTCC 540

1C1CU111CC CCCCTTUCCC CCCTTGCCCC CCCCCCCCCC CTTTTCC1CC CCCGT1CCCT 600

1CCC1CCTCC CCCCTTUT1C CCCGCATCUC CCCCCCG1CA CCCCTCCTCC GCCCTAUGUC 660

C11CCCCCC1 CTCCCGATU1 CCCCCCTTCC CCCCCCCC1C UCCTCCAlCl CCG1CCCCUC 720

GTCAGUUCTC 1TCCCCTTAC 1CTTGTA1UA UU1TCCCCCC TCT1C1CCC1 TTCCCTC11C 780

T1CACCCCG1 C1GCCCCC1C CCCTTCTUCC T1CUACCTCC TC1CCCCCC1 G1CCCTUCCC 840

C1G1CCCCCC CC1CCCCCCC CCGTAUACCU C1CCC1CTCC CC1CU1CTCC CCCCCCTCCT 900

184 424

291

ATCCTC1TCC TCCTCTCC

918 (2) NN / TIPS ABOUT SEQ NA No: 122:

(i) SEQUENCE TIMES:

(A) LENGTH: 918 pio bases (B) TYPE: nucleic acid (C) NNCN QUALITY: single (D) TOPOTHIA: linear (li) TYPE OF PARTICLE: other n "cluic acid

(ei) OPNS (A) DESCRIPTION: / description - SEQUENCE: SEQ NA "DNA (synthetic) no: 122: GCCAGTTCTT 60 TTSCSSC11C TllTCSCACT ACATCTCCTC TASAllCSTC ATTCCTCTTC TTCTTillTC 120 TllSTGGTTT TAATLATLAA CATlCCTCCA TCCT1CC11S TTCAAACCTC T11TTTCT1S 180 SCTG111111 GTCTCCllli ITGCCCSlll ICTTCllCAS TCTCCTCilT ITCCCilTll 240 CCTTCC1TS1 TCCTTAATTA CCCCCCTTTT TTCTTAT11C T1C1TTTTTT T11TCTTC1S 300 CCSCC1CT1S 11TCC1C1AC CG1T1A1CAC TTT1CCASAA ATC1CT1TTT ClCTTCCCCS 360 CCCTCCllTl CCTCTAllAA TAACllCCTC TG1C11CT11 C1CC11CTCT TCGClCCGGC 420 C1CTCC1CTT ACCCCCTATT ATCAATTTCC GTTTTGTCTT CAAACAATTT TlTAGCCCCC 480 C11STACC1S CTTTC1TCT1 CCAlACCill AlACTTAlAC 11C11C1ATT GlllGlTlll 540 ACSCCTT11C CCTCiCllTT CCCCCCTTGl C11GCCCCAC CCCCiClTli CGGCClTTll 600 11CCTATCC1 CTCCTCSCTT TTTTCiiiiT C1TTTTTC1C ITlCCCGGlT TCTTCTTTCG 111CTTTCTA 1ACCTCTTCC ClllTGTllT TTCCTTTATS CllTliilGT

660

292

184 424

CACIAAACAC 720 CG7AAAAAA1 AUGGCACAGA AAGACAAAGG AAAAGAAAAA AACAUlCACl CA1A1AAATA 780 GUCAUAAAUT AUGACAAAAA AGGAAGACAC AAAGC11AAA ACUAlUAAAA CGAAAlATAA 840 AAAAAGGUAA AUCTAGAGAA GAGAGACAGA AAACACATAA IGATGUACCA AAATCA1AAA TATCCAUTCU AGACACCACU ACAAGAUTCC AAAAGAGAAA CAGAAACAAA

900

CAATA1AA1A AA1AAUAG

918 (2) INFORMATION ON KEQ DD No .: 123:

(S) SEQUENCE FEATURES:

(A) LENGTH: 907 base pairs (B) GYO: acid nuniuSnowr (T) LARGE TlCD: single (D) GOOOLOGIT: linear (SS) CYO TROUBLE: Sns' kwa? nnniuSnow '(A) OOIK: / opSs - "DTT (synthetic) (xS) SEQUENCE OODS: SEQ DD no .: 123:

UAAT1TA1AA 60 AACACAACCA GCAAGAACAA AAACAAAAGG ACATGClCAT CGAAUACAAA AAlTAUUCAA 120 AAACACAAAA CCAGGAAGAA CACGAAAGAA AAGGCCAUUC AGCCCCAAAA G1CAAAACTC 180 CATAUUAUC1 AAACUGAAUC UGCGACTAGA AATGAUlAAC AUGAAACUUA ATG1AG7GAC 240 rATTAlACA AAAAAACGAA ACACGGGAGA GACCGAAAUT AUGAAAAAAA AlCAATAAAA 300 AACACCACCA UGAC1GAUAA AUGAATCCAG TGGGCUlCAi CGAUCA1AAA ACAAU1AACA 360 AAAACAUGCA UACCCCAAAG CAGAGAAACA ACAGClAAAA CUAUAAAAAT AUUUCCCAAU 420 AGAGATTACA AGAAAAAAAA ACACCCCATG AGAAGUAAAC CACTAAGAAA

ACCCATGACC AACAUUAAlA AACGCCAAGG GACAAGGACC AGACATC11T AAAUUCAAAA 480

184 424

293 ctccgcccct gccccttctc ciccacGCCc tcgtcgccgc cccGCGcccc ciGccaccca 540

CiTCCiCiCC TCCC1CC1CG CGCCGCT11C 1CCGCGGG1C CC1C1CCTCC TTGCGGCCC1 600

GCGCGCC1CC TTGGCGCCCC CCTTCCTCCC CTGCGCAGCC CCTCGGC1CC CGCGGG1CCC 660

CT1CCG1CTT yyTGCCCTTC CaacaCClGC 1CCCAGGAGG GCiGCGTTTC C1GA1GCTTG 720

1GGGGGG1CC ACyC1C1CCG 1CCGCGCG11 CGGCGGCTCC T1GCCCTC1C CCCC1CCGCC 780

1GCTG1GGCC TCCCCC1CC1 CCG1CGCC1G CiiCGTGCCi CCCG1C1CC1 TCCCCCCTGG 840

C1GTCCCGTG CCC1GTGGTT CGCCCTT1GC CiGCGCyTGi CCTGC1GCCT GCTG1GGCC1 900

TTGC11G

907 (2) INFORMATION ABOUT SEQ ID No: 124:

(i) SEQUENCE FEATURES:

(A) LENGTH: 918 pin zisid (B) TYPE: nucleic acid (C) NUMBER OF THREADS: single (I) TOPOLOGY: linear (ii) 1YS PARTICLES: ieey eskluieowy (T) DESCRIPTION: / description = "DNA (synthetic)

(; <i) OSLS SEQUENCE : SEQ II eu: 124: ccicacTGci 60 C1T1GA1GT1 CGCTCGCGTT aiacATycci TCGTGCGCCC TCC1GCCCC1 TTGC1GGTCC 120 CGCCCGCCC1 CGC1GGCCTG GcccTCTyic 1CC1GG1GGT CCGGCTCCT1 CGGCTrCCTG 180 TCC1CGCGCG C11CG1GAGG CC1GTCGGGT CCTTCClGCG TCCT1CGGG1 G11CGGGCTT TTCT1CGTGT iCiCCCGCCG TCTCTCCCCi C1GCCCCGCC CGCCCCCTC1

240

294

184 424

CCACATCCGA TCATC1TCGA T1CAT1T1AC TT1CAA — AAT TCC11TAA1G ACCGlCiTTC 300

CATCTiiTTG CCCTTCACCA AlCTCliGll CAGCATTlCi TA1ACT1CTT TGCITiCTCC 360

CC1CCT111C C1TCTCCTCC GACCTCTACT ATCAACCC1T CTCCTCClhC TAllCAATCh 420

C1T1A1TCTC CAAAC1TC1C ACCClACCiC CTCTC1TCCC TCCTCCCCCA TCCChCTill 480

CAilTCClTC TCChCCTTll TCCCCTiCll 11CCTCCTTT CAlCCCAlCT CCCTCClCGl 540

TGCATGACCA CAlChCACll TilTCCClAT TCC1TCTTCC TCAGCTCCCA AC1CCTTCTC 600

CTAlllAlll TTCCTCCCCT TATTCCTTTG TCGTC1TCCS CCCCCTCCTT ClTTCGATTC 660

CICiCCGACG TiCCCCCTCC CiCTCClCCT 1CTPTTCACC TCC111CCCT ClTTAGlCTT 720

CCTCiTTGCT CCCAT1TCCT TCACITCAiA CTC11CC11T 1CCCA1ATCT TC1CCCTTTT 780

CCTGCACCTT TCCTCCCCCC TTCTGTi — GC TTTA1CTT1T 1ΑΤΑ1Τ — Τ1Α SACCCA1AT1 840

TA1CA11CCA AiCCACICiG CATTCTIliA ICAiCiACCC TTCTGCTGTA TCTllTTATi 900

CCA1CAC11C TACAACCC

918 (2) INFORMATION ON SNQ ND No: 125:

(i) SEQUENCE CECSES:

(A) LENGTH: 848 pao za / ad (B) TY'P: acid / nucleic (C) QUANTITY of NlGl: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (1) OPNS: / description = "DNA (synthetic) (ii) SEQUENCE DESCRIPTION: SNQ ID go: 125: ·

CCTAACTTAT CTATAlTilT C11CG11ATT ATACATCACT TAA11ATACC ACCCGCACCT 60

184 424

295

TTGTTGGCTG TlClTAlTTT TC1TG1TG1C GSTlCTCTCA 1TT1GACGGC TTGAlCTTCT 120

TllTTTTAAG CTTCGGlGlG TlCTlCSCGG GTCGCTClGA ATTCCGllll TGTCGTAlGC 180

IhlGAGCCSl TTTTTTGTA1 TTTTTC1TTS CGCCCGTTTC TClTTlTllT TGGCCTTCGG 240

TllTACTTlG CCCCT11C1A GGT1GGCGAT CGGClCGiSC ITTlGGSSCC CTTGGTGTTT 300 riTAłCGlCA GGGTTG1GG1 IGTGCllGSS TSlTCGCATl ICllGGGTlG TGGAGGTTGG

TTGGlCGAlT CGTTC1GTGT 1A1G1C1ATC ACTCiTTTlC TTGTTGTGTC CACCGlGCTT 420

CiClSlTCTT CSAAC1TGGG 11TTT1GCTT GTTTT1C1GG GC11GCTG1G CGGGCATAAG 480

GlCCTTlClG CCCCTTGTG1 GllTTTCCil GCTTTGCTGT GCGGG1AGGT GGGCGTGGTG 540

SCCTTCGGCG GCGllCCGGT TTCCTGTGTT SllGiAllTl 1GGGTA1GCG 1GGGGCTCGT 600

GTlCTlTTlG CTTG1GGGT1 TTlSlCTTCT AlllASTClT TTTllGATTT TTATGTTTTG 660

TST1GGAGST GGAGTTCGCl TTTAGSlGTC T1TTT1CCGT TCITiGTTGT TTTGGT1TGT 720

ITTGCGGSTT GGAlTCGCGG SllAlllllA STTTSGSlll CGGCGGTTA1 GGGCC1iyCT 780

ShlTCGGGlG GllTGATTTl ITClTCGGSl GGllllSTGG GAlClTlGGG ATlAGTlGGC 840

TTTSGTCl

848 (2) INFORMATION ON SEQ H No .: 126:

(i) SEQUENCE TIMES:

(A) LENGTH: 918 pairs of bases (B) TYPE: nucleic acid (C) NUMBER OF THREADS: single (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description = "INA (synthetic)

296

184 424 (xi) SEQUENCE DESCRIPTION: SEQ ID wr: 126:

1CGACCC1CG 60 CCAG1ACT1G CUAGUCACTT CCCCCCCCCC CCCCUC1CCC CCCCTCACCT GC1CTTG1CC 120 C11CC1ACCG CAlGUjCCGAl TAClTCCTTA CCCTUCCUUC CC1CACCCCC C11CCCCCA1 180 CCCC1TA1A1 CCCCGTACGT UCCUTCACUC CCCTCUlCCC CUCCTCC11T 1GG1AGUC1A 240 CTCCCC1C1C ccgcc.cicci CUCCC1CCCT CCTCCCCUTC ClCCCCCTCh C11CCCCCA1 300 TCATCCCCAA GTCAGGTGAC TTUCCC1CCT TCCTTlCCAl CCCUCC1CTC GAGCC11CGA 360 CCCCCTC1CC C1CGCAGTCA CCCCAUCCCU TCUCUGUCll C11CUTCTCC CC1G1CU1CC 420 C1GCC1UCCC ACCCGCCCCT CCCCCCCC1C cccccccucc GAACGGCCCC CAGCACCCGC 480 CCCGCCCUTl CCGUACCACC UCCCCCCA11 CCCCCCACTC CACCCTCCTT A1CTCCCA1C 540 CCCCUCTCC1 AUUCCCTTCU CTCTTCCCTC TUCCTTGC11 C111CCCCCC CGCCTC1CCA 600 UllCCTCCTl CGTCAACATU ucuccccccu CTCCUCCTTC CCUCTCCCGC C1A1CCCGC1 660 UCACCCC1CC CC1GUACTTC CCC1CCCCCC CCATCC1CCC UA1CCCUT1C CCAG111CGC 720 CCCCCCT1CC CCCCCCTTCC CCTCC1CCTU CCTCGTCCCC CA1CCC1U1A 1A1CUTC1C1 780 CCTGUCTTTA 11CGGCCAA1 uccccuuccc CTCCUUTC1C C1C1CCCCCC CGCCTUUAT1 840 1C1CUCTTUC A1CCCTGTTC CCCCCTT1CC CCACCTUCCC CGCCCCCCTC CGGUTUCATC TCCCCUTACC GGGCCUTCTC CGCCCTT1UU CCCCUCAUCU CCCCCTTUUC

900

ACCCCUCCCC CCCCCCC1 918 (2) SEQ INFORMATION NA Na: 127:

184 424

297 (S) SEQUENCE FEATURES:

(T) LENGTH: 918 base pairs (B) TYPE: nunluSnoa acid (A) QUANTITY ri / 1: single (D) ΑΟΟΟΙΟΑΙΤ :: linear (SS) CYO MOLECULES: Snn 'nucleic acid (A) OODS: Uspi? - "DTT (synthetic) (xi) SEQ ID NO: SEQ DD No: 127:

G / AACAGUAr AACCCATCAT ACATGAAAAA ΑΑΑΑΑΑΑΑΑΤ GAAAUAGAGA AGGAGAAAAG 60

ATCGGlGAGA ACAAACAAGT AACTGACUCA GCACATAGTC GGATUACUGl GAUCCAATGG 120

AUAAGTAGCC AAAGGAAUAU GTCCCAAACC CATlGACAUC AACCAlACAC CAAACGAGGG 180

CTCGCGAAAC TTGGCGUACA TACGAAAAGA GGTTGAAAGG AAGGGCACUG GCGAAAAGAG 240

AGAAATAGCC AACGGATACA UlTTGCCGAG GAUGCAlCAr TATUlUCACA CGAGCGCGGC 300 rAAGTCCCAC AAACCGAUCA AUGGCAGAAA TCAGAATAAl GACAClATAA AGUAGUAGTC 360

AGUUUTCCAA AlGTAGUAGT CAGTTAGATG ATTACATAlG AAGAAAGGTA TCAACCAGCG 420

AATATATATA ACCAGATUCA TAACAAGGAA GA / TAGUTAC TAGAAACGAU GCCGAAAAAT 480

TGGAAGGUAl UCATCUGACU TTCAGGGACC ATAUTClUCU UGCAGCGAGT GGGGUT / CGA 540 lAAGTAUGGl lAAAGCTUGT UGAGAGAUGA GAUGTGlTTT UAGAGTCCGC AGCAATGAGG 600

CACGACACAA ITGAGATATA AUGGATCTAG AGAClCATAT UTATUGGATA AUAGAGCAAC 660

AAACAUGGAC ACAAAGTAAT UAAUGGAGGA UTUATATGrC IGCCCGGAUC AGUAAAAAAC 720

ACGCT1GA1G C1AGACCUCA AGACCACACC ATUGUCAACl TGAGGAAGAA CAAGGACGGA 780

298

184 424 tttatcctct ίαίτττταία gtgccugttt atgctttttg tagtttcttt acgctacttc 840

TCTGGATAAA TTTATTGTTG TTGGCCUCTT TCTTACCCTT GTTGGTTAAT TTATTGCTTC 900

TTACATTTTC ΤΤΑΊΊΑΤΑ 918 (2) INFORMATION ON EEQ ID No .: 128:

Sequence techniques:

(A) LENGTH: 918 pairs of bases (B) CYP: nGkiMSna acid (C) NUMBER OF THREADS: single (D) TOPOLOGY: iSniowa (SS) CYP PARTICLES: Leny nGnieLic acid (A) DESCRIPTION: / description = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: EEQ ID er: 128:

ATTAACrCTT tcatcggtac tcggccacgg agatggtatg gaagcaaatt attgttattg 60 tacttccatt ttcctgattg taagcattaa tgttgtttta cttttacccc tttaacttcc 120 taatttttaa atttctatcc tgttcgagc ctgcgcggcata atgcgcgtcata

CAGlACCTAA GCTTCTCTAA CTCTTGATTG GTGTGCTTTC TTTTTATCTT TCTATTTGTC 240

TArCAGTTAA GTCTTAGTAG CCTGCTTCAT GTTTAATAAG GTTCAUCAAC CTCCATCGGT 300

TlTCTGGTGA tttttcatta gttctgctaa taatgctatc gacacccttt gtgacttgtt 360

TCGGCTCACT tttttttttt gagtcttatc gttaattttg tttttttttt tcagcaattg 420

TlTGGlCTGT TAACTAGCCA CTTTAGTTTT AGTGCTTGTG CTGCTTGATC TTGTCGTTCA 480

ATGIATAGCT ttggttgcgg ctttucgtag acggttattt gtgtttgtat auagggttct 540

GCTAATATCC TTTTTTTTTT CTTCTTGATG TTTTATTTTT (GATTTCTAA TAACTGCTCG 600

184 424

299

T1T1ATCTTC AC1CCCCTTA TllCACCTTl SCTTAGTCGT TA1C11CTTA TCCTTC1TTC 660

ATCTTClCTC TCCCCTTC1T TCCCllGCCC ACCCTllill AATllGGAAC CTliCClCCC 720

CClCTTCCll TCTAClATCC CTCC11A1CA 1CCACCTTTT C1TCC1A111 llTCCCClTl 780

CGCTlililT AATCClllTT TATTTCTTTT CTACCCTTCT CGlllCllTC CCTTllATCC 840

CTTT1CTCTC CTTCTCCClT TTTCTAGGlT TCTTTTllCA TTCCCCTTCC CTTCTCCClT 900

ICCCTTACCC TCC1T1A1

918 (2) SEQ INFORMATION NA No: 129:

(i) SEQUENCE FEATURES:

(1) LENGTH: 918 pio bases (B) TYPE: nlk1einoay acid (C) NNCN NLQ: single (D) TOPOLOGY: linear (li) TYPE OF PARTICLE: other nlk1eineay quark (1) DESCRIPTION: / description - "DNA (synthetic)

(xi) OPNS SEQUENCE: SEQ NA no: 129: CTTClGCGGC 60 TTlCSlCClT TlGTiSClTC 1C1C1TTCTT TlClllllTT ATTT1TATTC TT1TC11CTT 120 TllSTllTTT TClCCCTllG C1T1TCTTCC TTTTC1T1G1 TTCAAATTCT TCCTTTCTCC 180 IGTTClllli TCTTlCGGll ICTCTTSCCl ITCCllllAS CCCATTCCCT ICGGllCGAG 240 CCTCCT1C11 CCCGTGGTTl TGTCTGTTTT CTCTTlTCCC CCTCTTTCCC TilTlCTCll 300 CGlCClCTAl ICTSlCCllC CCCCllillC TGTlCClCGA ATTCCTCTTC CCCCCClTCC 360 CTTTTllCCC llClTCCCll CGlCGGCCTC CCCCCllTll TCllilGCGT

300

184 424

CC11GTGGCC CG1C1CG1CC GT1C1C1GC1 420

CC1CCC1C1C CiCGCGlCCC CATCTTCC1C 480

CCTTTCCTGC TGCTTClGlC GGGG1CCCCC 540

CCliCiCCCC CTCCGCCTGC TTG1GGCC1C 600

CClGTycilC GCC1CGCGC1 CTGCCCCTGC 660

C11CT1CC1C C1CT1CCCTT 1TGCTTGGGG 720

ICGCCGCTCC TTClGlGCCC CG1GTCCC11 780

CGGCTGCGGC CCTCTTCCC1 CTCGlCCCiy 840

C1CCTTGGCG CCC1CCGGGG CC1CCTTGCC 900

G1CGCCCC1T C1CC1CCC1C TTCGGTG1C1

GCCT1CCGGC GCC1GC1CCG AGGGTGCG1C

C1C11CGTCG CGGGTIlCGG CGGCCCCCll

CGG11CCTCG C1GGCCTGCT TCGTGAC1CC

CCG1GCG11C CCCCTTTGCC TACCCCTC1C

1CGTGGGCGC CCCCGCTCCC GGTGTCCCCG

CTCCTGCGlC IGGIGCTCGC AGCCCCGGGG

ClGCCGCGCC TTTCIGGGCT GGTCCGTC1C

GCCCGCCTiC CTCCCCGGGG CTGGTCCGCG

CClCTCCGlC aicccnci

918 (2) INFORMATION ABOUT SEQ ID No: 130:

(i) SEQUENCE FEATURES:

(A) LENGTH: 915 pairs zisid (B) TYPE: nucleic acid (C) NUMBER OF THREADS: single (I) TOPOLOGY :: linear (ii) 1YS PARTICLES: ieey nucleic acid (C) DESCRIPTION: / description = "ING (synthetic ) (xi) SEQUENCE DESCRIPTION: SEQ II eo: 130:

GC1GTC1CC1 CTG1GC1GG1 60 CGCTGGTG11 G1GCG1CGC1 1GTTGTCCCC ACCTGCCCC1 TTCCTCGCCC CGGGCCGCCT CAC1CCCCGC CGCCiCiCiC 1CCTGA1CCT CCGGCTCClT 120

C1GCTTCCGC CCCTCCG1GC CTTCGTC11G ICTClCGGCG CCTTCGGCGC TGCCiCCCli 180

184 424

301

ATTTGiCCSl TTCGTC1TA1 TCTCCAACGA TiTCTCCCCT CCTCC1C11C CTC1CCCTCC 240

CTAClTCClG TCATCATCAi TGClliTiAC T — iCGATGAT TCCTCT1AAA GCTCGC1TCC 300

TATCTiTTTA CCCTTGAGCl AlCTCGClAl CAlCGlCACT TGTATGTCC1 TCllTGCPCC 360

CCTTCTTGAC CTTCTGTTCC AATCTCCACT GTAGACCC1T CTCCTCClhC TAlGCASPCC 420

CATAAGTCTC CAS1CATGCA TCTCCACCCT TTGCCTACAC CT1TCCCTCT iCCCTCTGCC 480

1GCTTT11CC TTITGTIACi TlGAGCCCGl GTGTATGG1G CCGATGCACA TGAClTTGCC 540

TCllCGiTGA CCCTCCCCCT TGA1CG11TT ATGTC1TCAC 1TGCACA1CT 1TG1CCC1CC 600

TTCCTCTCAT CCCTCCTCTC TCGTCTTTCT TCACA1TTCC TCCTCCPCCT TCGGCCCCPT 660

CllGiCCTCC TTGCAGCCCA TCTTCCCCCA CAT11C1TCA CClClCCTCA CA1GG1CCCC 720

ASTiCCATCT TCCTGGCCTT CCA1CACCT1 CTCClACill AiCTTCTTCT CCTCATGCCT 780

ITAilAliTT CCACCCCCT1 CiTCAllTAG TTCilCAACA TTTCTTCCCC CTCTCCCCCC 840

1CTTTTTACC TCCiATCCCT CA1TSA1CTT CCTCTCCACT CCCATCCCCT CCACACC1CA 900

CTTAlCGATT TCCCA

915 (2) SEQ INFORMATION NA No: 131:

(i) SEQUENCE CNGS:

(A) LENGTH: 915 bases (B) TYPE: nucleic acid (A) NLCL: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) OPNS: / list = "DNA (synthetic)

302

184 424 (xS) OPDS KEKWEN / JI: KEQ ID No .: 131:

CAGCAGAlAT ATAACATCCT AUTAAATACG ACAGAGAAAA CCAAUAUCGA AAATUAAAAA 60

CTUTTUCCAT GUAAGACAAG ACCrGCCCCA CAGCCAAGTA GATTUATlCA GAUCAAAATC 120

GCATCCGClA AGGACUAUCl AGGC1TAAGG GATUACAACC AAAAACCCCA TGAATGCACG 180

AGTUAUUACC TCAACAUTCC TAGACCCATA CCTATGGGAT GGU / GATlUG GUAAAGATAC 240

AUCAACGACA AGAAATAGCC UCACUlCGAG GUACAACCAT AGGUGUCCCA CATGATUTTA 300

GArAGUlTAC GGGACGCUAC CUACACGCCA GAAGAGCAAC GAUAGCUAUA GGACUUATGG 360

GAGUACCATA ACCATGATTA CAGTTAGATG AGGCAAAGUT ACAGGAA1AA AACCUCCTAA 420

ΤΑΤΑΑΑΤΤΤΑ ΑΑΑΑΑΑΑΑΑΤ UTAGATAGAC UGATACTAGA GAGACGAUCA GGGCCUATTG 480

CUCLATTRUGA CAAAGCC1CT ULCCCAGCTA AACUTATACU AAACGAT1CG ACACUTUCTA 540

GGATGCAGlA A1GUA1GUCT UATAUTAGUC GCCTCAGTUn GAAGCAGTGU TTTGTTCGTG 600

ATATCGGUAT AUAGCCATUl CTAUGTGTCC GGATGAGGCC UGG / AGGUGA CAUTATGATT 660

GGCCCAACUA GGAGTTGATA UUGACCGAGA AAACAGACGC AAAAGAGAAA TUGACTATTA 720

ATUCGGGTAA CAAAGGCCAG AAlCUUCACU GGUGCCCGGA CCAGGACrGG AUAAACAGAG 780

AAAAGGG1AU TACUCAlATG GAUTAAACGG CGUTATGATU ACAGGCATCG GGCTlATAGA 840

ACCUGAATGA UGACATGUTT GAlTUATGAG AATUCCGGGG AGAUGAUCAG UA1AAA1T1T 900

GAClAUCTTA ATTAC

915 (2) INFORMATION ON KEQ DD Tr: 132:

(S) SEQUENCE FEATURES:

(C) LENGTH: 915 base pairs

184 424

303 (B) TYPE: eGkirSeowr (T) QUANTITY OF THREADS: single (D) TOPOLOGY: ILeLowa (SS) TYPE OF PARTICLE: Seny nukIeSnname (A) OPLE: / description = "DNA (synthetic) (xS) SEQUENCE DESCRIPTION: EEQ NA no: 132:

CTTCATTCTG ttacgagtag tcacagagcc acatggtatg caactatatt atttttattt 60

GCCTGCCATT TCGCTAATTG CAAGGACGAA- (GTCCTTTGA GTTTCATACA TTTACATTCA 120

TCATCGTTGC GTTTACATAT TTCTTGAGCA CTGCCTCGCA GTGCCCCCAC TATATTACAC 180 acctatctac catgtttgca ttgttaattg tttttttttt CTCTTATTAT TCTATTTCTC 240

TCATAGTTAA TTCGTGGTAA CCTACCTCAT GTGTAATGCT GTTATTCCCG ATGTCTTGTT 300

GAGTTAUGGA TTTGTCGCTA GCTTTGTCGA TAGTATTATA GACCTTTTTT TTAAAATATT 360

TTCATGCACT TCCTTGCGTT A1TTGTGGTG AGTCATTTAT TTTTTTTTTT TACATCAGTT 420

TATACAGTGT TAAATCTUTT TTGCTCCTTT cttccccatg gtgtttttut atgctccgca 480 (TTTACATCC (CCACATTAA CCTGTGTCAT GTATCCTTAA TATTCCTTTT GTTCTTCTAC 540 caattcagtg tcctctcccc gtaatgtaga tttatggttt ctgtcttttg ttgtccccgc 600 tggttgctgt gccctttgtg tttttcgccc ctttgttctc ctttttttau cgtttatttt 660 tttttatacc ctgtcgttat (CTGTGTAAT tgttttacgt ttattttttt caatctttca 720

TATTTCTTTT CACCCAACCG cttctttttc agttgcctct caccctttat tttttctccc 780

GCAAAGTTTC CTAATAGCTT TTTTTTTTTT TTTTTTTTTT TTTATTTTTT CCGTTTTGTC 840

304

184 424

SS1T1GTTCT iriSTTTTTA TGTTTTGTST CGTSGlTTGS GTTllllTTT SllllCCTCT 900

TCCTTlTTTC TCTT1

915 (2) SEQ INFORMATION HI No: 133:

(i) SEQUENCE TIMES:

(C) E> STRENGTH: 915 bases (B) TYPE: nucleic acid (G) QUANTITY OF THREADS: single (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description = "INA ( synthetic) (xi) SEQUENCE DESCRIPTION: SEQ II no: 133:

ITlSlTCGTC TC1C1GTG1T GGlTGASlTT STATAlGlTC CSlllSllTT STTTGG1TT1 60

TClTTGGSTT TllATSlCGT GC1TGCTGS1 GlTlCTCTCS CTTTGSTGGC TTlSClTTTT 120

TllTTCTCSA ATTCGGAGAG CTTGGT1CGG GTlllTllll ATTCAlSCSl CGTSCTAGGT 180

S1TG1lC.11 CCTCTTGT1S CTCTG.1STT1 111CC1TTTC T1GTTSTGGT TlTlTTTCTT 240

TlSTACTClC CClCTllCiC GGTAGGTlAT CllTilGAll TTTGGGCSll STTGATlTGT 300

CllTTllTTl TTTTTlSGTA AlTlTllGil TllTllllTl CllCGllTlG IGClGGTTCT 360

TTlllTllCT TGCTCGGCTT 1GTGTTCST1 AlTlSTTTlC T1TTTGTG1T 1SC1GSCTTC 420

CllliCCTCG TlCSTACGGT CGCGGATCCT SlTTCGGlll SlCGGilGAT TC1G1TGGGG 480 llllTTlSGG T1T1GG1T1T ITlGGGllTS lllSTTTCTT TGTTGGSGlG lllGlllGGC 540

IClTGGGGlT G1TTGGG1TT TSGTTGCTCT TTSTTTT1TT CGGGGT1GTT TTTTGGSCAG 600 llTTlGTlGT CTTTCGllGG TTCGGlGllT TTTTTTllll TTTllGTGTG ITTST60

184 424

305

GGCGCCGCiG 720 CTCCCGGClG 1CCCTG1GCC CiCTiCCTCG IChiCCGCCG CCTGCTCCG.G 1CGGCGG1GC 780 CTTTCCTGCT GCilGiCGCG CGG1CCGCCC 1C1GC11CCG CGAGTTCGGC GGCC1GCCG1 840 CTCCCCCTCC GCCTCCTTCl CGCCTCCCC1 1CCTCGG1CG GCTCCTTCGT 1GC1CCCC1G 1CC11CGCC1 CAGCC1GG1C CC11CCCCCG CGGTTCCCCC TTTGCCTACA

900

CCTGTCCTGC TGCC1

915 (2) INFORMATION ON SEQ II No .:

(i) SEQUENCE FEATURES:

(A) LENGTH: 915 base pairs (B) TYS: eskleierwa (C) QUANTITY NLCL: single (I) TOPOLOGY: linear (ii) THOUSAND PARTICLES: ion nucleic acid (A) OSLS: / description = "DNG (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ID no: 134:

CClGGCTCCl 60 CTT1GA1CG1 CGCTGCTG11 G1GCG1CGC1 TTCCGCGCCC GCCTCCCCCT TrGCICGGCC 120 CGGCCCCCC1 CGCTGTC1GG CCC11C1C1G TCC1GCTCCG CCCGGCCCTT C1GCTTCCCC 180 AcciCGCcac C1TyG1CGGG GCTG1CGGCG TCT1TGGCGC TCCATCAGGT GTT1GGGCGC 240 TTCiTCllCG 1CTCCTACCC TClCTCCCCl CTGCCGCCGC CCCACCCTCT ccacciccaa 3 00 TCT1CG1CTG GGCAGGT1GC 1GGCGCCCG1 TCCGGGGCGG GCiGACGTTC 1C1C1CG1TG 360 CCCTTCGGCi TGCGCTGGTG CGGCGG1GCC TTGTCGGCCG TGGAGGCTCC CCCGC1GCAC CG1C1G11CC GC1CTC1CC1 G1CGGCCCC1 CTCC1CCGTC 1CGGGACTCT

420

306

184 424

TCCGAGCCCT ClSSClCGll CCTTA1TCT1 llllGCCGll AGCTCTllSC llllCGCATT 480

SlllTlClll ICGCCGCill AlTClTCCTT TCTTC1TT11 ICCClCCClC 11TA1TCT11 540

1CGCAACC11 1ACCTACCC1 TTCCTCATCT TCTTCCillT SlTTTTTTCi ITCCCCTTlC 600

CTCCTTCTCC C11TTTC1T1 llGGGTGTCT ICSCTTCGlT CCTTCTTATA CCCTACCCTT 660

STSCTCTACA llCiCTTCll T1CCCTTCTT TClCCTCTTT AATATCCCTC CTlllCllll 720

1C1T1CTCTT CCSTCCTClT lliCCilCGT ATCTCTTGTC TCCCiCClTC TGCTSCTCTl 780

1T1CCCTCC1 TTCCCCTTCC CTlTlCGGTT TlACCTTCTC ICAAACTCTT TTlTCAGTCG 840

TAT1CTTCCT ACAlCACiCC CACCCA1TCG TTlClllCCG ATTTTCTGTC CCTCTTTCCC 900

TC1CC1CTT1 TT1T1

915 (2) INFORMATION ABOUT SEQ ID No: 135:

(i) SEQUENCE FEATURES:

(A) LENGTH: 915 pio bases (B) TYPE: nucleic acid (C) NICN STRENGTH: single (D) TOPOLOCISt: linear (li) TYPE OF PARTICLE: other nlk1eSnoay acid (A) OPNS: / description - "DNA (synthetic) (el) SEQUENCE OPNS: SEQ NA no: 135:

CTCiiCClTC 60 TTSCCGClSC TlACGSGATC CCATATCCTT ClllCSllTC ATTC1TATTT TTCTTCCSTT 120 CCCCCGATCT ClATGCCCCC lATCTTCTTA TCTTClTCll TTllGATGTT TlGTTCCTGC 180 CTCCGlllSi CTTCCTCCll CTCCCGASll ITTClCllll C1TCCTA11C ICTCSlCCSl CCCCTGlTSS TCTCCCATTA T1CTTCTTTT TTCTTATlCT TCTCCTTTCT

240

184 424

307

TGATATTCeC 300 GTATCAGTAA TUCAGGGGAT hGTCACGAAh hCTGGGCACA AChGATGCGC hAhChGGGTA 360 CCTTGUAGTA ATCTCATTCA CeiCAGTACs GAGAGGTCGG TTUATGTTCC TTyyGGGiic 420 CGGCTTGGCT AACCGChATh AhCACCCCGh CGCCTTCGhT TAAAGACTCT TAhAAATCTC 480 CecACAGyyy AG1ATGG11A ATCCAGAGGG ATGAGATTAA UTTATAGGAT AGTCGGGUAT 540 CATTGCCTTT hTTTTTGGAG GGATTTAhyy TAGCACGGGT ACAACTGGGA CCTACGGGCT 600 GChCAhTTTh CTTGGTGTAG CGCGChGGAC AGGTCCGGCh CCTCCGGGGG GTCThGCAGA 660 GCThCTTGGG ACTCTAGThG CTCTTATAGG GCCGGATTAC AGCTCACAAT yAhTTClAhG 720 CCAhChTCG TATCCGTTAA CACChGThTT yAGGACAGGG TCUGGGCCTG AhTTGTTTAT 780 GAGGTCCTAT TChCGTCGhT AGTTCATGTT GCAACAhGGC ThChTCTTTT CTGCTGGChT 840 GTGCCCTCCT AUTCCGTATG AieCTGCThT GGTACGCCTA TGhCTTGCAT AGCATATTGA GTTAUTGCTC AUATUhGTAT CTThhGCCGA TATTGGhCTh TTTGTThTTT

900

GhGTATGTTA GChT

915 (2) SEQ INFORMATION NA Nn: 136:

(S) SEQUENCE FEATURES:

(1) LENGTH: 915 base pairs (B) TYh: nucleic acid (T) NUTTY NiCl: single (D) TOPOLOGY: linear (iS) THESE PARTICLES: other nukluSnoay acid (A) DESCRIPTION: / description ⁼ "DNA (synthetic) (xH) SEQUENCE OPNS: SEQ NA wr: 136:

308

184 424 —CTSACPGCT CTATlAG — lT C — 1TG1GAPT 1P1C1PC1GG G1A1—1—1CC 1CCP — CACCT 60

PGTCPT — lCC CGAGCaGCCT G11P — 1GGG1 G1CGGCPCP1 PCCT — lTG — 1 CCT111CCTT 120

GG1CPGCC11 1CCTGGa — 1G GTGCGPiaG— —CP1GC11—1 1CPG1GAlAG T — C1PC1 —— T 180

1PG — 1G — C11 PTCTTC — T1A PGTCC11CC1 P — GCGTCCCG GTGCC1C — 1C CGG1CCCTGP 240

CG1C1PCC11 GC1TC1PC1G G1AA — GPG1C P —— C11—11G PCCG — lliaG 1CT — 1CGTPC 300

T1TCPGTTP1 CCCTT — 1GC1 1TCGC1 — G11 C11C1GT1C— G1—1G —— CG— TG — 1G — CTGC 360

GCT — GT — GlC GTTCP — GTCC AAPCTCTlCP 1GC11CCCGT CTCCTGC — PC T111 — A1TCP 420

ClTAlATCTC ClCAClG — GG 1CCG1CPGGC CPGTG1PCCG GCCTG — G — Cl GCPPTGPTG1 480

Cl — GPCCTPC PCCTCGPPGG ——GGGT1C1G l — GGGGCCT— —A1CGC1GCP PGCGGC1C1— 540

G — C1 — G1CC1 CATCPC1CA1 GG1PGCCGAT —GC1PCPTGC GG1GCTTCC1 1C1CCTGCTC 600

Cli —— IGlGl TGCITGTCCT G1T — CPGGT1 ——1 —— GPCG1 GCCPCP — C — T C1G —— G1TGC 660

GGC11C1TG— C1TCTGCC1C PCCGCCGGCT T — P — 1CCGCG G1TTCCTAGT T1A1CTTCTT 720

CTP — 1CTCCC 1TGTCCPTCA C1GC1G1GTG 1 — CG1GPGGG C1T1TGTTC1 CCCPGT — CCT 780

1C1GCPTTCC PGCT — CCTGC P — PT — 1CPPT 1 — CGG —— Gl— CAT —— GlllC CC1G1TT — 1G 840

GlGaCCaGGG CGC1——1C1P PCP1G — 1GC1 —P — 1CCCGTG TGCT —— 1G — G 1TT — 1TTGC1 900

GC1C ——— TAC A1CTG

915 (2) SEQ INFORMATION NA No: 137:

(i) SEQUENCE CECSES:

(A) LENGTH: 915 bases (B) (C)

TYPE: Nucleic acid NLQNNCI: Single

184 424

309 (D) GCPCLOUNA: iSsSowi (SS) GYP PARTICLE: Sssy eunUeSeowA (A) DESCRIPTION: / description = "DNA (synthetic) (xS) SEQUENCE OPlE: EEQ NA so: 137:

cctaattttt 60 TTATAGTAAT CUATUACATT (TGTATCACT tgaatgtacc ACCTUCGTCA tttttttatt 120 ttaataacca taattataga UATCTTTCAG TCCTCGTUUA CTAAAGTTTA ttatgtttga 180 gtctuuatat cattctggtt tttuttaaug ACAAACGAAA TATATTGAUT gttuattcaa 240 TATTATATGA TCGCTACCTC TUTCTCTTCT CAUCTATUUC CUCACTTTCT TCATATTCAC 300 TTATCAACA1 utcatutugt TUUTACGAAT tctttuggga ACTUGTCTTC tatttcttgg 360 ctctatautg aucttauuaa caatactgct tauatuucuu TUUAUUTTCT ctuuuttaat 420 ttacttuact AATCTCTGTT GTCGATTCUT CTCCTTTUAC TAAAUCATCA TGTAGGGTTT 480 CAGATATGAG AACTTCUTGT TTTCTATAAA UCAUUGTTAC (TCTCATAAT tgttctgatt 540 CTGTTTTTCT UAUCTTCTAl TGTTTCCTCT GAUGGACAUT ucuttttctu gtttgataau 600 (((AUCTTCAT cttttutttt (TUTAITTCT ucgatatutc ATCATTTACA ctuttttctt 660 tgtgtcaccu atattacact GAGTTCTTAT uttgcttcca TUACTATTAC atcgtatatg 720 ttcautuctt AUAUUTACAT TTTTTGCCTG CATCTUTTCA cTaucctuca ttuugcttta 780 ttttgguaug aautgcagtt TGCATGGAGU ataccagttc ACAUUGTGTT tttutaucat 840 ttattcttct uctuugtuua tttattccau tacuttcata ACTUUUGTTC

(TATCTCATT tgtttcatct uuuttguttt tcgutataut tccutttttt ccttututcc 900

310

184 424

AGUAAGAGGA G / AGG

915 (2) INFORMATION ABOUT SEQ DD Tr: 138:

(S) SEQUENCE FEATURES:

(A) LENGTH: 915 bp (B) GYO: kwa? Nucluinic (A) TlCD DURABILITY: single (D) GOOOUOADT: US (SS) CYO PARTICLES: Snny nunluSsoa acid '(A) OPDK: / opSs - "DNT (synthetic) (xS) SEQUENCE OODS: SEQ DD No .: 138:

ATTTCCGAGG 60 CGAGTAGATG CAAGGAAAGG AGATAGTATG GAAAAACACT ATTGATAGTG GGUTGAGAGG 120 CAAA / ATTCG TTCGAACAAA ATCAGTGTGA GTCGAAGAAA TTGATATAGG GCAGGGATAA 180 ATTGAATGTG TGGTCTAAAG GCGAGACTUA ATGGTCATTT GATAGTACAG AGTCAGGAAA 240 GGTGGTAGAT GTGTGATTTA GAGCGGGTTG TGATCAGGAC TGTATTTGTG AGAAAGATAA 300 GTTGTTGTAC GCTTAUGGAT GAGCATGAAG GTTGACTATT ATGGTTCGGT GAGGGGGGGA 360 CCTGGATATA AATATAGGAA TAATAGGAGC GAGAGCUTAA GAATAATGCG TGAACGATCG 420 AAGTGAAG / T AAGTGTGATG AGCTAGGTAG TGTTGTGGGT GAAAAAAGTG TAGCATGTGG 480 TTAAAAGAAA CAGATGTATA GTGTATAAnn AGTTTAAGAT TTGCGGTGGA ACGGGAGAAG 540 ATTGATGATG AAATCAGGGG TCGGGTTGGA GATGGGGAAA TAAGGCTATT GGGGGGCGTA 600 AAAAAGGCAG TATTAGAGTA GTGTGTCGGT TGTCGACGGA GATTCGTGGA

AGGGGGAGTA TTTGATGGTA GGATGTTGAG AGCTGGATCA GTAAACCAAC TTTGGATGGA 660

184 424

311

GTGGTTCGCC 720 CTTTGCC1TC GCCTGTCCTG CTGCCTGCTG TGGTCTTTCC CTTGGGAGC1 TCGTGG1CCC 780 TGTTGCCGGC GlCCAGGGCG CGGGGCGTTC TGCGGGCTC1 CGCCCTTCTG CTGGGGGGGG 840 TGGTGGCTGC 1CGGGGGCGG CTGGGTCCCT CTTGCCTCTC GTCCCTCCTG GGCCGGCTTT CTGCTCCGGT CCGTCTCCTC CTTGGGGCCC TGCTGGGCCT CCTTCGAGCC

900

CTGCTTCCTC CACAG

915 (2) INFORMATION ON SEQ LI No .: 139:

(i) SEQUENCE FEATURES:

(A) LENGTH: 915 base pa (B) TYS: nucleic acid (C) NUMBER OF THREADS: single (I) TOPOLOGY: linear (ii) THOUSAND PARTICLES: other nucleic acid

(xi) DESCRIPTION (A) OSLS: / description = SEQUENCE: SEQ II "DNA (synthetic) eu: 139: mp CCTlGCTCCT 60 CTGTGCTGTT CG1TGGGGTT GTGCGTCTCT TGAGGGGCCC TCCTGCACCT TTCCTGGGCC 120 CGlTCCCCCT C1GTG1CG1G GGCCTCTCTT TCCTGTTGGT CCGGTGCCTT CGGCTTCCiG 180 GCC1GCGGGG CTTCGTG1GG GCTGTCGTGG GCTTCGlTCG 1CCCTCGGGT T1TCGGGC1G 240 TTCTTCC11G TCTCCGGCCG TGTCTGCCCT CTGCCTCGGC CCCACCCTCT CGTCGTCCTT 300 TC1TCT1C1G GGCGGGTGGC TCGCCGGCTi TCCGGGGTGC CC1GACGTTC 1CTCTCGTTG 360 CCCTTGCGCG GGCGClGGGC CAGCTGTCCG TGGTGGGCCG TGGAGGCTCC CCCGGTGGGC 420 CGTCTGGTCC AGTCTCTGCT ATCG1CCCCT CTCCTCCCTC TCGTGGATCT CCTG1GTCTC CCAGCT1CGC TCGCGGGGlT CCCGTTGCCT TCTTCC1GTC CT1CC1GCGC

480

312

184 424

TT1TTTTCAC CAGACCTlTl TTTCTTCGTG CTTGTC1GCC CiTGGlGGGT TTCClTTlli 540 illTTGCCCl CTlCCCGCTT TTTCCCTCT1 CCT1CTT1CG IGCTCTlliT TTCT11T1CC 600

TTCTTTT1TC 1TCTTT1TCT GTTTCACACC GGGCTCCCTT G1TCCTCG1C 1CTTTCCCCT 660

TT1TCTCTCC TCCCTTT1CT CTCTCCTGTG GGCTTTlCGT TilCCCASTC GS1GSTCCC1 720

ITCllCClll GGAGllGlCl CilCGTTCTG GC1CC1CTCC TTCTTTTGTT CC1CGCCCTC 780

IClCGClClG iCillTllTT 1CCACCCACT TCCTTCTTCT CTCTCCCG1G CGllCTTTCT 840

CCATA11TCT CCTCTTCTTT TCGGCCTTTC CGGCCGCTTG TTCClCGCGC 1TTTCTTCTC 900

GlCilTllll TTCT1

915 (2) NN / ORWATJE O SEQ ND No: 140:

(I) CHARACTERISTICS OF THE SEQUENCES:

(1) LENGTH: 915 pio bases (3) TYPE: nucleic acid (T) NNCN QUALITY: single (D) TOPOIOGNA: linear (II) TYPE OF PARTICLE: other nucleic acid (1) OPNS: / description - "DNA (synthetic) (xi) SEQUENCE OPNS: SEQ NA no: 140:

1CTAATCCTT CC1CA1CCCC TCATGAGATT ATGCATGAGT TlGllCCATT 1TTC1TACTT 60

TTCTCCC1TC GiClTAGTTT TAATGACCAl CACGTTTCTG TTTT1CTC1A TTCAGCTCTT 120

TlCTTCTTCC CTTCillill CTTCGTASGG GTTCTTAGGA ATTTAlAlCC CCCATTCCCT 180

1TTCCC1TA1 TCTCTCCT1A TTTCCGGCCA TGTCTGCTTT CC1CTCCCCC TlGCTGGTTT 240

184 424

313

CGAGGGGCGG 300 GGCCGCTCC1 GCTCGCGGCT GCGGAlCGAG GGCGGGC1AC CGGGGCGGGG GACGTCCGGG 360 GGGTGGGGGC CGGGGAGGCC GCGGCGTACG GAGGyGGCGl TGGAGGGGCC ccyycTGsiC 420 GGTGTGGTTG CACCGTGAGT CTCCCCCCGG CGGGGCCGGG TGCAGGAGTG CAGAGCGCCC 480 CCCSGGTGGC GCGCCAGGGG aggggcctga GCGCTGAGCC CCGGTTTCGA GGACCCCGGC 540 GTCCGGCGCT cggggcagcc GGCGGAlCCC CCGGCGGCCG GGCGThCGGG GATGGCGCCT 600 CGGGGGGCCG yCGTGTCCGT GCCGhGCGAy GTCGTAGTCC CCGGCGGTGG GACTTCCATG 660 GCCTGCGCGG CGCGCGGGCC CCGTGTCCGG AGGChCCCCG GGGGGCGACG CTTyTCCCGG 720 GGCGCGGCGC GGGCCTTGGG TGGGGGGAGC GGACGACCGC GAGGGAGGAG GCASCGGCGG 780 GGGCGCGGCT GGGGCCAGGC GCGGTGCGyC CGGAGGGGGT GGGGyCAGGA cggggcggac 840 TGGGCCGGCG GCGCCGCGGC TGGGTCGGGG GGGGGCGGGC GGyAGAGGGC CGTCGGCGCC GGyCGGTTGT GGCGGGCCGG GGCGGlSCCC AGCGCGCCGG CGGGCyCAGG

900

ATTACGGCGG GCCCG

915 (2) INFORMATION ABOUT SEQ II No: 141:

(i) SEQUENCE TIMES:

(A) LENGTH: 915 bases (B) TYPE: Nucrilic acid (C) NUMBER OF THREADS: single (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description = "INA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ II no: 141:

GCGGCGTGCG GGGGCGGGSG GGGGGCAACG CGCCCGTGCC CAClGCCCCT CCCGGCACCG 60

314

184 424

PPGCG — G1GC 120 C — AGCAlCCT CllP — lCGAl TACGTCPGP1 PCCPG1PGG1 CCG1G1CCGP CG1GPTCC11 180 1GCT —— 1—1G CTPC — T11GG TAPiTCaGGl 1CPT1TA111 PGC1TC1GGP IPPllGGCai 240 GGCTPC1T11 TCTCC11CC1 TTTCTGCCGP CGGCC1CGGG CGC1CCCPCT C — 1G1PGCAA 300 PClTClTCll TTG1G — P — CC Tl — CAG — 11G PCCGi — 1111 1CT — 1CGGGC P1PGP —— PG1 360 CCCTTG1GC1 llCTClG — Al ClGCAGTlCG G1G1GGGCG— PG-1GGCGGC CCG — IPGiaC 420 C — PCTGGTCC 11TGPCP1CT 1TA1GCCCGG CPCCPCCGTG G1A1—11GGG G1PAG1PCGC 480 CAiaClTGGC C1PCPTCCGT CTCTTGG11G 1CCT1CTCC— 11 — SaiTGGG CGPTPCCPGl 540 P — CTP — T1G— ii — ipccicc CTCTGCGTC1 —IGiATGC—— C11G1T — 1CG TCPCCCGCGC 600 CGCCTTCTPT TT1CCGGCG1 1TCCTCATP1 AAGT1CTTCG PG1CPCCC1T GTCGGGG1C1 660 —C1G1CT — 1T CAG — PGCCC1 TlTGTTGlCC CPTTGCCP1G 1CCTGTCCTG CTGGCP — GGG 720 P — 11CTTP1T CPTG —— 1G11 TK — GAllCCC IGaTIGIGGl G1CC11GGC1 C1——1G1PGG 780 TG —— 11C1TP G1CCCPPCGG CTGG1G1GG— PG1TG1C1GC 1CGG — G1A1G CTG —— 1CCG1 840 CPG — CCTCTC 1TCCCTCCTG ii — Γΐ — cppp CGGG1C1GGG CCGTGTCCPC CGT — GG — CCC TGGlllTCCP CCTGGG11CC CATCTGCCPC C1G1GG — GAG G1CC1C1GCP

900

ClCAlCGlGC GCAlP

915 (2) SEQ INFORMATION NA No: 142:

(i) SEQUENCE CECSES:

(A) LENGTH2: 921 base pairs (B) TYPE: nukiriGowr acid (C) NUMBER OF NNCI: single (D) TOPOLOGY: linear

184 424

315 (SS) THESE PARTICLES: other acid npkluSioay (A) OONS: / description aDEA (synthetic) (xS) SEQUENCE DESCRIPTION: SEQ NA aa: 142:

GTGACCTGTT 60 CGAhACGGAh CGAhGAAAGG ATACATCeCh CAAATAUACT ATCGGCACCG hhGTTGTATC 120 CGAACeCTCT CeihTATGAA GATThTGChA TCThGACTGA TCGAAATCGG GATTGCTGAG 180 CTTUTAGAGT GTCTTCAGGU ChGTClAGAA ChhAUAAACh GCAhCAGGGA GGAGGTllhC 240 ChGCUGlCCC GTTCACTATG TCTTCTTTTh UCCACTTCCG CACCCGCGCG CAGCTCACCA 300 TCATCAAGGC AyGCGATTGG TAAUACGGTC TGyAAACATh GACGGhCGAh GGGhGATCCC 360 TGATCAATTG CATGAATAAT ATTCCGhAGA TGGTTGCyGA GGCGCTCCGG TAATCUTCTT 420 TGCCAATTGC GACTATCCAC CTTTTGCCTC CUTCTAAAGA AhCGTAGAAA TChCCCllTA 480 CTGATGhhCA TCTTTGUTTh ACACCTGhCC CUCTTTChGT hGGGGACGGG AGCCGGGyAU 540 1AGGGAAAAC CCATAhGGAG GATACCAAGG CACATGACCh hTGGGGAGCA GTGATCCTGC 600 CTChGGATGG AUhTACGGTA GCACTGGGAC A1CTGGUATT TACGGGTCGT GTATCCCTCC 660 CTGTTCAGTh GhThGGACAG ThCCUGCTTC ccchGGTyyy CCGGCAGAGT CTTTTGGGAA 720 CTTAGTGGTC GCCATAGGGC AUGCCCACAG CTCACAAGTA hCCClCGGCT AhTTGTThGA 780 UTGGCCAATA TCTGTTTTTA GyCACGGhyC ThTGCCTGAG GCGGGhAGGA GUTTCTACTC 840 CThGTThTAG TGAACGTTGC GTTAATTGCG GCAccchyyc TGCCCCAGCG TCTCTTGChh IhGACCGCTG ATCCTTCATT CAACGTCGhC GTGACTCTCA hGhCTGGCAT

900

316

184 424

AUGACAGTCA GGTAnGGTTT A

921 (2) INFORMATION ON SEQ DD Tr: 143:

(S) SEQUENCE FEATURES:

CA) LENGTH: 927 bp (B) CYO: Owi? sucrose (A) SUMMARY TICl: single (D) C000U0G1T: ISnS (SS) THESE PARTICLES: Snny kwa nucluinic (T) OODK: / description - "DTT (synthetic) (xS) SEQUENCE OOD: KEQ DD no .: 143:

CGGAAAGGGG 60 TGAGAAGATG TGAGAAAAGG AGATTGTTTG GATAAAAATC TTTGA / CTTG GGATGCGAGT 120 TGAAATATTG CAAGAATCAA AACAGCGTGA GTCGATGAAA CTATCATTGG TCATGGTAAA 180 ATCGAAAAAA TGGTAGAAAG ATGAGCAAGA TCGGTAAAAA GGTAGATAAG AGGGACAGTC 240 CGTGGTAGAT GAGATATGCA GGGTGACTCG TGACACCCAT CAAAT / AGAG GCATATGGAA 300 GACGAAGTAT AGCAAAGCAG GAATCAAACG GTTGAAAAAA AGGAT / AGGC GAGGT1UGGA 360 TTCGGATACT TnTGTAGGAA TTCAACGATG GTAAAAACAA GAATAATGCC TGUAUTCAAG 420 TGGTGGGGTT TAGTGTGAGG AGTAATTGGG tgtttatgct GATAACAGTG TAGAAATGGT 480 TTATAAGAGG ATTGTTATTG AGCTGGTGAC TGAGGAGCGT TGGGTATGGA GGAUCATUCA 540 AAACTCTAAG AAAGAAAATG TCGACTCAGA ATTGGTGAGG AGTTAGATTT GGGTGGAGCC 600 TGGAAAGATG AAACGTAGGG GnATCCCCGG AATTTACGGA TGG / GATTAT GGGGGGCCGT 660 ACTGGGTGAA AATGGGTGCG TGTGGTTGGG AAATTCGACT AAACTG / TGG CUAAAGGACG GGGTGTTATA GCGGAGCATA AAACTGTATA TAAAGCTTAA GGTTTGAGGT

720

184 424

317

CTAGATTACT AACACTTGCT ΤΤΤΑΤΤΑΑΑΤ CTTTCTTACT TUAAUCTATT (TTAUUUTCC 780 accctcattc tcatatgatt ctttctcaat tutugcaacg attctacctc gucuttutct

840 tcattaugct tccuautcca cautgggttu ttttgatact cccaauacct tcacgucaua

900

CTUAUCTAUT ucccatauua acatcta

927 (2) INFORMATION ON EEQ ID No .: 144:

Sequence techniques:

(A) LENGTH :: 927 pio bases (B) TYPE: sunlMiezwA acid (C) QUANTITY OF THREADS: single (D) TOPOLOGY: ISN (SS) AYP PARTICLE: Sney eunUeLs acid (A) DESCRIPTION: / description = "DNA (synthetic ) (ii) SEQUENCE DESCRIPTION: EEQ ND so: 144:

CCTAATTUTT 60 ctatagttgt CGAGAGAGTT (TATGTCACT TAAAUAUACT ACCTUCACCT ATACTAGATT 120 ctaacaactt CAATUACUAA UATATCACTA tccttaatua CTUAAGCCAA CUGCTTCTAA 180 accautagat ctttttaguu tctttcaaua ACAAAUAAAA TUCATCAUUT aattgtutaa 240 TTCTTCAAAA ACTTCGACCA tttttgccct cttctactuc ctcattctct TUACATCCAG 300 TCATCATCAA AACCAUTUAT ttucaataat tccuutaaga (TAUATTTTC TATTTUUATA 360 CCCTTGAACG AUCCTAUUAA caacattacc aatauuuctu tatatuctct TTUTTTUAAT 420 cuacatutct AATTTCTACT ATCAACCCUT ctcctccttt TAAAUAGTCA CAAACATTTT 480 TCAACATUUT cctucttcct rCTGTTCACT ttaucaatuu AAAATAAGAA

318

184 424

ATTTACATGC IGClCGCCCC CCTCTACCCT GTTTTlGCll TAGC11TCTT CCT1TCC1CC 540

GGCCCllTGC TGCTGCGGCC CCAATTCCGA TCCCTTTCTT CTTCGTCCTT TGTGGlCCli 600

CTCCTTlCAC GGCTCCGTTT TCTCCTTCG1 iCCTTGCCCC CTTTCTTTG1 CACCTCCCTT 660

CTCTT1CCGG CCGCGACCGT C1CTCACA1C GATTTTllCC TCATCTTCCT ClGCTTGTAS 720

CCTTTCTTCT CGGCAAAGGT iGiTTTCCTG 1T1TTTCT11 111CCTCC1T TCTTT1T1TT 780

A1C1G1TTCC GCGGCA1C1C GCGCClGCTl GT1TTTTTC1 TCTCCTTT1T TTGTilGCTG 840

ClllCTCTCG CTGCGCTGTT TCCTilTTCT CCTGTTGTTC 1G1CG1C1CT iCGCGllTCG 900

CGCCllCTTG GCCCTTTCTT TGCGTCT

927 (2) NN / ORVATIONS ON rEQ ID No: 145:

(i) SEQUENCE FEATURES:

(A) LENGTH: 927 pio bases (B) TYPE: kwis n "kieSneas (C) QUANTITY NNCN: single (D) TOPOLOCN: linear (ii) TYPE OF PARTICLE: other nucleic acid (1) OPNS: / description -" DNA ( synthetic) (ei) SEQUENCE OPNS: rEQ ND no: 145:

CTTcCCTiCT CT1TCATC1T G1GTG1ASTT ITlGCCTlGC T1C1GGC1GG 1CCTGTCTTT 60

TT1TCCGCCT CGGCCCATCT TCAT1CCCCC iCClCGCTTl TCTTGGTGGA CTCCSATTTT 120

CC1TTCCCAA ACCTGGAGG1 CTTTCTC1CG 1TTCCT11C1 IGTTGiSGAl TGCATG11GT 180

ITTCCCGGAl TTCTTCGT1C TTTCT1CTCC TCTCCCTTTC TTGCCCTGGT TCCACTTTCT 240

CC1TCCTCSG TCATCATCGC 1CCA11TCAT T11T1CCAAC CTCCGCCGlG ICTCATCTCT 300

184 424

319

1G1C1GCTTT CCC1TGTCCG GlCCCCGGGG CGCCG11GC1 TTCCCCCCCC 1CCCGGCTCC 360

CCrrCTGGCC CCTCiCCiCC caicicicci CICGCCCCll CiCCTCCClC 1CGTGGT1C1 420

CCTGGTTCTC CCGACGTCGC ICTCGGCiTi CCCTiCCCGl CClGCCAGCC CCCGCTCGAC 480

GGGCCCGACC CACTCGCCA1 1C1CCCCGCC ITCGCCCTTC 1GC1CCGCCC CCTCCTGGCC 540

GCGCCGGGCC CTC1GCCCCC CGCTTGCC1C 1CC1CCC1CC TCGGGCGCC1 TTC1GGTC1G 600

C1CCCTCTCC 1CCTTCGGGC CCTCCCCCiC C1CCTTC1GG CCCCCCiTCC iCCCCCGGGC 660 ccccccccAG ctcicgtccc icccggigcc AiCTiccirc gcttcccccc cciiciccic 720

CCGGGCGTCC CTTTCCTCC1 ICTTCTCGCG CC1TCCTCCC ICliCliCCr GCCGiTCGGC 780

ClCGCCCCCC GCCCCCiCiC 11CCCCTCC1 CCCCCTCCTT GT1GCC1CCC CGiCCTCCii 840 ccncircTTC ciicciccca icicchicac cicaiacicc Gccccicccc ccgggttcac 900

CCTTTGCCTT CGCCTC1CC1 CC1CCC1

927 (2) INFORMATION ABOUT SEQ LI Nu: 146:

(i) SEQUENCE FEATURES:

(A) LENGTH: 927 pairs zisid (B) TYPE: eskluierwy acid (C) QUANTITY NLCL: single (D) TOPOLOGY: linirva (ii) TYPE OF PARTICLE: ieey eskleierwy acid (A) DESCRIPTION: / description = "ING (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ II en: 146:

CCIAiCTCCT CITTCTTGaI CCGIGTGTTT C1GCC1CGC1 TCGTCGCGCC GCCTCCCCCT 60

320

184 424

TTCATAGAAT 120 AUCAAACAAT ATATGAGUAC UATirAGAGA GTGCAAGGGA AAUACCAGTC GlCAGGAACC 180 AATTUGAUCU TCGAGTCAlG 1GTUTTTCCC ATGCAGCAAA GCAACGAUCC AGTCAllTCA 240 TCGGTCUTCA CTGTTCAGGA TUTATGAAGC GCGGCACCUG AUGCTAACTG A1CAATGACC 300 GGAGGATAAA UnGAlAGGCA TCCACCUCCG GTGUAGACAA CATCAGUGCT TCTATC1GTA 360 AAAGCGACAA AUTUGAUGAA ACCACUTCAC GAGAGUAGUU TlCCCUAGGG ATlCUTUCAT 420 A1TGGGCGAG CACAGGGAAT CTGCCAAACG GCTGGTTCCT TCAACACGTG ΑΑΤΤΤΑΑΑΑΑ 480 TCCATAGUCA GCGGACACGG AGAUTATlGA CAAGTGACAG 1GACGAUAGG ATUCATCCUG 540 ATACCTTClA AGCCGGGAAA TCTTGUATCC A1GAAGCGAG UCCACAATCC UCCGACAGUG 600 CCAGCAACGG TGCTCCAGAA ATGAGCUCCG AGTCGGCCGC CGACCGAGGC ATAGGAACTU 660 UGCAGGGCAC GAGAGGGAGC 1GCCTAAAUG GGTGGTACTA 1UUAACUCGG CACUACACAC 720 C1UACGAGCA GGATCTGGGA TGUClGGGAA CATATTCGGG GAGAUGCAAC IGlAUTTGAT 780 TGAGGGGCUG AUUAGGGTAA CGATGATCAC CACUGACAGC GUGGAGTTAG UCAAUGCAGA 840 TCGTCGGTGG ACGUTTUAAG ΙΤΤΤΑΤΑΑΑΑ CGTGAGCGGG ACGGCCCTCG AGATUTATGC 900 AAGAGGCGAG GACGACATUA TGCAlGAAUC GATGAGAGGT TAAGAAACCG AATCAAAAGC TTGGGGGCCG GGGTGGU

927 (2) INFORMATION ON SEQ DD No .: 147:

(S) SEQUENCE FEATURES:

(A) LENGTH: 927 base pairs (B) GYO: nucleic acid (T) QUANTITY NDCD: single (D) COOOUOAIA: USniowi (Si) TYPE STRAWBERRY / ZKD: Sine acid snklrinoay

184 424

321 (1) DESCRIPTION: / description = "INA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ II no: 147:

GGllAGCGGC GCCCCllGlT 60

CllGllGCGG GGAlGlAGTC 120

GllGCCGGAl 1GGTGGCGSG 180 llCGlllGCl TGGTGGGCS1 240

GGiGSGGGAl TGClCACClC 300

ClTTCCJCGl GGGCTGGGGG 360

TTGClCGlAG GGCGTGGTGG 420

GlllSSCGCG G1SGGCTGGG 480

ICCGlllGCl GCGTGAGGGT 540

GGG1GTCGGG TGTGATCGGT 600

IGGGllGCGS GCGCGGTTGG 660 lllGGGlGCG GG1TGTGGGG 720

1CGG1CGTCG GC1GGCCG1G 780

IGGlGGGGCG GGGGGGGCGC 840

GllllGGGGG 1G1GGSGCGG 900

GTlGllGGCl GTGCG1GG1T 927

GGCCGlAlCT SClGlhTSGG

GCCTGlGlll llGlTCTCTA

G1GGG1SCGG IGCllCAAGC

TCTGGA1GG1 TllGlGCCCG

GGCAGllGCG CGlGSlGSCG

GlCGGAGGCl GllGllTAGG

SGTGTGT1G1 CTTA1GGGGG

CGAC1GG1AS CGGTAllCGG

GGTGClGlll lllllG.lGGG

GGTCGlGGCl GTTGCGGlCC

SAGGGCGGC1 GGlGG.lCAGG

GGGGTGCGiG G1GG1GCTGG

GGTGTGGlTG IGJGliTTGG

TGG1G1GGGG GllllCCTCG

GCGGGAGTGG GTAlAGGCGG

GCGGCGG

T1S1GAG1GG AGGTGGCCCG

TGGTG1TGG1 GGGASSGCGG

AGTTCGlSAS TGGCTGAGGG

GTGGC1GGGG GlGCGGGGCG

CGG1GG.A1SG SGGG1GGGGG

TCG1GGGGG1 TGGllGGGGG

GCCGCGGllG TlGAGCATCT

CGGCG1GG1S 1GG1GCGGGG

GCGCGGGGGl ATllGTClGG

CGGGGGlTGl GGGGGGTGGG

GGCGGAGGGG AlGTGCGGGG

GCGGlSClGl 1GGCTTGGCG

GGGGGSAGGG GGGGA1GAGG

ITSSAGCGGl 1GGCGCGGCG

GGGCCTllGG 11GGGGTGGG

322

184 424 (2) INFORMATION ABOUT SEQ ID No: 148:

(i) SEQUENCE CECSES:

(A) LENGTH: 927 pao za / ad (B) TYPE: acid / nucleic (C) QUALITY NIGN: single (D) TOPOUO1NA: linear (ii) TYPE OF PARTICLE: other nucleic acid

(xi) DESCRIPTION (A) DESCRIPTION: / description = SEQUENCE: SEQ ID "DNA (synthetic) go: 148: mp ICTGGCTTCC 60 CTGTGGT1GT CllT — liATC ATGClTCACC TSAlCAiiCC ACCTGCACCT CT1ATG11CC 120 C1S1CAACCC CilT — iClGl TiCTTCCCTl CCCTCiTCTA CCTAiiCCCT CiGCTTCCGl 180 ACGCTTGlAC CCCCGTilCC ICTiCCiiin ACTCATISii TTCATASllT GPC1G1GCGG 240 TTCTTC1TG1 TCCCCAGCC1 TiTCTGCCCT CTiCCACTTC CICiCCCTCT CiGCGTCASG 300 TCGTC1TCGG CTAAG — TG1C TTlCAiCiiT TCC1T — AGAG ACTClClTTC TlTCTllCTl 360 CCCGniTCA llCTCllllA CSiCATCiCi TAlATllCiI TCTlCTCCCC CClliTTGGC 420 C1TCTTCTCC GlTCTCCiCC iTCGACCCTT CCCCTCCiTC TilSCSITCT CGTGGGTCCC 480 CG1GAATTTG 1CCC1CCCGC CTCTCATCCC CCCTTGT1CA ICCCTCTTli CG11TCCCTC 540 TCCTCCTT1T ClCCCTCCll ATCCTCCTTC —GGCCCAlCT TCCTCCAC1T llCAK-ACCA 600 CiiCTCiClA TllPCCCilh iCClTCTCCC TTAlCTTCCA GC1CCCTCTC ACAlllAATT 660 TTCiTTTCCT TlCGCTTiCi TTAilTTCCi cccTCTiciT CGTCTAATTC TiCilCAlCC TCTTCiACAT TlCGCCCCCi ICiCClCCCC CTT1CTACCT CCIiTTCCTC

720

184 424

323

AUCCCACTTC TCC1CTCCCC CCCCUCCCCC CCCA1CC1CC TUA1CCAUCT CCCAGATGTG 780

CACCCCGTTC CTCCCCCCUC CCCGCCTCCC UTTTCUUCCC CGCUCCGT1U C1A1TTTA1A 840

ACCCATATTU ATGCUACCAA 1UC1C1UUAC ATCCCUlGll CA1CTACCCC TCTTCTUGAT 900

G1A1CGACTG TCUCCC1GUT CCACCC1

927 (2) SEQ INFORMATION NA No: 149:

(i) SEQUENCE FEATURES:

(A) LENGTH: 927 base pairs (B) TYO: npnleSioay acid (T) NITTY NITi: single (D) TOPOLOGY: linear (Hi) TYO PARTICLES: Gray npnluSioay acid (A) OPNS: / description ⁼ aDEe (synthetic) ( xS) OONS SEQUENCE: SEQ NA wr: 149:

1CC1ACTTCT CTAGAACUCC ClACTCAGCC CCCCACCACC GAAA1A1ACC ACTTGCATCT 60

CTUCCGTCCC TGACCACCCG C1ACUCC11C UAC1CCCCCA CCCCU1GTUC CCGAieTCTT 120

CUCCCTCCAG ATCCUUC1C1 CTCC1CCAT1 UCCUCCCC1C ACCCC1AAAC C1TAGCATTT 180

CCTUAUTCAG TGCGCCTCAl CCCCCACCCC C1CCCUCCCC CC1CCCC11C CTCATCTTyT 240

CG1CACCCC1 GTACCACCCA UlCATGTTCC CTUCCCUCAC CCCUTT1CCC CCTTACTTTC 300

CAGCGGCTCC CTCCCTATCA AUCUCATTAl CCACCTCCCT CAUC1U1C11 TTGAGUCGTC 360

CC1TGCUACC CTTCCTTCCC A1CCTCCACG ACC1ACCCUC CCCCTCCUCC TAAAGAATCT 420

CACCCCTCTC TCieCACUTG CCCCCCUCCC CCCCCCCAUG 1CC11ACCCC ClCGCACCCU 480

UCTCCCCCTT TCACCCTCCT TCUCCTCCAA CCCCC1CTCC 1C1UAC1U1C TCTGGGCyTT 540

324

184 424 gtcciicigi cgcgctcccc cciciGCcic GciccGTTCi cccccrcccc CCCCATCTTC 600 iccicccccc cgccgcctcc iiciccccic ccaciccicc riaaacicci icciGCcicc 660

CG1C1CCTTC CCGICCrGTCT CCCCCACTCC CCCCCCC11C GCCCTTTCCC ITCCCCTCTC 720

CiCCTCCClC CTCTCGCCTT TCCCTTCGGC CGGICGGGrC CCCCCATCGG CCGCTCCTCC 780 icncaicaca TTCTCGCCCC CllGTCCCTT CTCC1GCG11 CGCICGICCC CGCTCCCGGC 840

CGACyCCCGC CCGCTTGCCh CiCCiCCCiC CTCCGGCGCC TiTCTClGCC CGiCCCiCTC 900 cTcciicccc ccctccccgc ccicctt

927 (2) INFORMATION ABOUT SEQ II No .: 150:

(i) SEQUENCE FEATURES:

(A) LENGTH: 927 pan zisid (B) TYS: nucleic acid (C) QUANTITY NICL: single (I) TOPOLOGY: linear (ii) THOUSAND PARTICLES: other eskluieque (A) DESCRIPTION: / description = "DNA (synthetic) (xi) SEQUENCE OSLS: SEQ LI er: 150:

1C1GCC1GC1 60 C1T1ATTCTT CGCTCAncTT GlGCGlCCCi inaacccacc TCCTGCTCCl TTCCTCGGCC 120 CCGGCACCCT CCCTCCClGC CGCCiClClG iccTcaicca CCCACCCCTT C1GCTTCCGC 180 CCC1CGGCCG CTTCGTGTCG ICTCTCGilC CCTTGCGGaG TGCCTCCCCi giicaccccn 240 TTCTTCGTCA TCTCCCGCCC TCTCTCCCCi CTCCCGClCC CCCACCCTC1 CICCGTCCGG iCGTCATCCT ClCAGCTGCC TCCCCGCGGT icccciarca TCTCTCCTTC

300

184 424

325

ClCTTCCCCS CTTCTCS1CS SCTGCAGG11 TlGTSCTlTC C1CS1C1T11 TlllllTCTT 360

TC111TCGGT ClCGTCCTCT llCTTCTAGT ICTGCTTTCC TCTCCTT1CT TAGClGGTTC 420

GlClllCTCT TSCGCSTlCC TACGACCATC ITCTlCAlll CCCTTSCCCT CACTCTTTT1 480

ClTTTCTSAT STTCCTCTC1 IGilSlllTi T1CCTCTC1S C1TTC1CA11 S11CCTTATT 540

CTTClTCTTl 111SSCCT11 CCGCAlClCG CCTASTACCl TCTTTTTCCT CTGCTTClTC 600

TCTlGTCTTT llCCTTCGll TlCGTCTlGTG T1C1ATTCTT ACCCTTCGTA TAlTACATCl 660

CCTCSCClTT CCCACCCTTA CTCTTT1CTT ATlTCClTTC TCCTCCGTCT ClCGClTTTC 720

CCTTClCCAl SACClAlSlT TTAGACllll CACATTSAll TACA11ATAC CTTGCCAlTA 780

1CCACTTTCT TCCGCillli SCCGACG1C1 ITATllGllG AACCCiClTT TATCC1TTTT 840

TTATTCCCTC CCCCCTACCT CCTTCCCGCl CCTT1CTCTT CTCTTCC11T CTClTCCCCT 900

TGTTTC1CS1 TTTA1CCCTC TTTCTCC

927 (2) SEQ INFORMATION NA No: 151:

(i) SEQUENCE FEATURES:

(A) LENGTH: 927 base pairs (B) TYPE: nucleic acid (C) NNCN STRENGTH: single (D) TOPOTHIA: linear (il) CYP PARTICLES: other nucleic acid (A) OPNS: / description - "DNA (synthetic) (el) SEQUENCE OPNS: SEQ NA no: 151:

CTCCCTTlCC TCCCSSCClC TilCllACTT CCCTACTSTT ClGAlACATT STTT1T1TTT 60

CCCTCCCACC TllACGCTTT CGCTGATlGA 1AT1CTTCCA CCTT1AT1C1 TTCAGGTTTT 120

326

184 424

TTlTTTTTAC 180 ATTTAGATAT TTTCGTAACG CTCCCTAAAA atttgtagcc ΤΤΤΑΤΤΑΑΑΤ attactctgc 240 ttttttttca TTTCCAACCA TCTTCCTTTT CTCTTATTAT TCTATTTTTT TAATATTTAA 300 TTATTATTAC ACTAGGTCGT CGATACCCAT ttttctgaca attcattttt TATTTGGCTA 360 TTTTTCAACC attgcatccg CAGTACTATC TACACACCAG tccgcttttt TTAACTCAAT 420 ttttttattt ACTTTCTGTT (TTGATTTAT tttttttttt TAAGCCATTT TCTCCATTTT 480 TACATATAGT TTATAAGCAT TTTAATCTTA cttctttcat TTCTTCATGT ttctttttgt 540 (aactatctt TATTCTCGTC tcactgccat AUTTTCTTTT tttttttatt tacttttctt 600 (TACTCCTAG TAACATGGTC tttttattat ttttcttttc tcatttttta (TCTTClTTA 660 ACTTCTTTTA TGACTCTCAT UCCTTCTCTA ttatgtttat TTACTCTTTA taattttgtt 720 ttttttttct CTTTCTCTTC tttttttttt tttattttat tctcctatca TACCACATTT 780 ΑΤΑΤΑΤΑΤΤΑ AATTCCGCCTA TAAAGTATTT cttcattatt (ATTTTTTTC ttttctccat 840 tccttctatt ATGGGGACAA TCUACATTTA TTTATTTTTT GTTTTTTTTC ttatcttttt 900 ttttctattt TTGTCTCTCT tccccttttt TTTATATTTT ttttttcatt TlATTTTTTT tatatactaa AATTATG

927 (2) INFORMATION ON EEQ ND No .: 152:

(S) TETHY SEQUENCE:

(A) LENGTH: 927 pairs zisid (B) TYPE: bitch (T) QUANTITY OF THREAD: single (D) TOPOLOGY: spear (SS) TYPE OF PARTICLE: isny eGkirSword (A) DESCRIPTION: / description = "DNA (synthetic)

184 424

327 (xi) OPDK KEKWEN / JD: KEQ DD No .: 152:

GGGCCAGCAT CGATCAGlAT GUCCCAAAGG ΑΤΑΑΑΑΑΑΑΑ TACACC1CTT AATCCCAGGG 60

GGCTTUGATG TGCAACAAAG ATAGAAGUAA CAGUrATCTA CGGGUCGUUC AAlACAGTCG 120

GUCATTGACC AGTTAGAUCU TGCCCCAAUC UTG1GAAAUA AGCCACCACC TUTATTAUGG 180

ATGAClUGAC GCTTGAUTCA GTGGAAATGA GGCTTUGATG GGUGGCA11A GlTATGGCTG 240

GUCTCTCTAA CGATAAGACC UUTAGGGAAG CUAT1ACCCT CAGlAUCACC CGTGCGCCCG 300

GAGATGCGCC GGGGTUCCAC ACAGTAGGAA ACAAC1TAA1 CACAUGlCAU GCGACGGCCG 360

GAU11TCAAG GGGAGAATAA CATTGGGAGG AGGCAAAGUT ACTGGAGUGG GCACCCAGTC 420

TAGCCAGCCA GACAAATUUC CTAGACCCTG AGGTTAAGGC CGCCAACCAC GTTGGCGTCA 480

UGCCClCGGA UTTGAGTCCG CTGCGGACGC UACGGACGAA GCCGAUTAC1 UUAAGTAGGA 540

ΑΑΤΤΤΑΑΑΑΑ UGCAACTC1A UGTGGACCAC GGATTGAGTT CGCAAATAAC AlTAGCTACT 600

CCCArCTCGA CGUCAGAAAC CCGTTGGTAG ACGCUCAGCC UGAAUGCAAA CUACGGCTAT 660

TAGGTCAGTC AAGATUTGAT UTGGGGCATC CGGlCAGCTC UATGACUCCC ATUAAAAAGG 720

GClCrCCACU ΑΑΑΑΑΑΑΑΑΤ ATACCATAGC TTGUAAAAAU CGAGAATGAG UCTAGAUGGA 780

GGUCTCGGAU AAAlUGAAAC AGTACAAGTG CTCTUAAGGG GATGATTTAT UGCGGAUTCG 840

TATUCAGAGA CTAlGGGGAT TACCGGGG / T GTGACATACA CCTGGUGCAA GAACGCCTTC 900

GTCTCGGCTA ΑΑΑΑΑΑΑΑΑΤ GGAGAAG

927 (2) DNFORMT / JE 0 SEQ ID No .: 153:

328

184 424 (i) SEQUENCE FEATURES:

(A) LENGTH: 927 base pairs (B) TYPE: nucleic acid (C) NUMBER OF THREADS: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: ieey eukltieow'y acid (A) DESCRIPTION: / description = "DNA ( synthetic) (xi) SEQUENCE DESCRIPTION: SEQ LD er: 153:

ccinacTCci 60 C1GTGGTCT1 C1GT1GCCTT ATCCGTCGCT TCGCGGCGCC nccTCcacci TllCTClCCC 120 CCGACCGCCl CGGTGACCGA GTCC1C1C1T Tccirahcca cccaaacchh cincTTCcac 180 GCCTCGGCGl CTTCC1GTGC GCiiiCGGCC ccTTcrcnaa Ticaicaich GTT1GG1CCG 240 iiCTiCCTGG iCTCCGCCCA TCTCTCCCCi CTCCCCClGC cicacccici CCrCAlCCGT 300 1CC1CG1CGG GCCCCCiCCC TGcccccrAT hccccccacn nciccciTTC 1C1CTGC11G 360 CCC11CG1CG CCCCCAGCAG CCGCGClGCG TGCCCCCCGl irraiccicc CC11GTCGGC 420 C11C11C1CC AGTC1CTGCT T1CCGCCCC1 ciccTCcilc lAiacccTCi CriCGGhChC 480 CGCACClCGC CT1CTTCC1C ACCTTCCCCC Accircicci aicaaaiGic C1TTTCC1GC 540 1CCTTC1TCG C1GC1CCCCC CTC1GCC1CC CCCGCTTCii cGicaaccic iccnacATCG 600 CCICCCCCCC CCCGCCTGCT Tcicacciyc GGC1CC1CG1 lAcacii CTT C1TCGC1CCC 660 CiCiCCTTCG CG1CCGTC1G GCCCCCiCCC cacacGThcn CCCTTTCCCT acncciiicc 720 1GCTGCCTCC 1CT1GCCTTT CCCTTGCGCG ccTGcraaac ccacGTCccr

iAiaccaccc ccctcggcgi ictggg.cccc ctcgcccttc iiciccaici gitcgtcccc 780

184 424

329

1CCC1UUTAC CCCG11UACC CCCCCTCCCC GCCGCCCCCC TUUUUCC1CG CCCCUTACC1 840

1CCC1CCCCC CCCCC11U1C CCCUCCTCUC CCCCCTTTCC CCCCTCCTCC CCCCCCTUTC 900

AUTACCACAl CTCCCC11T1 CCCCCAC

927 (2) SEQ INFORMATION NA Ni: 154:

(i) SEQUENCE FEATURES:

(A) LENGTH: 906pa; bases (B) TYh: npkluSioay acid (C) QUANTITY NiCl: single (D) TOPOLOGY: linear (Si) THESE PARTICLES: Gray iuklrSioay acid (A) DESCRIPTION: / description a '^ ΗΑ (synthetic) (xS) SEQUENCE OPNS: SEQ ND nd: 154:

TCCAGCTTCC ccccAcrygc ctactcaccg ccccctcccc taiatctccc ccctgcaccc 60

CTTCCTUACC CGCACACCCC CCCCUCCUlA 1CC1CCCCCA TCCT1CTU1A CCUCACCCTT 120

CTCCTTTCAC CCCC1UA111 CTTC1CACTU 1CC1CCC1TA ACTTClACCC G1CATCA1UC 180

CTCTCTlCCA CCCCCC1GAA CCTCT1ACCA CTCCCTCCCC CTUCCAC11C C1CACCCCCC 240

CUAC1TCCCC CCCGCAGCCC UTCC1UCT1C CUlCCCTCCC TCCUllAllA ACTGACTTTC 300

TACCTTTTCC CCCGC1A1CC ATC1CCUT1C CCCCCTTACU TAUA1TTCUU C1UCTTCCCC 360

CCUTTTTCCC CTCCCTlGCC 1ACCCCCCCC ACCCACCCUC CTCCTCC1TC CCCAGlATCC 42 0

TATACATCTC CAACCCGUGG TCCCCCCUCC CCCCGCCTTA TCTTCCCACC CCCGTTCC1A 480

UTACCTUCUC UCCGCCCGCC TCTC1CATU1 111CCCACCC TCTTC1CCA1 11CCTCCUUC 540

TUCCCCCC11 CTCCCCCCUC CCC1CCC1CG CUCUCCCCTC TATTCCCCC1 CCACCCTCCC 600

330

184 424

T1C11TCTTC AT1CTTTTT1 TACTlllTCC AlTTlCClCT TCllCCTTCG TTTTTT1CTT 660

SCACTCCCTC TCTCCTTTCT CCTCCATTCC A1TCT1C111 lACCCSSCAT TTCCCTllCl 720 llCATTAlCC TACliilTSC CCGGllllTC CTCATTTTCT C1TC11A1C1 ACTlCTiCTC 780

ICCTCllllT AATTCCCATT TCCTTCTTCT CTACTTTCTT CllllTACTC CTTTC11T11 840

CTTCCTTCCC CCCCC111CT TTClGCCllT TTCTTTCC1C TGTlllCCCl CCTTCCllTT 900

CSCASC

906 (2) SEQ INFORMATION NA No: 155:

(i) SEQUENCE TIMES:

(A) LENGTH: 993 piey zisid (B) TYPE: nlk1ilnewy acid (T) NOVITY NNCN: single (D) TOPOIOGNA: linear (II) TYPE OF PARTICLE: other nukIuSnoay quark (1) OPNS: / description - "dna (synthetic) (el) SEQUENCE OPNS: SEQ NA no: 155:

SCCCCCCSTT CCCTTCCllC CSTTC1TC11 1CT1T1T1CT ATTCGCllll CTTATGTlTC 60

CTTTCCTT11 ITTTlSlCCA TCCTCCTllT CSllATlCTC TTACTCCllC lilCTlGllT 120

TTCCCCTTCC TS11CTT111 C11TTTTCTA SliCTTiCTl ClASTTTACA CGGClGCTTC 180

CiCSCCilll TSATTTTTTC ClACTTTTCA CCSTCCCCCT CTTCTCCClT C1TTCT1TTT 240

TTCTCATACT TllTCCCTAC TlAClTClCC ClTTCCTlll CATCTTCCCA llllTTCCTl 300

CCCCACGCCl TTACTTCCCC CClAlTCCCl ISATSlTlCT CTCCllllll TllTGCCilT 360

184 424

331

TCCCCTTCT1 GACC1TCTCC TCCA1TCTCT ACTiTCAiCC CTTCTCCTCC ITCTAGlTAG 420

CCTCATiiGT CTCCAiiCAC TTCCCiCiGi ChCTTCCACC CC11TC1TCT TTTGCTCCCC 480

TTiCACTCTC TCTCCATCCC CTGCTCTCCC ChiilCTCCC CCCCCATCCi TCCCCTCCii 540

CCCTCGilCT iCTTGATCCA ACCCClhAiC ICCCTTCCCC CCT1CC1CGC ICTCCCCCiI 600

TCCCTCiail ICATiTCCCC CliiTTCIlT CCCiCCTTCl ICACACCTCA TCTCCiCCTC 660

CCCCACTCCT CC1CC1CC1T CTGTC1TCGT GTlliGlilC PG1C1GCCCC CCCTlCCGTC 720

CiCCCCACCC ilGTCTCCAC 1CCTTCCTTC 1CCTCT1CTT CCClTCCCCT CGCiTCICCT 780

TTCCTllCTi CTiiCCiTCT TC1CATCTTC CTT1ATCTCC CTT1CCCCTC CCTAClCGAC 840

ChTlClCAlC CC1TC1GC11 CTCCTICiTC iChACACClT hlTCCCCCTC C11CTCCCC1 900

CCCCA1G1CT TCCTTCCCS.i 1CGTTCA1G1 CAiTTliTCl ICATCCiCGC CTAC11C1CG 960

TClCTCCAll GlAACCTiTC TTCCiCGTil TCA

993 (2) INFORMATION ON SNQ ND No: 156:

(i) SEQUENCE CECSES:

(A) LENGTH: 993 pairs per / ad (B) TYPE: nucleic acid (C) QUANTITY of NlCl: single (D) hOPO-OILIA: linear (ii) TYPE OF PARTICLE: other nucleic acid (A) DESCRIPTION: / description = " DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ ND go: 156:

ACT1CTG1CT ICTCTiTASC TATClATTGA iCTiTACiCC ICCTAliTll ICCACCCTCA 60

CCTTCTCTll ACCCIAACiI CCTCAlTTAC T1GTACTCCP CC1TCCC11T TCiTCiailC 120

332

184 424

GTCGllGllG 180 GGSACGCGGS lllGCTCllS SG1GGTGTGG AGSAGlTCll 1S11GG1TC1 GGCSCCllll 240 TGAlCCCCGG ClATGCGGll GGSCGCGCGG GGTGTGGGAG llGGlGAGGG 1G1GGSGS1G 300 GlSTCACCCC TSlGGCllll 1CGTGGGC1G SlTTGGGGll ISlSGTGCGl ICGCSTGTGl 360 CClGCCChCl IGlCGGGGll 1CSGGSGCGT SGG1SG1GGG GllGCCGGlG 1GGGG1111G 420 11GGGCGCGG IGTiGCGTGl IGCCTCCCGG GlCGlGGTGG ICGCSSAGll IGlGSCllll 480 GCGAiSlGGl ITGTGGGlll TCGGGTGGGC GGTTGGSGSG SGllGllGTG llGllGGGGl 540 SGCTClGGGG GlGGGCTłGl GCGGCGCTGG SAGlGGlGlG CilGlGGGGl IGGGCGGllG 600 GGSGGGiyiG TGGGCTGCGl 1GGGGGGCGT GCGGCTCGGS 1G1GG1GGG1 GllllGllGG 660 IGchCGGCCG GGGGGClGll SGGGGGGTGG SG1TGTGG11 GGlGGTTGCS GlGGlGGllG 720 GlGAGGGGGl GGGGGGGCG1 1CGCTGGGCC GCGGCCGCll GGGGGGGSlG IGGGlGGGGG 780 SlllGTlGGC 1GTGSAGCCC IGSGIGGSCG TGAllSAGll GGlGClGlll llGlCllGlG 840 1GGSGG1GA1 IGCGCGCCGG 1GGCGGCGGG CGClGClGGG GISIGSGGTG ITGGllGTGl 900 llGAGCGCGl lllGCCGGGG CG1GGTCGGG CGllGCGGlG GGGGlGGGll IGGGTGGllG 960 TG3GAGGGTG GTTG1GGG11 GCGGCTG1GG IGGllTTGGl G1SGG11G1G GCGGllCiCl GGG1GG1CGG GACCCGGCll CCA

993 (2) SEQ II INFORMATION No: 157:

(i) SEQUENCE TIMES:

(A) LENGTH: 993 pao / bases (B) TYPE: nucleic acid (C) THREAD QUANTITY: single / ncza (ΰ) TOPOLOGY: linear

184 424

333 (SS) PARTICLE CYP: Ssey kwis SGkiuSeowA (A) DESCRIPTION: / description = "DNA (synthetic) (xS) SEQUENCE DESCRIPTION: EEQ NA er: 157:

gtctttaatc 60 ACCTTGTAAC CCTTCATCAC ACCATATATT atctaaatat ATTATTTATA tttttctctc 120 ATTTCAATAG ttttgattat tactattttt TTATTTTCGT CAGTTCACAT TCCTU1TCTT 180 TAAATTTACA catctttcta acttttttta ataattacga (AACCTATCG tctattcact 240 CGACACTTTC TAATTTTTAA ttatcttttt CTCTTATTAT (ATTCTGTTT cttttatatt 300 CCACTATTGT tcatttgtct tattcttact ACCTTTCCAG AAACTTAATC ttttattttt 360 CTGTTTTCCG ttaattctgt αααίααίαττ gtctatatcg tttcccattt tttttttctc 420 CATTCTTTUA TTTCGTTTTT ATTATTCATT tttttttctt ttttaaacag CTTTCTAAAT 480 TCTTGAGClT cttttttttt TCTTACTATT ttctattatc ctctttccta cttatttgtt 540 CCTGCACTCT ttttcaautc ttttattttt ttttatttta TTTACTCTAC tttttttctc 600 CTCTCCATAT AGTTATATTA ttatcttttt ttattttttt tttttacact ttttttttca 660 GATTCTTGCG acacttcaag aatctttatc ttcattcttt gctcttttat aacaattacc 720 CTUTTATTTG taatttctct tatttttatt CACTCATATT CTCTCAGTAT cttttctatg 780 TTTTTTAACT tttttttatt ttttttttta tttgtttttt CTGCTTUCTG cattttttca 840 CTTGATTTTG TCTTCCTTTT TCTTTTTCTT atcctttttt ttattcttct (ΑΑΤΤΤΑΤΑΤ TTTTTCACTT tatttttatt ttctatatct tttatttcca tcctctttat

900

334

184 424

TTGUTTCTTC ATAGCAGATA UTCCATGCAT UTAATUAACC TU1TTGTTUG TTGGTAUGTT 960

AATTCAlirC ATAGATAUGG TGGGUTGGCA TAC

993 (2) INFORMATION ON SEQ DD No .: 158:

(S) KEKWETCJD FEATURES:

(A) LENGTH: 993 base pairs (B) TYPE: nuOlrinoay acid (T) TlCD LARGE: single (D) GOOOUOGlT: linear (SS) CYO PARTICLES: Snny kwa? nunluinoay

(xS) OODS (A) DESCRIPTION: / opSn - SEQUE: SEQ DD "DNT (synthetic) no: 158: ZZ ΑΤΑΑΤΤΤΑΤΤ 60 CTGTCACAAT CCCGCCTGCA ATTAGAGAGT · ACłGTCCUAU CTGACCTGGA GTTTTUTTC1 120 ATATACAGAC TGCTCAGCAG UATUAAlGAT AGCTAGTGAC UGCGCUCAAA GTTAlCAGTT 180 TCCAGGCGAA UAUGGTGUGA A1GGGGCTAC AlCAGCCCUC CAACAGATTA UGGCGTUCUU 240 TACTCTGGTU TACTGGGTAA GACTUTGTAT GATAGGTGAA UGAGAGAGAG CATTlTTCrA 300 TAAGTAGCAG TACAUTAUGG UATTGUTCCC CCGGTGCGGC ACAATGCAAA GTATcrTTii 360 CTATCTCGGA ΑΤΑΑΑΑΑΑΑΑ UCAACAACAG AG1GAGAGGA TUATUACACA CTATAlCATA 420 CAAAAGCGAA ΤΤΑΑΑΤΑΤΑΑ AATACATATA TAGTTCTCTA UTGTAAAAAA GAGTCGCTAT 480 GTTACCATAG AGAGATGATG GATLATTLE AUTTAATG / 1 CUGGGTGAGU TTACTAGTl 540 GTTTGGTCGC ΑΤΑΑΑΑΑΑΑΑ UTAUCAUllU TTATUATGUA TAUGGAGTTl TAlTAATGGA 600 CAAAGAGGCG UTAGGATUGG AGATlGACAT TTATUGAUGA AUGTGUGGGA CGGlCTAGAC GTC / TGTAGG A1GTGATUGC AACCGATGUA GATACAUTTG AACCGGGCAU

660

184 424

335

CCTTCCUAUC CClGlClUAC UCGCCC1U1C GGC11C1CA1 CUCCCCATUA U1A1CCUCUC 720

1CCACCCACC CTCG1G1CCC CCCCGGTTCl CCTUG1CC1C TCUUACACTC CCCTT1CACC 780

CCCCUTTCCC CCCGU11CGC CC1CCCCCTC CC11CCCG1C ATCT1TCAUT CCTCCCUCUC 840

CCCCCCCCCC UC11CCCTCC CCGCGACCC1 1TTCCCCG1C AU1CCCC1UC ATTUACACCC 900

CCCTC1CCT1 UCCCCACCCC TTACCCCCTT CC1CC111C1 TCUCCTACCT TlCCCCCACC 960

ACCCUUCC1C AGAClGlCGe ACGyUUATCC CAA

993 (2) INFORMATION ON SEQ ID No .: 159:

(S) SEQUENCE FEATURES:

(1) LENGTH: 993 bases (B) TYh: nucleSiPay acid (T) QUANTITY of NiCI: single (D) TOPOLOGY: liSoan (iH) THESE PARTICLES: Gray nbkluSnoay acid

(xi) OOie (A) OONS: / description a SEQUENCE: SEQ NA , ^ 1 (synthetic) no: 159: zz CClUCCACCC 60 1CCCGCCAGG TCCC1CCTCC ACTACCCACC ACCTAeiTCT CCCACCCUCA CCCGGTCTU1 120 CCCC1CCC1C CCCCAACTAC TACllClGCC CTCTCCGTCC UlACClAlAC CTCC1CCCCC 180 CAGCCCTUTC TC1CCCC1CC CUT1CG1GCC ATAGCGGAUC AAATGCATCA T1CCCTUCUU 240 CAGCCCCGC1 CCCCCCCCCC CCCC1GCG1C CCCTTGCCCC TTCClCACCC CCCC1CCACC 300 ClCGCACCCG CCCTUCCTUC 1ACCU1C1C1 A1TTCTTG1A A1CACCTCC1 CTCGACCCU1 CCCCCCCCUA UCCCUC1CCU UACCA1CC1C ACUTAGATTU CUTCTTCUTC

360

336

184 424 yccccGGCir niccchciic Tcyrchchci gcicicggcc cciciccicc gicigggcgc 420 icTCATAcai cicccaccai GTCTacccnc ccicccaiic ccrcciiccc cicicctttc 480

CGGCGCCGGC CAGCCCGCil CCiGCTTCCT CCCCC1CTCC CCCCCTTCCT CCGCCiCiCC 540

1GCCGCGTTC 1AC1CCCCCT ICCCCACCCC CCCCGCGCC1 CilCCCTGCC 1TCGCCCTTG 600 ccccctgcca icicccTGcc ccararcTTC chGcicaaci cTTTTrarcT AcicaGcacc 660 aiccAGGCcr ttgcccacrcgc accccccciccgc accccccciccgc

CCC1AGCCCC iGGlGCTGCi CiCACCClCi C1GCCCG1CC CC1GGGCTCC CCiCaiCiCC 780

TGCCCCAGCC CCCCCClGCG 1C1GGCCC1C 1CCTTCG1CC CGCICCGTCr CGGCCTTTTC 840

CTCTACCAGG CGCTCCiGCn GCCCCiCCGG CCCC1G1CCC CCCCCTTGGi 1CCCCCCTTG 900

CGCACACiCC CGCTCCCC11 CiCCCCCTli CCCCCCGCCC 1C1G1CCCCC CCilCGCGCC 960

CTGCGAllGC CCCCiGCCCl CCGCCCClGG 1GG

993 (2) INFORMATION ABOUT SEQ II Nu: 160:

(i) SEQUENCE FEATURES:

(A) LENGTH: 1027 pir zisid (B) TYS: nucleic acid (C) NUMBER OF THREADS: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: ieey nucleic acid (A) OSLS: / description = "INA (synthetic) (xr) SEQUENCE OSLS: SEQ LD en: 160:

CTCGC1ACAC CCTTGGGCCC TCCCCCC1CC CiCCCCCCCG GCTTCC1GCT CGGCICTTTC 60

GliCAAGTGA GGGCCCTCCG ICCCGCiCGC iCTCCCClCC CCGACCCCC1 ClClCCCACC 120

184 424

337

TlTCllTCCT CTTATTTTll lllCTTClCl TTCTCTCilC ACCTCTT111 CSCCTTTCCC 180

1TCTTTTC11 CTCTTT1TCT TClTGCCCTT TClTACTCCC GlllTTCCCC 1S1CTSATTT 240

GlCllTlCGT TCTTTTCTTS TTlllCCTCT CCCCSCCTTC CCCllCCllC STCTTCTCG1 300

TTCCCCTTCC TTTTCilCCC ATT1TGCTC1 ClCCTTlTTl ACTCCCTTlC ClTCATCTiC 360

TlCTllCCCC ICCSATCCll S1C11TTTTC CTCCTCTClT TCCTTClCCC TCTCSCGCCl 420

1TTCTTCTTC TCCCCTCTCS ITCTTlllTA CillliiCGT T11CT1TCA1 CTATCGlTll 480

CCTCTTGCll CCCTlCTlCS TT1T1TTCT1 T1TT1TTTC1 TCTACCTCCl CCGTCGTCCT 540 llCACllGCA T1TC1CC11C TTTT1TC1CT TTCCCCTTCC CllCTTTGTC ITCTAAlTTT 600

TTllllTGAl C1S11S11ST TTCGCCCCCC ICTCTllClT TTTlllSlll CTTCCCClCG 660

AGTTlTSACC CCTCTCATCC TiCCillTCl 1C1TC1TCT1 1STATCTCTT CCCTACTTCG 720

CCCCTCTTTC CiSlCCCCTl CGTTClCTAC CTCCTCTClT CCCTllCTTC CCCillTCll 780

TCTTCCClGl CTTCTCTTCT TTCTTCClll GTGTClTlii TTTC111G11 IGCACTTTTT 840 lACTCCClCC TTSCTTTCCS TCGlGTCTAC TTCGGTlTTl TCCACTTTCT ClTTlTTlTT 900

CCiCCGCGlS TllSlCSACT CGClCCilTT TTTCTTTTGT llTTGATCCC CTTCCCCTCT 960

CA1TCATTC1 TCCAlTCTTC TillllTGCT CCACCCTCCC TTAT1CC1TC CCCTlTACTT 1020

TCCCCAC

1027 (2) SEQ INFORMATION NA No: 161:

(i) SEQUENCE TIMES:

(Α) LENGTH: 155 amino acids (B) TYPE: amino acid

338

184 424 (G) NICN NLITY: single (D) TOPOLOGY: linear (ii) PARTICLE TYPE: protein <xi) SEQUENCE OPNS: SEQ ID no: 161:

Sio Pos Alu 1 Pro Pr: Ala Cys JAp Liu Arg Val Ltu Sio Lys Leu 15 Leu 5 08 Sog Asp Sn Sis Va8 Leu Sis Ssi Aog Leu Cheese TlG Cys Pos Gla Val twenty 25 thirty Sis Pro Leu Liu Thr Sro Orl Leu Lru aau But ul Asp Phe Cheese Lau 35 40 45 lly Glu Trp Thousand LSs Background GuG Glu G8u Clu Lyi hives G ln Asp 18 e Lua 50 55 60 lly Ala Vaa 8hr Luu Liu Leu Glu Tly Val Myth Ala Ala log Gly Main 65 70 75 80 Ltu cir Po 8hr Cy: Liu Cheese Cheese Liu Leu ilr iln Liu Sio Gly Main 85 98 95 Vai log Leu 8eu 8eu ui | Ala Leu lln 108 Leu Liu how many Background Gin Liu 100 108 110 Pos Pro G In Gl. Arg Thr Thr Ala Hi s Lyo Ace a8O Ass Ala How much POs 115 120 U2 Ltu Ssi 8he Glu His Leu Pru Ar- G8y eru VaA g8g ihe Lep Underworld aau 130 135 110 Va1 ilr G1 | Sro THIS Liu CSP Val Aog Glu Pli 145 150 155

(2) INFORMATION ABOUT SEQ ID No: 162:

(i) SEQUENCE CECSES:

(A) LENGTH: 309 amino acids (B) TYPE: amino acid (C) NLGI NLQ: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: protein (xS) SEQUENCE DESCRIPTION: SEQ ID go: 162:

184 424

339

Sro 1 Psi Cli Sur Sur Cli C / s Asp Ues Gorg Vil Les Sro Iys Ces 15 Ues 5 10 Tog Asp Ses 0 is Val Leu His Sei sVg Sio SeA GV n Cys Prs OVu Gal twenty 25 thirty His Sur Lee SiO V1h Pro Vo0 Leu Hvu Irs But Gal 1 Asp Pooh lVr alH 35 40 45 Cly Gls Tip Lys Background Main Underworld Glu Glu iho Lys Ala GCn Asp IIe Veu 50 55 60 Gly Tli Val Tho Leu Lru Urs Glu Cly Val Underworld Cli Gll Arg VCy VCn 65 70 75 80 Leu Cly Pro iho <C / s Luu Seu Seo Ltu Lru how many Cle Cru SSE VCy V1n 85 90 95 Vil Move Leu Seu Vet Vly Gir Lea IV n Iru Lei Lv u Sip The SVn Leu 100 105 111 Cf. Srr Gic Liy Aig Vhr Tho Ala Uv p Or Ash svo Ass Ali pV e SOr 115 120 11! 5 Leu Hundred Phe how much His Lru Uru Arg Cly Lys VaO Aog Phe Leu Mei Veu 303 135 110 Vil Cly Gly Sro Tho Luu C / s Val Move Glu Phe how many how many Ais Vei ACa 145 150 15V 116 Sro Sur Ala Srr Pro Ali Cyrs CPO Ltu Aog Val Ces Sro Lus Vcu Veu 165 17V 175 Move TP0 Ses Nov Val Leu Nov Sei sVg Πο Sec gVn Cys Prs 0 Vu Gal 180 185 110 His Prr Leu Ssu vih Pro VoZ LeV Hvu Irs Ali SVl Pi; Pooh l v r Via 195 200 205 Cly Gls Ttp) Lys Thr Cln Myth GSu Gis 1ho Iys Ali Main Asp IIe Leu 210 215 2:20 Cly Ali Val 1ho Leu Les Ueu Glu Gly Val Underworld Ali Ali Arg Gly Alga 225 230 235 224 Ueu Gly Pro Tho CC / s Leu Sro & ΪΟ Uus Leu Gly how much Ces Cheese GCy Main 245 250 255 Vil Arg Leu SIU Vet V ly Gir Flax GVn lus Lei Lvu Sip The G 1 n Fox- 260 2fó5 227 Arg Tho iho Gll His Iys Cso Sur ise Gll Ilr Phr Ces Sro Phr you 275 280 285

340

184 424

Hin luu luu Arg Uly l'S ViU Arg Ohu luu Mut luu ViU li 'Gly Kur 290 295 300 Ahr luu Gys Vil Tog 305 (2) 1TFORMTTJE 0 SEQ DD Tg: 163:

(i) KEKWETCJD FEATURES:

(A) LENGTH: 312 amino acids (B) TYPE: amSnsnaa?

(T) TlCD DURABILITY: single (D) ΑΟΟΟΙΟΑΙΤ: linear (SS) CYO PARTICLES: bLow (xi) SEQUENCE OODS: KEQ DD No .: 163:

Hen 1 Oro Ala Oro Goal 5 Ala Cyn Asp leu Arg Val 10 Leu Sur lys Leu 15 Leu Arg Cnp Ssu His VaL Leu His Cheese Arg Luu Cheese Main Gys Oro Glu Lvl twenty 25 thirty iin Oro Leu Oro Thr Peo Vai Leu leu Pro Ala Val Aip LPh Lsu Leu 35 40 45 AU ' Alu Ti— Lys Thr Main Mut Glu Ulu Thr Lys Ala GIu Lep Lle Leu 50 5L 60 li ' Cli Val Ahr leu Leu Leu Glu Gly Val MeL Shhh Aii Arg 151 ' Main 65 0L 7L 80 luu UU ' Drank Ahr Thousand Luu Cheese Cheese leu Leu Gly Uln luu Hen Gly Main 85 9L 95 VII Arg Leu luu Luu Gly (background Luu Main Ker Leu Leu Aly Chr Gin Leu 100 105 111 Oro Oro GIi li ' Arg T> Ahr Ala Hin Lys Asp Pro LTn Ala Lle Phe 115 120 115 luu Hen Phe Uln His Leu luu COrg Ul ' Lys Val Arg PPh Leu Underworld Leu 13 0 15 L. 140 Vli UU ' GAy Lur Ahr Luu / yn Val Arg Glu PhL UU ' Asn Mut Ala Cheese 145 50L 55L 110 Oro Ali Peo Ogo Aii y? L Asp Leu COrg Val Leu Hen lys Leu Leu Arg 165 170 1115

184 424

341

Asp Sen HiH Sv1 Ceu H is Ssc Art liu 185 Gln Cys Pro GCr 110 Cal Oot 180 hio Utu Po; Thp 195 Pro aai Leu Ltu Phi 200 Ala Val Acp COr Cer 220 Llu Gly Ulu Trp Lys hhp 210 GLn Mtt Glu 215 liu TCr Cys Ala GTu 220 Acp Cle Llu Gly Ala Vai TTr Leu 225 Leu February 223 Glu GTy Val Met Ala Ala 225 Arg aCy Cln Igu 240 Tly hro TCr Ccs Ceu 245 Cheese Cheese Leu Luu Tly Gln Luu 250 Sei Gly Uln Val 255 Arg Leu Leu Llu 260 Cli. ACa Leu Gln Ser 265 Leu Leu Gly Background of GTn 220 C eu hpi hio Uln Gly Ccg 275 CLrr ICr Ala Hic; Lys 280 Asp Pro ACn Ala iCe 225 lit htu Sui hhe GTn CHs Ceu ueu Ltrg Gly Lyi VaS Arg Phe 290 255 300 Uiy Tly Ssu Thi Leu CCys CIlI 5Cig 305 310 SEQ INFORMATION NA Nn: 164: (S) SEQUENCE FEATURES: (A) LENGTH :: 313 amino acids (B) TYO: amino acid (T) NUMBER OF THREADS: single (D) TOPOLOGY: liroca / a (II) TYO PARTICLES: protein (xi) SEQUENCE DESCRIPTION: SEQ NA nn: 164: Leu Mut Mtt Vul Sti Ooo Ala Ono 1 Oooh 5 Ala Cys 1 after Uuu Cpg ViI Ltu 10 Sti Uys ^L here ^U here 15 Ang Asp Ser His twenty Val Leu His Sti Ang 2C Ltu Ser lln Css Piro thirty GTu Val His hio Leu Pro 35 ihp Pro Val Utu Leu 40 hio Ala ViI Asp PPr 45 Set Leu

Tly llu Cnp Lys Thn lln Mtt llu Ulu Ghp Lys Ala lln Asp ilu Ltu 50 55 60 '

342

184 424

Air 65 Ali Wl TTe Uru Leu 70 Llu Glu TAn Vi1 Met Ali Ala Aog Als GAe 75 80 Ltu Cls Poo Ttir Css eru Cheese Ter Tue Lru Gly Gla Leu Eto Aly GAn 85 90 95 Vi1 Gog Utu Uru Utu git Ala Glu Background Eto Utu Leu Gly TCh Tln Teu 100 115 111 Poo Poo (ls Air Aog The OTh Ala THs eys Asp Pro Ass Background T Ie The 115 112 112 Leu Ero PPe Main His Leu Leu Arg Gly Lys Incl Tlog PPh eru Underworld Leu 130 U3 140 VII rir GAe Ter Tho Leu cys Val TA-g Alu Phe GAy res Ass Mrt Ala 145 150 155 110 Eeo Poo Ali Tro Poo lii cys JCp Leu Aog Vi1 Leu Eeo Lys eru Leu 165 170 117 Aog Asp Eto His Vi1 Leu His Cheese Arg Uru Ero But Ces Too Glu Incl 180 115 119 His Poo eru Poo Tho Pro Incl Leu Leu Poo Ali VII Tas ore Cheese Leu 195 200 220 Air (lu Tro Lys Tho Main Underworld Glu Glu Tho Lys Ali Main Asp Ilr Leu 210 221 220 Nov Ali Val Thr eru Leu Leu Glu Gly Vi1 Underworld Ala Ali Aorg Gly (ln 225 200 235 240 Leu rir Drank Thr Thousand Leu Seo Cheese Leu Ltu ris Main Leu Cheese lira (ls 245 20T 225 VII Aog Ltu Uru Ltu GAy .Ala Leu Main Ero eru eru Gly Tlhs But eru 260 265 220 Poo Poo Yew Ais Gog Thr Tho Ali His Lys Asp Poo Arn Ala Ilt Pht 275 280 225 Ltu Ero Phe ris His Leu Llu .log rir Lys Incl Arg Phr Leu Underworld Leu 290 225 300 VII Yew Gly Cheese Background Leu C <c ^s Vai Arg

305 300 {2) INFORMATION ON EEQ ND No: 165:

(S) SEQUENCE FEATURES:

(A) LENGTH: 316 amino acids (B) CYP: amSezkwiS

184 424

343 (C) NLITY NNCN: single (D) TOPOIOGNA: linear (II) TYPE OF PARTICLE: protein

xi) SEQUENCE DESCRIPTION: SEQ ID no: 16: Sio Poo Ali Pro Poo Ali Cyp Asp Iiu log Vii Liu Sio Lys Liu Iru 1 5 10 15 log Asp Seo His Va1 Iiu His Gorg cheese Iiu Sio Cln Tys Piso Glu Vvl twenty 25 thirty His Ppo Peu Liu Thr Pro Va0 Ler op lio Ali Uit Asp Phr 'pr Sei 35 40 45 lly Gin Aig? Lys Tho lln Hit Glu Glu Cho Iys Ala Pin Asp Ali; Lii 50 55 60 lly lii Val TTh Peu Lpu Leu Gli UAy CaU Mel S A a lin Are ttly lii 65 70 75 80 Liu lly Pro TTh Pys Lpu Cheese See Opu Sio Gly U An Iiu Sei Gly Cln 85 90 95 VII log Leu Leu Leu lly lii Leu lln Seo Iru Leu Gly Tho Gln Liu 100 10A 110 Poo Poo Aln Gly Arg ThA Thr Alc Oas Tyo Asa Nov Asn Ali SPe IPp 115 12A 125 Ltu Ssi Phi Cln His Iiu leu Arg Gly Lys liai Arg PPe Leu Met Lie 130 135 110 Vi1 lly Gl (? Sei ATh Peu Cyu VaC SAg lln Phi g A y llu Aso lAy lly 145 150 155 116 isn Wit Ala Srr Ppo Pla Pri Pro oAa PA 'Asa 1pu Ccs Va1 ppu Leu 165 ŚL7A 175 Lys Liu Leu .Crg Syp Seo His Val Leu His Seo Arg Leu Seo Gln Cys 180 15A 190 Poo Gln Aai lin Pro Lau Poo Thi Upo ho 'Lec Opo lin Ali Va 1 Iiu 195 20A 220 Pooh Leu lly llu Top cheese Lys Gln background Metllu Glu Fat Lys iii GLa 210 215 222 Asp Ili Iiu Cly lii VII Tho Liu Iiu Liu ilu Cly Vi1 Mit iii Cli 225 230 235 240

344

184 424

Arg Cl 'Glu Luu Gly Oro Chr tin Leu Sur 250 Ssr luu luu Gly Main 255 Leu 245 Hen Aly Glu Val Lcg luu leu luu Gly lila Leu Uin Hen Leu Leu Gly 260 26L 270 Ahr Aln Leu Pro Oro Uin Giy Arg Thr Ahr Ala His Lys Aep Pro Acn 275 280 225 Ali Dlu POh Leu Hen Phu Main His Luu leu Arg Gly Lys Vvl Arg Phh 290 295 300 luu Mut Leu Wow UU ' Uly Cheese thr Lul tin Val Arg 305 310 315

(2) INFORMATION 0 SEQ DD No .: 166:

(S) SEQUENCE FEATURES:

(A) LENGTH: 302 amino acids (B) CYO: amino acid (T) LONG TlCD: single (D) GOeOUOGDT: linear (SS) GY0 PARTICLES: protein (xi) SEQUENCE OOD: SEQ DD NO .: 166:

Tsn 1 Thousand Hen Diu Mut 5 Diu Aip Alu Lii How much 1L His His Luu Lys Arg 15 Poo He Ali Pro Leu twenty leu Asp Pro Tsn Asn 25 Leu Ann cnp Glu Aip thirty Val Ssr How many luu Underworld 35 At?) Arg Asn Leu Arg 0L Luu Poo Asn luu Glu 45 Ler Phe Val Trg Ali 50 Val Lys Asn Leu Glu 55 Asn Aii Ssr Uiy Diu 60 Glu Ala How much Leu Arg 65 Asn ieu And Au He <S? S 7L Leu Half Cheese Ala Ahr 75 Ala Ala Oro Cheese Arg 80 His Pro about Di L lu Dlu 85 Ly Ala Gly Asp T: pL 0L ropes Ulu PhL Arg Glu 95 Lys euu Ahr Phe Tyr 100 Leu Val Thr Leu Glu 10L Main Ala Uln Glu Main 110 Main • Gyr

Vii Glu Gly Gly Uly Gly Ser Ool Gly GAy Uly Sur Gly Giy Giy Ser 115 20L 112

184 424

345

Asn Myth 13 0 Ali ayr 8ye / 8U -us 115 SiS P8O POs Main urn 110 liu lua U 8— GLy Sis Sio Lee u 8y 8 li Gpo hop Ala Pos Leu Cheese Hundred Cys Po Sro Main 145 150 115 160 lia Ltu Gli Geu A la aiy Cys Leu and 8r Llu Leu 0 8s liG lly Leu Sili 165 117 117 Liu Tro Main lira Leu Liu Tln Alu Leu Tlu Gly iii Cheese Po Clu Leu 180 118 110 lly Pos Thr Liu Asp Tlx Liu Gin Leu Jul Val Akia Asp Pooh Ala Tho 195 208 220 Background lii gsr IG8 lln Underworld Glu how many Liu Gly Underworld Ala Po Ala 8l ^ u Main 210 215 220 Pos Background Main G8y A la Underworld 8ro Alh S8e how many Cheese 1 8 a Ala Main Arg lua 225 230 225 240 how many ilr Gl— · yaa 8ee uah Ala Ses a 8 p Sro Main S 8r —Lu Lgu Glu Va0 245 250 225 Hundred Gro Arg Vai Leu log His Lei Ala Tln : 0178 Cheese Gly Gly Ssr ilr 260 2 (55 227 ilr Hundred Main Seo Phe Leu Leu L — S Cheese Lru Glu iln Va8 Arg Lys Ili 275 80 8 228 TlG yew Ace p8y Ala a 8 a Aia Κ8 Glu lyn Flax u8S —Si The

290 295 300 (2) SEQ INFORMATION NA No: 167:

(i) SEQUENCE CECSES:

(1) LENGTH: 317 amino acids (B) TYPE: amino acid (G) NLQI: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: protein (xi) SEQUENCE OPNS: SNQ ND go: 167:

iSG Uys Sio lii Myth Ili Asp liu Ili iii Sis Sis -here —Ys Arg Poo 5 10 15 Pos how many Poo -here Lru Asp Poo Asg iSG —Eu Asn Asp liu Asp Va1 Hundred

25 30

346

184 424

How many Ltu Mot 35 Asp Aog Asn Ltu log Luu 40 Poo Asn Ltu llu 45 Hundred Phu Val Arg lla ViI L / s Asn Luu Giu Asn Gla Seo Gly How many llu Ala How many Ltu 50 55 60 Arg isn Leu Gla Gro -ops Leu Pro Ger Ala Thi a o c Al a Mon Igp oms 65 70 75 80 iis Poo IIi Hi Gle Lye Ala Gly Aip Trp Gic G0i Phe Arg UGi Lpi 85 90 95 Ltu Tho PPe GGs Luu Val Tho Luu how many Gin Ala ropes llu Gla Main IG— 100 110 110 VII llu Gin ll / Gl / Gl / Suo Poo Gly Glu Poo Seo Mly Geo 0 li Cheese 115 120 125 Thr How much Asn Pro Suo Poo Poo Sur Lys Giu Suo iis L / s Suo Poo isn 130 135 110 Underworld lla TT— Gys Geu tu-G His Pro Mlu Giu Lie down uol Leu Lgl at 0 l Ho and 145 150 155 160 P Ltu Gin 0Io Gro Top Ala Pro Meu Cheese Ses Ops Ooh Soe GGe oo and 165 170 175 Ltu ropes Leu Ala ll / cys Luu Seo Main Leu Tack Seo Gl / Leu Phu Leu 180 lt58> 110 This ropes Gin Ltu Ltu ropes Gla Leu Glu Gly Ilo Sst Meo Gla Geu Gly 195 200 205 Pro Tho Leu. Asp Tho Leu Main Leu 1sp Val Al and Ais 0Ph Glo Tho Tho 210 215 222 How much hop Bullfinch Main Underworld Uto Glu Liu Mly Underworld But tGl A0 a Moose and about l uoi 225 300 235 240 Thr ropes Gly Ala Underworld Pr o Ala Phe Ala iia But swarming and he Uoi Iga L 0 1 245 200 255 Gly Gl / Val Leu Val Ala Seo His Leu Main Cheese Phe Ltu how many Val Suo 260 265 277 T / y log Val Ltu Log iis leu Hive Main Pro Cheese Gly ooh Geo ll / Gly 275 200 285 P ropes Cheese Phu Leu Leu Lys SeG Leu Glu Main Vv1 Mio Gys How many Main 290 290 330 Gl / Asp li / lla Gla Leu Main how many Lys Ltu T / s lla Tho 305 310 315

184 424

347 (2) SEQ INFORMATION NA No .: 168:

(i) SEQUENCE FEATURES:

(A) LENGTH: 302 amino acids (B) TYPE: amino acid (C) NNCN NLITY: single (D) TOPOLOGY: linear (II) TYPE OF PARTICLE: protein

."and) SEQUENCE OPNS: SEQ ND Well: 168: Csn 1 Cys Srr lii Mit Nil 5 Asp Glu Ali lii His His Aeu 5ys 51] Ppo 10 15 Poo lii Ppo Iiu Liu Syp 20 Poo / isn Ais : 25 Liu Asn Pcy Alu Aip Av1 Asi 30 lii Liu Mel Asp Aig Asn 35 Liu log 45 Leu Poo Asn Iiu Glu Arr PPh Av1 45 log lii Vv1 Lys Csn Liu 50 llu 55 Hn Ala Sio Gly Ili Alu Ala Ali Aer 60 log 65 isn Lii lln Poo Cys 70 Liu Pro Cheese lii Thr Ala Ala Piso Prr 51] 75 80 iis Poo 1li lii Ile Iys 85 Ali Gly? Aso Top Gln Glu Phe Arg Alu Ays 90 95 Ltu Cho PPh Tjye Liu Va1 100 The Leu Glu 105 lln .Ala Gln Glu Gln Gin AT? 110 Vi1 llu Giy lly Gly lly 115 Sio Poo 205 Gly Gly Gly Sio Gly Gly? Gly Sei 115 isn The myth of Al Pro ilu Leu 130 Gly 135 Oop Thr Leu Asp Thr Leu Gln Leu Aip 1-40 Vai 145 lii Asy Phi Ali Background 15 A. The How much Trp lln Gln Me5 Glu Glu Leu Gly? 005 110 Myth lii Piso Ala Liu lln 165 Pro Tho Main. lly Ala Me5 Pro Ala hlp Ala 170 175 Sio lii Phe Cln log Arg 180 lii lly Gly? 85 A. Vii Liu Va1 Ala Ser Hii Leu 190 lln Sio Phe Leu Glu Vi1 195 Cheese Tyo 00 A Arp Va5 iuA Aog His Liu Ala Gln 205

348

184 424

Sur Ku Cly ily euu ily Cly Siu 215 Cln Sru She Urs Les 222 Cys eyu Lrs 210 Glu Cle ViO Gog Lys III VCl GCy Acp VCu Tli Cli Les GCa V1a Vus 225 223 235 224 Move Cys Tli iho iyu Lus Vcu Vys Vis Vsu Glu Gls Uru Val Vce Vcu 245 250 225 Cly His & ιο Llu VCy Ile Sir Top ACa! Ρο Ues Ku Siar Cys Dog Kr 260 226 270 Cle Gll Ces GCi Veu Tli Cly cy-s Leu Kt Cle Lrs His Cheese GCy Vcu 275 280 255 Phr Cru iyu Gln VCy Luu Ces Cle Ala Veu Gls Cly Ile Cheese 290 295 330 INFORMATION ; About SEQ ID No: 169: (i) FEATURES SEQUENCE : (AND) LENGTH: 317 Amino Acids (B) TYPE: Amino Acid (C) LOCAL NLCL : single (AND) TOPOLOGY: linear (ii) THOUSAND PARTICLES : protein SEQUENCE DESCRIPTION: SEQ II no o V 69: Gse Cys Sn how many ert How many lPO Glu how many Ilt HP1 His Luu Lyv Arg Dog 1 5 10 15 Sur Cli Psi Vrs Cuu Asp Prr Asn Csn Cug Asn Asp Gls Asp Val To twenty 25 thirty Lira Luu meter Ais Vrg Av n Leu Arg leu Pro Asn Leu Git; Cheese Phe Val 35 0V 55 Move Tli Vil Ly / Asn Cuu how many Asn Ala Ser Cly Ile GSv Gli How much February 50 5V 60 Tog Csn Cug lin Sur CC / s Leu Pro Ala cheese hho gll ali Prr Cheese Arg 65 70 75 80 His Sur Ily how many Ilr Lys Ala Gly Asp Τρ Cle llu Phi Aog Glu Lu / 85 90 95 Cru hho Phs tir Vee Sv1 Vir Leu du Gis Ali dn how many Main Main Tan 100 1D) 5 111

184 424

349

ViI Tlu Gly 115 Gly ilr gly Sui Pro 110 Gly llu hi Sti GTy 112 Pro How much Cerium Chi lit Asn Piro Sui Pro It Cheese Lys liu Sti His Lys Cheese Po Asn 130 135 114 Mtt Ala Pro Glu Luu GT | Cro Chi Leu Asp Thhr Leu Tin Leu TAp Vl1 145 110 115 116 Ala Asp Phe Ala Chi TGt Cle Cip GTn ropes MaU Glu Ulu Leu GTy MaU 165 110 117 Ala hi Alley Ltu Gir Pro Chi Tir GTy Ala Mrt Piro Aia Phe Ala Csr 180 H8 110 Ala Oht Main Arg Arg Ci and a Tly Gly Vći1 Ltu Val Ala Ssr His Llu GTn 195 200 220 Sui Ohe Leu GTu Wow Vulture Tin Arg vaa Ltu Apg His Luu Ala GTu Cro 210 215 222 Sui Uiy Gly Cheese Tly GT | Cerium Tln Cheese hhr Llu Utu Lys Cheese Llu Glu 225 223 223 224 Tln ViI Arg Ccs how many GTa Cly Asp Gly Ala AAa Ltu Tln Glu Lys Leu 245 225 225 Cys Ala Thr rep LyC Leu Cys His Piro liu Glu Leu Val Leu Luu Gly 260 226 270 His Sei Leu Gly how many Pro Crp> Ala Piro Ltu Cheese Cheese CCys Pro Cheese GTn 275 280 228 Ala Leu Main Leu Ala Tly Cys Leu Cheese lln Leu His Cheese Tly Leu Phe 290 295 330 Ltu Type Main Gly Utu Feb Main Ala Leu Tlu GTy how much Cheese 305 331 331

(2) INFORMATION ABOUT SEQ ID No .: 170:

(i) SEQUENCE FEATURES:

(A) LENGTH: 302 amino acids (B) TYh: amino acid (C) QUANTITY of NlTN: single (D) TOPOLOGY: linear (li) GYh PARTICLES: protein (xi) SEQUENCE DESCRIPTION: SEQ ND n ;: 170:

350

184 424

Asn 1 Cys Cheese And lu LeM GLe 5 Aur HCg u L e Dlu 10 Hii U Li Leu Lye Arg 15 Lso Oro Ala Pro L eu Lee ulp Pro Ohm Sl n Csn Ase beehive Si? Ace ul Tsc twenty 25 thirty Diu luu Meu And e? And this Asn Leu Leu Leu Tog Ase hive POo Sec SAe Luu 35 40 45 Crg Ala Vai lys Ass luu Clu Asn Aii Sur Uiy Dlu Alu Ala Dlu luu 50 55 60 Arg Asn Leu Ali Leo Ays Leu Oro Sur liii Ahr Ala Ali Loro Lsu Arg 65 70 75 80 His Oro How many Lin Lii Lys Ala Uly App Trp Gin Alu Fire AAg LAu lys 85 90 95 Luu Ahr PPh Lys Leu Val The Ahr Glu euu Alu at Ln Aln Main l Ln G | n 100 105 110 Vel Glu Aly GAy Aly LAy Leo Oro Gi ' GUy Aly Ssr Aly AAy L Ay L eu 115 120 125 Cou MuG Ali Mel Ali Leo Aii leu Uln Pro Cho Main Aly Ala Ael Lro 130 135 140 Cli Ohu Ali Ler Ala Ohu ropes Arg Arg But Aly CL Uy Val Leu Val Ala 145 150 155 110 Hen His Leu GAn Ler Ohu luu Glu VaU Cheese tyr Arg Val Leu Arg His 165 17 L. 115 Luu Ala GAa Leo Leu Gly Giy Ans Gly K1g Sei 'L n Nov Phe Olu leu 180 18L 190 Lys Sur luu GIi Lii Wow Trg Lys Ul Glu Gly Asp Gly Ala Alu Leu 195 200 205 ropes Clu Lys Leu Lys Ala Ahr tyr Lys Leu tin His Peo AAe LAu Leu 210 21.5 220 VII luu Leu Gly His Hen Luu Gly How much Pr Trp Ala Pro Luu Cheese Sur 225 230 23L 240 Thousand Oro Cheese Main Ala Luu Uin Leu (Ula Gly <y? s Leu Cheese Main Leu HSo 245 20L 255 Hen Aly Leu Phe Leu Tyr Gir uin Leu Ans Glu uL a luu Glu S Ly How much 260 65L 270 Hen Pro Ulu Leu Gly Pro Ahr Leu Asp Thr Leu Uin Leu Lcp Val Aii 275 20L 285

184 424

351 asp Phe Cli iho iho ily iop Cln Cln Met Glu Clu Ulg Cly 290 295 033 (2) INFORMATION ABOUT SEQ LI Nu: 171:

(i) SEQUENCE FEATURES:

(A) DISTANCE: 331 vaiisorwwińó (B) TYPE: amino acid (C) LOOSENESS OF THREAD: single (I) TOPOLOGY: linear (ii) THOUSAND PARTICLES: protein (xi) SEQUENCE DESCRIPTION: SEQ LD no: 171:

Aso 1 C / s Ssr ily Met 5 How much Asp GOu How much ilt His 10 His Leu Lys (Oy 15 Pro Sur Cli Prs Zet Vee Gvp ipn Asp Avn Aso Ace Lvp GLu Aso Val Cheese twenty 25 thirty How much Ues Underworld tkis Arg Arn Aso Aria Gvu log Asn Seu GOu Cheese Phe Val 35 40 45 Move Ali Val Lys Gsn Les Glu Asn Ala Κο GCy Ha GCe ACa He Vnu 50 60 Tog Aso Leu Main Vrs Lynx Crs Pro S er Air Thr Ala Ala Pio S er .lig 65 70 75 80 His Sur How much how much He UAS ULs GIA lvp Coy Main G Vu Phe Ara, Glu Lys 85 90 95 Luu Tho Phe yttrium Vee sva HVr Lei About Vu LLs Ala G ln (Oh Lu Main Main Tm 100 15V 111 Vil Yew Gly GCn V Cy Gly les Pro Gly Pio Pro S er GSy Pro How much here 115 : ΐ:> 0 115 iho How much Asn Pro Sro Pro Pro Cheese Lys Glu SSE Vis Lys; Cheese Pro Asn 130 13V 110 Mrt Tli Underworld Ali Vrs A Va Ali Main Pro rio Gir: G ly Alv Mil Pro .HSl 145 150 1L ^ 5 110 She Ali Cheese But Vhs U Vn Cul Arg A Va Gly Gig, Val Leu Val Ala ln 165 170 175 His Leu Main S n Vhs U vu ULs Val S er Tin Arg Val Uov Arv His lov 180 85V 119

352

184 424

Ali lln Pro Seo lly lly Sio Gly? lly Cheese lln Sto Phe Liu Leu Lys 195 220 220 Sio Iiu Gln Ali AaV 1A0 Pys Ali Gln lly Asp Gly Ala Ala Leu Gln 210 221 220 llu Iys Leu (5ys Ala Shr Clił Ly. Sap Lys Hia Sio POo Gli Uin yiU 555 220 225 240 Liu Iiu Gly? Ais Ser Ppu Gly Ile Sao Not Alc pin Aeu Ser 'Ar Lyu 245 250 550 Poo Sio lln lii Liu lln Iiu Ali lly Tys Liu Sio Cln Liu iis Aug 260 265 270 lly Iiu Phe Leu Tyo lln lly Leu Ltu lln Ali Leu Glu Gly Ale Ser 275 280 2255 Poo liu Leu Gly Pro Thr Leu 5Vsp Tłir Liu lln Leu App Va5 Ala Asp 290 229 300 Pooh Cli Fat Background 5Ii Tta Cln lln Met llu Gilu Liu lly 305 310 331 2) SEQ INFORMATION ND No .: 172: (i) SEQUENCE FEATURES: (A) LENGTH : 302 amino acids (B) TYPE: amino acid (C) NNCN NLITY: Single (D) TOPOIOGNA: linear (li) TYPE OF PARTICLE: protein xi) OPNS SEQUENCE: SEQ ND no: : 172: isn Gys Sei Ile Mit lii Asp llu lit Ile His His Liu Lys losg Poo 1 5 05 15 Poo lii Poo Leu Leu Asp Poo Asn isn Leu Asn Asp Clu Asp Va1 Ser twenty 25 30 lii Iru Met Asp Arg Ann Leu log Liu Pr. A ^ n Leu llu Ser Phe Val 35 40 45 log Bullfinch Val Lys isn leu Glu Asn lii Cheese Gly Ile (llu Ala Ile Leu 50 55 00 log Csn Leu Gln Piso Cys Leu Pro Sto Ala Thr Ali Ali Poo loA log 65 70 55 80

184 424

353

Sis Poo How much I ii 81i 85 l8S ASs Gln ai | Gsp gpi G8u how many Aro lira Cyu 99 95 -here Background Phe 18 (( 8ee V8l aau Lei Oli Alu IGs a 8 n TlG Gli hive TlG 100 105 111 Vai llu G1 | liy lly Gly Ssi 8po Gly Gly Gir Sio Gly Gly Gly Cheese 115 112 125 Asg Myth Alu Background TlG Gly Alu 8ei Poo Ala Phe Ala Cheese Ala Phe Main 130 : 3: 35 140 Aog Aog Alu cir Gly Val Liu wi Ala Cheese HSs Ltu lln Sio Phe Leu 145 115 115 160 llu Vai Ssr Tro log Vaa Aiu Aig His Leu Alu Main :, 2: 0 Hundred Gly Gly 165 170 115 Sio ilr Gly Ssi 8lu Cheese sro Leo lei —Eu Sis 08U -here Gic unl Vv | 180 185 110 —Rs Ili Glu 81y 831 p 8y Ais ΙΟΙ Ι18 —Lu Gli G8S liu Cye Pli Thr 195 220 205 Gro —Ys Ler Cys His Pro Glu 81i liu Val Leu Liu Gly His Sei: Lru 210 218 220 lly lii Poo Top how many Pro Leu S8r Cheese Cys Pr o Cheese Main Al a Leu (Sin 225 223 223 240 -here Aia Gly Ars Liu Cheese ropes Lei Sis Cheese Gly Trump Ph8 Trump Tyr Aln 245 250 255 ilr Ltu Leu G lu 81a a 8u -here Gly hives Nur Pop S 8u liu Gl— uio Thr 260 265 2-70 -here GPO Thl -here TlG Leu Aip 8aa Aia Asp Phe Ala Tho Thr How much Pop 275 2 28 285 iln CiG Underworld 81u 81u Leu Trump Us 8 11 8 lua Alh S8U lia Pre 290 : 298 300

(2) SEQ INFORMATION NA No: 173:

(i) SEQUENCE CECSES:

(i) LENGTH: 317 mm (B) TYPE: amino acid (C) QUANTITY of NiGi: single (D) TOPOLOGY; linear (ii) TYPE OF PARTICLE: protein

354

184 424

xi) SEQUENCE OPTION: EEQ ND - no .: 17: Gse 1 Tys Eeo lit Mtt ULt SsG 5 Clu lit lit Ηΐ o Hio Lut Lso Og. Όο 10 15 Poo Gli Poo Uru Leu Asp Poo 20 Gss Ass 25 Leu Gsn Asp (Ou Asp Vi1 Ero 30 How much Leu Met: Ars Grg Ast Leu 35 Arg 40 Leo Pro Ase Uou Glu Cheese Phe eeU 45 Aog Ali Val Tys Ass Ltu (lu 50 55 Asn (tli Erg (lr Ilu Glu Ala Ile Llm 60 Aog 65 Gse Let TAn Pro (Tys Leu 70 Poo Eto Ale Cho lii Ali Poo Ero Ta »75 80 His Poo Iluniane Ile Lys Ciii 85 GAy .Asp Ttp Cle Glu Phe Aog (lu Lus 90 95 Uru Tho Pho Lis Teu Va 1 Thr 100 Leu Glu 105 Gln Air UTn Glu Gln Gln fig 110 Vi1 (lu Gly Alu Gly Gly Ser 115 Prr 120 GTy GOo Prr Aor Gly Pro o0e Eto 112 Tho lle Ars Too Ter Pro Poro 130 135 Cheese Lys GLo Ses sTs Lys Ser OHi Usn 110 Underworld 145 Ali ΤΤτ GAn GL_r Ali Met 150 Poo Ali POh Gli Cheese Akii PhL Cle Targ 155 116 Aog Ali GAe Gly Val Leu Va1 165 Ala Ero HHi Leu Gln Ero Pht Ltu GAu 170 117 Vi1 Eeo Tyi Oag Tal Leu Aru 180 Hic Leu 180 ALu Gic loo les Glp oTy Ero 190 Air (ls Ser Ole Ter Phe Leu 195 Leu 2200 Lys Sru Lee sTu GLo VaL Aog linen 220 lle But GCn 013X3 Gly Ali Ala 210 2210 Leu Main Alu Lyo Lst Tys Ali Tho Tys 222 Lys 225 Utu Cys His Pro Glu Glu 200 Leu Vi1 Leu Leu Gly His Eeo Leu Gly 235 22 (0 Ilr Poo Ttg TAu Pro Leu Ser 245 Cheese cys Oos OTn Als Leu GTn Leu 250 Belt 225 Ali (ls Cys see Ter GTn Len 260 His Uer 250 ELp Ler ATe Leu Tyo L 0n GLu 270

184 424

355

Leu Leu Main 275 Ala Leu Glu Gly How much 280 Cheese Pro Glu Leu Gly 285 Pro Thr Leu Asp Thr 290 Leu Main Leu Asp Val 295 Ala Asp Phe Ala Thr 300 Thr How much Trp Main Main 305 Underworld Glu Glu Leu Gly 310 Underworld Ala Pro Ala Leu 315 Main Pro (2) INFORMATION 0 SEQ ID No. : 174:

(i) SEQUENCE FEATURES:

(AND) LENGTH: 302 amino acids (ii) (xi) DESCRIPTION (B) TYPE: amino acid (C) NUMBER OF THREADS: single (D) TOPOLOGY: linear Molecule type: protein SEQUENCE: SEQ ID NO: 174: Asn Cys 1 Cheese How many Met Ile 5 Asp Glu Ile Ile His His Leu Lys Arg Pro 10 15 Pro Ala Pro Leu Leu Asp twenty Pro Asn Asn Leu Asn Asp Glu Asp Val Ser 25 30 How much Leu Underworld 35 Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Cheese Phe Val 40 45 Arg Ala 50 Val Lys Asn Leu Glu 55 Asn Ala Ser Gly Ile Glu Ala Ile Leu 60 Arg Asn 65 Leu Gln Pro Cys 70 Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg 75 80 His Pro How much How many Ile Lys 85 Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys 90 95 Leu Thr Phe Tyr Leu Val 100 Thr Leu Glu Gln Ala Gln Glu Gln Gln Tyr 105 110 Val Glu Gly 115 Gly Gly Gly Cheese Pro Gly Gly Gly Ser Gly Gly Gly Ser 120 125 Asn Met 13 0 Ala Ala Phe cheese Main 135 Arg Arg Ala Gly Gly Val Leu Val Ala 140 His cheese 145 Leu Gln Cheese Phe 150 Leu Glu Val Ser Tyr Arg Val Leu Arg His 155 160

356

184 424

Ltu Ali Gln Poo Ser 165 lly lly sio Gly Cly Sio 0 Gla Sio Phi Leu Lii 175 Lys Sio Leu llu Main Vi1 log Lys 1li Cln how many Aip lly Ali Ala Lira 180 118 119 lln llu Lys Iiu Thousand iia TTo Tyr Lys Leu Thousand His Pro Alu Glu Lira 195 200 220 Vi1 Liu Leu lly iis Cheese Iiu Gly Ili Peo Flail iii Poo Leu Cheese Ssi 210 221 222 Cys Poo Cheese lln Ala Iiu lln Iiu Ala Gly Cys Liu Sio lln Leu Hii 225 230 235 224 Sio lly Leu Pooh Leu Cyo Cln Gly Leu Wow lln Ali Liu llu Gly Ili 500 255 255 Hundred Poo Glu Iiu Gly Poo The Leu Aip Che Leu Main Liu Asp Vi1 Ali 260 226 220 Asp Pooh Ala Background ThA How much Top lln Gin Myth Glu Glu Lii Gly? Myth Ali 275 280 228 Poo Gli Leu Cln Pro Background Main. lly Ala Underworld Pro Ala PPn Ala 290 229 330 nn / oumatje O SEQ NE and No. : 175:

(i) SEQUENCE TIMES:

(1) LENGTH: 317 Amino Acids (B) TYPE: Amino Acid (C) NNCI NLITY: single (D) TOPOIOGNA: ain0oaa (ll) TYPE PARTICLES: protein (ei) OPNS SEQUENCE: SEQ NA no : 175: isn Thousand Sei lii Met lir Asp llu liii Nile HPa His Liu Lys log Piso 1 5 10 15 Poo Sil Po Leu Leu Asp Poo Asn Asn Iru Asn Asp llu Asp Vi1 Cheese 20 25 thirty lit Liu Mel Asp log Asn Leu log Leu Poo Asn Leu Clu Sap Pooh Val 35 40 45 log Ali Vv1 Iys Asn Liu Glu Asn Ali Sio GSy How much llu Ala lit Leu 50 55 60

184 424

357

Aog Asn 65 Ler lin Pro G / s 70 Leu Piso Ala cheese Thr 75 Ala Alu Geo Suo Al80 iis Pro about Ii OIo How many Lys Ala Gly Asp Mir Main Glu PPh Gco how many Lyi 85 90 95 Ltu Tho Phh Tyr Lie down Nol Lithium Lev U0u Tho thuja uin Glu Gls a 0 n C | i 100 110 rn ViI Glu Gly Gly Gly Gly Cheese Piso Gly Mlu Poo Hundred Gly Geo OIa Gsu 115 110 112 Tho Ilo Asn Per Underworld Geo Geo Ger L / s Glu Seo His Lys Oso Geo Mm 130 115 114 Mut Ala Cheese Ali MPh Mla Gio Mrg Ala Gly Gly Incl Leu wi Mli Geo 145 150 155 116 iis Leu Glu Ger Phu Luu Glu Incl Cheese Gir: Aog Val Leu Glsg iis Leu 165 100 117 Ala Main Pro Cheese Gly Ooh lar Gly / Oy Suo lic / et Ghe Lie down Igu Sur 180 115 119 Hundred Luu Glu Main wi Aog Lys How much Main Gly Asp ll / Ala Ala Glu Mlu 195 200 225 Glu L / s Leu Cys Mli MTh Ml— Gys Ltu y-s His Piso Glu Glu Llu Val 210 221 220 Ltu Luu Gly H ii Oso Geu Mly How many Poo Top Ala Piso Leu Sei: Ssr oyy 225 230 235 224 Poo Cheese G lu Mla ltu Gin Leu Ala Gly cy-s Ltu Hundred Main Leu iis Ssr 245 200 225 Gly Luu hU G Uug Tyr Main Gly Luu Leu Main lla Luu Glu Gly He Cheese 260 265 220 Pro how many Leu Gly Peo Tho Luu Asp Thr Leu ropes Ltu Asp Val Ala Asp 275 280 285 Phu Ala Thh Tlh OIo Mir Min Main Mut Glu Glu Luu Gly Underworld Ala Piso 290 229 300 GIi Luu GGe Geo Glh Min Mly Ala Mut Poo Ala Phu Ala

305: 31.0 315 (2) INFORMATION ABOUT SEQ II No: 170:

(i) SEQUENCE TIMES:

(A) LENGTH: 305 amino acids (B) TYPE: amino acid

358

184 424 (A) QUANTITY NI / D: single (D) GOOOUOAIA: iSniowi (SS) GYO PARTICLES: protein

xi) OPDK KEKWETCJD: KEQ ID no .: 6: 6: And he 1 Tyo Sru Lin Ael Lle 5 Gift Main CAi Lle Hii Uli Hnn Lyi PLg leu 10 15 Oro Ale Poo luu luu Aop 20 Oro Tone Asn 25 Luu Ann Tnp Ulu Aop Vil Ser 30 Dlu Leu MuG Acp Arg Aon 35 Leu Arg 40 Luu Oro Ann Leu LAu Lsu LPh Lv1 45 Arg Ale Vv1 Lyo Aon Leu 50 Alu 55 And he Aii Kur Gly Lin LAn Lin Lin Leu 60 Arg 65 Tone Leu Ulu Oro Cyn 7L Leu Peo Sur Ala Tho Ala Ala Pro Ser Arg 75 80 His Oro Iln Dlu Diu Ly85 1l.a GAy Aop Ti— Gin Glu Phe COrg Glu Lys 90 95 Luu TGh Ohu Tyr luu Val 100 Gho Leu Giu 105 Uin Ale Gln Glu GAn LAe Ays 111 Vel Glu Ul 'Gly Aly Uly 115 Seu Oro 120 Gi ' ily Giy Ser Gly GAy LAy Lsu 112 And he MuG Ain Tyr Lyo Leu 130 Cyo 135 His Pro liu Glu Leu Val Leu Leu LAy 110 Hi o 145 Sur Leu LAy Lii 1lo 150 Poo OCa l LO Oro See U Lr Kur Prs O.r on 155 116 You leu GAa Leu Ala iLy 165 Ali Dream U Lr Klo Leu SLs luu GlH? Lu Pl: 170 175 Leu Tys- Alu Gly Leu Leu 180 Gin Ala Leu 15L Giu Cis Ile Cheese Pro GIu Leu 110 how many Pro Tho Leu. Tsc Tho 195 Leu Uin 200 Leu Inp Val Ale Asp Phe Ala ΊΑ / τ 205 Ahr Diu Ττρ Gin Gln MeG 210 Alu 215 Glu Leu Gi 'MuG Cie Pro Ala Leu GAn 220 Oro 225 Cho GIn Gly Lle 1l t 230 Mut ooc lAe Phu Sen lLa SUo Gln l.g Aha 235 220

184 424

359

Ala Tly Tly Val Lru 245 ViI Ala Dup His Ltu 250 Tln De; hhr Utu Tlu 255 ViI Dtp You; Arg ViI 260 Luu Arg His Leu A1a 655 lln Prc Thr Pro Leu 270 Gly Prp Ala Dr; Cheese 275 Leu Pio Uln Dup Phe Luc Ltu Lyc Cheese Leu 285 Glu Main AiI Arg Uys 290 How much Gir Tly Asp Tly 295 Ala CHa Ltu Main Ulu 330 Lys Leu 5ys ACi

Chi

305 (2) SEQ INFORMATION NA No: 177:

(i) SEQUENCE FEATURES:

(A) LENGTH: 320 amino acids (B) TYO: amino acid (C) NNCN NUTTY: single (D) TOPOLOGY: lSiSoan (II) TYO PARTICLES: protein (xi) OPNS SEEWEEC ^ CJi CEQ ID nCi 177:

Csr Cys 1 Cheese And li Aea 5 I 5e Nnr Gir p 5 e Ulu Hii 15 UCs leu is! Scg 15 Pr u hi Ala Pro Llu Ceu ucp Asp Asp Oc n Asu Asc Aa p LUu Si a Val Asp twenty 25 thirty lit Ueu Underworld Acp Apg 5ln Utu Arg Ltu Pro Asn Leu GTu Asu CPh Val 35 40 45 Ang Ala Val Lys Csr Leu Tlu Csr Ala Cheese Tly How much Glu AAa Cli Leu 50 55 60 Arg Asn Llu Main Pro Cys Leu Pro Dup Ala Thn Ala Ala Pro Cheese Arg 65 70 75 80 His hi How much How much How much Uys Ala Gly Asp Trp Ulw Glu Ohr Arg Glu Lys 85 05 95 Ltu Thi Oht Tcr Ceu ual ICg How many u5u Tlu Alu 1 Cn acu 1 5 u beehive Τ | η 100 105 110 Wow Ulu Gly GTy uir Gly Stn hi Gly Glu Pro Cheese Gly Pro How much Sui 115 120 115

360

184 424

iho Lira 13 0 Acn Aro Sfau Pro Pro 115 Ssr VL / Cis Sns His 114 VU / Vro Acs Myth Cli This Cys Ces cy-s His Poro Glu Clu Llu Gal Vi ^ u Viu V1y GHi 145 115 115 116 Sro Cru GCy Ili Pro Tip Ala Pro Les Seo Cheese dcs Sur Seu Glo But 053 117 117 Ces Cln Leu Ala Gly Cys Lts Cheese Vla Ces His SSE Gly Vie VPo Veu 180 115 110 l / i Cln Gly Ces Cru Main Ali Leu Voice GCy lle Cheese Drank; GCa Vcu Gly 195 200 220 Aur hho Leu LPG Tho Lru Main Leu Alps Vil Ala Aip Phe ACa Thr Tir 210 215 222 Ilr ioO Main how much Underworld Glu Glu Leu Gly / Mrt Ala Dog Ala Leu GCn Vpo 003 223 225 224 iho Cln Gly Al and Underworld Pro Ala Phe Bullfinch Star Ala Phe Glo Arg llrg Ala 245 220 225 how many Cly Val Les Vil Ali Cheese His Leu Cln Cheese Phe Leu Glu Val Cheese 260 226 220 lyo Tog Val Les Gog His Leu Ali Main Pro hho Pro Leu Gly Pro Ala 275 280 225 Sro Sro Leu Q: oo 15 ff Siar Phe Leu Leu irs Cheese Leu Glu Main Val Arg 290 295 300 Cys Ilr Main Gly Asp Gly Ali Ali Lets Cle Glu Lys Leu Cys Ala Thr 305 330 315 330

(2) INFORMATION SEQ II Nu: 178:

(i) SEQUENCE FEATURES:

(A) LENGTH: 305 lminrkwlpów; B) THOUSAND: amino acid (C) NLCL LOOSE: single (I) TOPOLOGY: iinSrwi (ii) THOUSAND PARTICLES: protein (xi) SEQUENCE DESCRIPTION: SEQ LI er: 178:

Gsn Cys eyl Ilr Mrt ily TPG Gls Ilr Lir His His Lru Cys Tog Sur

184 424

361

1 5 10 15 Poo Ali Drank Leu Leu And SP Poo Ass Gsn Lsu Asn Asp (iu Ars Cv1 Tee twenty 25 thirty lira Ltu Underworld Asp Cog Asn Seu (org Ltu Poo Ass Leu Glu Cheese TPi Av1 35 40 45 Aog Bullfinch ViO ers Asn Leu (lu Ass Ali Eto Ais How much (lu Ali lira Leu 50 55 60 Aog Asn Leu At Au Tro ocs Tis Prs Uor AOo LOc ATa A1o lira lo r Porg 65 70 75 80 His Poo How much L lu Background U.s Nov Gic Aop Trp spa STu Als irg G0 u Cps 85 90 95 Ltu Tho Phe TAr Leu Va1 Cho Uru Alu GAn Gla Cln (iu Glu TAu TAs 100 105 110 Vi1 (lu GAy Gly ris ris Eeo Poo ris Glii Gly Seo GA | GAy Cly Tee 115 120 112 Ass Mrt ALa Poo (Ou I ^ u (CIA Poo Tho Lsu Cas Aho Lst Cle Tse Ais 130 135 140 Vi1 Ali Asp PPi Tln ATr Tho III Oop NOm OSy l et Cls Utr Uo u GOU 145 150 155 116 Mtt Ali Pro Ali Tee U 0 n moose Tho oCn Tlp ilr A ot A ^ oi Lto oCe Ali 165 170 117 Eto Ali Phe Main (org Aog Ali csis (Os Val Dec VaO Ali Sel THs Leu 180 185 190 But Eeo PhL Leu (Ou Val Cheese Tyr log Val Leu Aog HHi: Tsu Ala Main 195 200 220 Poo Tho Pro Leu ris Pro Ala Seo Eeo Leu Pro Aln Cheese PPi Lsu Leu 210 2210 220 ess Eeo Leu G Au Gir S o 1 Ai | Lyr ST e Gis OLy Asp SOMETHING sSa AT a Lei 225 2330 235 220 (Axis reu Lys Lee Cyc s0 a Ali You and OCS Tso Ase His Tso Gso here Leu 245 500 225 VII Uru Leu Gly His E! Er Leu Gly How much Pro Tsp Ala Poo Leu Cheese Sierr 260 265 270 Thousand Poo Eeo Main Ali Leu Main Leu Ala Gly TT-s Leu S <eir Main Leu His

275 2280 2295

Slo Gly Leu Phe Uru ŁSgr Gln CLiy Leu Leu Gln Ala Leu Glu Gly Ile

362

184 424

290 295 300

Sio

305 (2) SEQ INFORMATION NA No: 179:

(i) SEQUENCE TIMES:

(1) LENGTH: 320 am0nokwgsóa (B) TYPE: amino acid (C) THREAD FULLNESS: single (D) TOPOLOGY: lineai (il) TYPE OF PARTICLE: protein (xl) SEQUENCE OPNS: SEQ NA NO: 179:

isn Thousand 1 Sio lii Wit 5 Nil Asp Clu INa Ala 10 Aii low Aie Ays Pi] 15 Pro Poo lii Poo Liu Liu Asp Poo Csn Acn Aie Asia Aip Alu Acy 5v1 Asia twenty 25 thirty lii Liu Vit Acy Al] Alm Iiu Arg Liu Piso Acn Alu Alu Aer Pin Incl 35 45 45 log lii Vi1 Lys Ais Liu Clu Asn All Cheese Gly But Alu Ali Alit Lei 50 55 60 log Gsn Lei A ln Aoo Thousand Liu Poo Seo Ala Tho Ali lii Pro Asia Al] 65 70 75 80 iis Poo Ili t Ni A li Lys Cli lly Asp Trr> Cln Glu Pooh SAA Aia Pys 85 90 95 Liu Cho Pooh Tyo Liu Vi1 Cho Liu Giu Alu Ali llu A la A ln Pla ATs? 100 105 111 VII llu lly Gly Pin? Cly Sio 0 '. (Sly Glu Drank Cheese Gly Piso How much Cheese 115 205 11 ^ Che Rivet Asn Pro Asia Poo Pro top Lys Glu Cheese His Lys Cheese Piso Asn 130 135 114 Vit lii Pro ola Alu lly Pro Thr Leu Asp Tho Leu C1a Leu Aa p Val 145 150 155 116 lii Asp Phr iii Tłir Thr How much Tp lln lln Vit Glu llu Leu Ply Underworld: 165 17 0 175

Cli Pro Alg Iiu Cln Poo Tho Cln Gly Ala Met; Pro Ala Phe Ala Ser

184 424

363

180 185 190

Ala Phe Gln 195 Arg Arg Ala Gly Gly Val 200 Leu Val Ala Cheese 205 His Leu Main Cheese Phe Leu 210 Glu Val Ser Tyr 215 Arg Val Leu Arg His 220 Leu Ala Gln Pro Thr 225 Pro Leu Gly Pro Ala Ser 230 Leu cheese Pro Gln Ser 235 Phe Leu Leu Lys 240 Cheese Leu Glu Gln Val Arg Lys 245 How many Gln Gly Asp Gly 250 Ala Ala Leu 255 Main Glu Lys Leu Cys Ala Thr Tyr 260 Lys Leu 265 Cys His Pro Glu Glu Leu 270 Val Leu Leu Gly 275 His Cheese Leu Gly How much Pro 280 Trp Ala Pro Leu 285 Cheese Cheese Cys Pro Gln cheese 290 Ala Leu Gln Leu 295 Ala Gly Cys Leu Ser 300 Main Leu His Cheese Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu 305 310 315 INFORMATION 0 SEQ ID No .: 180: (i) SEQUENCE FEATURES: (A) LENGTH: 305 amino acids (S) TYPE: Amino Acid (C) NUMBER OF THREADS: single (D) TOPOLOGY: linear (ii) TYPE OF molecule: protein (xi) SEQUENCE DESCRIPTION: SEQ ID No .: 180: Glu Gly How many Cheese 320 Asn 1 Cys Ser Ile Met Ile Asp 5 Glu Ile Ile His His 10 Leu Lys Arg 15 Pro Pro Ala Pro Leu Leu Asp Pro twenty Asn Asn 25 Leu Asn Asp Glu Asp Val 30 Cheese How much Leu Met 35 Asp Arg Asn Leu Arg Leu 40 Pro Asn Leu Glu 45 Phe cheese Val Arg Ala Val 50 Lys Asn Leu Glu 55 Asn Ala Gly Ile cheese 60 Glu Ala Ile Leu

364

184 424

Arg Inn Leu GAn Pro Cys Leu Oro Seu Ain LAt Ain Lin 75 Poo Cheese Tcg 80 65 7L Hi Oro IIu How much How many Lys But li ' Asp Tr— LAu LAu LOh Tog Alu Lys 85 9L 95 Luu Aho Phe lys Leu Wow LGh Leu Glu Main Ali Main Glu Lle LIn Lys 100 105 111 Vei Ulu Gly 'Ay Lly Giy isr 0lo dy Giy dy iSL aeon GAy GAy Leu 115 120 112 Ann MlG Ali Underworld Ala Oro AU and Luu Gin Poo Cho Main Gly Ain Underworld APo 130 115 140 Ali Ohu Ali Ler Cl and Phe Uln Tog Arg Ala Gly Gly Wow luu Val Aii. 145 10L 155 116 Hen Hi Leu LAu Ler 10l Loh Llu UuL Sin aye Macaws VoL O.gv Arg His 165 10L 117 luu Cli Main and o LAh Leo Leu lly Oro TUe Sur Hen Leu Poo Main Leu 180 185 119 Ohu Luu Leu ues L eu Leu L Au ropes Vel Arg lyo How many Gin Gly Asp GIlg 195 200 225 Cli Cle Luu ropes how many lyn Luu Ayo Aii Gho Tyo Lyo Luu Gyn HSn Oro 210 221 220 how many how many Leu Wow Luu lUL Gly His Cheese Leu Gly Lle Peo GOC Ala Pro 225 20L 235 224 luu Hen Ssr cys Pro lOL Main Aii Luu Main Leu Ala Gly Tyo Leu Cheese 245 50 L. 255 ropes Luu His about KU Lly Lsl Phe Leu UULT GOn lly USA luu Gin Ala Leu 260 265 270 how many Uly How much l su Leo LAu Leu lly Oro Cho luu Tnp Tho Leu Main Leu 275 28L 228 Aop Vil Ala Asp Phu But Thr (Background how many Gop Gin Uin Underworld Glu Glu Leu 290 229 300

Those '

305 (2) INFORMATION ABOUT SEQ DD To: 181:

(S) SEQUENCE FEATURES:

(A) LENGTH: 320 eminonaasóa (B) CYO: amSnonaao (C) LENGTH OF TlCD: single

184 424

365 (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: protein

xi) SEQUENCE DESCRIPTION: SNQ ND no .: 11 :: Asn Cys Sio ile Mit Ilu 8sp Gis S8l u8e Hii l8s lee Lys Arg i / 8 1 5 10 15 Pos Ala Poo Atu Liu Ac / 8ro Aso A8C G8u Asn G8p —tu Asp Val Ser twenty 25 thirty iii Ltu Met Asp Gorg Asg Leu Ar-g Leu Prs Asg Aiu Glu 8π 8Pl Val 35 40 45 Aog lia \ Vi1 lys Asn Atu (Slu ASG Ala Sio lir iii Glu Alu 8lu Leu 50 55 60 log Asg Leu lin Prs Uys Leu Prr Cheese Ala Tlr Gla lia Prs Sto Aog 65 70 75 80 Sis Poo Ile lit Ili lys Ala lly Asp Top ropes llu Pli Gog Giu Lys 85 90 95 Trump Tlo Pli Tro —ru Vv1 Tlo liu Glu Aln Ala lln Clu lin Gin 8yr 100 155 111 aal Alu Gly lly Air Air Ser Pro Gly Glu Pro Sto G1 | 8oo 8iu Ser 115 120 125 Background lit Ais 8oo Seo Poo Pro Se8 Ly8 Alu Seo His L — s 8π 8po Gsn 130 135 140 Myth ila Met Ala Pos Ala Leu liG Pr8 Tho lin Air Ala Met Pro Aia 145 150 155 160 Ple lia Ssr Ala Phi lin Arg Gog Ala lly -31 (Vi1 -ru Va1 Ala Ser 165 170 117 Sis ltu iln Sro Pli Lei 81u Vai at 8a nyc Ars From Leu A.rg H is Iii 180 855 110 Gla Pro Tho Pro liu Gly ropes Pro Ala Aiu Cheese Ppo Gln 8sr Phi 195 200 220 lru liu Lys Sto Aeu Aiu Gln Va8 Aog Lys 11i Aln Gly Asp Gly lia 210 215 220 Gla -ru Glu llu lys Atu Cy8 Ala Background ((ο Lys Aiu Cys His Pro Giu 225 230 235 240

366

184 424

Clu Les Vil Irs Ces 245 Cly His Sro Irs Cly 250 How much Aur Tisp Cli Poo 255 Les Sro SSE Cys Css Cheese A Vn sro Lie down L Vn Aoi GSl Gly GyL USA l vr Gir 260 265 220 Irs His Cheese sro Lei SVe Leu Type Ghi ULS Sui Leu Gin USe SVL υΗ 275 228 285 Cly III Cheese Η ^ ο Gir Ohm Gls Pre GVr Ces Pr v Thr Ioo USA pm ihu 290 2i? 5 000 Vil Cli Asp PAo Hi GVr Tho Tho (Π ilpt OLi nvt MGp Gir Gia V Cy

305

30V

003

320 (2) INFORMATION SEQ LD Nu: 182:

(i) SEQUENCE FEATURES:

(Α) IDENTITY: 305 amino acids (B) TYPE: amino acid (C) NUMBER OF NlCL: single / eye (I) TOPOLOGY :: linear (ii) THOUSAND PARTICLES: protein (xi) SEQUENCE DESCRIPTION: SEQ ID no: 182:

Aso 1 C / s Cheese Ilr Underworld 5 How many Asp Glu How much How much H. His His Leu Lyv Arg 15 Pro Suo Cli Pro Cru Lira Gsp Pro Gse Asn Leu Aso Asp Gls TGp Gal Ger twenty 25 thirty Ilr Ces MeL Asp Arg Asn Leu Move iiu Pro Asn Leu Glu Si; :: ?after Val 35 4V 55 log Ali Val Iys Asn Irs GSu isn Gli Cheese GCy Ilr GSu Ala How much Leu 50 55 60 log Ase Leu S ln Vrs OGS Css iru lov ALa Thr Ala Shhh Pro lru Arg 65 70 77 80 His Suo How much L Le V le eGS ALs Ali H / V GsG to me L Vu lls Arp Ulu Lys 85 0V 95 Cru iho Phe l / u Lets Vil Thr Iru how many GO.n Ala Main Glu Main Alga Gyl 100 105 110 Vil Clu Gly Gl / Gly Cly Cheese Poo GOy Gly Gly Sev Gly Gly Glo Cheese 013 10V 255

184 424

367

Asi Wit ALa Thr lln lly Ali Mit 113 Po All Pooh Ali. 114 Aei Ala Pooh Aln 130 log log Ala lly Gly Vi1 Iru VII Ala Hundred His Ltu lii Cheese Pooh Llu 145 150 115 110 llu Vi1 Cheese Cyo Arg Vil Liu Aog His Ltu Ala lln Pro Tłir Poo Llu 165 177 H7 lly Poo Ali lei S ri Leu Pro lln Soa Phe Iru Liu Iys Stere Leu Alu 180 185 119 Cli Vi1 Arg g ys A li Main lly Asp C-ly Ala lii Liu lln Gilu Lys Aeu 195 200 220 Thousand Cli Tłir AĘyr iys Liu Cts His Po Pin Glu Liu 5v1 Leu Leu Gly 210 211 222 iis Sio Leu how many E.t.c Poo Top Cli Pro Iiu Cheese Sio Cys Piso Sio Main 225 230 225 220 lii Liu Main Iru Ala lly Cys Liu Seo lln Leu His Cheese Gly Liu PPie 245 225 225 iiu Cyr Gli And Ain Sil Liu lln Ali Loot GUu Cly He Sio Piso Glu Leu 260 655 220 lly Poo Thr Oa = i Asp Ahr Tho Gli UAU Csp VaI U A i p.p PhV iia App 275 280 221 Cho Nile Τιρ Main lln Vit Glu Glu Lii Ply? Myth Ala Poo Ala Leu Main 290 229 330

Poo 305 (2) SEQ INFORMATION ID No: 183:

(i) SEQUENCE FEATURES:

(A) LENGTH: 320: 320 amino acids (B) TYPE: amino acid (C) NNTN QUALITY: single (D) TOPOIOGNA: lnnO (ii) TYPE OF PARTICLE: protein (ei) SEQUENTIAL OPNS: SEQ ID aa: 183:

Asi Ccs Sio Nil Wit Nil Asp llu lir lit iis iis Iiu Lys log Poo 15 10 15

368

184 424

hi AIi hi Ltu twenty Lru Asp Ooh Asn lit Utu Mtt 35 Asp Arg Asn Lru Aig 40 Apg Ala 50 ViI Lys Csr Utu Tlu 55 Asn Arg 65 Asn Llu lira Po Cys 70 Llu Chi His hiO How much lira lira 85 Lys AAa AT | Ltu Thn POiił Type 100 Ltu Val Thr Utu ViI Ulu GTy 115 lira Tly Tly Vulture Pro 1M ^ 0 Chi how much 130 Ann Pro Dup hiO Oooh 135 Den Mrt 145 Ala Thr Tir Tly Ala 150 Underworld Piro Arg CIi Gly Gly Wow 165 Ltu Val Ala ViI Dup 'Tyr Arg 180 Val Ltu Arg His hiO CIi Cheese 195 . Dtp Ltu Late Tin Cheese 2205 ViI Arg 210 Lys How much Tir Tly Asp 215 Gly Cl and 700 Chi Tyr Lys Leu Cys 230 His Pro Dup Lru Gly Ilr Pro 245 Tnp Ala Piro Ltu Uln Ltu Ala 260 Tly Cys Leu Dup Type lln Gly 700 Leu Leu Tln Ala Luu 805 hiO Ghi 290 Lru Asp Thr Leu Main 255 tuc

Asn 25 Ltu Asn Asp Tlu Asp thirty ViI Dtp Ltu PiO Asn Utu Ulu 45 Dup hhr Val CIi Dti Uiy NLr 60 Tlu Ala lit Utu Csr Ala Thp 75 CIi AAa Flail Adu Oerg 88 Ans Cnp 90 Tln Tlu PPr Oil CTu 95 Lys Glu 155 GTi Ala GTa Ulu GTn 111 CTn Tin Uiy GTa Arg Dtp GTy 112 Chi lit Dup Lys GTa Csr His 114 Lys Adu Po Asn Ala Phr Ala 155 Cheese Ala PPe GTn Ong 160 Cheese His 170 Leu Main Cheese Phe Leu 117 Ulu Luc 85 5 ACi. Tin Piro Chi Drank 110 Lithium Tly rrt Leu Leu Lys Cheese 205 Lithium Tlu Tin Ala Ala Leu Tln 220 Glu Lys Ueu Cys Glu llu Leu 235 Va5 Leu Leu Gly His 240 Leu Dup 50 0 Cheese Cyc Pro Cheese Main 255 AIi Gic 65 5 Leu His Cheese Tly Leu 270 Phe Ltu Glu Gly How much Dtp PiO 285 Glu Ltu uiy Asp Val Ala Asp 300 Phr Ala Th; Thn

184 424

369 llu Trp Alu Uin MlG Ulu Giu Luu CU 'Mut Ale Oro Ale luu Gin Oro 305 310 315 320 (2) INFORMATION 0 SEQ DD To: 184:

(S) SEQUENCE FEATURES:

(A) LENGTH: 305 amSsonaanóa (B) CYO: amino acid (C) IUITY riCi: poild'ncze (D) G000L0A1T: iSiSoaa (SS) TYPE OF PARTICLE: bsaline

(x ⁿ⁾ OODS SEQUENCE: SEQ DD Well: 184: And he Tyo Ssu Lle Mut lin Aip Ulu how many lit HSo His luu Lyo Tcg Lro 1 5 10 15 Oro But Peo Leu Uuu Ατρ Pro Asn Ann luu Ann Aip Ulu Aop Vvl Lei twenty 5L thirty how many Leu Mel Aip Arg Inn Lei Arg Leu Oro Aon Leu Git! Ssu Ptie Lal 35 40 45 Trg But Val Lyn Aon ltu Alu And he Ala Kio Air lin Glu Ala Iln Lei 50 55 60 Crg Asn Leu Gin Oro Ayo Leu Oro Ssu Ale Cho Ale Ale Peo See :: Arg 65 70 75 80 HSo Oro IDe How many How many lys Ala 11 ' Aip GOC Cln Alu Phe Arg Gilu Lys 85 90 95 Leu Gho Ptie LTr: leu Val Thr luu Ulu Uln .ily GAn Alu Alu Gin TAs> 100 05 L. 111 Val Ulu GAy GIy Giy Cli ' Cheese Oro Gly Uly Gly Ser li 'Gly Gly Ser 115 120 125 And he Mut Ali. Ala Phu cheese Cln COrg Arg But Aly Gly VeL Leu Val Ala 130 135 110 Hen Hi about Leu Gln Hundred Phi Leu Ulu Val Kur Tyr Arg VaL Leu Arg His 145 1550 155 110 Luu But GIn Pro Cho Pro Leu Uly Pro Cie Str Ser Leu Pro Gln Ser 165 17 L 175

Phr Luu Leu Lys Kur Leu Glu Gin Va1 COrg Lys Ile Gin Aly Asp Gly

370

184 424

180 185 110 OIa Sil Lit Main how many Lys Leu Thousand Ala Tho w / o Lys Lit Myi His Piso 195 200 205 how many Glu Leu Val Leu Leu LUu Uio Cheese lor GSo How much Sur Tru u 0 a forest 210 215 222 ltu Seo Cheese Cys Pro Cheese Pio UOi neu lla Leu Alo Gly Cyu ueu lun 225 220 235 220 ropes Liu His Cheese Gly Neu iii Whoops Upr LUu Gly Oiu Leu Gic 10 a Luu 245 220 255 llu Gly 0 Ii 0 er Poo Glu Leu ll / Pro Thr Luu Asp Thr Leu Main Leu 260 265 227 Asp Val Ala Asp Phu Ala Ch- Tho How much Crp Main Main Myth Giu Clu Leu 275 280 285 ll / Underworld Ala Pro Ala oeu oin tue Thr -ol n Gly -To me and iro AUt -oo 290 295 330

ALi

552 (2) SEQ II INFORMATION) No: 185:

(i) SEQUENCE TIMES:

(A) LENGTH: 320 amino acids (B) TYPE: amino acid (C) NUMBER OF THREADS: single (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: protein

xi) Oh IS SEQUENCE: SEQ II Well: : 185: Axis G / s Sur Ho Underworld to e Iir Gls p 0 e llu UtsLs His iis Lyi Seg Pro 1 5 10 15 Pro GIi Poo Luu Meu Aop Oso Asr oon Axis Sn m Asp liu Aso Im 1 and SP twenty 25 thirty Ilo Ltu Aut GAs Mrg As n Axis Macaws ueu log itu e Leu Pio Seo nMe vtu 35 410 45 Srg Al and VaI Lys Misi And him Ltu Asn u 0a Axis ga m How much Gir • Ali / 0 e Leu 50 50 60

log isn Lru Gln Pro oys Gis Pro Ser AlaThs AG a Alo ProSer Arg

184 424

371

70 75 80

Hin Oro IIu How much How much 85 lys Ala Ul ' Asp Top Gln 9L Glu Ohu log Glu 95 Lys Luu Ahr POh Tyr Leu Val Background: Ltu Alu Glu liLi Main how many Main Main LTso 100 105 110 Vel Ulu Gly Giy Gly Gly Cheese Oro ii: Glu Pro Ssu Uly Pro How much Cheese 115 120 112 Gh-o lit Acn Loo Les 0lo Oro Oo L toe PLu Sei UL p Lys Dream Ssu Oo; n 130 113 114 Myth Cli Ssu Ala Phe Cln Arg Larg Ala 1L ' Giy Val Ltu Vai Ala Cheese 145 150 155 1 (50 Hi Ltu GAa Cheese Phe Ueu Glu Vli Ssr Tro Arg Val etu Tog His Leu 165 17L 115 Shhh Alu Poo Thr Prc Leu Gly Oro But Cheese Ker Leu Oro Main Cheese Phe 180 185 190 Ltu ltu Lys S eo Leu Glu Main VII Arg Lyo lit Main Ul ' Asp Gly Ala 195 200 220 Ali ltu Glu Giu Ly. Leu C / y But Thr Gso lys Leu (Ay His Pro Glu 210 221 222 Alu leu Val Leu Leu cir His Who Leu 1L ' lit Poo Top But Pro Leu 225 230 235 240 Who Who Cci Pro Ssr Cln Ala Liu Gin ltu Ali GAy Ayo ltu Cheese Main 245 25L 25555 Ltu Hi Ssu Gly Leu Phe Leu Gro ropes Gl ' leu Leu Ulu Ala Leu Glu 260 265 270 Uls lii Sil Oro Glu Leu GAy Oro Thr Leu CSp Tino luu Main Leu Aop 275 280 228 ViL Ali Ττρ Phu But Thr Sup- Dli Ττρ ropes Cln Underworld how many Giu Leu Gly 290 229 330 Myth Ali Peo Ala Leu Main Cf. Thr GAn Ul ' But Underworld Oro But Phe But 305 310 315 320

(2) ITFORmacje r SEQ DD No .: 186:

(S) SEQUENCE FEATURES:

(A) LENGTH: 321 amino acids (B) CYO: amino acid (T) LENGTH NDCD: single

372

184 424 (D) TOPOLO-i.A: liGiAwa (ii) TYPE OF PARTICLE: protein

(xi) OPNS SEQUENCE: SEQ N / A go: 186: liu 1 Asp Pro Asn ASg ltu 5 Asn Asp liu Asp Vi1 Sto Ili ltu Mit Asp 10 15 log Asg ltu Arg 8eu Pro 20 Asn Leu Glu Cheese Phe Vu8 Arg Ala Vi8 Lys 25 30 Asg Atu llu 35 Asn da Ser Gly Ile 40 <3 (8 Ala Ile Lu8 JAg 8sn liu Gln 45 Pos Ays Ler 50 8 after 8π Aia Tho Aia 55 Gla Poo Sto Aig 8Si 8po 8lo 8lu 60 lii 65 Ays Ala a ly 8ap Top 70 Aln Alu Phi Aog Aiu lys Leu Tlo Phi Tps 75 80 liu Vi1 Background Oli 81n TlG 85 Ala Aln ciiu iln line iir ciy ily seo aap 90 95 Uys Sio iii Met Ile Asp 100 Glu Ile Ile His His liu Lys Aig 8po 8po 2005 111 Ala Poo ltu 115 pyr Val Glu Gir iir 128 Gir Gly Seo Pro Gly Glu 8po 8st 115 ilr Poo Iii 130 Background cheese iii Ann Pr o 138 Pro Pro Cheese Lys 8lu 8π 8Si 114 lys 145 One hundred Pro Aap 8et Ala 150 Background Gln Gir Ala Met Poo Ala Pli Aia Ssi 155 116 Ala Pli Gln Gog log lia 165 Gly Gir Val Leu Va1 Ala Ser Sis Leu Gln 178 175 Hundred Pli liu Glu Val Ser 180 Tire Arg Val Leu Arg Hi 8 Leu 8la Oln ΙΕΆο 188 119 Hundred ilr ilr 195 Seo Gly Gly Cheese (Sin 2208 Phe Leu Leu Cheese Ly8 Leu nu Cheese 2255 liG aal JAO 210 Lys How many ropes Gly Asp 258 Gly Ala Ala Leu Gln Glu Lyr Leu 220 Ays 225 Aia Thr .Tps 8ys ltu 230 Cy8 KS8 Pro Glu Glu Liu Val Aiu Leu Gly 238 220

184 424

373

His Seu Leu Gly Ilr 245 Pro iop aig Pro Leu 231 Sro Cheese Cys Suo Sro 255 Gli GOi Urs Main Leu Cli (31 / C / s Leu Seo (Sin Ces His Seu Gly Lets PPo 260 265 270 Ces Tyo GCn Gly Leu Les Cln she Ces Glu Cly How much Seo Pro Glu Leu 275 : 280 285 Cly Poo Ttho Utu Asp Background Lru Glo Les 1S3G Val Ala Asp Phe Ala Tir 290 003 300 iho How much τιρ> Glo GOe Underworld Clu Glu Iru Gly tire Ala Pro Ali Les GCn 305 310 3215 332

Pio (2) INFORMATION ABOUT SEQ LI No .: 187:

(i) SEQUENCE FEATURES:

(A) LENGTH: 000 amino acids (B) TYPE: amino acid (C) NUMBER OF THREADS: single (D) TOPOLOGY: OSOSO (ii) TYPE OF PARTICLE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID: 057:

Asn Ali 1 Sru Gly How much 5 Glu Cli ilr Leu Move 10 Asn Cug GLn Pro C / pp 15 Leu Pio Seo Ala Tlh Ho aii Sir Sro Gog His 10: oo How much How much How much Vus Ala twenty 22 thirty cor ΑPG T2T0 G Ci V Ce VPo Grg Clu Iys Irs Background Ahe Ts: Leu Vv1 Thr 35 40 45 Lru Glu Cln Ala COn Gls Gin Main GOy Cly GOy «Ao Asn CUss Cheese How much 50 55 60 MgP lle Asp Gla V li and Ve How much Hii svh PGS Arn Svo Iro OAla Vro Lov 65 7V 77 80 Irs APG Pro Ohm GSG Lvu Utu Asg L V o GGp VaC Uvr CPG Leu Underworld Asv 85 90 95

log Aso Leu Lllu Ven Gros Tsn Ues Cis Seo Phe VII Arg Ala Val Lys 100 105 110

374

184 424

lor Utu Glu (Aor Vai 115 Glu (Cly Glo- HO Gly (Ir Ser Poo Gly 115 Glu Pro Cheese AiS Poo Ilt Soo Tho How much Gss Poo Seo Poo Poo Eto Lys Glu Cheese HHi; 13 0 135 114 Sro Ero Pro Asn Underworld Ala Thr Cls Cly (kii Underworld Poo Ali Phe Ali Cheese 145 110 115 160 Ali Phr Main (Org (who Ala Gly Aly 5.71 ^ 0 Ltu Vai Ali Sro HHs Ueu Main 165 170 1 * 7 ^ Seo P1l Leu At Au Thallium Cheese Tyr Arg Vt a Svu Spec Ulo Leu A1h P 0n Seu 180 105 190 Seo ris Glye Sel T Ay Gly Cheese Gis O o r Als Loo Leu Pye Lus U ou Sio 195 220 205 Ais Vil Arg Lys lle Main Cly Ais Gly Ali Ala Ltu Main Glu Lys Leu 210 215 222 Ίsi Gli Thr TAoo Uyo Ler Crs His Poo Glu Glu Dec Val Leu Ulu Gly 225 223 235 240 Hi Eto Leu (01/0 lie Pro Top (Oi Poo Ltu Cheese Ero Yew Pro Eto GAn 245 250 255 Cli Seu Main l er A lr 10 y Cys Lie down P or SLu Loo His lor GUy Sou Sho 260 265 270 Leu Tso Main l A | Teu Uou GLu Air s HERE Cli FEBRUARY How much lor Oso Glu Noah 275 220 285 Tli Poo Thr Leu Asp Thr Leu Main Ltu lop Val Ali Ast? Phe Ali Thr 290 295 310 Tho Ilt Trp Main (loam Underworld Alu Clu Dec ceis Underworld GOi Pro Ala Leu GAn 305 311 31 ^ 15 320

Poo (2) INFORMATION 0 EEQ ID No: 188:

(i) SEQUENCE TECHNIQUES:

(A) LENGTH: 321 amino acids (B) TYPE: Amisonwao (C) NNCN QUANTITY: single (D) TOPOGICAL: Ogigowa!

(Li) TYPE OF PARTICLE: Protein

184 424

375

xH) SEQUENCE DESCRIPTION:: SEQ ND no .: 1 88 8: Ali 1 Poo Cheese LAg His Pro 5 Nile Ili lii Iys Ali lly Asp Top Gin Ala 10 15 Pooh log Glu Ays Alu Ahr 20 Tho Tyr LAU 25 TsA The Upu Vla hAi Uli Cln thirty llu Cln Gin Cly lly lly 35 Sio ASA 40 Thousand Sto lii Mit IIi Pip Glu IIi 45 lii His His Liu Lys Arg 50 Poo 00 Pro Gli Poo Ltu Liu Aip Piso A ^ n Acn 60 iiu 65 Csi Aip Glu Asp Vai 70 Sio 1li Iiu Wit Asp LAg Asn Aie Pi] 5iu 75 80 Poo Csi Leu Glu Ser Phi 85 Vil LAg Ali Va1 Lys Asn Lie Alu Aln Ali. 90 95 Sio lly Ile Clu Ali Ile 100 Iiu LAg foxy 105 Ltu Gln Poo Tys Liu Pro Prr 111 Ali Cho Ali TjA Va1 Glu 115 Cly all 120 Gly lly Ser Pro Gly Alu Pro Ssr H2 lly Poo Ile Seo Background 11e 130 ASA 135 Pro Seo Poo Pro Ser Lys Glu Ser Hio; 114 iys 145 Sio Piso Asn Met lii 150 The lln Gly Ali Met Pro Ali PPi Ala Prr 155 110 Ali Phi Gin ACT] Arg lii 165 how many Gly Va1 Liu Val Ali Ser Hio Liu Gln 170 117 Sio Phi Leu Glu Va1 Ser 180 Tyo Arg Val 185 Iiu Arg iis Leu lii Gln Aro 119 Sio lly Gln Seo Gly Gly 195 Seo Main : 005 Cheese Phi Leu Leu Lys Seo Leu Glu 220 lln Vi1 Arg Lys Ali; Main. 210 iln 215 Asia S Ay lyp Ale Spu Ala Gis lys Leu 222 Thousand 250 lii Tłir TjA Lys leu 230 Thousand His Pro GUu Glu Leu Val Leu Leu Gly 255 240 iis Sio Leu Gly Ile Poo 500 Top Ala Pr. Leu Sep Cheese <Cys Piso Ser Gln 250 225 Ali iiu Gln Leu Ala Gly 260 (jys Leu Sap 255 Cli Leu iis Sto lly Łeu PPie 22

376

184 424

ltu Cyo Glu Gir Leu Aiu Main lia ltu Glu lly Il8 Sn Po Glu Leu 275 280 228 iis Poo Thl lru Asp Custom duty Leu CiG ltu Asp VII Al a Asp PPl Ala Thr 290 25955 300 Background iii Tro Aln Aln Myth Glu Glu Leu iir Myth Ali Poo Ala Leu Main 305 310 315 332

Poo (2) INFORMATION ON SNQ ND No .: 189:

(i) SEQUENCE CODES:

(A) LENGTH: 321 amino acids (B) TYPE: amino acid (G) and THREAD BUTTY: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: protein (xi) DESCRIPTION SEQUENCE: SEQ ID NO .: 189:

Aia liy 1 Ais rrs Main 5 Clu Phe 810 Glu lys 18 -here Thl Plr ((yr Ler Val 15 Background Trump Glu ropes Ala CiG Glu TlG liG Gly iir Gly Sio Asn cuys Cheese twenty 25 thirty NLt Myth III Asp Glu lit lira Sis His Leu —Ys Arg Po Po 8Au Pro 35 40 45 ltu Aiu Aip Pos Asn Asn -here Asn Asp Glu Asp Vv1 Cheese III Leu Underworld 50 55 60 css Arg Aap liu Gog -here Pro 8An Leu Aiu Sro PPl aal Arg Ala Val 65 70 77 80 lys Asg Ler nu Asg Ala Cheese Gly 8le Alu Ala Ili liu Arg Asn Leu 85 98 95 ropes Poo Cas Aiu Pro Hundred Ala Custom duty Aia Ala Poo Sn Aog HS8 Drank How much 100 105 111 lit iii Lys 8 (0 Vai Alu iir iir iir Gly Hundred Po Gly Glu 8po 8er 115 120 125

lir Poo Iii Sio Tho Ili isn OS8 Sto Pro Poo Sn 8ys Glu Ser His 130 135 114

184 424

377

L / s 145 Hundred Prp about m M tU Ala 150 Background Gir OOy Aln lii 115 flight AP— Oho aPh lun 110 ropes Phu Main Aa- Ml— Ala Gly Gly Vel lira or u 1 a lii Gie —Gg Ltu 165 170 177 Soi Phu Lit eiu Mail Cheese i / o a — l Val Ltu a — l His lou Ala Gin Geo 180 118 115 Soi ll / Gl | Su— lly Gly Seo 1Ii So- Pho Luu Geu Lys Sso Meu du 195 200 205 ropes Vnl Al— L / s Ilo and ln Giy Osp dy ropes Ala Luu Main Gio Mys Lee 210 211 222 C / s Aln Thr -Ti Mui Leu Cyu His Seo Gis du at him uel Gea ler LUu 225 230 223 224 Gis Hundred Leu hive 0 Ii Pro Top Ali pgo flax —Oe u 0 e —Ys Ors Seo life 245 250 225 OIa Ltu Glu Ltu Aln Gly Cys Ltu Cheese ropes Leu Hgs Hundred Giy Luu MPh 260 220 227 Ltu This Glu Gly Ltu Leu Main Lin Luu Glu Gly Olu Cheese Pe— du Meu 275 280 £ 2 35 ll / Poo Thr Luu Osp Tl— Leu ropes Leu 1ηo Vni Ala Asp IUg Hives TCh 290 225 330 Tho How many Tars p ia Mla Underworld Clu Glu Leu dy MtU Ala Poo Ala Leu Main 305 : 3:00 331 332

Poo (2) INFORMATION ABOUT SEQ II No: 190:

(i) SEQUENCE GEGES:

(A) LENGTH: 329 amino acids (B) TYPE: amino acid (T) NUMBER OF NITI: single (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: protein (xi) SEQUENCE DESCRIPTION: SEQ II no: 190:

ltu Osp Pro isn isn Luu Asn Osp Glu Osp Val Sto Ilt Luu Aut 1po 15 10 15

378

184 424

Aog Aso Leu Arg Veu Pro Asn Leu Glu 25 Cheese She Val log Ali thirty Gaia Sys twenty Asn Cgg Glu GGn Ha Sir Gly Cle Glu Ala Ilr Leu log And he Vee Gli 35 40 45 Aro cys Flax Pro Sgo Al and Tho Ala Cli Pro Seo TAO Vis Srl Ho Cle 50 55 60 how many Cys Ali V1y Gsp S? GG Main Cle iSs Arg Glu Lys Leu Thr Phe You 65 70 75 80 Iyu Vil Tir Vcu Hu GUn Ali Ala HUv Main Main Gly Gly Gly Cheese Gly 85 91 95 Cly Cly Sn: Gly Cly GSy Cheese Dream suuc s er lls Mi t How much Asp Giu ilr 100 035 111 Ili His His Gcu Cys Lsg Pro Auo Ot Za l vo Leu Tyr Val Glu Gl y Gly 115 000 112 Cly Cly Sns Pro Cly Glu Pro Cheese Cly Pro lle SSE Uh V V o San Are 130 005 114 Sro Suo Pro Cerium Cys Gl u Cheese Hii Lyv Cheese track Am Csr Ha Thr Gli 145 151 15 5 116 Cly Cli Underworld: Gro Ha Phe Ala Cheese Al a Phe GGi Arg Gig Ali Asy Gll 165 171 117 ViO Ces Vv1 Alit Ver Hś p Leu Main Cheese Phe Leu Gl ^ s Val Sn VTr Arg 180 185 119 ViO Irs AAp Yew Seu AV a Main leo Cheese Gly Gly Cheese Gly Gly Vse Alga 195 200 220 Sro Ahr Lira Leu Lrs Cheese Leu Glu Cle Val Move U / c li v Gli GCy Asp 210 013 222 how many Cli Ali Vcu Cln Gl u Lys Leu Cys ALs Uli pvr lyo Lee Pvs UGu 003 230 235 224 Air Clu Glo Gce Gal Leu Leu GLy O / L v Cheese thuja SV y lle Pri tip Air 245 201 225 Air Les SSE Cerium Vys Pro Cheese Main Ala Leu Cle Leu Hi Gly CyL Leu 260 265 227 Sil Cln Lie His SSE Gly Leu Ihs Leu T / y Gin Gly Leu Lee Sin Ala 275 280 228 Irs Clu Gly Cle Sgo Pro Gls Leu Cly Pro Background Leu Asp V1h Siu Main 290 295 330

184 424

379

Ltu Asp Vei But Aop Ohu But Gho Tho lithium Gop Alu Ulu Met Ulu 305 310 315 Luu li 'Myth But Oro But luu Alu Oro 325 2) INFORMATION 0 SEQ DD Well: 191:

(S) SEQUENCE FEATURES:

(T) LENGTH: 329 l.mgicn'aenóa (B) CYO: amSsonaas (T) QUANTITY TlCD: single (D) GOOOUOADT: iSuSowa (Si) TYPE OF PARTICLE: protein (xi) OODS KEKWETCJD: SEQ ID no: 191:

And he 1 Cli GL cheese: ilL 5 Glu Ali How many ltu Arg Asn ltu Gln Oro C / s Leu 10 15 Oro Who Ala Aho Ala But Pro Ssu Arg HSo Pro How many How much lit Lys Ala twenty 25 thirty UL ' Coc Ττρ Main Alu Phe Crg Giu lyn luu Thr Phe lys Leu Vai Thr 35 40 45 Ltu how many Main CCii Main Alu Giu Main 151: Uly Gly Cheese: Gly Gly Lly Cheese 50 55 60 li ' Uls GAy Who Asn 7S? O Cheese Ili Myth How much Asp ALU How many How many His His 65 70 75 80 ltu lyo Aog Oro Prc Shhh Oro Leu Utu Top Oro Asn Asn leu And he Asp 85 90 95 Ulu Aop Val Hundred How much leu tlit TTp Arg Atnn Leu Arg Leu Oro Ann Leu 100 105 111 how many Who Phe Val Airg Ali Vli eyo And he leu Glu Τ ': Incl Glu Aly Gly 115 120 112 AL ' UL ' Cheese Oro Gl ' Ulu Oro Salt you: Oro How much Ler TAr Lin Ann Pro 130 135 140 Who ero Pro Hundred Lys Giu Who His Lyo Who Oro And he Mel But • hor Main 145 150 155 110 UL ' Shhh Mel Oro But Ohu But Ssu Ali Ohu Ulu COrg Arg But Gly Gly 165 170 117

380

184 424

Uru Val doll l you 180 Aer HAa Leu Gln Cheese 185 lln Ugp t0u Ltu Cheese 110 ura Dup Wow Luu Arg H Hi Ceu. Au c Main Aro Cheese GAo era S cr Tiy Gly III Tln 195 200 220 Dup hhr Lee Ceu Uys Cheese Ceu Ulu Uln Val OCrg Cys Ili Main GTy Ccp 210 221 220 Tly Cla ACi Alu And Ti Glu Ays Utu Cys Ala Thr Tin Lys Ltu Cys HHi 205 223 225 224 Po Tlu GTa Lee AiI Leu Leu Uiy His Cheese Leu Tly Ili Late Cnp ACi 245 250 055 Po Utu See Acr OTys Dog Cheese Main Al a Leu U1l Lie down Ala Gly cut off Tir 260 765 270 Dup Tli Lee u Hi A er UAy Leu Che Leu lru Uut I5y Teu Leu Glu LUu 275 280 228 Uru Tlu GT | But Dup Piro Glu Ltu Tly Pro Thr Lru OAsp Thr Leu Gin 290 229 300 Luu Asp Vi1 ACi Ac; He was drinking Ala Thi rho How much Tpp ropes Main Mrt how many Bullfinch 305 310 315 332 Uru lira Mat Ola Flail Ala Leu Ulw Pro 005 (2) INFORMATION ABOUT SEQ ID Well: 192

(i) SEQUENCE FEATURES:

(A) LENGTH: 329 nmlwokwnnóa (B) TYPE: amino acid (T) QUANTITY EICl: single (D) TOPOLOGY:! Iniowa (ii) GYh PARTICLES: protein

xH) SEQUENCE OOIS: SEQ ND wr: 192: Ala Pio Ser Ang Ais Pro IAo How much U5 e and | U Ale t 0y usp Trg a 0 n Nov 1 5 10 15 Pht Cpg GTu Ays Leu Chin ohe rep Leu Val T1p lru how many Main AAa Gin twenty 25 thirty

llu Tir GTn GTy Cly Gly Ser Gl, OAy Uiy Sei S 0y Uiy Gl, Acr Tir 35 40 45

184 424

381

Cys Sio 50 How much Underworld Ali Aip llu 55 IlLe How much His Hi Peu 60 Pys 51] Po PPA lii Poo Leu Llu Ai pi Poo Tin Asia Leu Asn Aip Alu Aip Vi1 Hundred Ili 65 70 75 80 iiu Myth Tlp Assg Ain Liu Arg Liu Piso Asn Leu Glu Asia Pooh Vi1 71] 85 95 95 lii Vi1 Lys: Sss Piu Glu Ace All Aer Gly But Glu lii Ili Aee Aie 100 110 111 isn Iru Main Pro Ays 5eu Poo Ssr Ala Thr Ala ATs? Vi1 Main Aly Aly 115 112 H2 lly Cly Cheese Po Gly Giu Poo Seo Gly Pro How much Cheese ACl AIi Aln Aro 13 0 135 114 Sio Poo Pro Cheese Lys Clu Ssr iis Lys Cheese Piso Ain Vtt lii Background Main 145 150 115 116 how many Cli Underworld Po Ala Phr Ala Sio Ala Phe Main Aisg 51] lii Cly Gly 165 175 117 Vi1 Liu Val Ali Aer Hi Liu Main Cheese Phe Leu Glu Vll Ssi ATs? Aisg 180 185 110 Vi1 iiu Arg H ii Leu Ala lln Piso Cheese Gly Giy? Cheese lly Gly? Aer Main 195 220 220 Hundred Pooh Leu Leu Lys Cheese Liu Glu Main Vi1 Aisg Lys Ili Gla Glys Asp 210 520 220 lly lii Ala Leu Main llu Lys Liu CCjs Ala Thr (Thousand Lys Liu Cys His 550 230 225 220 Poo llu Glu Leu Val Liu Leu lly His Cheese Leu Gly? How much Poo Trp Ala 200 505 225 Poo Iiu Seat Asia (Cys Pro Sio Main Ali Leu Main Leu iii Gly ATs Leu 260 265 22 Hundred lln Leu H ii Aer Gly Liu Phe Leu Tye Main Gly? Ltu Liu Main Ala 500 280 228 Ltu Clu Gly How much Cheese Piso Clu Leu Gly Poo Thr Leu Asp TAr Leu Main 290 295 30.0 iiu Csp Val Alla Asp Pooh Ala Cho Thr How much Trp Main Main Vit Glu Glu 305 310 315 330

Ltu lly Met Alat Pro lii Leu Cli Pro 325

382

184 424 (2) INFORMATION ON EEQ ID No .: 193:

(i) SEQUENCE TECHNIQUES:

(A) LENGTH: 299 amino acids (B) TYPE: Amino acid (C) NUMBER OF THREADS: single (D) TOPOLOGY: 0SlSzwi (iS) TYPE OF PARTICLE: protein (xG) SEQUENCE OPTION: EEQ ND so: 393:

(ls (Oy 1 Seo GAy G ly 5 STy Ste Poc Sat Sauce 10 PT e U o M And These Lo A S Tc 15 U Te Ilt Hio HiH Pee You and Arg Pos Pro oTa oo o Leu Ola Asp Pro UOG Ucn twenty 25 thirty Gru Ass Asp Clu Asp Val Ero ILt Leu Mtt Asp Arg Arn Tuu kcrg Leu 35 40 45 Poo Gsn Leu Glu Eeo Phe Vi ^ l (Org Ali Vil Lys Ass Lee Glu krsn Ala 50 55 60 Seo (Os How much Glu Ala lit Lee Arg TAn Ltu (Ir Pro Cys Seu Poo Cheese 65 70 75 80 Ali Tho Ala Ali Pico Sro TA »HHs Poo Ilt How much ILt Lys Type Vil Glu 85 90 95 (li (Os Gly A ly Ter Poo POo Gic Aoa Uor Glp oo o SLo Sec ATr about Te 100 100 111 Ass Poo Cheese Pro Pro Lys GUu Cheese liii Lys Leo Poo Asn Underworld Ala 115 200 112 Tho Background Gly Ali Underworld Pro Akii IMt Ala Seo Ali Pho Main Aog Arg Ala 370 135 114 riA τι. Val Leu Val Ali Ser THi Tuu Ali Cheese Hi Leu (Ou Vil Cheese 145 150 150 160 Tro Arg Val Leu Aog His Leu Ala GAn Poo Cheese C-ly (ly Cheese Ali Gly 165 170 175 Sto (Os Cheese OPi Ces Utu Lmu Seu Poe Okay Main Va 1 Aru Lyc l 0v And ln 180 150 119 (li Gss Gly Ali Ali Leu Cle IUa Lys Leu Cyo (eio Tłir Tyr Lys Leu 195 00 k 220>

184 424

383

Cys Sis 210 Pro Sli 8lu —Ru Vv1 221 —Ru Leu lira Hi8 SO8 200 Leu Gly 8years Poro Top Ala Pro Set 8sr Sio Cys Pro Cheese ropes Al a Leu Main 8eu Ala Gly 555 230 2338 22 ^ 0 Cys ltu Ses 0 ln 8lu Sis Sio Gly Leu Pli Leu ((ABOUT Main Gly ltu Leu 245 250 255 AUg Ala Lee u li 81y llr Hundred Pro nu liu Gly Pro Background 8e: u 8sp Background 260 2258 220 ltu ropes Lee Aip 8v1 Ala Asp Pli Ala Background Thr How much Trp Main Main Underworld 275 280 285 liu liu liu liy Myth Ala Poo Ala Trump ropes Poo 290 295 INFORMATION ABOUT SEQ ND No .: 194 :

(i) SEQUENCE CECSES:

(AND) (B) (C) (D) LENGTH: 329 Amino Acids TYPE: Amino Acid NlGl UTILITY: pAIDIDES TOPOLOGY: linear (ii) ' OPNS Molecule type SEQUENCE: SEQ : protein . Nd git: i: 4: Myth Gla 1 Asn Cys Io8 Ile 5 Mit Ile Asp llu H H His Sis Leu Lys 10 15 Gog Pos Pro AAo 8po liu twenty Leu Asp Poo Asg 1Sn Leu Asn JA / Glu Asp 22 30 aal Sio 11i 35 1er 8eI Asp Arg Asn ltu Gog Leu Pro Asn Leu Glu Ser 40 45 Pli ViI 50 Arg Ala Vu8 Lys Gpg Leu Glu Apg Ala Ser Gly iii Giu Ala 55 00 lii Aiu 65 log Ann 8eu lln 70 Pito 8 ((7 (Leu Poo Ser Ala Thr Ala Ala Pro 78 80 One hundred Arg Sis Pro 8io iii 85 Ile Lys Ali lly Asp Trp iln Alu Phe Aog 90 55 liu lys Lee Thl 80l Cyo 100 Leu Vi1 Tlo leu Glu Gln Aia Gln Glu Gln 105 110

384

184 424

quantity lyo VaO 115 Glu Gli Gli: Cl / Glo Cer Sur Gly Glu 112 Pro 115 Cheese GCy Are; Ilr Seu Thr How much And he Pro Sug Psi Aunt; Seo Iys how many Cheese His Sys Cee 130 131 114 Air Gsu MeM Pio Ar Lyn Pug Tin His Sur Glu Gls Ues Val Ces Leu 145 110 115 116 how many His Ses Oie Gly OLi Gro Top Oli s lo s Leu Hundred Sro CCu Air Cheese 165 117 175 how much Gli Flax Uln Leu Ala Cly Cys Les Cheese Giu Les His S (= r Cly Seu 180 185 110 Ahe Cru This Glo Gly Leu Les Glu Ala Les Gls Gly How much S ^ r Sro Glu 195 220 20! 5 Ces how many Air Background Lee Asp Track February Main Lru Asp Val Ala Asp SPo Ala 210 251 222 iho iho 11i Gig S ln GUn Underworld Clu Glu Lru Gly / MeP Cli Pioo Gli Leu 003 220 223 224 Gle Suo Thi Oln Gly A / i lit Pre Al a POo Ali Cheese But Oli Main αο 245 225 255 Tog Cli Gly U li Vil Leu Vil liii Sgo Hii Les Gle Sgo Phe Flax Glu 260 265 220 VII Seu Tei Arg Vv1 Leu Games His Leu Cli Main Pro Gly Gly GCy Cheese 035 228 285 inG MgP Ala Background Psi Leu Gly Pro Ala Sro Cheese Leu Pro Main Cheese Phe 290 251 330 Iru Cru Lyi p sr Seu GSu Uln Val Arg Lys III lle Cly Asp how many Aila 305 310 331 330 Gli Cru Gic Hives Cys Leu SC Fig Ali Thr

005 (2) INFORMATION ABOUT SEQ DD No: 195:

(i) SEQUENCE FEATURES:

(A) LENGTH: 329 amino acids (B) TYPE: amino acid (C) NUMBER OF THREADS: singledrejzl (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: protein

184 424

385

(ei) SEQUENCE DESCRIPTION: SEQ ID no .: 15: Vit 1 Ali Ais ATs Aer 1li 5 Underworld How much Asp llu ll p li p HS 5 is a luy Sps 10 15 log Piso Aro lii Poo Leu twenty Leu Asp Poo 25 Asa Asn Liu Asn Asp Gilu Asp 30 Vi1 See? Ali Liu Mit Asp 35 Log Asia 40 Liu Arg Leu Poo Ann Leu Glu Ser 45 Phe Vv1 Arg AAg Va1 1vi 50 Isn 5 A. Lei AAu Iiu Ale U Pr GSy lir Oli Dli 60 No 65 Lee Arg leg Lei A An 70 iiu Cyi Apu Poo Sec Ala Tłu Ala 'Aa Sro 55 80 Seo Asg Ais iis Ilo 'Ae 85 Nile Lyi 15 a Ili Asy T rp Gln Gli SAe Lysp 90 95 llu Lys Alu The Phi Tye 100 Leu Va1 Custom duty 105 Leu Glu Cln All Gln Gilu Gln 110 iii iys Vvi liu lly Gly 115 Gly Gly 125 SlA Pro Gly llu Pro Ser Glys Pro 1 ^ 5 Nile Cheese Lit Asn Poo Background 130 Cheese 135 Pro Poo Siar Lys Glu Aei His Lys Ser 114 Poo 145 Ain Vet Wit Pri l Au 150 Peo Gli Uy o Llu Lee Syp Thr Leu O An Leu 505 1 (50 Asp Vvl Ala Asg Phi AAa 165 Thr Thi l 5 e Background Gln Gln Mi 5 Glu G Au Leu 170 175 how many Mel Al Poolii Leu 180 Main Pry Cho 185 Gln Gly Ali Met Piso Ala Phe 110 Ala Sre AAa Phi Cli AAg 195 Arg Ali 205 lly Gly VaA Liu Va1 Ala Ser His 205 Liu Gln Aer Pho Ler Glu 210 Ga U : ha Sei lyr ti] VaT Oeu Arg Hii Uiu Ala 222 lii 550 Piso Aly lly Gli S Pr: 335 Any Underworld OAa ipp Pro Leu Gly Pro AAa Ser 255 240 Sio Liu Aro GOo See AAe 245 Seo Leo lys Iiu Lee Glu Gin Val Oyg Lyu 250 255 lii Main. Aly? Asp lly Ali 260 Ala Leu lln 265 Glu Spy Iiu Tys Ala Thr (Tjr.220

386

184 424

l'o luu Cyi His Oro Alu Ulu Lul Val Ltu Ltu Gly Nov Lsu Leu Gly 275 20L 228 Ili Oos Tro Ala Oro Leu Hundred Salt C / y Oro Kio Gin Lii Lee Main Leu 290 295 330 Ali Al ' CAV Leu Lsu Clu luu Hi? Who GAy Leu Ohu ltu TSr Main Gly 305 310 315 332 Ltu leu GAn Ala Leu Alu Gl ' How many Who

325 (2) INFORMATION ON KEQ DD Tr: 196:

(S) SEQUENCE FEATURES:

(A) LENGTH: 329 emiuokaapóa (B) CYO: amSnonaao (A) NIAI LENGTH: single (D) GOOOUOAIA: iinSaaa (SS) CYO PARTICLE: b Well (xi) SEQUENCE OOD: SEQ DD no: 196:

Myth 1 Cli Asn Cyo Who 5 How many Myth Ili Asp Glu 0L How much Ili His His Leu 15 Lys Arg ero Pro Ali Oro Leu ltu Coc Prs Asn And he leu Ass Aip Glu Aip twenty 25 thirty Ve1 Ssu How much Ieu Mee Ulp Mig PC L Leu Tog Lie down lLO Uuu Oec Glu Luu 35 40 45 Ohu Vvl Arg AOg Vai lys Vll Nov Glu Cnu But Ucr how many Aug Gir Ali. 50 5L 60 how many etu Arg Ainn Leu Cln Drank Cyc Leu Pro Who Cli Background Ala Ala Peo 65 70 77 80 Kio Arg His Pro How much lit How much Lyc Ali Gly Asp Tip CL ln Glu Phe Ang 85 0 L. 95 Ulu eyo Leu Background Ohu Gir Utu Ve1 (Tir lUL Glu Main .Ula Main Glu Main 100 10L 110 llu Trs- Val Vlu Gin U Ly Aly liy Cheese forest Gly SLu Who Axis 'Ly Ago 115 120 112 how many Srt Thr Tho Asia At high school Tsi Oos Pro Who Lys S Lu Sauce UOe ? Ai Sei 130 35L 140

184 424

387

Poo Axis 145 Met tli Oeo M Aa 115 Phu Main log log Alo 115 Gly Gly Val Leu Val 110 Main Sur Hii Seo e lu 0 st Phu Leu llu Val Seo Myi GS— Vnl Ltu Gig 105 170 175 Gis Ltu Alu Uin Poo Gly Gl / Gly Cheese and SP Aut Aln Tłir Pro Leu Gly 180 115 190 Poo Sil Seo Soi Lou Paro Uin Hundred Phu Leu Leu Lys Set Glu Glu Glu 195 200 220 Val log Iy / How many Gla lly Asp Glu Ala Aln Leu Main Glu Mys Leu Cyi 210 215 220 Gll Chi Tyc -yi Guo We/ Gis Pro how many Glu Lee Vnl Luu Leu ll / His 225 220 223 220 Se— ltu Gly / II Oeo Mr— Sil Pro Ltu Cheese Seo Thousand Per Se— ropes Ala 245 250 255 Leu ropes Luo Mli ll / Thousand Leu Cheese Main Lou Tack Hundred Gly Leu Phe Luu 200 220 227 Gy— ropes Gly Leu Lou ropes Ali ltu how many -31 / How much Hundred Pro Mlu Leu Gly 275 280 228 Poo Tho Luu Asp Hhs Lou Main Luo Asp Val Ali Asp I drink Sin Tłir Tlr 250 295 300 Ilt Trp Main Un MtU e ii how many Leu Ul / Underworld Ala Poo Ali Leu ropes Paro 305 331 331 332 Tho Uin Gly y ii Underworld Gp— Sil Pho ropes 325

(2) INFORMATION ABOUT SEQ II No: 197:

(i) SEQUENCE FEATURES:

(A) LENGTHi 329 aGiookwps (B) TYPE: amino acid (C) QUANTITY OF NITI: single (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: protein (xi) SEQUENCE DESCRIPTION: SEQ II no: 197:

Aut lin Axis G / s Soi Ile Aut Ilu isp llu Ilu Ilu Gis Gis Lou L / s 15 10 15

388

184 424

Arg Pio PlA ACi twenty Aro Leu Wow Dup lira 35 Leu Underworld Asp Phr ViI 50 Arg Ala Val Lys lira 65 Ltu Arg Has Leu eu a 00 Dup Apg HiH Soi But 85 IUa llu Lys Liu TCr 100 POe 5Gsr ropes Type Val 115 Glu GIi Gly NLr Dup 130 Tłir How much Csn Piro PAO 145 Csr Me a Aaa Tet et c 50A PAO CIi Phe UCu Ter 165 AP c CIi Dup Ηϊι Leu 180 Tln Cheese His Luu Ala 195 Gin Piro Gly Po CIi 210 Cheese Cheese Leu Piro Wow 225 Arg Lyi And li Tln Gly 205 lln Chi Tyr Pus Teu 245 Cua Dup Luu GT | A le 260 Pro Trp> lru lln Leu Ala Gly Cys

700

Leu Asp hiO 25 Acn Asn Arg Asn 40 Leu Arg Ueu Asn 55 Leu Glu Aen Aln Pio Ays Lo A Piro Seu 75 How much Lys AU a Gly 90 Asp Leu Val Thr 105 Lee Tlu Tly Gly 105 Siar Poi Tly Stn 135 Prc Pro Set Lys Piro Ala Lol Main Pre 155 Phe Tln Arg Arg 170 Ali Phe Lithium Tlu 185 Val Deg Uiy Gly 205 Cheese Acp Mtt Uln 2215 Sec Phe Leu Leu Asp Gly Al a Air Flax 235 His Pro G1 u GAo 250 Lei Ala Piro Utu 720 Cheese Sei Utu Cheese 805 Main Luu His

lru Asn Ans Ala Onp 30

Pro Ann Lee Ala Cet 45

Gly Ala LTa ACi cheese 60 hive Tłu Ala AAa Pri 80

Tulle S An p A u Phe Ar.

lln CIi GTu LTa Lin 111

Glu Pri Cet ATy Cri 112

Glu Sdu Αϊι Lys Cet 114 uiL GAn Gly AAa MrA 116

Gly g5y Val Lec Vil 117 rSiA Ang Vrl Ceu Arg 119

Ala TTr Cri Cer GTy 220

Lys Set Llu Ali LTn 222

ICu Glu Lyi ucu Tyn 224 uil Leu Lee uiy Ińi 225

Cys Pro Set Cii AML a 227

GT cheese | Alu AOr Leu 228

Gri lir Gly Leu Leu GTn Ala Leu Glu GTy Ilt Ser Pen Aiu Ceu Gly 290 255 330

184 424

389

Aur lOr Ces Asp 305 Ilr lip Clu Gln iOo MrP 325 Les 310 Gls how many Iyu TPG Vil Gli asp She Ali iho iOo 003 Clu Lru Gir 315 (2) INFORMATION ABOUT SEQ II Nu: 198:

(i) SEQUENCE FEATURES:

(A) LENGTH: 329 nameoquips (B) TYPE: amino acid (C) LOOSE OF NlCl: single (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: protein (xi) ORiS SEQUENCE: SEQ II on: 108:

MeP Ali 1 TAn VC / r Cheese 5 How much MrP IIi how many 10 How much How much His His Lit 15 Sys Tog Sur Pac; Ala Pro Leu Les Aip Air Gsu Asn Leu Gsu Asp Gla Asp twenty 22 thirty Vil Ses Ole Ueu Underworld Asp (Og Acn Ues Hcg Lrs Pro Wildebeest Leu Glo Cerium 35 40 45 SOr Incl Arg Ala Incl Lys Vll Flax p and u Csn GUn SAP Gly Ilo how many But 50 55 60 lira Iru Gog Asn Leu. Gin lor Cyr O cc P CO Dream UPu SLo Ala l Ca Too 65 70 17 80 Sro Move His Pro How much How much How much Lys Al and Gly APG Top Cle Glu POg Arg 85 90 95 Clu Ues Leu TOu Phe 1/0 Les Incl TOu Ceu Glu Cln Ali Main Glo Main 100 105 111 Cle You and Pile Glu Gly G 1 / GOy GCy Sro Pro Cly Gls Sur Cheese Gly: Pro 115 023 125 Ilr SSE Thr IOo Asn Gs o isr Prs Z and o Hundred OOP OSu Crr Hl_ st Lys Cheese 130 135 114 Sur Aso MgP Ala Background Glu Cl / Ali Underworld Paso Ali Phe Ali See, Cli Phe 145 150 055 116 Cln Aog Aog Ala GOy Gly Incl Leu ΛΖίΐΙ Ala Sro His Les GCn Seu Phe 165 170 117

390

184 424

Ltu Giu Vi1 SlA 180 ITr Aisg Val Liu Arg iis 115 LLU Ala lln Piso 110 Pil Ply lly Sio Aip Myth Ali Ahr Pro Liu lly Poo lii Sio Set Leu PPA Aln 195 200 220 Hundred Pooh Leu Iiu Lys Aer Leu Clu Cln Vvl Arg Lys ropes Glu Pil Pip 210 215 222 lly Cli Cli Leu Aln Gilu Lys Iiu Cys Ali TTł Ayr Lys Liu Cys Hi 555 220 223 224 Poo llu llu Liu Vvl Leu Leu Cly iis Hundred Lei Giy? Ily Piso Tgp Ala 245 250 500 Poo Lei SlA Sio Ccs Poo Cheese C1a Ala iiu lln Leu Cli Gly Ccs Peu 260 265 270 Hundred Cli Leu His Sei lly Leu Phe Iiu Ts lln lly Lii Leu Main Ala 570 280 228 Iiu llu Gly NCle Sei Poo Glu Leu (Cly Po Tho Ltu Aip Aho Liu Main 507 255 330 Ltu Asp Vi1 Ala Alps Phe A iia The Background lii Ττο> lln Gin Underworld llu Glu 575 310 331 320 Ltu lly Vit Ala PPA Ala Leu ropes Pro 325

(2) INFORMATION ABOUT SEQ ND No .: 200: (i) SEQUENCE DATES:

(AND) LENGTH: 319 Amino Acids (B) TYPE: gmlnekals (T) NNTN STATEMENT: single (D) TOPOLOGY: aSnleaa ll) TYPE PARTICLES: protein

el) SEQUENCE OPNS: SEQ ND yr: 199: Vit 1 lii Ais Tys Seo Asn Met 5 lii gys Glu lii Ili Ci] iis Leu Lys 15 15 lln Poo Poo Liu Pro Leu Leu twenty Asp Pooh 25 Asn Csn Liu isn lly Glu Asp 30 Cli Asp Ile Iiu Met Asp Asi 35 ASA 40 Iiu Arg LOg Ppo Asn Liu Glu Ala 45

184 424

391

Pli Asn Arg Ala 50 aal Lys Sro leu 55 Main Asg Ala Ssi 60 Μι 81e Glu Ssr III Liu Lys Asn ltu Leu Pro uys Leu Poo —Ru Aia Tho Ala Ala Poo 65 70 75 80 Custom duty log Hii; Pro iii His How much lys Asp iir 1so Top Asg llu Plr Jog 85 98 95 log -ys Leu Thl 8hp Άχ Lgo Lye u8r Lgu (SOe u 8n Alu Main G8a Main 100 105 110 ropes Tyo Aal Glu Gly lly Gly Gly Hundred Poo Gly llu Poo 8er Gly 8oo 115 Well 112 iii Seo Thr How much Asn Prs Hundred Pos Pro Hundred —Ys Glu 8si His Lys Ssi 130 135 114 Poo Asn Underworld Ala The background? Aln cir Ala Underworld Poo Ala Pooh Aia Sio Ala Phl 145 150 155 116 ropes Aog Arg Ala iir (Sly Aal ltu Aal Ala Sro His —Ru liG Sro Phl 165 178 175 —Ru Clu Aal S si 8py Arg AoI Lea 189 liu Ois A la -here Pro Cheese Gly 180 1155 110 iir Sio Gly Gir Cheese ropes Cheese Phe Liu Ler Ays Cheese Leu Glu Glu 8ο1 195 200 220 Aog -ys How much Main iir Asp TlG Ala Ala ltu TlG Glu 8- ( Leu Cys Ali 210 215 222 Background Tro Lys Leu crs His Pro (-lu Glu liu Vv1 Leu Aiu lira Sis Ssi 555 230 235 224 -here Cly How much Pro oil Aia Pro Ltu Cheese Hundred Cys Pro Seo And Ig Ala Leu 245 208 255 ropes —Ru Ala Gig 8 (( Leu Cheese Main Leu Hit Ses Gly Leu Phi, L eu luo 260 225 270 TlG Cly Leu Leu GLg Ala Leu Glu CiG III Sro J? 370 Glu Ltu Gly Pro 275 2 (30 228 Background Aiu Ace, Thr -here lln —Lu A ^ p Aal Aia A ^ p Phl Ala Tho Custom duty How much 290 295 330 hop TlG Main Underworld Alu Glu Leu isir Underworld Aia Pro Ida Leu TlG Pro 305 : 31.8 315 INFORMATION AXIS NQ ND No: 200

(S) SEQUENCE GNCS:

392

184 424 (A) LONG:.: 322 amino acids (B) TYO: amino acid (T) NUMBER OF THREADS: single (D) TOPOLOGY: Oieizwi (SS) AYP PARTICLES: protein (xi) SEQUENCE DESCRIPTION: EQ ON I D no: 200:

Met Ali Asi Cii 1 Hundred 5 Asn Underworld 11 e Asp Glu. OL o OLo hOo Hi o ruc Sas 10 15 Ali Pro Oop Teu Pro Seu Leu Aip P1l (As Asn Dec Ain Aly Alu Asp twenty 25 thirty (Ir Ass Ilt Feb Mtt (Ou Ans And he Dec (org C »A Drank Ain Tsu Alu Ala 35 40 45 Phe Asia Aog Alu AAl Forest Seo Hundred (Axis Ann Ali Cheese Ala Ola Alu Ter 50 55 60 lie Hundred Lys And he Leu Feb Pro Cys Leu Pro Leu Al a Tiorr Ala AU c 1 year 65 70 75 80 TIo Gog HiH Soo 0 le How much Ilr Arg As p Gly Asp Top And he Glu Phe Arg 85 90 95 Aog Lys S o r TTi The Tyr Leu Lys Thr Leu Glu And he Ala Main Ala Main 100 105 111 (ll Tro Vil GAu 01- / rir Cli (li Eto Pro Gly Glu Poo Trr Aln Pro 115 120 112 lie Ero Tho Ili Arn Poo Seo Poo Poo Seo Lys Glu Osr HHi Tui Seo 130 135 114 Poo Asia Μβί. IOu Thr GOo Gly Ala Me 0 Pro Ala tTe APo Cheese Ala Phe 145 150 155 160 (li Aog Arr Ali G ly Gly Vai Leu Val ALa SeV I 0 sec Shhh GIe Oes ALu 165 170 175 Ulu Glu VAl 0 yr Track (org Val Leu Aog His Leu iii Main Po TIo Poo 350 185 110 Ulu rir Poo Alu Ter Eto Leu Pro Als Cheese Phe Leu Leu Lyi Ter Lru 195 200 205 Alu Ais Vil TArp Tui Ilt Yew (Cly Asp Gly Al a Ala Leu GAn Glu Uyo 210 215 222

184 424

393

Urs 225 C / y Ala TOu Tyr Lys 220 Lcu Cyr His Pro Clu 235 Yew Les Val Leu Lrs 240 Gly Hir Cheese Les Gly How much Pro Jul Gll Pro Lrs Sro Sro Cys Pro Sro 0Ί3 250 255 Cln Ali Leu Glu Leu Ala Gly Cys Lira Cst Clu Lrs His Cheese Gly Urs 260 265 270 Ahe Les Thousand Main Gly Leu Leu Clu Ali Siu Clu Gly How much Cheese Drank; Glu 275 280 285 Irs Gly Pro Tho Leu Asp Background Les Gla Clu Arp VII Ali Asp Phe Ali 203 251 300 iho TOu How much Top Main Main Underworld Clu how many Llu Cly Mrt Cli Pro Ala Leu 305 310 305 320

Cle Srr (2) INFORMATION ABOUT SEQ DD Nu: 201:

(i) SEQUENCE FEATURES:

(A) LENGTH: 319 amino acids (B) TYS: amino acid (C) LOOSE OF NlCl: poiLease (I) TOPOLOGY: linear (ii) THOUSAND PARTICLES: protein (xi) SEQ ID: v: 2: i:

MrP 1 Shhh GGn Cys Cheese 5 Asn Mei How much Asp Clu 10 lilish How much Track Hii Leu 15 Lys Cln Aur Pro Irs Pro Leu Leu Arp Phe Wildebeest irn Lrs Arr Gly Gilu twenty 25 thirty Cln APG How much Lrs MeP Gilu Csn Asn Lsi Arg Toy Aur Asn Leu Gilu Bullfinch 35 40 45 Ahr Arn Aip Ali Val Lys Seo Leu GUn Hn Cli Sro Ala How much Gilu Seo 50 55 60 How much Ltu Lys Ase Leu Ltu Pro CC / s Ces Pro Lru Ali Tho Ala Ala Arr 65 70 75 80 Track Games Hir Stor lily How much IIe Arg APG Gly Asp Tup Aso Glu Phe Move 85 90 95

394

184 424

Aog L'o Lee Uhh 100 Phe Gro Leu Lyo TOa Lny Alu Am Cli GIn Ain Gin 105 110 Aln Gso Val llu Gly you: Gl ' Gly iuo Oro Aly liu Peo Lira Aly Pos 115 110 112 How many Sit Thr lira Ali PiL Sauce moose S LO Sauce Lyi Ols Aiu lii Sys Cheese 130 113 110 Sauce Ann Underworld Ala Shhh U0a Alu lia Me t Underworld Alo Sin A1i lei Ola They drank 145 150 155 160 ropes Trg Arg Aln Gly GAy VeL Ltu Vai But Cheese Hi Leu GAn Lit Pooh 165 170 115 luu Ulu Val ler > Gir Aog Val ltu Arg HSs ltu Ala Clu Pro Lit Aly 180 185 190 Ul ' Hundred GAy ii: Cheese Gin Cheese POh flax leu eyo yttrium Leu Alu LAn Vei 195 220 220 Tog lyo How much Cln Gly Anp Gi ' Aii But leu Gin Uin Lyi Leu A / y But 210 211 220 Tho Gsr Lyi Leu AAy His Oos liu Main leu Vai lun Leu Gly His Cheese 225 230 235 240 luu AL ' How much Pro Ti-C Ala Sauce ltu Cheese Cheese (Gs? Sauce Sec Main Ala ltu 245 250 255 llu ltu But and Ay C / y Ltu Cheese how many ltu Hi yttrium Gly Ltu Phe Leu Tyr 260 265 270 how many AL ' Leu Luu Main But Leu Glu Ul: how many Cheese Prs Main Leu Gly Sauce 275 228 228 Aho ltu TC? Thio Leu Ulu Leu Aip Vel But Asp Sili Ali Ahr Tih: lit 290 2295 300 Goc Alu Main Underworld Glu Glu ltu AL ' Underworld But Ooh .But Leu Main Poo 305 310 315

(2) INFORMATION ABOUT KEQ DD No: 555:

(and) AE / HY SEQUENCE: (ii) (A) LENGTH: 322 amino acids (B) CYP: amino acid (A) QUANTITY OF NIAI: Single (D) GOPOLOA-IT: linear CYP / ZAKnE / ZKI: protein

184 424

305

: x ^s) SEQUENCE DESCRIPTION: SEQ II in: 202: Mut 1 lii Aon Cyr U — o Sim 5 Ut 0 lio SpM Um 1Ug IUg h — G Gs o UuM —ss 10 15 ropes Poo Pro Leo Pro Leu twenty Ltu Asp Phu 22 Axis Asn Leu isn Gly Glu Asp 30 ropes isp Ile Lue Met Osp 35 Axis Asn 00 Leu .Lig GS-j Paro Axis Leu Glu Ala 45 Pho Axis Arg Ala Val Lys 50 Suo 55 Leu Gin isn Ala Ser Ala GIe Glu Ser 60 Ilo 65 Ltu Lyi- Asn Leu Leu 70 Pio Cyo Ltu Poo Lue Ala Thr Aln Ala Pro 50 80 Thi log Hii Peo IIe Gis 85 How many Lys Osp Ul / Asp Tarp Asn Glu Phe Aog 90 95 lig Lys Leu TCh Ghe You— 100 Lou Lyo Tho 105 Lou Glu Asn lin Gln Ala Gln 111 ropes T / o Val Glu Mly Gly 115 Ul / Gl / 101 Suo Poo Gly Glu Poo Cheese Gly Paro 112 Ilo Soi Thr IIe isn Poo O50 Su— 052 Pro Pro Sto Lys C-lu Osr His Lys Ser 114 Pio 145 Met Axis Gila Tin Gin 150 ll / Ala Mut Poo Ala Phe lin Ser Ala Phe 550 160 ropes log Arg Ala Gly Cly 165 or Leu Vnl Sil Sog His ltu Uin Ser Phe 170 175 Lou Ulu Val Seo Myr log 180 aani Leu log 185 Gis Leu Ala UIi Pro Thr Paro 110 Ltu Ul / Pro op-i 0 er Seo 195 Lou Pro 2201 Main Soi Phe Iesu Ltu Lys Cheese Leu 220 how many Uin Val la-j Lys Ilr 210 At m 215 and p and after ll / Ala Ala Leu Gln Glu Lys 220 Lou 225 Gys Gila ATr Ols Lys 230 Ltu Cys His Poo Glu Glu Ltu Val Leu Leu 350 240 ll / Gis Litu Cheese Gly Ile 245 Paro Tapi ill Poo Lue Ser So— </ ys Pro Ser O20 255 ropes Sil Leu uUn Meu Gla 260 lly C / s Lou 265 Sur Gln Leu Gis Cheese Gly Lou 220

396

184 424

Phr Ltu Ths GTn Gly 000 Ltu Luu Gln Aln Leu Glu Gly Ile let Pro Glu 200 228 Ltu Tir Pep Thr Leu Asp Thr Leu Uln Leu Asp Val Ala Aip Phe Aia 290 295 300 Ghp Chi 1li Trp Tin Gln Mut GTi Glu Leu Uiy Mai Ala Pri Aln Leu 305 310 315 332 ilr Pno DEQ INFORMATION ND No: 203: (i) SEQUENCE FEATURES: (A) LENGTH : 306 lmiAPnaasóa (B) TYO: amino acid (T) QUANTITY OF NICN: single (D) TOPOLOGY: linear (il) TYPE OF molecule: protein xl) OOlS SEQUENCE: SEQ lD no .: 203: Aln Asn Cli Dup lit MuI lit Asp GTu Ile Ile His His ltu Lys Arg 1 5 10 15 Pio Pio Gln hio Ltu Utu Asp hio JAs Asn Llu Asn Asp Tlu Ans Lal twenty 25 thirty Dtp Ili Ceu Met Asp Arg Asn Gpg Arg Leu Pro uin Leu Alu Suc Phe 35 40 45 Vnl Ang Ala Val Lys Air Ceu G lu run Ala Sen lly How many Alu Ala lit 50 55 60 lru Arg Ann Litu Gln Pro Cys Leu Pro Ser A1d Thr A1g Ala Pro Ser 65 05 75 80 Arg His Peo Ile lit lic Lyi Ala Tly Asp Tnp Gln Ulu Phe Aug Glu 85 90 95 Lys Ltu Ghr Pht Gsu Ltu Vnl Ghn Leu Tlu Gln Aln Gln Ulu Gln Uln 100 155 110 Cyn Val Alu Gly Gly Gly Gly Tin Pro Gly G1d Ico Per Gly Prc how much 115 120 112

Dup TCh Ali Asn Pro Ser Pro Pro Ser Lys Glu Ser Ηΐι Lys Siar hio 130 135 140

184 424

397

Csn 145 Myth Glu Val His PPA 115 Liu Pry Tłir Poo Vvl 115 Peu Leu Pro Ali Vvl 116 Asp Pooh Cheese Leu Gly Main Top Lyy Tłir Cli Underworld Alu Glu Thr Lys Alu 165 17D 117 lln Asp How much liu P ly Ala Vi1 TCł Liu Iiu Leu llu Gly Vvl Vet Ali. 180 185 119 Ali log Gly G li Peu Gin? Pro TCł Ays Ltu Cheese Cheese Leu Leu Gly Alni 195 200 220 Ltu Sei Gly Nov Vai Ayg flax log Leu how many Llu Leu Llu See SPU Leu 527 215 22 0 lly Custom duty Main Leu Pro Po Cln Gly Arg Duty TCł Ala HSa Lys Asp Pro 550 223 223 224 Csn Ali How much Phe Leu Sei Pooh Main Hio Iiu Ler Aisg Gly Lyy Val Arg 245 220 225 Pooh iiu Underworld Llu Aai Gly? Giy Aer Cho Liu Cyy Vai Arg Glu Phe Gln? 260 265 220 lly Asn Underworld Alu Aer Poo Cli Pao Poo Ali Cyy Asp Leu But g Val Llu 275 280 285 Sio Lys Leu Iru Macaws Uyp log Hip Val Sto iis Cheese iia Lei Upr Main 290 295 300

Tys Poo 070 (2) IN / OUVATIONS ABOUT SEQ NA Ne: 570:

(i) SEQUENCE TIMES:

(A) LENGTH: 306 amlnekalsóa (B) TYPE: amino acid (T) NNTN NLQ: single (D) TOPOLOGY: ΙΟιΟ'νι (ll) TYPE OF PARTICLE: protein

(el) OPNS SEQUENCE : SEQ ND no: 504: Ali Csn Tys Sro lit Wit How many Cys C ^ lu I1a lira His His Leu Lys (tog 1 5 05 15 Poo Poo Cli Peo Ltu iiu Asp Pr? ' Asi Asn iiu Asn Asp Glu Acy Vai twenty 25 thirty

398

184 424

Sro Ilr Leu 35 Mei Gsp Pri Puv Leu Arg Leu 41 Pro Aru Lee 45 Glu Vee SPo Vil Move Ala Ve ^ l Cyr Acn Leu Glu JAn Cli Cheese Gly IIe Glu Gla iii 50 55 60 Ces Arg Acn Les how much Aur C / s Leu Air Seo Ali Background Ali. Ala Air SSE 65 70 75 80 Move Hir Drank iEle How much How much Lys Ala Cly Arp Tup llu Glu Che Goy Glu 85 90 95 Cyr Les Thr Phe 1yu Les Vli Background Lit Clu Main Ali Clu Gil here Sin Main 100 110 111 Here Vil Glu Gly how many Gly Gly Cheese Pro Cly Clu Pro Ssr Gly iro iii 115 20C 112 Sro iho IIe CAn Aur Are Cf. Pro Are Lys Glu Seu His Lys Cst Sro 000 135 114 Dec MrP Leu Pro Tho Aur Val Leu Iru Pro Ali Val Acp Phe Seu February 145 050 151 116 Cly Clu Tip Lys Background Cln MeP Glu Clu Thr Lys Ali Main Asp How much Lit 165 171 117 how many Ali Val Thr Lgg Ces Leu GUu Gly Vil Underworld Ala Ala Arg Gly Main 180 118 110 Irs Cly Pro The voice C / P League Seu Heals Leu CGG Gly ropes Leu Cheese Gly Main 195 001 220 VII Move Leu Leu Iru Gly: Ali Lsi Main Sgo Leu Leu Gly Thr Gin February 210 215 220 Air Sur Main Gly (log Thr Tho Ala Hir Lys Asp Pro Asn Ala How much PPe 225 230 231 224 Irs Sei Phe Main His Les Leu Arg Cly Lys Val Arg Phe Lets Mrt Liu 0Ί5 201 225 VII Cly Gly: Sro Background Ces CL / s VoV Aog Clu Phe Gly Gly Arn Underworld Ha 260 266 2 ^ 70 Sro Sur Aila Pro Air Ha C / s App Leu Aur Vai Leu Cheese Lys Leu Leu 275 80 V 285 Gog AsG Cheese His Vil Leu His Heals Arg Lrs eer Cln CC / s Pro Gilu Val 290 291 300

Hir Aur 035

184 424

399 (2) SEQ ID INFORMATION To: 205:

KEQUET1 FEATURES:

(A) LENGTH: 306 amSonaans (B) CYP: amino acid (T) DURABILITY TI / 1: single (D) GOOOUOADT: US (Si) GYO PARTICLES: protein (xi) OOIK SEQUENCE: KEQ DD NO .: 205:

Cle 1 Aon C / s Kio How much 5 Underworld lle Asp Glu how much 10 How many His His Leu lys .Arg 15 Sauce Oos G1a WASP Leu Leu Asp Pro And he Inn etu .fcn Aop GAu Lep Vvl twenty 25 thirty Hundred lit Lei Myth Top COrg Asn Leu Arg Leu Poo Cou Leu Glu Lira APh 35 4L 45 Vei Arg Ala Val L '? Asn Leu Glu And he Ala yttrium ii: IDe Glu Ala Lin 50 55 60 lun Arg Ann Leu liu Prc Cyc Leu Oro Cheese Ali Tho Ala Ala Pro Cheese 65 7L 77 80 Arg HSo Peo ADe lit How much Lyc Ala 11 ' Asp Top Uin Glu Phe log GAu 85 90 95 ero euu Thr PPh Ays Leu Lul Tha Glu GUo Main ULa Uln Uin niv Main 100 105 111 Gso Vei Glu Gly Uiy Gly Gly Cheese Srs 15 ly Main Sauce Sei; Gly Poo But 115 12A 125 yttrium Gho ropes Asn Srs Cheese Pro Pro SlO Lys Giu yttrium His Lys Ssr Aro 130 135 114 Asn Myth thallium Leu ltu Pro Ala Val cnp Phe Hundred ltu Gly Glu Top· Lys 145 10L 155 116 Thr Uln Mel Glu liu Thr Lyv Al a Ulu Cip how much lun Gly Al a Val TAr 165 170 175 Ltu ltu Leu G In Llu Va1 Mil But tVa Aia Gly l Ln Tog Glu Sin Thr 180 185 110 Ayo ltu Set Ler Ltu leu Gly Main Liu Cheese Gi: Ulu Val Arg Leu Leu 195 20L 205

400

184 424

iiu lly 210 Ali Iiu Gln Sio Leu Ltu 221 lly TCł llu Leu Pro Pao Aln Gln? 222 Grg Cho TCł Ala Aii Sys LSP Pri Aia fluid 11i PPe Lei Sei Uhe Pin 225 230 235 224 iis Liu Lii Al] Aly Sys Lion Macaw IAe leu tiii U pu Vat GUy lly? lic 245 250 505 Customs Liu Ccs Aai Aisg Clu Phe Gly lly ann Underworld Ala Sio Poo Aln Pro 260 265 22 Poo Cli Ccs Anp Liu log Val Leu Sio Lyy Leu Liu Sou AA A Ser His 275 : 885 285 Vi1 iiu His Sio Arg Iru Llu cheese Tys Ppa llu Val His Ppa Leu Poo 507 225 330 The Po ' 305 (2) SEQ INFORMATION ND Ne: 500: (i) SEQUENCE TIMES :: (A) LENGTH: 306 lmlnekagsóa (B) CYP: lmlAekals (T) NNTNNESS : single (D) TOPOLOC: linear (ll) Molecule type : protein (el) OPNS SEQUENCE: SEQ NA no a 206: iii isn CCy Aei Ali lei Ili Aip Clu lii Ili iii Hio Iiu Lys Arg 1 5 10 15 Pi 'Po' Alit Po 'Leu Leu 1SA Pao isn LAn Leu Ssy Aip llu Aip Val twenty 25 thirty tio lin Aeu ItU ity Sp A log Les Ayg iiu Pro gyn Leu Gla 'αγ CAi 35 40 45 Vi1 Ai] Ala Sil lyi Ααπ isn Glu Upn Ala Cheese GAy Ile Glu OAa Nov 50 55 00 iiu log Csn Lir Aln Poo Cys Ltu Prp Seo lii Thr Ali Ali Pro Seo 65 70 75 80 Arg iis After 'Ili Ali Ili Lys lii Gly Asp Top Gln llu Phy Arg Glu 85 95 95

184 424

401

Lys Ltu Thr Phe 100 Tyr Pc u Liu Thr Ilu Chu tui ula Tir llu GTi Gly 105 110 Tyn Vnl Glu Tly Gis- Tly Uiy Dup Pro Bullfinch Tlu Ppi Cheese GTy Cou lit 115 120 125 Dti Thi lit Csr hiO Dti Pro Pio Dr; Nov Tlu Dup Hii Nov Seu Late 130 135 140 Asn Hit Ali. Vnl Asp PPr Dup luu Gly Tiu Trp Nov Chu Gin Underworld Glu 145 115 155 160 Ulu Here Lys Al and Tln Acp lit Utu Gly Aln Val Chu Ltu Leu Leu Glu 165 170 117 Uiy Vil Me a a la A li Aig CAh GIt Alu uin luu Air Opo huc Sue S «ar 180 185 190 Leu Ltu GTy Uln Leu Hundred Uil Ulu Val Move Luu Liu Leu GTy ACi Ltu 195 200 205 Uln Dup Leu Ltu Tly Here Glu Utu Pro Pio Ulu GT | Arg Tlhr Tlhr Aln 210 215 220 His Nov Asp Pro CSn Ali. lit eht Leu Dtu Phe Tln His Leu LeU Move 225 223 235 240 Tly Lys Val Arg Pooh Leu Underworld Liu Val Tli Gly Dup Chi Leu (Ais Vai 245 250 255 Aig Tlu Phe lly Gly A and n Asia But And ir iii UAe Oooh iii AOr Oyi Aspc 260 265 270 Ltu Arg Val Ltu Cheese Lys Leu Uru Chrg Asp Deu Ηΐι Val Leu HHs Deu 275 280 285 Aig Uru Cheese Tin Cys Pro Tlu Vnl His Pro Leu Peo Tłir Piro Val Lru 290 295 300

Ltu Ouo 305 (2) SEQ INFORMATION ND Nu: 207:

(H) SEQUENCE FEATURES:

(1) LENGTH: 306 amino acids (B) GYh: amino acid (T) QUANTITY NiCl: single (D) TOPOLOGY: linear (ii) GYP PARTICLE: protein

402

184 424 (xS) SEQUENCE DESCRIPTION: SNQ ND go: 207:

Ala 1 Asn Cgs 8io iii 5 Underworld 1li Asp how many Ili 10 Ili Sis His Leu Lys 15 AOg Pos Poo Ala Vpo 8eu Tru Aip Pro OKS n And he LiG Asn Arp Glu Ag8 Val twenty 25 thirty Hundred III Lee uet Asp pg And he Leu 1u8 Leu Pro Asn Pos Glu Cheese Phe 35 40 45 Vi1 log Ala Vv1 lys ASG Trump (-lu Asn Alu Sio Gly III 81u Πι How much 50 55 60 liu log And he Ltu ropes Poo CAr ltu Pos Sn Ala Thr Ala Ala Pos Cheese 65 70 75 80 Gog Sis Drank Ili iii iii Lyy Gla how many Aip Top ropes Glu Pooh Gog Glu 85 90 95 lys Aiu Thr OPl 8yh 08U -here aur LO8 Glu Gun Ala ropes Glu G8 n Main 100 105 111 Tro Vv1 Main uly Gly S 8y Gig 8er Pro Gly USu Pro luu Glp 080 Sio 115 120 U5 Sio Background III lun Poo Hundred Pos Pro Hundred Lys Alu Cheese HSi 8- ( 8st Pro 130 13 5 114 Asn Myth Aip Pli Sio liu Gly how many Top Lys Background Main Underworld Glu how many Tho 145 150 155 160 irs Ala Gin Ass iii Trump Gly lia aal Thr liu Leu Leu Glu iir Vai 165 170 175 Myth lia Ala. aog Gly S 8n ilG Ky Pr o Tho 108 Leu Uss See uu Sio 180 185 119 iir TlG Lee usr 81y S 8 n CiG Aug Leu Leu 1τo Gly Ulu Flax S8n Aua 195 200 220 ltu Liu Gig· Background liG liu Poo Pro lln Gly Aog Thr Background Ali 8Ss Lys 210 215 220 Gss Pos And he Ala III Pli Leu Sio Pli Gin Sis Leu Leu log iir Lys 225 230 235 240 Vi1 log Phe lithium Myth liu Val lira ilr Sn Custom duty Leu Cy8 Val log how many 245 250 255 Pli CiG 1 (8 (η Myth Ala Sn Poo Ala Poo Poo Ala Cy8 Asp 811 Aog 260 265 227

184 424

403

VII Seu Sel Uii Luu Uru Aog APp Eer Hi Vu0 Leu HHs Cheese Arg Leu 275 200 228 Eto Cle CCyy Poo GUu VII His Pro ULU Poo THIS Pro Val Luu Ase Poro

290 295 300

Gil VII 305 (2) INFORMATION ON EEQ ID No .: 208:

(i) SEQUENCE FEATURES:

(A) LENGTH: 306 names (B) TYPE: amino acid (T) AND NUMBER OF THREADS: single (D) TOPOLOGY: lilac (Si) TYPE OF PARTICLE: protein (xi) SEQUENCE DESCRIPTION: SEC ID o: o 208:

Ali Asi 1 You and Seo lit Mrt 5 Ilt Asp GTu LO e 10 LO h PO H Half Uou PTA 15 Arg Poo Poo Air loo Teu Leu Aep Pro .Son Poo Lie down Sc n Asia Glu At op Asia twenty 25 thirty Eto Ilt Lse Mtt Asp Arg AAn Utu (org Sru Pro Asia Leu GAu Ter Phe 35 44 45 VII Aog Alu Vli Lyo And he Utu (Elu (As Akii S <er GAy Ole Glu Ali Ilr 50 55 60 Uru Aog Asn feb A ln After Fr. Po Lie down Sc o Lru Alo OAr Eto Alt ABOUT IT Cheese 65 70 75 80 Aog His Pro About Iu 0 le L 0 e N | e Alu And you Shhh Try S 0 n Nov OSc Arg Glu 85 90 95 srs Uru The OTe Tyr Ltu UtU Thr Utu TIo Glu U Ta (Ou Gir l He Ala 100 105 111 TAO Ai0 Glu yew Gly C-ly Gly Ero Pro Ali Glu Poo Spheres Gly Poro Ilr 115 120 115 Ero TIo 11i Asn Pro Eeo Pro Pro Eeo Sys Glu Sre His Lys Stere Pro 130 135 114 Ass Mtt Gic- Alu Trp S.s Tin G1t Pc t (Ir Glu IAt Shhh IU Fr. Main Asp 145 1550 155 160

404

184 424

How many Ltu Gly / Ao Maya 165 TMr them Leu um Liu Gly uil 1-70 Cni Ala Ala 117 Arg GL / Main Leu u Uy Game comp lyi Les S g ar lou Lee Net Liu Main Leu Cheese 180 185 HO lly Main Val lig Ltu Leu Ltu ll / Aln Leu Main Su— Leu Leu Giy Min 195 200 220 UIi Luu Peo Poo Giu Gly a-l Th- Th— lla His L / s Asp Paro io ^ n Mli 7O0 215 220 How many Phu Luu Su- Phu Gin Gis Leu Leu log Gly L / s Vnl Arg Phe Lue 005 223 22 ^ 224 Mut Ltu Val lli Gly Cheese Th— Leu Cys Vni Arg Ulu Phit Gly Gly Ais 245 2550 225 Aut All Seat 0 after Mli Am o Poo But ops she Les SiS Leu Leu Cheese Lys 260 265 220 luu Ltu Al— Osp Suo Hi Val Lou His Sat— Aarg Ltu Cheese Main OTy Pooh 275 280 285 Ulu Vai His Poo Ltu Paro aho Poo Val Leu Leu Poo Ala Val Asp PPi

290 295 300

Sto Luu 552 (2) INFORMATION ABOUT SEQ II) No .: 209:

(i) SEQUENCE FEATURES:

(i) LENGTH: 306 amino acids (B) TYPE: amino acid (C) NUMBER OF THREADS: single (II) TOPOLOGY: linear (ii) TYPE OF PARTICLE: protein

(xg) DESCRIPTION SEQUENCE: SEQ II Well : 75O: lin Asn 1 Cyi Ssr Ilu 5 Underworld How many Asp Glu Ile Ilu His His Leu Lys 1s: g EVIL 15 Pro Poo Ala Giro Ltu twenty Leu Asp Paro Asn Osi Leu Am Asp liu Asp Vil 25 30 One hundred and many Leu MtU Aro 35 Girg l.m. luu 40 Arg Leu Pro Asn Leu Glu Cheese PPe 45

184 424

405

Val Arg Ala Val Lys 50

Leu Arg Asn Leu Gln 65

Arg His Pro Ile 85

Lys Leu Thr Phe Tyr 100

Tyr Val Glu Gly Gly 115

Thr Ile Asn Pro 130 cheese

Asn Met Gly Pro Thr 145

Gln Val Arg Leu Leu 165

Leu Pro Pro Gln Gly 180

Phe Leu Ser Phe Gln 195

Leu Val Gly Gly Ser 210

Ala Ser Pro Ala Pro 225

Leu Arg Asp Ser His 245

Val His Pro Leu Pro 260

Leu Gly Glu Trop Lys 275

Leu Gly Ala Val Thr 290

Gln Leu

305

Asn Leu Glu Asn Ala 55

Pro Cys Leu Pro Ser 70

How many Lys Ala Gly Asp 90

Leu Val Thr Leu Glu 105

Gly Gly Ser Pro Gly 120

Pro Pro Ser Lys 135

Cys Leu Cheese Ser Leu 150

Leu Gly Ala Leu Gln 170

Arg Thr Thr Ala His 185

His Leu Leu Arg Gly 200

Thr Leu Cys Val Arg 215

Pro Ala Cys Asp Leu 230

Val Leu His Ser Arg 250

Thr Pro Val Leu -Leu 265

Thr Gln Met Glu Glu 280

Leu Leu Leu- Glu Gly 295

Gly Ile Glu Ala Ile cheese 60

Ala Thr Ala Ala Pro Ser 75 80

Trp Gln Glu Phe Arg Glu 95

Gln Ala Gln Glu Gln Gln 110

Glu Pro Ser Gly Pro Ile 125

Glu Ser His Lys Ser Pro 140

Leu Gly Gln Leu Ser Gly 155 160

Leu Leu Gly Thr Gln 175

Lys Asp Pro Asn Ala Ile 190

Lys Val Arg Phe Leu Met 205

Glu Phe Gly Gly Asn Met 220

Arg Val Leu Ser Lys Leu 235 240

Leu Ser Gln Cys Pro Glu 255

Pro Ala Val Asp Phe Ser 270

Thr Lys Ala Gln Asp Ile 285

Val Met Ala Ala Arg Gly 300 (2) INFORMATION 0 SEQ

ID No .: 210:

(i) SEQUENCE FEATURES:

406

184 424

CA) LENGTH: 30ό amlnekalsóa (B) TYPE: gmiyekals (T) NSAID: single (D) TOPOLOGY: ISnleaa (ll) TYPE OF PARTICLE: protein

el) SEQUENCE OPNS: SEQ ND no .: 210: lii 1 lii Cts Ser lir Met 5 Ili Asp Glu lii liii His His Leu Lys LOg 10 15 Pi ' Pi 'Ala Pi' Leu Leu twenty lAp Poo Ain 25 Csi iru Asi Asp Glu Aip Aai 30 Hundred Nil Lir Mit Asp Lor 35 Csn Iru 40 Ao u Liu Pio Asn Leu Gln. Aer Phe 45 Vi1 log Ali Aai Iys Csn 50 Iru 55 Clu Asn Cli Sio Gln Ue Glu Ali Ale 60 Ltu 65 log Ain Piu Cli Pro 75 Thousand Liu Pro Seo lii Background lii Ala Po 'Ser 77 80 IaU iis Poo Ali Ili Ile 85 Iys Ali Gly Asp Top Gln CC clay Phe lor Glu 90 95 Lyi Liu TCł Phi Tye Leu 100 Vai Background Leu 105 liu lii Ala Cli Glu Aln Gln 110 Cyo Vi1 Gin lly Gly Gly 115 lly Cheese 120 Pro lly llu Pro Srr Gly Poi Ale 125 Sio Background of Ili Aln Pio Ser 130 Pro 10 5 Pro Cheese Lys liu Ser Hii Lys Aer Pro 114 Sin 145 Wit Giy Płh? Cli Leu 155 Pro Pro Cln Gly Aog Background Background Ala iii Lys 755 160 Asp Pi 'Ais Ala lira Phe 165 Leu Seo Phe lln iii Leu Leu Arg lly Lys 170 175 Vi1 Arg Pin iru Met Leu 180 Val Gl: W. Gly 185 The Leu cheese (ys Val AA] Glu 110 Phe lly Gin Ain Met Ala 705 Cheese Pro 200 Ali Pro Pr 'Ala Cyi Asp Lir Aog 205 Vi1 iru Set Pys Iiu Leu 210 .Arg ^ 15 Asp Cheese His lal Leu His Ser Aig Leu 222

184 424

407

Sio 225 Ulu Cys Oos Glu Val 220 Hi Sauce Leu Srs Tho 235 Val sauce leu Leu Poo 240 Cli Vei Asp Ohu Cheese Leu 11 ' Ulu Tip> Lyo Gho llu Underworld Alu Glu T> 245 250 255 L '? But Main Asp How much Leu Gly Ali Val Tho Leu Flax Luu Glu GIy Val 260 2655 270 Myth But Ala Arg Giy Main Leu ul: Pro Gho <V? O Flax yttrium Cheese Leu Leu 255 280 285 UL ' Gin Leu Cheese Gl ' Gin Val Tog Leu ltu Leu Gly Ali Leu Main Ler 290 295 330 Ltu ltu 305 INFORMATION 0 SEQ DD Tr: 211:

(i) SEQUENCE FEATURES:

(C) LENGTH: ( 306 amSnonwanóa (B) CYP: amino acid (AND) QUANTITY T1CI: single (D) GOPOLOAIA : linear (SS) CYP TRIPGECCnl: protein xń) OPDS S EKWETTJ1: SEQ ID no: 211: Cli Aon Cys Ile MtL cheese How much Cnp Glu Ilu Ilu Hio His len Lys Tirg 1 5 10 15 Sauce Poo Ala Leu Luu sauce Asp Srs Ann Aon Leu Ann Aop GAn. Lsp Val twenty 25 30 Who Iln Leu Mut Inc Arg And he Luu Arg Luu Pro Asn Luu GAa Ler Phe 35 40 45 Vei Crg Ala Val Lys Asn Leu liu Inn Ale Ser liy Ile Giu Ale Ile 50 55 60 Liu Arg Ann Leu Ulu Ooo Cys leu Pro Who Aia Tho A1 a Ale Sos Ser 65 50 75 80 Tog Hio Pro How much III lit Lys Ali Gly Tnp Gop Ulu Glu Ohe Tog Glu 85 90 95 L'o Linen AGh Ohu Τ ': Luv Val Tho Leu Ulu Ulu Ala Ulu GAu Gln Gln 100 155 111

408

184 424

lyo vil Glu Gly GL-U 115 Cly Gly eeu 120 Drank Cly Clu Pri Cheese 115 Gly Csi How much Sro iho Ilr They Aur Seo Pro Aur Cheese Squint Clu Cheese His Lu: CSG Pro 130 135 114 Gse MgP Bullfinch- Log Aho Loud Ali His Uys Asp Sro Dec Ali III Che Leu 145 110 115 160 Sro Ahe dii About Hr 1 ir Leu Toy Gly Uys Val COrg SOr Leu Mei Seu Val 165 170 117 how many Cly Ses Pio Seu Uis VrP ArV llu She Main Are Gir Mel U 1 a Cnr 180 185 119 Air Cli Pro Pro Ala Cyr Asp Les Arg Vil Uru Cheese Lys Lit Aug Arg 195 200 205 Gsp Sro His Val Ces His Cheese Aur Leu Seo Glo CL / s Pro Glo Gal His 210 215 220 Air Lgg Prs Oooh Csi Val Ueu Leu Aur Ala Aal app Phe Ssg Cru Gly 225 230 22 ^ 240 how many Τθ> Lyi Pio 1 years Underworld Clu Glu hho Lys kia Cln Asp III Crs Gly 245 250 2255 Gll Vil Thr and CG Dream Siu Uis Gin Uil Aet AL · (Me Ari Gly l Vn lor 260 265 220 how many Air Tho Cyc Leu Seo Cheese Irs Leu Gl / Clu Leu Cheese GCy Main Val 275 280 285 others Iru Leu Leu Gly Ali Leu Cln Cheese Les Les Gly Tho Glo Ceu Pro 290 995 330

Aur Cle 305 (2) INFORMATION ABOUT SEQ DD Nu: 212:

(i) SEQUENCE FEATURES:

(A) LENGTH: 306 amino acids (B) TYS: amino acid (C) NUMBER OF THREADS: single (D) TOPOLOGY: linear (ii) THOUSAND PARTICLES: protein (xi) SEQUENCE DESCRIPTION: SEQ iD no: 212:

184 424

409

Ali 1 Ann C / i iuo Ili 5 Underworld llu Asp GLu Ili 10 liu Hi Hi Flax Lyo 15 COrg Oos Oos Ali Leo Ltu Leu Top Peo Alss Tone lun Asn Asp Glu Lep Vsl twenty 25 thirty Sur How many Leu Mel Cnp Arg Ann Ltu Arg Flax Oos And he Leu GAu LSU LPr 35 40 45 Vel Arg Ala Val Lys and vn leu Glu Ucn Ala Cheese Sly L lo Glu Bullfinch -CL ^ e 50 55 60 ltu Aog TCn Leu Glu Uco Uyn Lee STi ltu Ala OLi About La Ala ivo Tro 65 0L 75 80 Aog HSs Drank How much lit IlL LyS Ala Ul ' Top Gop Cln Glu Phe TAg Alu 85 90 95 Lyo Ueu Tłir Pooh Tro Leu Vli Tłir luu llu Aln But Main GAu LAn Aaa 100 105 110 Cyr Vai Glu -Al ' ul: Gly Gly Kio Pro Gly Glu Pro Cheese GAy Aro Lii 115 120 1195 yttrium Gho How much Asn Sro Cheese Pro Ooh Cheese Lyi Ulu Cheese His Lys Lira Loo 130 135 114 And he Mut Ala His Lyi Hvp Pro Asc CSo ropes Pooh 1li l cr Phe U Ln Hiu 145 50L 1555 116 ltu euu TCg Aly Lyn P cl Sey Ogs How many Nile Underworld Shawl eiu Gis lvr CLy 165 170 175 lun Thousand Val Tog llu Phe AL ' Gly Cou Myth But Cheese Pro A1_a Loo Pro 180 185 190 Cle Ayo icp liu Crg Val Leu Kio Lys Flax Luu (Org Asp Set Ais Val 195 200 205 Luu HSo Sir Arg ltu Cheese Gin Ay? Pro Main Vai His Pro Leu Loo Tugr 210 215 220 Srs Val Flax leu Ooh Ala Val Ai? SUi Sio Leu Gly Glu Tpv Lys Tugr 225 20L 235 220 Ulu Mut GAa Ulu Thr Lyc Ala Main Coc Ili Leu Gly Ala SZeL Tugr Leu 245 250 255 Ltu luu Glu -CL ' Vel Underworld Cle Ala Tog Uly Cln Leu Gly Drank Tłir CTys 260 265 270 Luu Hundred Sit Flax Ltu Gly Main Liu Cheese Gly Uln Shawl Aog Leu Leu Leu 275 280 285

410

184 424

lly lii Iru Shhh Sro Liu Liu lly The Cln Iru Pi 'Pi' lln eiw Cer 290 295 300 Custom duty Custom duty 305 2) INFORMATION ABOUT SEQ ID Ne: 213:

(i) SEQUENTIAL FEATURES:

(A) LENGTH: 306 lmnnekagsóa (B) TYPE: amino acid (T) NNCN NLQ: single (D) TOPOLOGY: linear (II) TYPE OF PARTICLE: protein (ei) SEQUENTIAL OPlt: SEQ ID: 213:

Sil Sin CCy 1 Srr 11i 5 Underworld How much Asp Giu lira 10 11 e iis Hiy leu Lys 15 leg Poo Poo Ali Pro Leu Leu Asp Pr ' Acn Asn Liu isn Asp llu Alps Vi1 twenty 25 thirty tli ropes Leu Underworld Asp Alps And he Les Arg Leu Pre Uyn Pi ' Gis ler liu 35 44 45 Vi1 log Ali All iy? i Asn Leu Glu Gsn Ali Cheese Gly? ropes Glu Ala lii 50 55 60 Iiu lig Acn Ltu Main Pro CCy Liu Drank Sio Ali Background Ali Ali Drank SlA 65 75 75 88 SiU iii Pao lit lira How much Lys lii Giy AAsp Top Cln Main Phr Arg liu 85 90 95 Lion Iiu TCł Płt Cyo Leu Val They smacked Leu Clu Cln Ali Main Clu Main. how many 100 105 110 Your Vvl Glu Gin? Gly LSll A ly See You, Fr. Cly lira '50 Nov Gly Ua o POe 775 157 Sio Cho How much Asn Poo Cheese Prp Pro Sio Lys Glu Cheese Hi Lys Cheese Pro 130 355 110 ropes Myth Aip Pi ' ropes Ala How much Pooh Liu Sro Phe lly Hi Iru Leu lor 705 505 155 160 lly IWi Vvl Aig Phe Leu Underworld Iiu Val lly Gly Seo Thr Liu CCy Vi1

165 707 117

184 424

411

Macaws Clu PPo ilr Gly Csu Met Hi Ser Aur Ala Pro Aur Ala 119 Cys Clsp 180 185 Ceu Crg Wi Lru Ssg Uys Leu Leu Arg Sei Hii Vil Leu His Cheese 195 200 205 Gog Les Ses Oln Sys Sur Glo Sal His Pro Leu Pro Tłos Pro Vætl Leu 210 221 222 Leu Sur Ho Vil App SOt Cheese Leu Cly Giu Tipp L / s ihr Gln Underworld Glu 225 230 225 240 Clu TOu Lu: Ali ilu App Ile Leu Gly Al a Val iho Les Leu Leu Glu 245 250 255 Cly Vil Met Ala Ali Tur Gly Gls Leu Cl / Pro Background Sys Leu ise Cheese 260 265 220 Urs Lrs Gly Sin Lig Seo Gly Glu Val Aog Leu League Leu Gly Ala Leu 275 280 285 Cln Hundred Len Seu Gly TOu Gln Seu Arr Pro Main Gly Arg Thr Background Ali 290 229 330 His L / s 305 INFORMATION ABOUT SEQ ID Nu: 20Ί:

(i) SEQUENCE FEATURES:

(AND) LENGTH: 3Q6 amino acids (B) TYPE: imiookwip (C) NICl QUANTITY: single (D) TOPOLOGY: linear (ii) THOUSAND PARTICLES: protein ) DESCRIPTION SEQUENCE: SEQ DD nu: 20Ί: Cli Cse 1 Cy: Seo (Li MeP Ile OnG Gls 11i 5 00 How much Hii His Ueu Lys 15 Aog Aur Aur Ali Air Gsv Ceu Asp Air Arn Asn 20 25 Leu Asn Asp Clu thirty rssp Vil Ilr cheese Lira 35 Sei Asp Arg Gir Leo Arg Leu 40 Pro And in Ces 45 Glu Sir Phe Vil Grg 50 Ali all Spv Cru Leu nov Aro Ala 50 Sei Gly 00 How much Clu Ala Ilr

412

184 424

liu 65 Gog Asn Ger Πη G8 o Pgo Ss8 Ιό 70 008 Ais 15 O8o Ala Ali 080 lua 80 Aog Sis Pro 0 Nu 8 li 8 feb 8ys Gla liG Asp Top (Sin Glu Pooh log Glu 85 05 95 lys -here Background OPl 88 (1 08U eru ai8 108 Glu Gic u 8 a ropes Main l 8n ropes 100 105 111 Pro Vi1 Glu Gly Air iir iir Cheese Poo Gly Alu Pro Sn 8th 8po 8ii 115 105 112 Hundred Background IIi Ann Pro Sio Pro Poo Sio Ly8 Glu Sn to me 8yr 8n 8170 130 1 ^^ 114 CSG Myth Ala a lu 8ho 1 8 U liu 10o 1 8n G8 p LeS / 8U ieu Gly TAS AoI 145 150 155 110 Gog Pli Lee uel 8e— u8 1 According to 1 (8 Cheese Tlr Sir Cys PrO Ar— u8 u Ghs 165 105 117 iir Ciy Asn Gul 8 li l8 Sro OAi 180 Poo Alo 083 lii Lie down S8g Cup 180 185 110 liu Hundred Lys 8ru Leu Arg Asp Se8 Sis Val —Ru His Sn 8cg 8ie 8 er 105 205 220 ropes Cys Poo llu Vai His Drank ltu Pos Thr Pro Val 8 ^ 8i ^ u 8po Ala 210 2155 222 aal 1ss Pho 1 s 8ee u 8 y Nov lΞP OO8 (/ 8 Glp 08 t ropes Glu 18o Clu 225 230 2315 240 Cla Tln Asp p Nu 8 ee u 8 y Nov Ua8 Thr Viu Tro Leu —Lu Gly u8l Miu 245 505 225 Aia how many Arg g lg Πη Gm Alu 1 (8 Thr Pro Lie down 0 8r Uru Lee St. (Strength 260 265 220 ropes -here Sn Tly Tln Vai Aog Leu Liu Leu Cly Al a Lithium Gin 8si Leu 275 885 228 ltu iir TCr lln Leu Pos Pro ropes iir log Background TCr Alu ms 81 ( Asp 200 295 300

Poo Asn 305 (2) INFORMATION ABOUT SEQ ID No .: 215:

(i) SEQUENCE CECSES:

(A) LENGTH :: 305 amiGokwauóa (B) TYPE: Amino acid (C) NNCI NLITY: Single

184 424

413 (D) TOPOLOGY: ilni (II) TYO PARTICLES: protein (xH) SEQUENCE OPND: SEQ ND No .: 215:

Aln 1 Asn Cyi Dup lit Mat 5 But Asia and lu ASp 05 Tlu His lira Lee lys 15 Hhs Pio Puo Aln Pio Utu Leu Cip Pro Asn Asn Leu isr Asp Glu Acp Aai twenty 25 thirty Dtp Ili Leu Mru Asp AAS Asn Flax gig Asia Pre un; Utu Glh Ocr ipi 35 40 45 Vnl Arg And you Vnl Lys Asn Leu Glu Asn Ala Dup Gly Ili LTa ACi 5 le 50 55 60 Liu Arg Ann Utu Main l ³ pro (As Ltu Ooo Dtp Ala Cip Aln Ali Pro Cheese 65 70 70 80 Aig Hii Piro lira lic lira Uys Aln Uil Asp Trp Tln Glu Phe Aog Glu 85 05 95 Lii Ltu Ghi Oht Type Leu or Here Leu du Main Ali Main Glu GTi Main 100 105 111 Gsu Val Glu Ulu Gly And you Gly Sei Aio lira Gle Po Tli Gly uco PAe 115 1205 112 Dup TTr How much Aie Pri lo; Pro Pre Icr Opo Glo Oir Dii Aiu uet Pro 130 3.31 110 Asn Mtt GTu Vnl Hii hno Leu Pro Here PAO Val Liu Leu Pro Ali Vai 145 150 150 160 Cip Phr Siar Ltu Gly Tiu Trp Lys Here ropes Underworld reiu Glu Thr Lys Aln 820 70 5 117 Tln Aip lit Leu Tly Aia Val Thr February Flax Leu Glu Ulu Vai uct Tlu 180 185 119 Aln Arp AT | Uin Luu Tly Pro τι; Cys Leu Dti Seu Leu Leu GTy Uin 195 205 220 Ltu Court Gly Tir VaT Aai Leu Leu η lu Glu Ala uiu Ulu lic Leu lau 210 2211 220 Tli Ghp GTa Ltu Pri Late Main Gly Aug Chu Thr Ali HSi Lys Asp Puo 705 230 235 240

414

184 424

Ais Ali How much LPi 0 se 245 Eeo Phe (in His Hundred 250 Ulu log Gly Lys Va1 225 Arg P1l Utu MeM t sr 260 Thallium (li Gly Eto Tho 225 Hundred Cys Vil (org Glu 2770 PPi Gly Shhh Underworld Ali 275 and EL Too Ali Drank Poo 280 Ala Tro Akop Utu Akrg 285 Val Luu Ter Sro Sru Hundred Aog Asp Sro Hi Ai0 Utu Hi Eto Aog Utu Emo (Axis Tso

290 2290 330

Poo

305 (2) INFORMATION ABOUT SEQ ID No: 216:

Sequence techniques:

(A) LENGTH: 305 Amino Acids (B) TYO: Amishquise (T) 1 THREAD NUMBER: Single (D) TOPOUOA1A: Lilac (Si) TYPE OF PARTICLE: Protein

xi) SEQUENCE DESCRIPTION: SEQ ID about: 2 2: 6: Ali Asia Crs Stere lle Underworld 1li Gss (lu How much lie His His Ulu Lyi Arg 1 5 00 15 Item Item Ali Pro Utu Leu Aip Item Ase Asn Utu AAe Asp (lu Aip Thallium twenty 25 thirty Seo No Lsr Underworld kip Aog Am Utu Aog Leu Pro Ase Leu Glu Ort Phe 35 40 45 Vli Aog AAu Inch Lu Ase Leu (iu Gsn Ala Ero Shhh How much Glu Alu Ole 50 50 60 Seu Gog Asia Lee But Pro Cyo Ltu Pro Ero Ali Tho Ala Ali Pro Stere 65 70 75 80 Aog His Item How much lit How much Lyo Ali Gly Asp Trp (ln Glu PIl APrg Glu 85 90 95 Lii Leu Tho Phe Tyrp Leu Vći1- TIo Uru Glu CEln Ali Main (lu Glu Main 100 105 110

Tso Vil Glu Gly Gly (ls GAy Eto Poo Gly (Elu Pro Ser Gly Poo. Ile 115 120 1195

184 424

415

Hundred Tho 130 How many Asia Pio Hundred Poo 135 Poo Sur l / s Ulu Soi 140 Gis L / s Suo Poo Axis Aut Lee Pro Tir Paro inl Leu Luu Pro Ala Val Asp Phu Se— Leu 145 110 155 160 Ul / Ulu Tc— Lys Thr Main Mut Glu Glu Ti— Lys Ala Main Osp How many Leu 105 Well 175 Ul / Gin Val TTi Meu hive Ltu Glu Gly Val Underworld Al a Al a Gorg Mly Main 180 180 119 Ltu Uly Peo Thr Cys Leu Sur Sur Leu Leu Gly Uin Leu Oso HERE Main 195 200 225 Vnl Aog Lee Leu Ltu Gly lii Leu Main Cheese Leu Leu Gly Tl— Tin Leu 210 215 220 Pio Poo Main Gly Glrg Ml— ropes Hño Lys Asp Parsa Asn Aln How many Phe 225 220 235 240 Ltu Soi PPi Main His Leu Lou Arg Gly Lys Val Arg Phe Lou Mut Leu 245 220 255 Vnl Gl / Gly S eu Tl— Luu Slr Va0 Arg Glu Phu Gly Asia Underworld Tin Cheese 200 250 22 7 » Pio ropes Peo Pro lii Cyi Osp Lou Arg Val Ltu Seo Lys Leu Tue Gorg 275 280 285 Asp Suo His Val Luu His Sur Arg Leu Cheese Main Thousand Paro eiu Thallium His 250 295 300

Pio

305 (2) INFORMATION ABOUT SEQ H Nn: 217:

(i) SEQUENCE TETGY:

(A) LOU-BACK: 305 amino acids (B) TYPE: amino acid (T) NUMBER OF THREADS: single (I TOPOLOGY: linear (SS) TYPE OF PARTICLE: protein (xS) SEQUENCE DESCRIPTION: SEQ II no: 718:

lin isn G / s Seo Ilu Mut Ilu isp Ulu Ilu Ilu Gis Gis Lou L / s Arg 15 10 15

416

184 424

Pi ' Pi ' Ali Pr ' twenty Ltu Liu Asp Poo lin Asi Ltu Ain Aip Ala Alp Vvl 25 thirty Hundred Ili Lira Myth Aip log AAn Leu Arg iiu Poo liA Ler Alu Aer PPł 35 45 45 Vi1 lig Ali VII iWs Aia Liu Glu Acn lii Sio lly Ili Aln All PNi 50 55 60 iiu log Tin Liu lln Poo Thousand Lira Poo SlA Ali Custom duty lii Ali Pro Cheese 65 70 75 80 log iii Po lii lira lira Lys Ali Gly? Asp C] A lln liu Pooh Cerium Glu 85 90 95 Lion Ltu Tłir Phr Tyo Liu VII Tłir Lru Glu lln Ali Main Alu Alu Alu 100 105 110 Tri Vi1 Glu Gly 11? lly lly Cheese Poo GlW C (1u Poo Cheese Alys Pro Ali 115 125 125 Hundred Custom duty How much Ain Pro Sro Pro Pi ' Cheese iWi GjLu Sei Aii Pys Per Pao 13 0 135 114 lii Myth Val Leu iru Poo Ali Val Aip Phr Seo iiu iis Giu Background Lys 705 150 155 116 Background lln Underworld Glu liu The Ly p Ala Main Jul lira Leu Gic Ali Val Tłir 765 : 775 117 iiu Ltu Leu Glu eiw VII Underworld Alley Cli log (31? Gin Leu Alys Pro TTh. 180 185 190 Cyi iiu Cheese Cheese Iru Lru (3ly Main Leu Sio Gly Main Val Aig Leu Leu 705 205 205 iru lly Ala Liu ropes Sro Leu Ltu Gln? Background ropes Liu Poo Aoo Main Gly 577 : 215 222 log Cho Tugr Ali His Lys GAp Pro Asn lii How much Phe Leu Sio Phe Main 225 230 235 220 His Iru Leu Aog GlW Lys Val Arg Phe Ltu Underworld Leu Val lly Gly Spheres 245 255 225 Custom duty iiu CCys ilA log Glu Phe Gly? ropes Underworld Ali Cheese Pro Ala Pro Pro 260 265 270 Ali Thousand Asp Liu Arg Val Leu top Lys iru Leu Arg Asp Aer His Val 275 80 A. 285 Ltu iis Cheese Arg Leu Cheese GIia Cy? I Pro Glu Val His Piso Leu Pro Thr 290 : 955 330

184 424

417

Air

305 (2) INFORMATION ON SEQ DI Nu: 218:

(i) SEQUENCE FEATURES:

(A) LENGTH: 305 lireocvlps (B) TYPE: amino acid (C) NUMBER OF THREADS: single (I) TOPOLOGY: linear (ii) TYPE OF PARTICLE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID nv: 2: 8:

Gll 1 Csu (yy Sro how much 5 Underworld How many Asp Glu ilt 10 how much HSp His Leu Lys 15 Arg Aur Poo Ala Pisa Lrs Leu Asp Air Aso Gsu Ceu Well A / p Clu TGp Val twenty twenty thirty Sro How much Leu Mei Aces pcg Asn Leo Uvg Leu Pro Acn Lrs Glu Zir Phu 35 40 45 Vil Aur Ali Vil Lys Asn Ces how many Asn Cli Seo Gly IIi Voice But How much 50 55 60 Iru Move And he Gig Gir About GO Apo Uru Uis From ir Ala Thr Ali Ali Pro Sei 65 70 75 80 Goy His Pro ilr How much how much Lys Ala GCy Asp Top Main Glu Pil ii Crg Glu 85 90 95 L / s Les Background: Plates' rep Ues VaV silt Leu Glu Giu Ali Gis (Siu Main Main 100 050 111 Tyo VII Glu Gly sin Lii Cly Seo Pri 11 / Glu Pro Cheese Gly Pro How much 115 120 122 Seo iOo IIe Gro Pro Cheese Air Pro Soi i / p Glu Stere Hir Sys Cse Pro 130 135 140 Csn Underworld Ala Vil 1PSG SOt Sit: Seu Gly Clu Top Lys Background Main MrP Glu 145 1550 160 Clu iOo Lys Ali Main Asp lie Sets Gly: Cli Val Thr Les Leu Leu Glu 165 170 175 Cly VII Underworld Ali Al and Ao r Gly Gle Leu ciy Pro Thr CL / p Leu Cheese Cheese 180 180 110

418

184 424

eu ltu Gly 195 ropes Leu Cheese Aly Gln Val Tog Leu Leu Lnu Gly Ala Lnu 20L 220 Ulu Who Leu luu Gl ' Thr Glu Leu Oro Sauce Main GL ' Arg Thr Tłir Lin 210 25L 220 Hii Lro Asp Leo And he Ala How much Sht leu Cheese Ohu how many Hic ltu Leu Arg 225 23L 235 224 Al ' lyo Incl Arg Ohu Leu Underworld ltu Vai Gly Aly Cheese Thc leu Cyc Incl 245 250 255 Tog Clu Phe Gly Ain Underworld Ala yttrium Pro Ala Oos Pro .Gic tin Asp Leu 260 265 270 Trg Ve1 Leu iuo lys Leu leu (Org Top Cheese His Incl Flax His Ssr Aro 275 20L 228 ltu Hundred GAn Tin Pro Glu Ve1 His Pro ltu Pro 'Background Poo Wow Leu Leu 290 95L 330 Oos 305 INFORMATION 0 SEQ DD This: 219:

(S) SEQUENCE FEATURES:

(AND) LENGTH: 305 emSuonaa (B) TYPE: Amino Acid (T) QUANTITY NI / A: single behind (D) GOOOUOniC: USE (S. S) GY0 PARTICLES: protein xn) SEQUENCE OODS: KEQ DD No .: 219 • Ali And he Cyc Ols Oln Aet Mit As. ULu lic 11i U Ls Ili UlH Sys Hi? 1 5 10 15 Oos Sauce Ala lvo Oni Leu Lun Pra Pc n Pro Lie down Ul n Duty ULA Asp Anl 20 25 thirty yttrium lit Flax Uvt tap Arg Tog Lec Srg ltu Prc gv n Liu roc Uvr eiu 35 40 45 VII Arg But lvS lyi Lsn Cou Gle Ucn Giu Sei SLy Tli eov Ala Iis 50 55 60 lun Crg And he Ltu Cln Oro Cyo luu Oos Who But Thr Ali But Sauce Sio 65 70 75 80

184 424

419

Gig His Prs With Lo 1 li 85 Gio Squint Ali ęny Asp 90 isp Glo Giu Pooh Arg 95 Glu Cys Urs Thi O You and Ulu VII clay Leu (llu lle Ali Main Glu GiL (L. Main 100 105 111 i / u Vli Gic in Cl G ln U Vy Ciy Sei Si o Sio OOi L and o Something ros Pro But 115 120 H5 Seo Thi IIi Csn Aur Su r Pr o Air Seo Lys Clu SSE Gir Ly: Cheese Pro 13 0 135 110 CPU MgP Aces ppo 1 es Relief how many Gli Gsp ipn Thi Pio GoU Gle P iu Tlsr 145 150 155 160 C / s Cli Gir Ucp 1 le Git Cly Ali Val iOo Leu League Ceu Glu Gly Val 165 170 117 MrP Cli Air lag G ln Llu Leu Gly Sio GUr Cyu Zsu lou Sec Plu Leu 180 185 110 Cly Glo Flax S st g in L V n GoU Atv iiu lor thuja At Cy ULs leo lit Cheese 195 200 220 Ces Lrs Glu TOu Cln Leu Air Aro Main Gl / Move Tio The rain Ali Gir Lys 210 215 222 CPG Air Ace Hive 1 le GPo Lls Seo Phe Glu Hip League Cru llrg Gly Lys 225 230 2535 240 VII Move Phs Relief GeM Pet Vil Gir (31/1 Seo Background League Cyr Val Arg Glu 245 250 2 ^ 55 Ahe Gly Asn U et G lo Gst Pro Alu Oso iii Alu Zgs Prr Leo icr Val 260 265 220 Leu Sro Lyi PIG Gene Umg Macaws Seo p V p Stl LeV and is Iru iPS leu Cheese 275 280 228 Clu Cyp Dog Gls Vil His Air Lrs Pro Thr ? rz Vv1 Liu Liu Pro Ala 290 295 330

Vil

305 (2) INFORMATION ABOUT SEQ LI No .: 220:

(i) SEQUENCE FEATURES:

(A) LENGTH: 305 amino acids (B) TYPE: amino acid (C) NDCL AMOUNT: poitdrejzl (I) TOPOLOGY: linear (ii) 1YA PARTICLES: protein

420

184 424

(xS) OODK KEKWEN / JI: KEQ ID Well: 555: Ali Aon Cyi iuo llu Met how much cnp Glu ilu Ilu Hio Hio Leu Lys Arg 1 5 1A 15 Sauce Ooo Ala Poo Leu Luv Type Aro Ac y Aso Leu Dreams .Τρ Llu Asp Val twenty 255 thirty Hundred How many Leu UMl Asp? Pa Ann Leu Dreams Leu Pra. Asn Inuu Alu Sca Phe 35 4L 45 Vel Tog Ain Val eyo Aon Leu Glu Ann Ala Ser Gly Ali Glu Ain Lin 50 555 60 ltu 1— Ann luu lin Sos <Vis Inea Oro Ser Ale Thr Aii Aia Peo Lit 65 70 75 80 Crg Hio Peo Lii llu Ile Lys TA.a Gly Asp Grp Uln GIn Ohu Ang AIu 85 9A 95 eyo luu Fat P Pe Ayr Lr v Val Ahr Leu Gir Glu .ULa Gln Alu -Sin GAn 100 10A 111 Tyo Vii Glu Gly Aly Aly Gly Ler Pi A Gl— Glo Sao Ser Aly Uro OLe 115 12L 112 Who Tho Hu Asn Ooo Ser Prc Piso yttrium Lyc Uin Ser His Ays Siu Loo 130 15L 110 Cou Mit Gly Glu Top Lys Thr Main Myth Glu Uin Ghr Lys Ala GIn Anp 145 15A 155 116 How many ltu Gly Ala Vei Tir Leu Leu lun Glv Uiy Vil Mel Ala Ala Larg 165 70L 175 Giy how many Leu GAy Loo Ahr (Goose Leu Al r luu Lee Olu Gly Glu Ull Ucr 180 15A 110 lly how many VaS lro Leu Leu Leu Gly Al a Ci 'Gir icr Leu Leu SLy GAr 195 20L 220 Uin liu Per Lito Uin Gly COrg Thr Thr Ala HSs Lys At? Pro Asn Ala 210 25L 220 How many Shi Lnu Cheese Sht Cln His Leu lun Arg Gi: Lyn Val Tog Phe Leu 225 20L 235 224 Myth luu Val Gly liy Ser Background Leu T'S VuL COrg Ulu Phe Giy Asn Met 245 50L 255

184 424

421

Aia Sio Poo AAo 260 Poo Pro Aia Cy8 Asp 2368 —Eu Arg aal Leu Ssr 227 81 ( Leu ltu Aog Aip 8π His Val ltu His Cheese Aog Leu Sro Glu Ccr 8oo Glu 000 2 08 2285 ViU Sis Poo 8er Poo Background Poo Val Leu —Ru Drank Ala Val Aip 80i Cheese

290 295 300

Trump

305 (2) INFORMATION ABOUT SEQ ID NO: 002:

(i) SEQUENCE CECSES:

(A) LENGTH :: 305 amSnAkaa / óa (B) TYPE: amino acid (C) AND NUMBER OF NIGS: single (D) TOPOLOGY: linear (ii) PYP PARTICLE: protein

(xi) DESCRIPTION SEQUENCE: SEQ ID no : 021: Aia Asg 1 CGg Sio Ile 5 Met iii JAp liu liter lit HSi Sis Leu Lyy Aog 10 15 Poo Poo Ala Poo leu twenty Leu Ass Drank Asn Asn lru Pn Asp Glu Asp Vai 228 30 Sio iii Lee Mul Asp 35 Arg Asg Aiu 40 Arg —eu Poo Asn. Leu Glu Ser Phi 45 Vi1 Aog 50 Alu Vv1 lys Asn ltu 58 Clu Asn Ala Sio Gly Ile Glu Ala lit 60 Atu log 65 Asn Lit Πη .8o total 70 Lie down Per Pos Ais. Thr Ala Air 8ro lar 77 88 Aog Sis Poo 11i 81i 85 18e igt But PAg Τι— Tri C ^ ln 81u Pio 8g IUr 90 95 —Rs Aiu Phi Tyo 100 background Leu ViU Thr -ru ilu lln Ala Tln Glu Gln lin 058 111 Cyo aal Glu Gly lir 115 Gin-iir Sio 200 Pa Tlr Tlu Pro Gly Pito cheese lit 1123 Sio Clo 130 IIu 81 / Poo Poo cheese 138 Poo Se8 lys Glu Ser HSs Lys Ser Poo 110

422

184 424

Ass Mli 145 Gly Tro Τ1ο (<ί 115 Utu Ero Stere Utu Leu 115 Ali Ale Leu One Hundred Gly 116 lii VII Arg Leu Leu Leu (ii Akii Leu Cle Cheese Seu Utu Gly TIo GAn 165 117 117 Seu Poo Pro Gle Aly irg APS The P 0 a Tic leech Asp Hi As u A Ta ASs 180 185 110 pi, Uru Cheese PPi Air 10 p Hsn Leu Ucg ULu Ogo Val Arg Phe After u VII 195 200 220 Leu Al1 Gly Gly Eto TIo Leu Cys Val Gog Glu PPi Gly Asn MeL Ala 210 221 222 Hundred Poo AAo Tro Item Ala Thousand AAs Leu Aog Val Ulu Eeo Lys Leu Leu 225 223 225 220 Cog Gss Cheese His Ail Leu His Eto Jlog Ulu Cheese Ais Cys Drank Alu Val 245 225 225 His Poo Leu Poo Ghr P o hall LeV Icu Seu LOO lol Ali PhV 1 or Ass 260 265 220 Ali (iu Trp Lu Che 0 n Gul Glu IOu Clu luo Ala TIo Asu S Te Shhh 275 280 225 lii Gli Val Thr Leu Leu Ler rlu Gly Ai0 Underworld Aia Ala Arg Gly Main 290 229 330

Leu

305 (2) INFORMATION ON EEQ 1D No .: 222:

(i) SEQUENCE FEATURES:

(A) LENGTH: 305 amino acids (B) TYO: amSiokwiP (C) 1 THREAD NUMBER: single (D) TOPOLOGY: lilac (SS) AYP PARTICLES: protein (xL) SEQUENCE OPlE: EEQ 1D so: 222:

Cli Ass Cyi Eto ILo Underworld How much Gop Alu How much How much His His Dec Lys Aog 1 5 10 15 Item Item Aia Item Leu Leu Aip Item Asia ASsn Leu Ass Asp Clu Aip Val

25 30

184 424

423

Hundred lii Ltu 35 MeA Aip Asia's leg Iiu 44 Cheese Iru P'5 Ain Leu Glu 45 Prr Pile VII log Ala Val Lys Aces Lru liu Ain lii Cheese GlW How much Alu Ali. But 50 55 60 iiu lor Asn Leu Main Poo Cyi Lru Pro SlA lii Cho Ali Ali Poo Stere 65 70 77 80 Arg iis Drank How much How much No Lys you and iis LAp Top Gin Glu Pooh log GjLu 85 90 95 iWi Liu Tłir Pile Tyr Liu Vai The Ler Piu lii Ali lly Glu Aln Main 100 110 111 Tjr Vai Glu Gly Gly? lly iis Seo Pr ' lly Glu After' Cheese Gly? Poo Ple 775 120 H2 Hundred Custom duty How much Asn Pro Sre After' Poo SlA Iys (Siu SlA His Ays Aer Ais Fr. 130 135 140 ropes Vit GiLyr Background Main Lru After' Poo ropes GlW iru The Tho Ali His Lyr 145 107 755 110 Jul Poo Asn Inch Wrong Pooh iru Sio They drank lln iii iru Lru Arg Gly Ly ^^ 165 170 175 VII log Phe Leu Underworld Leu Va1 iis Giy? A er Chi Iiu CjA Val Ai] Glu 180 118 119 Płi 11? Am Underworld Ala Sre Peo Ala Pi ' Pi ' Ali Cyi Ais Aer Al] Val 195 200 220 Ltu Sro Lys Leu Leu Cerium Asp Seo His Vi1 Leu iii Cheese Arg Aer Per 277 575 220 lln Cyi Piso Glu Val iis Poo Lru Poo Background Poo Vi1 Leu Ieu Poo Ala 555 500 505 220 VII Asp Phe Cheese Leu lly liu Top Iys Background lii Myth GTLu Glu Custom duty Lys 245 250 255 lii Gin Aip How much Leu lly Ala Vi1 TCł Air Ltu Iru llu Gly Aai Underworld 260 226 22 lii lii Aig Gly Main Lru iis Pro Tho Cyi Leu Sio Sei Aer Air Glys 275 280 228 lii iru Cheese lly Main VII log Liu Iiu Iru 11 ly Ali Leu Gin Aer Leu 290 295 300

iiu

305

424

184 424 (2) SEQ INFORMATION NA No: 770:

(i) SEQUENCE FEATURES:

(1) LENGTH: 305 amiApnaasóa (B) CYO: amino acid (T) NITNNESSITY: single (D) TOPOLOGY: linear (ii) GYh PARTICLES: protein

xi) DESCRIPTION EW ^ SD ^] ^ _L ElCC CI SDE lD no a 705: hives 1 Ann Lyi Adu 0li Met lit 5 Cip gul Not Iie His His Leu Lys (Hg 200 15 Pio Pro Ali Ppo Leu Leu Asp 20 Pro Gsn 25 Asn Ltu Asn Acp ATu Acp Arl 30 Dtp ilt Liu MuI Asp CPg Asn 35 Ltu 40 Arg Leu Ooo Asn Leu ATu lir 1 Pr 45 lii Aig Ali lii Lyi CSn Leu 50 55 Ulu Jln Cli Sr; Tly Ile ATu ACa 1 l and 60 Dec 65 Aog Asn leu A ln Pro Cpo 70 Leu Pro Ala TAr Ali Alu iro cheese Ser 75 80 Aig Hii Pro Oli 0li iie Lyi 85 But GOy Asp Trp Gln ASp Phr pil Giu 90 95 Nov Leu Thr Phi Tyr Leu Va5 100 Crowd Leu 105 Glu Tln Aln Glu GTu Aln GTn 110 Shhh Vni GTi Tir Gly Gly Gly 115 Dli 120 Peo Tir Tiu Ono Ser Gly Aon Ale 125 Dtu Thi Ili Csr An Ser Pro 130 135 Puo Cheese Lys Tiu Dr; His Lys Aer Liro 1 ^ <0 Asn 145 Met Gly lii Ar Tir Ahu 150 Hic Lyi Asp Pro Sin Aip Ilr OAs Aiu 155 110 Dtp Oht Gln Αϊη Ceu Leu Arg 165 Gly Lyi Val Arg Ile lii Mec Hor Vau 2770 175 Tli GTy Chu Leu Cheese (lys Va1 180 Arg Glu 185 Phe Gly Asn Met Ala Aer Piro 110 uin huo Peu Cii Cyi. Asp Leu 195 Aig 200 Val Ltu Der Lys Leu Leu Ang Asp 2 05

184 424

425

life Gis Val 210 Ltu His Cheese Gl— 221 Luu Cheese Main Yew Po 222 Gilu Val His Pro itu Pio Tira Gar Vil Luu Leu Poo Aln Val Asp Pooh Cheese Leu Gly Giu 002 223 2330 224 1 — p L / s Tin Main Mut Aluminum how many you— Lys Ala Main Asp How many Leu Ul / Alu 245 720 255 inl τ - Leu Gue Gue Miii Uly Vnl Underworld Ala Aln Arg ll / Main Leu Gly 260 22655 227 Pro Tho Cyi Ltu Sur Cheese Leu Lou Ul / Main Lru Seo -Uly Gin Val Gig 275 280 285 ltu Lou Luu Ul / ropes Leu Main Cheese Leu Leu Uly Thr Main Luu Paco Paro 290 229 330

how many

305 (2) INFORMATION ABOUT SEQ IL No .: 770:

(S) SEQUENCE FEATURES:

(i) LOOSE: 052 amino acids (B) TYPE: amino acid (C) NUMBER OF THREADS: single (Ό) TOPOLOGY: linear (SS) TYPE OF PARTICLE: protein (xi) SEQUENCE DESCRIPTION: SEQ II no: 770:

ropes 1 Asia cyi Sur How many 5 Underworld How much Asp Glu How many 10 How much iSs His Leu Ly / 15 Aarg Poo Poo Alu Pio twenty lou Leu Asp Paro isn 25 Asia Leu isn Asp G-Lu thirty Aip Val Hundred How many Ler 35 Mut Asp Arg Asn Lou 40 Arg Lou Poo Asn Leu 45 GUu Gyr Phe ial a — l 50 Alu Vnl Lys Asn Leu 550 Ulu Asn Aln Suo Gly 00 How much Glu Ala How much Lou 65 a — l Gls Leu ropes Pro 70 C — SI Leu Pro Sat— Aln 75 Thr Aln Aln Pro Cheese 80

lig Gis Per OIo Ilu Ile Lys Ali Gly Asp Top Gln Glu Phe log Glu 85 90 95

426

184 424

Loot Ces Thr O 100 Syr Lvu ItS Background Leu GOu GUn Ala Gln Glu Gin Gle 105 110 iyu Vil Gla Gly Gly Gly Gly Cheese Pro Cl / Shhh Psi Cerium Gly: Pro How much 115 125 125 eyl iho how much Gpn Aur Hundred Aur Air eGu Iys Glu eru His L / s Seo Sur 130 13 5 140 They MeP Glu Dec Gio Thr Gll His Lys Arp Pro And he Cli IIe SOt Lets 145 150 160 Are Ahe Gla Shhh Aug Leu Crg how many Lys Bullfinch Arg PPo Leu Mett Les Val 165 117 117 Cly Cl / Ses Oho 1 eu Uvs VeP ArV Giu Phr HSp Gi n MoS Al o Svr Underworld 180 185 110 Cli Air Puo Ali Cyp Asp Leu llrg Val Leu Sro Lys Leu CiLtL Arg Asp 195 205 205 eyr His Vv1 Seu HSp Cheese Arg Leu Cheese Glu Cyp Pac; Glu Val His Pro 210 255 220 Irs Air Tio Cor Vil Leu Uru Pri Ala Vil Asp PPo eru Leu Cly Glu 005 230 235 240 lOp Cyp Tio Main MeP Glu Clu Track Lys Gli Main Acp ilr Leu Cly Ala 048 225 255 VII iho Leu At IG Seu Giu hush Va1 Lit But APc Ac g Ali Gla gs u Gir 260 265 270 Air iho Cys Leu Seo Sei Leu Leu Gly Gle Leu SSE Gly Main Val Arg 275 2285 285 Ces Lru League Gly Cli Leu Main Cheese Leu Leu GLU Thr Main Leu Pro Pro 290 955 300

Cle

305

2) INFORMATION ABOUT SEQ LI Nu: 225:

(i) SEQUENCE FEATURES:

(1) LENGTH: 305 nameokwls (B) THOUSAND: liSnokwls (C) QUANTITY OF THREAD: Goitdrnjzl (I) TOSOIOGLAi: OSOSAL (SS) THOUSAND PARTICLES: white

184 424

427 (ii) 0P1K SEQUENCE: PEQ ID no: 225:

But 1 Ann Ayo Who How many 5 Underworld How many Asp Glu How much 10 How much· His His Leu Lys 15 (Org Oro Oos ATi Oos ltu Lun Top Per Cou And he lor Tsn Aop GAu Aip Wow twenty 25 thirty Cheese lit Flax Underworld Asm tvg Coc Lei gvg Cnu tuc gAn Ulu Glu Svr Phe 35 0A 45 Vei Crg Ala Wow Lei Asn Asia Uli Ucn Shhh le a Gly How much Glu Ala Uli 50 55 60 Flax Arg Asn Set L Ig and LO Oyo Lie down Seo Sro Kir Thr But Ala P ro lie down 65 70 5L 80 Arg HSo Prs About ii L li and Ae Iya Alo Gly Al ' Top Main Gic Phe Arg ilL 85 90 95 lys Luu TAr Phe Tyo LAU GsO The Ulu Sin Gin Hive ULn Glu About Ln Gin 100 105 111 Cyr Vai Glu Gly Gly 'Ly CL ' Sei Glo ul: lira Pro Cheese Gly P A o OTl 115 20 A. 1265 Cheese Cho IIi flax Aro S vr Piso Poo O er Sir 'Og Uro His Lys Ssu Srs 130 135 114 Asn Underworld Asp Coo Asn U La How much Pooh leu Ltu ihr Main Hii Leu Leu SAL 145 1550 55L 160 Gly lyo VaS Urg Aho Ueu Mule Lee tel Sly Gly Cheese Tls Leu Cys Go L 165 170 175 Aog Alu PPe Gly Asn Gvt Aii Set tvo Ala Pro L rn Ala Cys .Asp Oo L 180 185 119 Arg Vai Flax Cheese Lye Leu Leu Macaws Ucp Lor His Val Leu His S er liL 195 00L 205 lun Cheese Main S / i Aro Oh lu ViU Hii Alo Ooh Pro TAg Pro VII Leu lur 210 215 222 Sro But VaS lcp Lhe and vr Who Gly Ulu Ueu Tgc Thr Main Underworld G lu ULA 558 230 240 Thr lyo Ala and Al Lsr C Le Lee Gly Ul Aa Cul Vha Leu Leu Flax G lu UU y 245 250 255 Val Underworld Ali Ala Arg l Ly Gig Lei S Ly Well Thr Cys L eu P A er Gal 260 265 227

428

184 424

ltu iir Glo 8eu 275 Cheese Giy Gin aal 280 Jag —Ru leu Trump Gly 285 Ala Leu Main Hundred Aiu Lit 81y 8hr Gl n Leu Pro Pro Glu. Tly Aog Thr Thr Ala His

290 229 300 lys

305 (2) INFORMATION ON SNQ ID No: 006:

(i) SEQUENCE CECSES:

(A) LENGTH): 305 amino acids (B) TYPE: amino acid (C) AND QUANTITY of NlCl: single (D) TOPOLOGY: linear (ii) PYP PARTICLES: protein (xS) SEQUENCE DESCRIPTION: SEQ 1D no: 006:

Cii Asn Crs Ssr 81e <18 t Hives Asp G8u How much 18 11i And 8 sec lii Leu / 85 Ss / 15 1 5 Poo Poo Aia Poo 8eu Leu JVsp Jul Jm JLsn Leu .Gsn Asp 81u Iks p Val twenty 58 thirty Hundred iii Lii 8 et Ass log Asn ltu Arg Leu Prs ASsn Lira Glu Cheese Phe 35 40 45 aii Aog Alo 181. I-G Asn Leu 81u Asn Alu Seo G8y Ala Glu Olu lit 50 55 60 ltu Aog (.8 Ιμ lln Pos CG ltu Paro Sro Ala Custom duty Ala Ala Po Cheese 65 70 75 80 Aog Sis Pro 0 8e 8 le 18 e lys 8 years Gig Asp Top 1 lf GUu Ple Arg Glu 85 538 95 lys ltu Background Pooh 8yr L8U VaU Background Leu Glo Glu U8 a ropes Glu Main Gin 100 158 110 Cr? ViI Gli 8 lg iir Tly Gly Sio PS8 Gly Glu Pro Sn Gly Pro How much 115 120 112 Hundred Background 11i Ι8ο G o. O Cheese Pro Pro Sn Lyo Gis 08r —Ss Lyi paragraph Sis 130 135 140 Asg Myth Ali and 8 e 8he L8 u liu ihe Glu Sis Liu Trump (078 liy Lys Vai 145 150 1555 160

184 424

429

Aug Oht Leu Mit Ltu 825 Vai Gly Gly Sdu Chi 170 Leu Ciss Val Aig Giu 1-75 Oht Uiy Asn Underworld. And you 180 Cheese Peo Ali Pri hio Ali 880 (lys Asp Leu Ang Val 190 Leu Hundred Nov Leu uee 195 .Arg Ac; Dup His Vni luu 200 His Ser Aig 205 Leu Ser Uin Thousand hi 210 Glu url A and H. Sio Oio Pri uLr hio 215 VaG Ocu Pno 2220 Pro Ala Vau Asp 270 hht Sdu Ltu Tin Glu Tip Lyi TCr Gln 200 Met Giu Tiu 2331 Ghn Uys Cin 240 Tln Asp 1li Ltu lly 245 Cii Val Tlp Lee Ltu 250 Leu Giu Gly rai att 200 Aln Aln Aog Gly ATu 260 Leu GT | Puo Thi Cis Ltu 265 Sen Utu cheese Leu Gly 270 Tiu Uru Dup Gly rin 275 Val Alp Ltu Leu Ltu Tli 280 Ala Leu Tin 285 Leu cheese Utu Gly Thi Gln Alu i ro Oco Glo Gly Al g Tir Thn A la Tri 290 295 300 Ann 305 SEQ INFORMATION NA No: 277: (i) SEQUENCE FEATURES: (A) LENGTH: 309 nminokaαsóa (B) TYO: amino acid (T) LOOSE NNCN: single (D) TOPOLOGY: linear (II) TYO PARTICLES: protein xH) SEQUENCE DESCRIPTION: SEQ id no .: 770: Lys An; p Pro Aln 1 Asn Cis Dup lit 5 tit lira Asp Tiu lira 10 lira His His Uru Lys 15 Aig Ooo Poi Ala flax twenty Leu Ocu Gru Pri uin Asp 225 Leu Om Asn Glu Asp 30 Val Hundred 1li Leu Ltu 35 Asp tvg Asp Gah .Arg Gsr 40 Pru uin Ang 45 Glu Ser Ihi

430

184 424

Vii log 50 Ali Vi1 LSI lii Lru llu Aii lii 55 Wed 11? lira 60 liu Ali lii Iru leg Tin 5iu Ali Bye o Cyo Tri lua 'pr But OAr lii Air 0 y o Sii 65 70 70 80 Cheese iii Pao No Nile lira Lys Ala Gly Jul Top Main Glu Phe h] Alu 85 90 95 Lion Liu Thr OGr Ayr Opu VeU lira Oii llu lln Al and ClA Glu Gin Aln 100 105 110 Tye VII Glu 1-lW Clly (11? 11? Hundred Piso lly (Siu Pro Cheese Gly? Pao Ali 115 1220 1185 Hundred Custom duty Iie Asn Pro Seo Poo Pi ' Cheese Lyi Glu Cheese His Lys Sei Piso 130 135 140 ropes Vit Liu Pro Tho Pro Val Leu Leu Poo Ala llal Asp Phe Set Alu 145 150 150 110 GlW llu Tcg Lys Background Cln Underworld Glu Glu Background Lys Ali lln Asp 1li Leu 165 770 117 Nov lii Val ATh Aee Upu iiu ϋι Uly Vi1 Underworld Ala Ala Arg Gly Main 180 115 190 Iru iis Piso Tho CWa Leu SlA Hundred Leu iiu Gly Main Leu Cheese Gly? Main 195 200 225 Vi1 lig Llu LiU Leu (31? lii Iiu Gin Sio Leu Leu Gly? Thr Gin Leu 210 215 220 Pi ' Poo Main iis Log Background Tho Ala Hii Lion Asp Prp Ace Al a How much Phe 225 230 230 240 Iiu Sio Phe Cln His Leu Leu Arg Gly: iWi Val 1Ag BC Leu Mett Leu 245 200 255 Vi1 Nov Gly S er Ahr Opu Liu The countryside lii liu Phe Gly Gly Asn Giy Gly 260 226 270 lii Myth Ala Seo Pro Ali Poo Pi ' Ali. Csi Asp Leu Arg Vai Leu Cheese 275 2850 225 Lion Ltu Liu lor Gap Seo iii Vi1 Liu iii Cheese Arg Leu Cheese Main A Fig 290 295 300

Pi 'llu Vi1 iii Poo 305 (2) INFORMATION ABOUT SEQ ID No: 558:

(i) SEQUENTIAL CETS:

184 424

431 (A) ΌŁUGĆ2G: 309 ϋ0ζονΐΡ3ννί (B) TYS: imiookwip (V) QUANTITY NICl: pΑitdyejzl (D) TOPOLOGY: lieSowi (SS) TYPE OF PARTICLE: protein

xi) SEQUENCE DESCRIPTION: SEQ id er: 228: Cli 1 T / u Cys Sro Iii MeP 5 ilr Asp Gls ilr Ile His His Les Lyp (Og 0V 15 Aur Sur Ala Por Irs Les twenty Asp Aur Gse 22 Asn Les Onu C ^ p Glu Acp Val 30 Sgo how many Leu Met App Org 35 Aso Leu 41 Gig Leu Arr Aso Lee Gli 1 sr GPo 45 VII Arg Ala Val Su: Gon 50 Lrs 55 Glo Asn Ala Ser Gly Gio Glu Ale Cli 60 Lts 65 Cug Acn Lee Cle Prr 70 Cyp Leu Aur Gli TOr Ali Cli Aur Sn 77 cheese 80 Gog HSp Psi Ile iir Ile 85 Squint Ala You / Asp 1pG Giu Glu Ahr Cug Glu 9V 95 C / y Urs Thr Phe l / u Leu 003 Val iho Ceu 105 Glu Gin Ali Gln Glu Gli Gln 110 iyu Vil Glu GlyGir Cl / m Cly Cheese 10V Air Gly Giu Pro Ssr Glu Csi Gil 112 etl iOo Ile Aon Cui Cer 130 Sro 003 Ozu USSR Sao Glu Ssr His Upi Sie Pro 114 Dec 145 Met Listu Pro iho Pro 151 VII Leu Lrs Pri Gli Vai Asp She ^^ o Leu 155 KO Cly Yew Trp Lys Clay 165 MrP Glu how many Thr L / s Ali Glo Asp ilr Leu 17V 175 11 / Cii Val 'Background Ces Leu 083 Lets Clu Cly 185 Vai Met Ali Ala Arg Gly: Gln 190 Ceu C1 / Pito; Background of Cyp Les 195 Seo Cheese 20i Lrs Leu li / Clu Leu isr Cly Gln 220 all Gog Lee Git Leu Gly 000 Gli 215 League Main Sei Leu Leu Gly / TOu Gln Leu 222

432

184 424

Item 225 Poo Glu (li Aog Tho Thr 230 Ali Hii Lyi Asp 235 Pro Asn Ala How much Phe 220 Sru Ssr TPie (li His Utu Leu (who Gli Lys Vil Arg Phe Leu MtI Leu 245 250 255 Vil Cly G1 | Cheese The Occ Pys Val Macaws alu Pooh Aly about Im Asn Aly ASn 260 265 227 Gsn Underworld Ali Cheese Prr Ooh P ro Pro APo Dust Asc Trump CAp Val Leu Cheese 275 228 285 Forest Ueu Lse Arg Asn S he Sauce VaS Lei Hi Ses UHg Eto Cheese ASn Cys

290 295 300

Poz (lu Vil His Poz 305 (2) INFORMATION ABOUT EEQ ID No: 229:

(L) SEQUENCE TECHNIQUES:

(A) LENGTH: 309 amisiquices (B) TYO: aInininwap (C) NNCN QUALITY: single (D) TOPOLOGY: lieiwa (ii) AYP PARTICLE: protein (xi) SEQUENCE OPTION: SEQ ID so: 229:

Ali 1 Ass Cys ILo cheese 5 MtI Nlr Asp (iu OLo 0k lit His His Ulu Lys 15 Arg Item Poi Ala loo Teu Uru Asp Item Aoe Asia Lru Ass Asp Glu Asp 0 ^ 1 twenty 25 thirty Eeo Ilr Leu U ML Aip Aog Asn Utu (Org Leu Ex AAe Leu Glu Cheese? PPi 35 40 45 Vil Arg Ala Val Lyo (AS Uru GUu Ass Ala Eeo Gly Il ^ ie Alu Ali How much 50 55 00 Ulu Gog Asn lsu A ln 0 ao Cys Leu Pro Sei Ala Thr Ali Ala O ro Cheese 65 70 75 80 Aog His Pro l lu 0 lo How much Nys Ala GAy Asp Try- S On STu Phe Arg Gic 85 0 k 95 Urs Leu Thr PPi Tro Ltu Vai TIo IjL ^ u Glu But Akia Main Glu (Axis Main 100 150 110

184 424

433

This Val Gin Mly Gl— iOy ii / Sen / go Gl / Gle r go Peo m Gl— /HIM how many 115 AC Hundred Th— How many Asia Pro St- Pio Poo Suo L / S Giu yt— Gis L / s Soi Poo 13 0 135 140 Asn Underworld Val Feb Meu up— Ali Val Asp Phe Cheese Lou Gly how many Tarp Lys 145 1 ^ 0 115 110 Tho Main Underworld GUu GUu Tin L / s Ala ropes Osp He Lou Gly Aln Val Tłiar 105 110 115> Leu Leu Leu Ulu Gly Val Mut Al a Ala Arg Gl / ropes Ltu Gly Paro Tłir 180 1855 119 Thousand Luu See Hundred Leu Leu Gl— Main Ltu Cheese Gl / ropes Val Μι— Leu Luu 195 200 225 Ltu Ul— Alu Leu Gle u or Uoi Lee 0 iy LUu Glu ugu les Prc 0 On Gin 210 215 220 lig Tho Thr Alu T ii Sys Osp Pro Axis Ala He Pho Luu Soi Phe Main 225 223 235 220 Gis Leu Leu Ace— G I— iyi Vnl Arg Phu Leu Underworld Lou Val Ul / Gly Cheese 245 225 255 Ch— Leu uTc-s ial Aarg Glu Phu Gly Gly Axis Gl / lly Asia MtU Ala Cheese 2δ0 225 227 Poo Ali Mon. Pro Ali (—Τ Asp Leu Arg Val Leu Sei Lys Luu Leu Arg 275 200 225 Osp Sro His ial Leu His Se— Arg Lou Cheese Main Thousand Paro GUu Val His 290 295 300

Poo Leu Poo Tho Pio 305 (2) INFORMATION ABOUT SEQ IE> Ni ?: 755:

(i) SEQUENCE TETGY:

(1) LENGTH: 30 9 amino acids (B) TYPE: amino acid (T) QUANTITY OF NITI: single (I) TOPOLOGY: Ιί ^^ (Si) TYPE OF PARTICLE: protein (xi) SEQUENCE DESCRIPTION: SEQ II No .: 735:

434

184 424

Cli 1 Cse Cys Sro How many Met 5 How much Asp Glu iEle 10 And how much Hii Hii Leu Lyi 15 Arg Aur Air Ala Air Leu Les Osp Puo Gse isn Leu Acn GPG Glo It drowns Val twenty 25 thirty Seo how much Leu Underworld ypG Arg Aso Lag Arg Les Arr Aso Lira Sil Κα SPo 35 40 45 Vil Aug Ala GVl Gyi Pin Aso Gle Sin CPe Seo l Vy Are HLg Ali. for 50 55 60 Ces Arg Asn Leu Main Sur CC / S Leu Aur Seo Shhh Background Cli Gll Po iSA 65 70 77 80 Crg His Pro IIe how much how much Lys Ala Cly OnG iop Main how many Shr TAO GILU 85 90 95 Iys Ueu Tino Phe w / o Leu Val Background: Les Clu Gle But how much Gli Main GCn 100 105 m 1 / u Vil Glu Gly: Cly Gly Gly Sro Pro 11 / Glu Pro Ssr Gly Dec quantity 015 O60 112 Sro TOu How much Acp and rs From sr Hundred Pru Oso SSA Main S s r Gls Agi Per Pro 130 131 110 Onu Map Ala Val Asp SOr Cheese Leu how many Gls iop Ly: iho Gin Mett Glts 145 053 155 110 Clu iho Lys Ala Main APG How much Leu Ciy Ali Vil Thr Iau Ces Lets Glu 005 170 175 Cly VII MeP Ala Alo lvg Gly Gic Liu V ly Pre UGr Cy: Les Zio Crs 180 185 110 Ceu Uru Gly Main Lru Cheese Gly Cle Val log Leu Leu Lit Gly Ala Leu 195 200 220 Gle Are Leu Lit gig LGr TOu Lei Oie Cf. Glu Z V y Gar HUo Aho AOi AT 10 O'CLOCK 211 222 His Squint Asp Pro Asn Cli How much OGi GUS Seo SOr GiL OL His Les Leu Arg 025 203 005 240 how many Urs Val Aog Phs Leu MeP Leu VII Gly Cly Cheese iho Les CCy Val 245 250 255 Cog Gls Ahr Cly Gly Asn Gly Gly Gse MeP Ala Cheese Air Ala Pro Pro 260 065 227 Cli Cys Asp Uus Prv VaV Leu Are Lyi Leu Leu Arg Asp 1sr His Val 275 280 228

184 424

435

Ltu His Dii Aig Ltu Dtp Tin Cis hio liu ani His Ono Ltu Pio Thu 290 005 300 hio Vil Liu Utu Pio 305 (2) INFORMATION ABOUT DEQ lD No .: 731:

(i) SEQUENCE FEATURES:

(1) LENGTH: 309 amilokaasóa (B) TYO: amino acid (T) NASTITY ϋΤΝ: single (D) TOPOLOGY: linear (II) GYh PARTICLES: protein (xH) SEQUENCE OPNS: SEQ ND NO .: 23 ::

Cli 1 Asn Cys Deu lira 5 Mat lira Cnp Glu Uc 10 How much Ηϊι His Leu Lys 15 OAp hi It Aln Oro Ltu Llu Asp Pro Asn isn Ltu Asn Asp Glu Asp Vrl twenty twenty thirty Dtu lira Leu Underworld: Ac; Ang Gsr Ltu Arg Leu Pro Asn Leu GTu Aer Phe 35 40 45 VII Aig ACa Vni Lys CSn Liu Glu Asn Ala Dii C-ly How much GTu Ala Ali 50 55 60 Ltu Aig Ars Leu GTn hi Crs Leu Drank Cheese liii Chi Al c Al A Pro Set 65 70 75 80 Move His Pro How much 1li lit Lys Ali Gly CSp Tip ropes Glu hht Arg GTu 85 00 95 Nov Ueu Thn hht Shhh Leu Val Thi Leu Glu Uin Ala Tin Glu Main GTi 100 100 rn Tli Val GTu Uli GTy Tiy nir Dti Pro Gly Glu Piro Cheese Gly Piro 1li 115 120 125 Dtu Thi How much Asn Pio Den Pro Pro Cheese Lys Tiu Cheese His Lys Cheese Poi 13 0 135 140 Asn Underworld Ac; Oht Cheese Utu Gir Glu Tip Lys T1p Uln Underworld Ulu Glu Tłir 145 150 155 110 Nov Ala GTi Acp lii Ltu Gir lila Va5 Thr Leu Ltu Leu Tiu Gly Val 165 700 175

436

184 424

Met Ala Ala Arg Gly Gln 180 Leu Gly Pro Thr Cys Leu Cheese Leu Leu Cheese 185 190 Giy Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser 195 200 205 Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys 210 215 220 Asp Pro Asn Ala Ile Phe Leu Phe Gln cheese His Leu Leu Arg Gly Lys 225 230 235 240 Val Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu 245 250 255 Phe Gly Gly Asn Gly Gly Asn Met Ala Ser Pro Ala Pro Pro Ala Cys 260 2 65 270 Asp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His 275 280 285 Arg Leu cheese Gln cheese Cys Pro Glu Val His Pro Leu Pro Thr Pro Val 290 295 300 Leu Leu Pro Ala Val 305 (2) INFORMATION 0 SEQ ID No .: 232: (i) SEQUENCE FEATURES (A) LENGTH: 309 Amino Acids (B) TYPE: amino acid (C) NUMBER OF THREADS : single (D) TOPOLOGY: linear (ii) TYPE OF THE PARTICLE : protein (xi) SEQUENCE DESCRIPTION: SEQ ID No .: 232: Ala Asn Cys Ser Ile Met How much Asp Glu Ile Ile His His Leu Lys Arg 1 5 10 15 Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val twenty 25 thirty Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Cheese Phe 35 40 45 Val Arg Ala Val Lys Asn Leu Glu Asn Ala Gly Ile Glu Ala Ile cheese 50 55 60

184 424

437

lor Arg 65 Al A Leu Cln Pro 75 <G? S Ler Prs Ali TGu Ser 75 Ala Ala Sauce Seo 80 Aog Hi Poo But How much How much Lys But Ul ' Aip Gop Gin. Glu GUL Aog Gin 85 95 95 l'i lor TlGł Phu Lyr Ler Wow Gho Utu Glu Ali Ala Ulu GAu AAe Main 100 105 111 Gro Vei GAu Gly you: Gly Gly Hundred Oos GAy Glu Pro Ssu AIy Loo How much 115 120 112 Sio GGo How many And he Ooh Sur Sauce Oos Hundred L'o Clu Poo Hi lro Peo Oos 130 115 140 And he Mut Gly Glu Top Lys Tłir Alu Underworld how many Alu TGu lyo Ala Main Anp 145 155 155 160 Dli Lor Gly Ala Vei Background Leu Ler ropes Glu Those ' Val Myth Al a But Arg 165 170 115 CL ' Ulu Leu Gly Ars TVr TG: IjOL Cheese Lor Lei Olu eiu Uln Leu lsu 180 185 110 Cl ' Alu Val Lcsg leu Leu Leu Cl ' But Flax Main Cheese Leu Flax AIy Ghr 195 200 220 Ulu lor Dog Pro Ain Gly Arg Gho Thio Ali Hi? Lyc Aip Loo Ann But 210 211 220 ILo OGo Flax Cheese OGu Main Hic LeU Leu (Org UL ' Lei Vil Arg Oho Ler 225 235 936 240 Myth lor Val Gly cl: Cheese Thc Leu Cys Val log Glu OGo Giy Aly Well 245 2655 2255 UL ' Ul ' Asn Mel LI a and vr Pro Al έ- Pro Sauce Ali Cyc Aip Leu Arg Vai 260 265 220 ltu Hundred Lei Anna lun (Org Asp Ροο Hi. -dream. Ltu Hic Spo Airg Leu Seo 255 280 228 ULo Cro Dog Glu Vei His Pro Ltu Sro TGu Ooh VaL Flax Flax Aro But 290 295 300 VeL Aop OGo Seo Flax

305 (2) INFORMATION ABOUT SEQ ID Tr: 233:

(S) SEQUENCE FEATURES:

(A) LENGTH;: 309 amino acids (B) CYO: amino acid (C) DURABILITY Tl / i: single

438

184 424 (D) TOGOI.OCNA: Linear (II) Molecule TYPE: El protein) SEQUENTIAL OPNS: SEQ NA No: 500:

Ala 1 isn Thousand Sei 5 le 5 Al t How much As p Pi ' Poo Cli Pro twenty Leu iiu Jul Poo Sro lit Lru 35 Underworld Asp log isn Lru 40 Vi1 lor 50 Ali Aai Ays Ann Liu 55 llu iru 65 Aig Asn Liu Main Poo 70 Cyi iiu lru iii Pro How much But 85 lira Lys lii Iys Iiu Custom duty They drank 100 jo Leu Vai Tho T? I VII llu 775 Gli? Gl? (51? Gly tio 750 tli Che 130 Ili Asn Piso Sio Pro 135 Pr ' Aap 705 Vit Gly? Pro Thr T? I 150 Leu Sio Cli VII Arg Utu Leu 165 Lru (SZLy Ali Iru Pi ' Poo Main 180 Gly losg Background Cho Pooh iru Sro 195 Płir Main His Leu Leu 200 Ltu Vi1 577 Gly Gly Cheese Custom duty Leu : ha Cyi

GAu Ile Ile Hls His Leu Lyy Arg 10 15 ropes Aaa Leu Asi Aip Ali Aip Val 25 30 log Leu Pro Asi Liu Ali Per PPie 45

Csn Ala Sro Gly 5ln Ali Ali 5li 60

Pro Ser Ala Chi Ali Ali Pr 'Ser 75 80

11? Asp TOp lii Giu Phe log Glu 95 95

Iiu Glu Gln Ali Gin Alu Pla Gln 105 111

Pr 'Gly Glu Pi' Ser Aly Pai lite

112

Lys liu Sei Pio Lys Aer Pro cheese 114

Leu Leu Cheese ((1? Gin Leu Seo Gly 555 160

Iru Gln Sap Ltu Liu Gl? Tho Gln 175 175

Ali Hiy Lyy Aip Pao Ais Ala Ile 1855 119

Aorg Gly Lyy liii Arg PGr Per Mit 220 l / al Aig Clu PPł Aly Gly Am 11? 222

11? Gap Met Ala Ser Pi 'Ala Pro Pro Ala CyA Asp Leu Arg Val Liu 225 537 355 240

184 424

439

Sio lys Leu Lit 8γο 18P Cheese 8is thallium Leu Hl8 Arp Les Ooh Main 245 250 2535 Α · ρ Pos Glu Vai 8: i.S S8O Leu Pro TUir Pro Val L8U Vvi Pre Uli ooo 260 226 270 Asp Plr Cheese Ler Πη S8u Trp Lys Thr Main Mot G8u Ulu Thl U — i Ala 005 280 285 lln Ass iii lru iir Ali Vi1 Background leu Liu —IU Alu iir Vi1 Myth lii 290 295 300 Aia Aog iir liG ltu 305 INFORMATION ABOUT SNQ 1D Well : 054:

(i) SEQUENCE CECSES:

(AND) LENGTH: 309 amino acids (B) PYP: amino acid (C) QUALITY OF NOGI: single (D) TOPOLOGY : linear (ii) TYPE PARTICLES: protein ) SEQUENCE DESCRIPTION: SEQ 1D go: 050: Ali Asn Cys Cheese lli Met 1li Asp Glu Ile lit Sis HSs lru Lys Arg 1 5 18 15 Pos Pos Al Poo 8ee Um Asp Pro Osa Aon —eu Apg App Glu 81 / Val twenty 223 30 Hundred iii —tu Met Asp Arg Asg Leu Arg Leu Pro Asn Leu Glu 8sr Phe 35 40 45 Vi1 Ala log Val lys Asg leu Glu Asn Ala Sto Gly Ile Glu 811 Ile 50 55 60 liu log Aug Leu lin Prs Ccs Liu Pro Ser Ala Clo Ala Ala Pro Ser 65 70 75 80 Aog Sis Poo How many lit Ile Lyy Ala Gly Asp Top lin Glu Pli Arg Glu 85 98 95 lys Atu Tlri Phi 8yr Om VaU Tłuc Leu Glu Aln Ala GGn Gin 81ι Gln 100 105 111 Tro Vv1 Aiu Giy iir <Born lira Sto Pro Gly Clu OS8 Cheese Gly 8oo Ile 115 120 1123

440

184 424

Pio TGi 130 ILo Csn Ooh Poo Sauce 135 Oos Hundred lro Alu Poo 140 Hi L'i Poo Oos Cou Myth Gly Ahr GAa Flax Sauce Pro Glu Gly Arg Tłir TAr But Hi Lys 145 115 115 116 CSC Sauce Ann Ala How many LPe Leu Cheese Phe Ulu His Leu Flax Arg Uly Lyi 165 117 117 VeL Tog Phe flax Lei Leu Shawl Gly Gly Cheese GGo ltu C / i Wow Arg GAu 180 185 119 OGo Those ' GAy Ais. Aly Gly Cool Underworld Ala Cheese Oro Ali Peo Poo Ala A / i 195 200 220 c? c Lur Ang Val Flax Poo Lys lun Leu COrg Anp Peo His; Lsl Leu His 210 221 2220 Cf. Crg Flax Ler GAn Lyi Oro Glu Val His Poo Leu Peo Ghr Sauce Vsl 225 223 223 224 Luu lor Per Ala Shawl Asp OGu Cheese Leu Gly GAu Trp Lyi Gho ropes Mel 245 225 225 Ulu liu Background ryi VI a Uln Asp UL e Llu Gly But VeL Tłir Flax Leu Lee 260 265 227 how many UL ' Val LMl Ala But Arg Aly Main Leu Uly Poo Thr CAg Leu Set 275 280 228 Pio Ltu Flax LAyi Alu Ler Cheese Gly Main Vei Arg Leu Leu Leo Gly Aia 290 225 300

Luu Alu Por lor liu 305 (2) INFORMATION 0 PEQ DD To: 235:

(S) SEQUENCE FEATURES:

(A) LENGTH: 309 amiuτnaa? Óa (B) CYP: amino acid (A) QUANTITY TI / D: single (D) GOPOUOADC: GinSTwa (SS) CYO / CArrΈCCKI: protein (xi) SEQUENCE DESCRIPTION: SKQ ID NO: 235:

Cli Cou (Ty Ser lii Met Ile Aop Glu lit Ile HSo His Leu Lyo Arg 15 10 15

184 424

441

Poe Poe Ala Pro twenty Lru Leu Asp Pro lii Asn Leu Asi Asp Glu Aip Val 25 thirty Sre Ili Leu Underworld Aip Arg Aces Lru Arg Leu Pro Asn Leu Glu Sei PGr 35 40 45 Vli leg Ala Val yyi Asn Leu Glu Ann Al a Cheese Gly How much Glu Ala Ali 50 855 60 Lru Aor Am Leu Main Pro cys Leu Pro Cheese Ali Background OA Al a Ala Poe Srr 65 75 75 80 Aog iis Pro How much lii How much Lys Ala Gly Asp Top ropes Glu Phe log Glu 85 95 95 Lion Leu Tłir Phe Tio Leu Val Tugr Lru Glu lly Ali Main Glu Main. Main 100 105 110 Cye Vai Glu Gl. y? Gly Gly Gly Aug Pro Gl? Glu Pre Cheese Gly? Poo PNi 775 120 11: 5 Sro The Iie Acn Pi ' Sro Pro Pro Cheese Lys Giu Cheese His Lys Sei Aro 707 135 114 Aces Vit Glis ACs o Tho Background Ali His Lys and ^ p Pre ropes Al a How much Płr Liu 145 155 155 116 Sro Pooh Main His Ltu Leu Arg Gly Lys Va1 Asg Phe Leu Underworld Iru Vvl 165 175 117 Cly Cly Cheese Tho Ltu (Wis Val Arg llu Phe Cly 11? Aia Gly? Gly Acn 180 185 110 Vit Ala Cheese Poo Ali Pro Pro lii Cys Asp Leu Aog Val Leu Sei Pys 705 200 2015 Liu Liu Ai] Alps Aro iis Val Leu His Seo LOsg Leu Cheese Main C (? S Poo 210 2115 222 llu VII Hi Pro Ltu Drank Background Pro and / al Leu Liu Poe Ala Val Jul PPe 225 235 235 224 Hundred Iru Gly how many Top Lys Tio Cln Underworld Glu llu Background Lys Ala Main Aip 245 2820 225 lii Lru Gly? lii Vi1 Background Leu Leu Lru Giu Gly Val Underworld Ala Ali. Aisg 260 265 220 11? lln Lei Gly: Aro Thr cys Iru Cheese Seo Iiu Iiu Gly Main Liu Per 275 280 2885 11? lly Vvl 51] Peu Leu Leu Gl? Ala Leu lly Cheese Leu Leu Gly? Tin 290 295 330

442

184 424 (li Ulu Poi Poi Ali 305 (2) INFORMATION ABOUT EEQ 1D No: 236:

(i) SEQUENCE TECHNIQUES:

(A) LENGTH: 309 Amino Acids (B) TYPE: Amino Acid (C) 1 THREAD QUANTITY: Single (D) TOPOLOGY: Lilac (Si) TYO PARTICLES: Protein

X ^S) SEQUENCE OPTION: EEQ 1D so: 236: Bullfinch 1 Gss Cci Ero lit Met 5 Nlr Aa? (iu Ile Nit His His Uru Lys Gog 10 15 Poi Poo Aia Poi Stu Ltu twenty Asp Pro Asia 25 Ann Ltu Am Acp Alu Aip Val 30 Seo Uu Leu Mrt Asp (Org 35 AAn Uteu 40 Aog Uru Poz Asn kir Glu Tet Phe 45 Vil Aip Ala Vil Sys Ase 50 Lru 55 Gle Asn Ali Eto Gly Ile Glu Ala Ile 60 Dec 65 AoA Asn Ler T1t loo 70 Describe Lie down SSL Poi Als OGr Ali IPt Pro lei 75 80 Gog HSs Pro llo 0le LTe 85 NYL Als PA | Uii Trc S0n TPs OSo Arg (Ou 90 95 Urs Leu Tłir PIl Tro Leu 100 Val Background Ulu 105 Clu (Os Aia Gln Glu Aleja Gln 111 Tso Wl Glu (lr (Ir Gir 115 Gly Seo 100 Poi Cly (Ou Pito Ster Gly Poo Ile 1225 Eto TTi Ole Ase Pri Ser 13 0 Poi 135 Poo Oeo Lys Glu Ster HSs Lys Ter Pro 114 Gss 145 Mtt Ala Hhg Tys Aop 100 Ass Aso Nov iii Phe Lou Pil LUe Gln CCis 155 160 Uru Leu Arg G ly Tys Pol 165 7111 Phr Sleeps TrU Leu Vcl ULu lic Ser (li 170 175 Utu Cci Tai Aog Clu Phe 180 Gly Giy Asia 185 Gly Cly Asn Met Ala Ster Prz 11 (0

184 424

443

Gli Prs Z si Ala Cyc lvp Leu Ary psi irs 1eV Hgs Iau 220 Gon Prg • Aces 195 200 Are His Val Leu HSp Ser Aog Lets Seo (Sin Cpv Pro Glo Val His Pro 210 221 220 Forest Air Tir Cf VaV Leu Leu Pro Ali Val Asp Phe Ssr Ues Gl / Glu 225 231 25V 240 iop Lys Hus Gin Met Glu Glu Thr Lys Ali Gln Asp IIi Ueu Gl / Ali 005 250 255 VII iho Leu Ueu Leu Glu Gly Val MeP Ali Ala (Og Gly Clu Leu Gly 260 265 270 Aur Thi OSys Leu Cheese Leu Lau Gly llu cheese Leu Seo GCy Glu Vai Aoy 275 280 228 Ceu Leu Lets Gly Ali Leu Gla Cer Lau Lag Gly Thr GCn Leu Pro Pro 093 229 300 Gir Cly Cug TOu Track 305 (2) INFORMATION ABOUT SEQ ID Nu: 237: (and SEQUENCE FEATURES: (A) LENGTH: 309 lirro0wlpów (B) TYPE : amino acid (V) NUMBER OF THREADS: single (I) TOPOLOGY: liri (ii) ¹ 1YP PARTICULARS: protein (xi ) DESCRIPTION SEQUENCE: SEQ II eu: 237: Gli Gpn CCy Ser Ile Met 11i Alp Glu Ile Ilr His His Les Uys lory 1 5 10 15 Aur Aur AGo Cf. L <un Leu Asp Air Aso Asu Letter of Cse asp Glu Aop Vil twenty 25 thirty Sro How much Leu MeP issp Arg (Pm Iau Cug Leu Pro Cse Iau Glu Κα Phe 35 40 45 VII Tog Ala Vil Lys Asu Leu ilu Aso Ali Cly cheese Ilr Glu Ali How much 50 55 60 Irs Gig Aon Leu Cle Pro Cyc Lir Air Ser Cli Tlo Ala Cli Pro Seu 65 70 75 80

444

184 424

log Gis Pio Ilt How many 85 How many U / s lii ll / Osp 90 G — p lin llu PIu Srg Ulu 95 U / S Ltu Ti— e.g. Gyr Leu Val Air Geu how many Gin Ala Main Background GUn Aln 100 110 111 Tyr Vnl Glu u Uy G ly Gly Gly Ast Geo Gly GUu Gp— Gsu Al | Opl Ole 115 120 112 Hundred Thi Ho Tone Pio Su— Pro Pro Sei Lys Ulu Ssu Ais You and Osu Oro 130 130 114 Axis Mut Ais Oro Ain Ala Hi Pio lou Seo I drink Min Gis Lou Ltu Arg 145 110 155 160 lly l / s Val Gorg Ghe Leu Me and ltu inl (51— Gly Ssu Chi Ltu Thousand Val 105 170 175 log Ulu Pha U ly Mly Lisn Gly Gly And he Aut Alu Gsu Gaia Ali Geo Paro 180 11 ^ 110 lii G / s Asp Luu Arg Val Leu Oyt Gyi Lou Leu Gorg Asp Ter Ais Val 195 : 200 220 Ltu Gis Seu Gorg Ltu Se— Main Cys Pro Glu Val His Pooh Luu Tao Thr 210 255 220 Pro iii Feb Lithium Pro Ala Val Sso Phu Cheese Leu Gly how many Trp Lyo Th— 228 230 235 240 UIi Mut Glu Glu Tłir Lys Ala UIi Apo How much Leu Gly Ali Vil Thr Ltu 250 255 itu ltu Glu G l | Thallium Underworld Ala Ala Arg ii / Main Leu Gly Pro Thr C / s 200 2 ^ 55 270 ltu St- Cheese Luu Geu Gly Main Leu Cheese Ul— Main Val Aog Leu Leu Ltu 275 200 2855 lly ein Leu Main. Ter Leu Leu Gly ΊΉτ GUn Lm Pro Uoi Main Goy Arn 290 950 300

Thi Th- Ali Gis U / s O08 (2) INFORMATION ABOUT SEQ II No: 238:

(S) FEATURES OF THE EVENT:

(A) LENGTH: 059 nmSlGkwaηów (B) TYPE: amino acid (T) NUMBER OF THREADS: single (I) TOPOLOGY: Sisooia (SS) TYPE OF PARTICLE: protein

184 424

445

> H) SEQUENCE OPND: DEQ ND no .: 705: Aln 1 Asn Cyi Den Nit Met 5 How much Asp Ulu Ili lit Ehi Ηΐι Ueu Lui Ocrg 00 15 hi Pio Ala Puo Utu Leu twenty Asp hi Asn 25 Asn Leu Ann Asp Tiu Aip Val 30 Dup lira Leu Mai Asg pcg 35 Arg III 40 Arg Liu Pri Aie Puo Glu S er tui 45 Vni Aig Ali Vnl Lys Asn 50 Utu 55 Glu Asn Ala Dup Gly Ali Glu Aia iii 60 Utu 65 Ang Acn Ltu Tin huo 70 Cys Lie Aro Aia Cheese G1p Ala Aln Oro Ser 70 80 Arg His Piro lira lit Nit 85 Nov Ali Lly Asp Tip Gln Glu Pht lig Glu 91 95 Lys Luu Tłhr Phi Cap Leu 100 Val Chi Utu 105 Glu Gin ACa Gln Ulu Gil GTn 111 Gap Vnl Glu GTy Aln A0y 115 Tli l and 1 200 Pro Str Glu Oli liu Gly Aro lii 1225 Dtp Chi Ile Asn Ono Cheese 130 hi 135 Poi Cheese Lui Ulu Sir His Lys Ser Piro 114 Asn 145 Mtt ALa Nit Oht Leu 150 Dtp Phe ropes Hii Leu Leu Arg Tly Uys Val 155 110 Aig hht Leu MuI Ltu Vnl 165 Nile Gl | Dtu Ch; Leu Cys Val Aig Ulu Phe 705 1127 Uiy Uli Acn Gly Tli Asn 180 Underworld Ali Dtp 185 Aoc Ala Piro Piro Aln CCis Ocip 119 Lru Cug Val Lee Dtp Lys 195 Leu Ltu 00 0 Arg Anp Den His Val Luu Hili Ser 205 Aig Ltu Che Tin Cyi Piro 210 Tiu 780 Vi5 His Ppi Uru Piro Thr Pro Val Leu 220 Dec 225 huo Ala Vnl Asp hhr 230 Deu Liu Tli liu Tip Lys Thu Tin Met Glu 255 240 Tiu Chi Lys Ala Tin Asp 245 Rivet Lit Uli Ali Val TP Leu Utu Leu Giu 50 0 225

446

184 424

iir VII MeG Ala 260 Cli coe how many Main Iru 265 Cly Pro Thr C / s Leu 220 Ssr SSA Iau Lau Glu Main Iru Are Gly GiL te VII Arg Leu Leu Urs Gly Ala Lit 275 280 285 Clr eru Lia Leu Cly iho Gle Lets Sur Aur Main Gly Toy Thr Tir: Ali 290 29S 300

His Uys Asp Sur Aso 035 (2) INFORMATION ABOUT SEQ II Nu: 239:

(i) SEQUENCE FEATURES:

(1) LENGTH: 302 amino acids (B) TYPE: amino acid (C) NUMBER OF THREADS: GAiAdyejzl (I) TOPOLOGY: linear (SS) TYPE OF PARTICLE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO .: 2 (39:

Gll 1 Cse C / s Seo Ili 5 Map He Gsp du Clu 10 11i U 1 s How much Leti Pis 15 Arp Aoo Cf. Gli Sur Ces Iau Acp Cro Oi n Asn Leu Sn n Aa. Gic Jul wp twenty 25 thirty Sro How much Leu Ces Asm Asg CSG Leu Aop Iru lei Ac n Cf. Gla Lee llu 35 40 45 Vil AAO Ala Inch Lys Ui n Ces Glo Lin UAu Sei Sip Cli Glu Ala How much 50 55 60 Irs Move Acn Les Cle Pro Cys Ceu Pro Hundred Ala Background Ali Ali Prr Cheese 65 0V 5V 80 Grg His Pro And how much IlA lii Cyp Oli Gly GPG Opp Main Glu Phe log Glu 85 90 95 irs Ueu iłrr Ahr lyo Ceu Incl Shi Dog Nov Main Ui a Clu Gic ropes Gle O30 105 111 1/1 Incl Glu hush Gia U Vy Cly Sei Lii Sig OOi Svo moose Gly Pro How much 115 120 112 Sro TTr How much How much Pro Lira Aur Prs 1 sec Apo Gir Zse ULs Lyi Cheese Pro 300 135 114

184 424

447

Apg Mit Asp 145 Pos Asg Ali 151 lli 80i 8et 8π 8ho lln : 1: 55 His Lei liu Arg 160 iir irs Vai Aog Pli Lee Uel 8 er 811 81y 81y Sn Thr Leu Cys Val 165 110 175 Aog liu Phe Gly 81y Asn Myth Ala Sro Pro Ala Pro Pos Ala 8 (0 Asp 180 185 110 liu Aog Val Lee 8sr Lys —Eu Leu log Asp His cheese Vai Leu 8Si Cheese 105 200 225 Aog Lii 8er One hundred Cyi Gco Glu Val His Pio LeS S8O POa Pre Val Leo 210 215 2320 ltu Poo Ala Vi1 Asp 118 108 lU 8 1-8 08 Top Lyo Thr Main Mrt Glu 225 232 235 240 liu Tlo —ys Ala lin Aso pil 8iu 81 ((811. 831 Uhl ieu Leu —1U Glu 245 220 255 lly Vi1 Mel Alu Ala Aog iir (Sin Aiu Gly Pro Th8 Cys Leu 8si Cheese 260 200 220 lru Atu Gly 8ln Leu Sio Gir Main. Vi1 Aog Leu Leu Ltu Gly Ala Leu 275 280 285 lin Ssi 8eu Aiu Gl— Ulu Main Gly Oig 8hr Tli G8a Heals Lyi 200 295 300 (2) INFORMATION About SEC ND No .: 040:

(S) SEQUENCE GNCS:

(AND) LENGTH: 83 pairs for / ad (B) TYPE: kwa / GuklrSnAwy (G) I1QUE NlGl: GAjudyGcya (D) TOPOLOGY: linearly (SS) TYPE PARTICLES: another acid GvkUrSnAay (AND) DESCRIPTION: / ApSu = "DNA (synthetic)

(xS) SEQUENCE DESCRIPTION: g ^ 8D no .: 24 8:

iChrUGlCCl rAAAGrilCC CCCCirCCIA IGAGCCriia liouicicon TCCCAACACC 60

1U1TA1A1TC C1TCCC1CCC CCC (2) INFORMATION ON SNO 1D No: 042:

448

184 424 (S) CLAIM FEATURES:

(AND) LENGTH: 82 par: rules (B) GYO: kwa? nukieSuτa: (T) TlCD QUANTITY: single (D) topology .: iSni (SS) TYPE / TRUCKS: Sony kwa? nnklennτa: (AND) OOIK: / description = "DNT (synthetic)"

(xS) SEQUENCE OOD: PEQ ID no: 2 L1:

AAllllCUAA GAGCACGGAA TTTATGGATG 1TGGCUAATU ACACGGTTAA CAGTTCGTAU 60

AGAlTCiUGG AUATCATGAA UU (2) INFORMT / JE O PEQ DD No: 242:

(S) SEQUENCE FEATURES:

(AND) LENGTH: 8 lminτnaasóa (B) GYP: amino acid (T) NUMBER OF NIAI: single (D) GOPOLOAIC: iSoSτa'a (SS) CYP PARTICLES: bSalt OODK SEQUENCE: PEQ DD oo: 242:

1L 'liy Uly Seo Ul' Gi: Cl: Poo 1 5 (2) SEQ INFORMATION DD No .: 243: (S) SEQUENCE FEATURES:

(AND) LENGTH: 12 amSoτkaa ya (B) CYP: amSoτnaes (AND) QUANTITY NI / A: Single (D) GOOOUOADT: iSoSowa SS) GYO TCArGETZKi: bSalka

(xi) SEQUE CODE: SEQ DD no: 503:

ui 'ul: ii: eto u | y uiy ci: Poo ci' uiy uiy Poo

184 424

449

10 (2) INFORMATION ON EEQ ID No .: 24 4:

(i) SEQUENCE FEATURES:

(AND) LENGTH2: 7 amino acids (B) TYO: imLnokwis (C) NICE QUANTITY: single (D) TOPOLOGY: lSeiiwi (SS) AYP PARTICLES: protein (xi) OPLE SEQUENCE: EEQ ID no:

Sto (ii (li Elg Ali (li Eeo 1 5 (2) INFORMATION ABOUT EEQ ID No .: 245:

(L) SEQUENCE FEATURES:

(G) LENGTH: 6 Amisiquis (B) TYPE: amino acid (C) NUMBER OF THREADS: sijudriczi (D) TOPOLOGY: liiiiwi (SS) AYP PARTICLES: protein (xi) SEQUENCE DESCRIPTION: EEO 1D so: 245:

(Ou PIl (li Ase Met Gli 1 5 (2) INFORMATION ABOUT EEQ ID No .: 246:

(i) SEQUENCE FEATURES:

(i) LENGTH: 7 imSnikwisów (B) TYO: imSiokwis (C) THREAD QUANTITY: single (D) TOPOLOGY: Axis (SS) PARTICLE TYPE: bHAMS (xS) SEQUENCE DESCRIPTION: EEQ NA so: 246:

Alu PIm GUu Ali Ann inn Ala

450

184 424

5 (2) INFORMATION ABOUT SEQ ID NO .: 247:

(i) SEQUENCE FEATURES:

(A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) NUMBER OF THREADS: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 247:

Glu Phe Gly Gly Asn Gly Gly Asn Met Ala 15 10 (2) INFORMATION ABOUT SEQ ID NO .: 248:

(i) SEQUENCE FEATURES:

(A) LENGTH: 309 amino acids (B) TYPE: amino acid (C) NUMBER OF THREADS: single (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: protein

xi) SEQUENCE DESCRIPTION: SEQ ID no .: 248: Ala 1 Asn Cys Ser Ile Met 5 How much Asp Glu Ile Ile His His Leu Lys Arg 10 15 Pro Pro Ala Pro Leu Leu twenty Asp Pro Asn 25 Asn Leu Asn Asp Glu Asp Val 30 Cheese How many Leu Met Asp Arg 35 Asn Leu 40 Arg Leu Pro Asn Leu Glu Ser Phe 45 Val Arg Ala Val Lys Asn 50 Leu 55 Glu Asn Ala Ser Gly Ile Glu Ala Ile 60 Leu 65 Arg Asn Leu Gln Pro 70 Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser 75 80 Arg His Pro Ile Ile Leu 85 Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu 90 95

Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln

184 424

451

100 105 110 Cyo Vai Glu you: Uiy Gl: Gly Hundred Drank lly Ulu Piso Ler GjLyi Pro IDe 115 120 125 Hundred GGo How many Aso Poo Sur Prs Oos Sur Ly? Cir Poo Hi lro Peo Oro 130 13 5 140 Asn Myth Flax Ooh Tho Cf. VeL lor Leu Poo But Val Cip Cf. Hundred Leu 145 110 155 160 Uly Alu Ttg L'1 Gho GAn Mut Alu Glu Tho lro Ala Cou Anp lit Leu 165 170 175 ul: But VaS UGr Lee Leu Lun Gle U Ly Or is A Ala Ali Arg yeah Main 180 185 110 Lun Ul ' Dog Tho You? Flax Cheese Sur Leu ltu you: GAn Leu Siu Gly GAu 195 200 205 Vei Arg Leu Flax Leu Gly Ais Lie down lLr Well Leu Leu lllu Thr Main leu 210 215 220 Oos Oos Glu hive ' Aog Tier Ghr But His L: o Aop Piso flax Ala How many PPe 996 220 105 240 Lun Hundred Phr Ulu Hi Leu Lur COg Gly L'o VeL Airg OGo Flax Myth Leu 245 2950 2525 Vel CU ' Gly y sleep AGe Leu Lii VaA Pvg Slu OgL Gly GLu Asn Uly Gly 260 265 220 And he Mut Alu Lii Loo Ala iii Pro Oho lei Asp L eu Inc lul gsu Ler 255 280 285 Lyo ltu Flax L'i Coc Cheese Hi Vel Leu Hi Peo Arg Leu Sir Main Cyi 290 295 300

Clu Vei HSo Poo 305 (2) INFORMT / JE 0 KEQ ID To: 249:

(i) AE / HY KEKWEN / JD:

(T) LENGTH: 459 pairs of failures (B) CYP: nuclease acid (A) QUANTITY NIAI: single (D) GOPOLOAIC: other (iS) TYPE / CArGEACKi: other nνnllSnτwr (T) OPIK: / opin = "DTT (synthetic )

452

184 424 (ei) SEQUENCE OPNS: r = Q NA No: 540:

TGCCTCGCTC TGCCCCCCCG CGACCTGTGA GCTCCClGCl CCTCiCTTCG C1CCCCCTAT 60

ITTTCCCCCC IClGACCCAG CCAGClTTCA GAGlCCTACC GTTTGCTCAC 1TGC1CTTCC 120

TCCCTCCCCl CGGGCCTCCG TCCCyGAGAl TClGCACCCT ClCCCilCCS CATTAACCTG 180

T1CC1GACCT ClGlGGCllC CACCCTTCCC TTCilllGAG T11CGGTAGC ACCGCGATAl 240

TCCGCACTCC CCCCTTCTCC ΙΤΤΤΤΤΤΤΤΙ GCCCACTCTC TTGClCCGlC TTCTTCTTCT 007

TCreiCCTTT CGCllllCTC CCCTlllCCC ccgcttgccg cataccccag iattacgctc 360

TAT1AGG1CT CCAlCGCCCC TCCTTTlAGT CCTTAATATT TGTCCCGA1G 111GGC1TGC 057

CCCCC11CGT TCGriGGAGI GTTCCTCTCC CGTGCTAGG

459 (2) INFORMATION ABOUT SEQ ID NO: 500:

(i) SEQUENTIAL TIMES:

(A) LENGTH: 457 pio bases (B) TYPE: NUCLIC ACID (C) NNTN EFFICACY: single (D) TOPOIOGNA: InSoaa (ii) TYPE OF PARTICLE: other nukluinoa kwis?

(xl) OPNS (1) DESCRIPTION: / άϊα = SEQUENCE: SEQ ID "DNA (synthetic) ie: 500: TTCTTClCTT 60 ClCCCGCTCG TGATCTCTll GCTCCClGri 1GCCGCCCCG CGCTTCTCCC GCCCCCTlCA 120 GTA11CTG1G TC1GT1TCC1 G1G1CTTACT CTCTGCCCAC ACTC1CTTTG TCGCTCGTCG 180 CIGICTCCIG CCCGGG1G1A TGilGAGCCT 1GAT1G1GG1 GATT11GGCA T1GGAC1CCT T1G11GTAGC GACCTTTTCG CCG11GG1AG T11T1GCAGC ATGG1GGC1A

507

184 424

453

TTCCCGCTTC TTACTCTTCT ATTTTTTTTA (ΤΤΤΑΤΤΤΤΤ TTCTATATCT TTCTTTCTTT 300 tttaauuttt tctatagttt tttcccaatt cattatactg ttgtatttca taagtatttt 360

CiTCCTATCT TCTTAACTTT TTCATATTTC ΤΤΤΊΤΑΑΤΑΑ ΑΤΑΤΑΤΑΤΤΑ TTTCATCTTA 420

CGGCCAACAT TTGTTTTTTC TCTTATC

447 (2) INFORMATION ABOUT EEQ ID No: 251:

(S) SEQUENCE FEATURES:

(A) LENGTH: 459 base pairs (B) AYP: quis euklMSeiwr (C) QUANTITY NICl: single (D) TOPOLOGY: lilac (iS) TYPE OF PARTICLE: insi kwis eukleSiiwi (A) DESCRIPTION: / ipis = "DNA (synthetic) (xi) SEQUENCE OPlE: EEQ ID no: 251:

TTTTTAATAT TATTACTTAT TCATTTTTTA ATTCTTATTA GATTTTTTTT TCATTCTTAT 60 ttttttcgta ctatattcgc ttacactcta ταττττταίτ ttatctttgt atttttcttu 120

TTCTTTCTTC TCCCTTTTGr TTTCTCATAA ΤΤΤΑΑΑΑΤΤΤ ΑΤΑΤΑΤΑΤΤΑ (ΑΤΤΑΑΤΑΊΑ 180 taatgtattt ττατααταττ catttttttt ttcaagacac tcatcttatt ATCCCAATAA 240 ttatcattta tttatttttt atttttttttat αατταττctttττttttttat αατταττctttττtttttttat αατταττctttτctτtctttat αατατττctτctτ

ΤΤΤΑΑΑΑΤΤΤ TCTATAATTT TCTTCAAATT TAATTTTTTT TATGACATGA CATTATAATT 360

TATGAAUATT TCACTGCTGT TCCTTGCGTT TTTTACTATT ΤΑΤΤΤΤΑΑΑΑ ΑΑΑΑΤΤΑΤΑΤ 420

TTCTTAGTCT TTAIATCACA TTTTATTTTT TATATCACC

459 (2) INFORMATION ON EEQ ND No: 252:

454

184 424 (i) SEQUENCE FEATURES:

(A) LENGTH: 153 αminpnaaIA (B) TYPE: amino acid (T) NOMINITY ENTN: single (D) TOPOLOGY: linear (li) GYh PARTICLES: protein

xl) OhiS SEQUENCE: SEQ NA no: 707: Dii hio Cin huo hio Cii cyns ^ S> Leu OCah Vil Ltu Dtp Lys Luu Ceu 1 5 10 15 Aig Asp Ser Ihs Arl Leu His Sei Sis Alu Sec Hln Luu lia lla TsS twenty 25 thirty His Puo Leu Poi ACh Lei Vni Utu Ιπ Pro Ala Vrl Asp Phe Set Ceu 35 40 45 ilr Ulu Tcp Cyi Cip Uin Underworld Glu Tiu Thr Gis Ala Ali Asp Ili Let 50 50 60 nir Cin Val Chi Gru Leu Leu Glu Tiy Val Mit Aln Aln Arg Gly GTa 65 70 75 80 etu Uli Pro Chi Cyi Leu Cheese Liu cheese Leu Tli Uin Leu Dtu Gly GTa 85 90 95 lii Leu Llu Alu Lly leagues Gir Lei llu uir Len liu Stp luc Gun Tis 100 105 110 Pio hio Gln GT | Ar; Thr Ghr Air Alc lys Asp Sao Ass ip a AO A CSn 115 120 125 Leu Dii Pilił LTa His Leu Leu Arg Tli Lys Vnl .Arg PPe Leu Met Ceu 130 325 140 lii nir GT | let Chi Leu lii lii Cpg 145 150

(2) INFORMATION V EQ V ND No .: 703:

(i) SEQUENCE FEATURES:

(A) LENGTH: 149 amino acids (B) TYPE: aminpnaαI (C) NNCNNESSITY: single (D) TOPOLOGY: linear.

(ii) THESE PARTICLES: protein

184 424

455

xi) SEQUENCE DESCRIPTION: SET ID n: i 253: erl 1 Aur Gli Aur Aur Cii Lpi 5 PpT Les Arg Val Leu Sir Lys Leu Leu 00 15 Gig Csp Ser His Val Leu Hiv 20 Cru cheese 25 Leu Ssr Cln CCc: iro Glu CVl1 30 His Pro 1eu irs OOi luu Vii 35 Les Les 40 Pro Ala Vil Acp CPo Ter Leu 45 how many Glo Grp Tup ULs Gln Tri 50 55 HUv Glu MUt Lyi UVa Clu Asp 0le Leu 60 liy 65 Cli Val iho Les Leu Leu 00 Gls Cly Val MeP Ali Ala log Cly Gln 75 80 irs Cly Pro TOu Cys Leu Ser 85 S <ar Les Leu Ciy Gln Luu Ser Ciy Gli 00 95 Vil Cug Leu Crs Ces Gly Ala 100 Leu Glo 105 Llu Ues Gly Tho Gli Gly Cheese 111 Crg Thr Thr TOu lit Sys Asp 115 Pro Aso : 225 Ala Iii Ahr Lir Cse Che Gln 115 His Lit Ceu Atu Gly Ats GiL Lsi Phe Vii Mel giu Pot Gly Gly Ser

130 135 140 iOo Uru Cys all Goy 145 (2) INFORMATION ABOUT SEO ID No: 254:

(i) SEQUENCE FEATURES:

(A) LENGTH: 153 imiuokwip / (B) TYPE: imSuAkwip (V) NUMBER OF THREADS: single / nczi (D) TOPOLOGY: linear (ii) TYPE OF PARTICLE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID un: 254:

Sil Air Gli Aur Air Cii Cy: Asy p iu Lrs CoU Leu Sli Lyi Siu Leu 15 10 15

Goy isp Sao HSp ViH Ueu Hii Ser Arg Luu Luu Gln Sys Pro G lu CLsG

456

184 424

twenty 255 thirty Sis Poo Lee U 80 8hr Ooh 811 -here —Ru Pro Ala Vai Asp Pli Sio -here 35 45 45 iir Tlu Trp pys Πιτ O8n GuG Glu G8u how many Lyi U 8a Tlr Ace— SAi Gig 50 58 66 iir Ala Val Background Leu ltu —Ru Glu iir Va1 Underworld Ala Ali Arg iir TlG 65 70 75 80 ltu liG Pro Background GS-S ltu Sro Cheese liu Leu Gly Gin Leu Cheese lly lln 85 00 05 Vai log Lee U 8 U L ee Relief Πι Aiu TlG Cheese Leu Trump (Lira Custom duty Main Liu 100 285 110 Poo Poo Main G 8 y S87g Thr Thr Ala iSi Lys Ace— P8O Oso Alo A 8 e APg 115 120 112 ltu Hundred 1I8 IG 8 His Leu Luu Aog ilr Lys Val log Phe Trump Underworld Leu 130 355 140 Vli iir Gly 0 8r Thr O8U -ru VaG Pg

145 150 (2) INFORMATION ABOUT SEQ ID No: 000:

(i) SEQUENCE CECSES:

(A) LENGTH: 64 pairs of bases (B) TYPE: nukUrSnAar acid (G) NIGN UTILITY: single (D) TOPOLOGY: SGn0aaa (ii) TYPE OF PARTICLE: Sggg acid GvkUrSGAar (A) OP1S: / opLu = "DNA (synthetic) (xi) SEQUENCE DESCRIPTION: SEQ (CD no .: 003:

iiCTUUGccA TTCicuiccr icccirccci chccricrcc Aicrccr — ii ccicucuiuu 60

ATll (2) INFORMATION ON SEG ND No: 006:

(i) SEQUENCE FEATURES:

(A) LENGTH: 153 amino acids (B) TYPE: aIniGAkaas (C) AMOUNT OF NlCl: single

184 424

457 (II) TOPOLOGY: nGnGGwa (Si) TYPE OF PARTICLE: protein (ix) FEATURE:

(A) NAME / KEY: Site mGd / fSkGwalr (B) LOCATION: 017 (I) OTHER INFORMATION: / HwaLA = "Item 007 is deleted or Luu, Ala, Vai, Ilr, Pro, Phr, Trp or Mrt (Sx) CEGGA:

(A) N1ZW1 / KLUTZ: Site modified (B) LOCATION: 113 (I) OTHER INFORMATION: / note = "position 113 removes sSa or Pro, Phr, Ala, Vnl, Lru, Ile, Trp or Mrt (Sx) FEATURE:

(A) N1 NAME / KEY: Site modified (B) POSITION: 114 (I) OTHER Ε ^ ΟΕΜΑΟΙΤΕ: / note = "oo / life p 114 removes sS or Poo, Phu, Aln, Vnl, Lru, Ilu, Trp or Mrt (Sx) FEATURE:

(A) rlZWi / KLUGZ: Site modified (B) LOCATION: 115 (I) OTHER AND NrΟRMAΟJΕ: / uwaLa = "ρο / γ ^ τ 111 uuuw or Clu, Gly, Sro, Tho, Gyr or O.si (xS ) SEQUENCE DESCRIPTION: SEQ W no: 256:

Su— 1 Poo ropes Paro Game 5 oh oh lyi Aces Arg Val Sauce 10 at HERE Sig Lys Leu 15 Lue log Osp Hundred His Tai Igu Hiu Cheese Arg Leg Cheese u ln Cys Pro Glu —S 0 twenty 25 thirty Gis Poo Leu P ro Background loro hal Leu Leu Pio Ala Val Asp Plie Cheese Luu 35 40 45 Gly Ulu Cip Lys Th- Ulu Aut llu how many this- U / s ropes Glu 1 ^ How many Lou 50 55 60 Ul / Aln Val Thr 0 EU Tur Mayor Min T Uy Thallium Finish Ala Ala Hg Giy GUn 65 70 75 80 Leu Gl / Pro Background Cys Tur Geu Geo G born Gue Tly 1 iii ueu Set Gly Main 85 90 95 Val Arg Leu Leu Teu hives Ala Leu Main Cheese Leu ueu Glp ruo Main hu G 100 105 110

Xaa Xaa Xaa Mly Arg Tho Thr Ala His Lyp Asp Osp Not Ala Ile Uhr

458

184 424

115 120 125 Hundred Seu Phe PIl Hic Sou Hss Ars UOy Lys Vai Acy AAe Peu let goo 130 155 140 Vil Gly Gly llA Thr Oh cu Τι ^ ο VaL Ucg

145 150 (2) INFORMATION ON EEQ 1D No: 257:

(i) SEQUENCE FEATURES:

(i) LENGTH: 464 SAGA bases (B) TYO: nuclLSniwy (T) QUANTITY OF THREADS: single (D) TOPOLOGY: AXIS (SS) TYPE OF PARTICLE: Sili lunUMSllwu (A) DESCRIPTION: / isLp = "DNA (synthetic) (xS) SEQUENCE OPlE: EEQ ID so: 257:

TTATAATTCA 60 TTACTTTATA ATUATCCATA CAGTACTCTC ATGTTTAAAC AAATTGTTTU TATTTTTATT 120 ΑΑΑΤΊΤΤΑΑΊ AlTTACACTA ΑΤΑΑΑΤΑΤΑΑ TTTTGTTTTU αταταττααα attatttata 180 TCTACATTAA tatgcttttt ΑΑ1ΑΑΑΊΑΑΑ TAACAATTAG ααααατττατ tatctatata 240 CAT1ATTCTT TAGAGTCATT LATCAGAATA CTTTTTTATC ACCCTTATCT tttttttata 300 TCTAGTTATT attgacacat AAAATTATTC ΑΑΑΑΤΤΤΤΑΑ ταααααίταα TCTTTTATTT 360 αατταττττττ CAUTCiCTAT AAAAATCCTl ατατατατατ αατααταααα ατττίτίααα 420 TAAiTTATTT ACTTCGATTT TTATAAATl TTTATTTTTT τταττταααα CATTTTATCA ATTTTTCCAT ΑΤΑΤΑΑΑΑΤΑ TTATATATAC (YES

464 (2) INFORMATION ABOUT EEQ ID No: 258:

(i) SEQUENCE FEATURES:

(A) LENGTH: 419 s and bases (B) TYO: nucleic acid (C) NUMBER OF NITI: single

184 424

459 (D) TOPOLOGY: linear (li) GYh PARTICLES: others nucluinpal acid (1) OhNS: / description = "DNA (synthetic) (ci) OONS SEQUENCE: SEQ ND ni: 705:

CCCTTGCCCC CTUCCCCCCC CCTACCTACT CACGTCCACA TCACCC1CGU CUCCClCTTG 60

CACCTTCUCC UGCCCC1A1C ClCCCCACCn UCTCAUCCUT CCCTACCCTU CCTGATCTAC Γ00 nccTTcnACc ccccnccccn nuncuccccn gcattucctc caguacccta ucucagttat 180

CCUTCACTUC TTCAATGCGT CTCUACCCCC GCCCACTCCT TCCCCCCUCC CCG1CCUTAT 240

CCCTCCTACC CCCCCTCCCC CGTCATTCCT iGUACCGUCA AGAUTCCCTT 1AAAUUCTGA 300

CUCCCTATTC TUCTUCCCTC TCTCAAGCUC UTTACCAUCA GTACTCAUAU TUCTTGTiAG 360

Tccccccnnn cuucttcccg gtcuucttcc ccaccactta attcaccuca gtccagctt 419

184 424

I. Construction of a tandem duplicated matrix

174

1st copy of the gene

174 linker - ^^ 2nd copy of the gene

II. PCR amplification of the tandem duplicated template

jsftyt | S7

FIG. 4

184 424 first step of PCR amplification new start

97 174

ligation fragments

174 1

F1G.3

First step of PCR amplification \ fresh start

-

a third step of PCR amplification of hybridizing fragments

174 linker linker 11_ 96 adding oligo new start and new stop

174 Linker

F1G.2

184 424

Publishing Department of the UP RP. Circulation of 70 copies. Price PLN 6.00.

Claims (11)

Patent claims 1. A hematopoietic protein selected from: SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ IDNN: 220, SEQ ID SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 209, NO: 210, SEQ ID NO: 21E SEEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: NO: 220, SEQ ID NO: 22E SSQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 225, IEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: NO: 230, SEQ ID NO: 234, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238, and SEQ ID NO: 239. 2. A nucleic acid molecule encoding a hematopoietic protein selected from SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ LD NO: 218, SEQ ID NO: 218, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: NO: 223, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: NO: 228, SEQ ID NO: 242, SEQ ID NO: 230, S ^ <Q ID NO: 231, SEQ ID NO: 232, SEQ ID NO: NO: 233, SEQ ΙΟΝ! ^ SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: NO: 238 and SEQ ID NO: 239. 3. The nucleic acid molecule according to claim 1 2. The method of claim 2, characterized in that it is selected from SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124 , SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 12 ^, SEQ ID NO: 1 ^ 328, SEQ ID NO: 129, SEQ ID URI 30, SEQ ID NO: 131, SEQ ID NO: 132, SEQ SEQ ID NO: 134, SEQ ID N ^ HSi SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO. ^^ SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO. NO: 142, SEQ ID SEQ ID NO: 1: M, SEQ ID NO: ^ SEQ ID NO: 146, SEQ ID NO: NO: 147i SEQ IDNRrMS, SEQ ID NO349, SEQ ID NO: 150, SEQ IID NO: 151, SEQ ID RR: 152, SEQ ID NO: 153, SEQ ID NO: 154, and sequences equivalent to these sequences due to the degeneracy of the genetic code. A method for producing a hematopoietic protein, characterized in that it comprises: culturing, under appropriate nutritional conditions, host cells transformed or transfected with a replicating vector containing a nucleic acid molecule encoding a hematopoietic protein so as to express said hematopoietic protein, and recovering said hematopoietic protein, the molecule being nucleic acid encodes a hematopoietic protein selected from SEQ ID NO: 403, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: ^ (^ '^, SEQ ID NO: 208, SEQ ID NO: 208, NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: MR212, SEQ ID NO: E, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 217, SEQ ID NO: 217, SEQ ID NO: E, SEQ ID NO: W, SEQ ID NO: 220, SEQ ID NO. ^ E SEQ ID NO: 222, SEQ ID NO. ^ E, SEQ ID RR: 224, SEQ ID NO. No. 1, SEQ ID NO: 224, SEQ ID NO: 227, SEQ ID SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: E, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238, and SEQ ID NO: 239. 5. The method according to p. 4. The process as claimed in claim 4, wherein the nucleic acid molecule is selected from SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 140, SEQ ID NO: 121, SEQ ID NO: SEQ ID NO: ^, SEQ ID NO: 124, SEQ ID SEQ ID N 1 10 and SEQ ID NO: ^ SEQ ID NO: 128, SEQ D NR399, SEQ Π) NRzEI, SEQDDNR: 13E SEQ DD 184 424 NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ UD NO: 139, SEQ UD NO: 140 and SEQ ID NO: 14L SEQ ID NO: 142, SQQ ID NO: 1R3, SEQ ID NO: 144, SEQ ID NO: 145i SEQ ID NO: 146i SEQ ID NO: 147i SEQ ID NO: 148, SSQ UD NO: 149, SEQ ID M <: 150, SEQ ID NRH55, SEQ ID NO: 132 and SEQ ID NO: 153, SEQ D ^^ 3 :: 354, and the sequences equivalent to these sequences resulting from the degeneracy of the geeetnyaeegn code. 6. A pharmaceutical composition characterized in that the selection of hematopoietic proteins is selected from the source: SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 203, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NNROS, SEQ IID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ IID NO: 212, SEQ ID NO: R13, SEQ ID NO: 214, S ^ <) ID NO: 213, SEQ ID NOR16, SEQ ID NO: 217, SEQ ID NO: 18, SEQ ID NO: 219, ID NO: 220, SEQ ID NO: 221, SEQ IID NO: 222, SEQ ID NO: 224, S ^ <Q ID NO: 223, SEQ ID NO: 226, SEQ IiD NO: 227, SQQ ID NO: 28, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SQQ ID NO: 232, SQQ ID NO: 234, SEQ ID NO: 233, SEQ ID NO: 236, SEQ IID NO: 237, SEQ ID NO: 23S and SEQ ID NO: 239 and a pharmaceutically acceptable carrier. A pharmaceutical composition according to claim 1 6. The method of claim 6, additionally comprising at least one colony stimulating factor, c ^^, lymphokine, interleukin, hematopoietic factor selected from the group consisting of: GM-CSf, G-CSF, c-mpl ligand (TPO), MGDF , M-CSF, erntoopoietin (QPO), EL-1, IL-4, IL-2, IL-3, IL-3, IL-6, IL-7, IL-S, IL-9, IL-10, IL-11, IL-12, IL-13, IL-13, LIF, flt3 ligand, stem cell factor (SCF). S. Use of a hematopoietic protein selected from: SEQ ID NO: 203, SEQ ID NO: 204, SQQ ID NNR05, SEQ IID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ UD NO: 209, SEQ ID NNR10, SEQ IID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ IID NO: 214, SEQ ID NO: 15, SEQ IID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ UD NO: 219, SEQ ID NO: 219, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223. SEQ IID NO: 224, SEQ ID NNR25, SEQ IID NO: 226, SEQ ID NO: 227, SEQ ID NO: 228, SEQ IID NO: 229, SEQ ID NO: 230, SEQ IID SEQ ID NO: 232, SEQ ID NOR33, SEQ IID NO: 234, SEQ ID NO: 233, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 23S and SEQ ID NO: 239 for the manufacture of a medicament for stimulating the production of hematopoietic cells in a patient. An agent for stimulating the production of hematopoietic cells in a patient, comprising an active agent and a pharmaceutically acceptable carrier, characterized in that the active agent is a hematopoietic protein selected from: SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 203, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 20S, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: : 214, SEQ ID NO: 213, SEQ ID NO: 213, SEQ ID NO: 217, SEQ ID NO: 21S, SEQ ID NO: 219, SEQ IID NO: 220, SEQ ID NO: 21, SEQ IID SEQ ID RR: 223, SEQ ID NO: 224, SEQ IID NO: 223, SEQ ID NO: 229, SEQ ID NO: 227, SEQ ID NO: 22S, SEQ ID NO: 229, SEQ IID NO: 230, SEQ ID NO: 234, SEQ IID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ IID NO: 233, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 23S and SEQ ID NO: 239. 10. A method for the selective ex vivo expansion of hematopoietic cells, characterized by the steps of: (a) breeding okdzinlonyeh nnmóeek krvkotwkc5oc0 wy> c: sheep honing with a hematopoietic protein selected from: SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 203, SEQ ID NNRO6, SEQ IID NO: 207, SEQ ID NO : 20S, SEQ ID NO: 209, SEQ IID NO: 210, SEQ ID NO: 214, SEQ IID 1NRRtt, SEQ ID NO: 213, SEQ ID NO: 214, SEQ IID NO: 213, SEQ ID NO: 213, SEQ ID NO: 217, SEQ ID NO: 21S, SEQ ID NO: 219, SEQ IID NO: 220, SEQ ID NO: 21, EQ IID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ IID NO: 223, SEQ ID NO: :: 26, SEQ ID NO: 227, SEQ ID NO: 22S, SEQ ID NO: 229, SEQ IID NO: 230, SEQ ID NNR31,, EQ IID NO: 232, SEQ ID NRRH, SEQ ID NO: 234, SEQ UD 184 424 NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238 and SEQ ID NO: 239; and (b) harvesting the cultured cells. 11. A method for selecting ax viao of matrix cells, characterized by the steps of: (a) separating the stem cells from other cells, (b) culturing the separated hematopoietic cells in a culture medium containing a hematopoietic protein selected from: SEQ ID NO: 203, SEQ ID NO: 204, SEQ iD NO: 205, SEQ ID SEQ ID NO- .207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: NO: 215, SEQ ID NO: 216, SEQ ID SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: NO: 230, SEQ ID NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238 and SEQ ID NO: 239; and (c) harvesting the cultured cells. The present invention relates to multi-functional hematopoietic receptor agonists. Colony stimulating factors (CSEs) that stimulate bone marrow cell differentiation and / or proliferation have become much more interesting because of their therapeutic potential to restore depleted levels of stem cell derived hematopoietic cells. CSFs in both human and murine systems have been identified and distinguished according to their activity. For example, granulocyte CSF (G-CSF) and macrophage CSF (M-CSF) stimulate in vitro the formation of neutrophilic granulocyte and macrophage colonies, respectively, while GM-CSF and injerlneinα-3 (IL-3) have broader activity and stimulate the formation of colonies of macrophages, neutrophilic and eosinophilic granulocytes are present. IL-3 also stimulates the formation of fattening colonies, mngakαriocytes, and pure and mixed erythroid colonies. US 4,8,729 and US 4,959,455 disclose human IL-3 and IL-3 gibbon cDNAs and the sequences of the proteins they encode. The disclosed hIL-3, at position 8 in the protein sequence, has serine rather than proline. International Patent Application (PCT) WO 88/00598 discloses a gibbon-like IL-3 and human hIL-3 contains a Ser ⁸ ap Pro ⁸ substitution, user ^ et ^ u ^ to Ser, thereby breaking the disulfide bridge, and replacing one or more amino acids at glycosylation sites. US 4,810,643 discloses a DNA sequence encoding human G-CSF. WO 91/02754 discloses fusion proteins composed of GM-CSF and IL-3 which have increased biological activity compared to GM-CSF or IL-3 alone. Non-glycosylated IL-3 and GM-CSF analog proteins are also disclosed as components of the multi-functional hematopoietic receptor agonist. WO 92/04455 discloses fusion proteins consisting of an IL-3 fused with a lymphokine selected from the group consisting of IL-3, IL-6, IL-7, IL-9, IL-11, EPO and G-cSf. WO 95/21197 and WO 95/21254 disclose fusion proteins having broad multifunctional hematopoietic properties. GB 2 285 446 relates to the c-mpl ligand (thrombopoietin) and various forms of thrombopoietin which have been found to affect the replication, differentiation and maturation of megakaryocytes and megakaryocytic ancestors that can be used to treat thrombocytopenia. EP 675 201 A1 relates to c-mpl ligand (MGDF), allelic variants of the c-mpl ligand and c-mpl ligand attached to water-soluble polymers such as polyethylene glycol. 184 424 WO 95/21920 describes murine and human c-mpl ligand and polypeptide fragments thereof. Proteins are useful for in vivo and ex vivo therapy to stimulate platelet production. Protein rearrangement In evolution, rearrangement of DNA sequences plays an important role in the variability of protein structure and function. Gene duplication and exon mixing provide an important mechanism for the rapid formation of diversity and thus provide organisms with a competitive advantage, especially due to the low rate of primary mutation (Doolittle, Protein Science 1: 191-200, 192). 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 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. USA 76: 3218-3222, 1979; Teather and Erfle, J. Bacteriol. 172: 3837-3841, 1990; Schiming et al., Eur. J. Biochem. 204: 13-19, 1992; Yamiuchi and Minamikawa, FEBBS Lett. 260: 127130, 1991; MacGregor et al., FEBBS Lett. 378: 263-266). The first in vitro use of this type of rearrangement in proteins was reported by Goldenberg and Creighton (J.Mol. Biol. 165: 407-413, 1983). The new N-terminus is selected at an internal site (breakpoint) of the original sequence, the new sequence having the same amino acid order as the original sequence, from the breakpoint until reaching an amino acid that lies at or near the C-terminus. At this point, the new sequence is joined , either directly or through an additional portion of the sequence (linker), with the amino acid at or near the original N-terminus, and the new sequence continues in the same order as the original sequence until it reaches a point that is at or near the amino acid that was N -terminal to the breakpoint of the original sequence, the remainder forming the new C-terminus of the chain. This approach has been used for proteins ranging in size from 58 to 462 amino acids (Goldenberg and Creighton, J.Mol. Biol. 165: 407-413, 1983; Li and Coffino, Mol. Cell. Biol. 13: 2377-2383, 1993). The proteins studied represented a wide range of structural classes, including proteins that mainly contain α-helix (interleukin-4; Kreitman et al., Cytokine 7: 311-318, 1995), the β surface (interleukin-1; Horlick et al., Protein Eng. 5: 427-431, 1992), or a mixture of the two (yeast phosphoribosyl anthranilate isomerase; Luger et al., Science 243: 206-210, 1989). In these sequence reorganization studies, many categories of protein activity were presented: T4 lysozyme enzymes dihydrofolate reductase T1 ribonuclease β-glucanase Bacillusa transcamaboylase aspartate phosphoribosyl isomerase anthranilate pepsin / / pepsinogen n-glyceraldehyde-3-phosphate dehydrogenase decarboxylase Zhang et al., Biochemistry 32: 12311-12318 !. 1993; Zhang et al., Nature Struct. Biol. 1: 434-438 (1995) Buchwalder et al., Biochemistiy 31: 1621- ^ 16 ^ 0, 1994; (Protssova et al., Prot. English. 7: 1373-1377, 1995) Mullins et al, J.Am.Chem. Soc. 116: 5529-5533,1994; Garret et al., Protein Science 5: 204-211, 1996) Hahn et al, Proc. Natl. Acad. Sci-USA 91: 104174 0421, 1994) Yang and Scładmurn, Proc. Natl. Acad. Sci. USA 90: 11980-11984, 1993) Puge, and ΐη. , Science 243: 206-210,1989; Luge, and rn. . Prot-Egg. 3: 249-25, 1990) Un et al ,, Portem Science 4, 15946611995) Yingais ΐ rn ,, Pr ^ cteem Science 4, 9944000, 1995) U, Coffino, Mol. Cell. Biol. Yeast omitin phosphoglycerate dehydrogenase Enzyme Inhibitor Alkaline Pancreatinic Trypsin Inhibitor Interleukin 1β 13: 2377-2383, 1993) Ritco-Vonsovici et al, Biochemistiy 341: 16543-16 ^ 551, 1995) Goldenberg and Creighton, J.Mol.Biol. 165: 407-413, 1983) Horlick et al. Protein Eng. 5: 427-431,1992) Kreimian et al, Cytokine 7: 311-318, 1995) Tyrosine kinase recognition domain Interleukin-4 α-spectrin domain SH3 omp a transmembrane proteins Viguera et al, J.Mol. Biol. 247: 670-681,1995) Koebnik and Kromier, Ι.ΜοΙ.ΒΐοΙ. 250: 617 - ^^^, 1995) Pseudomonas interleukin-4-exotoxin chimeric proteins Kreitman et al., Proc. Natl. Acad. Sci. USA 91: 6889-6893,1994). The results of these studies were highly variable. In many cases, significantly lower activity, solubility, or thermodynamic stability was observed (E. coli dihydrofolate reductase, aspartate transcarbamoylase, anthranilate isomerazaphosphorybosyl-anthranilate, glyceraldehyde-3-phosphate dehydrogenase, yeast ornithine decarboxylase, omp A, phosphoric glycerate dehydrogenase). In other cases, the sequence rebuilt proteins were found to have many nearly identical properties to their natural counterpart (basic pancreatinic trypsin inhibitor, T4 lysozyme, T1 ribonuclease, Bacillus β-glucanase, interleukin 1β, α-spectrin SH3 domain, pepsinogen, interleukin4). In exceptional cases, unexpected improvements in certain properties of the natural sequence were observed, e.g. solubility or refolding rate for the SH3 α-spectrin domain rebuilt sequences and receptor affinity, and the antitumor activity of the linked Pseudomonas interleukin-4-exotoxin molecule, which was transposed (Kreitman et al. , Proc. Natl. Acad. Sci. USA 91: 6889-6893,1994; Kreitman et al., Cancer Res. 55: 3357-3363,1995). The original intention of this type of study was to investigate the role of short-range and long-range interactions in protein folding and stability. Rebuilding this type of sequence transforms a subset of long-range interactions in the original sequence into short-range interactions, and vice versa. The fact that many of these sequence rearrangements can achieve conformation with at least some activity is convincing evidence that protein folding occurs through multiple folding pathways (Viguera et al., J.Mol. Biol. 247: 670-681, 1995). In the case of the SH3 α-spectrin domain, selection of new ends at positions corresponding to the twists of the hairpin β loop resulted in proteins with somewhat less stability but which were nevertheless capable of folding. The internal breakpoint positions used in the studies cited herein are only on the surface of the proteins and are distributed across a linear sequence with no apparent end or center preference (the deviation of the corresponding distance from the original N-terminus to the breakpoint is approximately 10-80% of the total sequence length) . The linkers joining the original Ni C ends in these studies varied from 0 to 9 residues. In one case (Yang and Schachman, Proc. Natl. Acad. Sci. USA 90: 11980-11984, 1993), part of the sequence was deleted from the original C-terminal segment and the fusion was made from the C-terminus truncated to the N-terminus. hydrophilic residues such as Gly and Ser are often used in linkers. Viguera et al., 184,424 (J.Mol.Biol.247: 670-681, 1995) compared the joining of the original N and C termini with 3 or 4 residue linkers; The 3 residue liner was less thermodynamically stable. Prolasov. and ii ^., (Protein Eng. 7: 1373-1377, 194) used 3 or 5 residue linkers to join the original N-terminus of E. coli dihydrofolate reductase; only the 3 residue linker produced a protein with good efficiency. The revealed new hematopoietic proteins represent the patterns: R1-L1-R2, R2-L1-R1, _Rj-R2 or R2-R1 wherein R1 and R2 are independently selected Tia from the group consisting of: (I) A polypeptide containing and the modified sequence of human G-CSF of the formula: 1 10 Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser • Xaa Leu twenty Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly Ala 30 40 Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa Xaa 50 Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly How much Pro Trp Ala 60 70 Pro Leu Cheese Xaa Cheese Pro Xaa Cheese Ala Leu Xaa Leu Ala Gly Xaa 80 Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu 90 100 Gln Ala Leu Glu Gly Ile Cheese Pro Glu Leu Gly Pro Thr Leu Xaa 110 Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp Main 120 130 Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr Main 100 Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala Gly 150 160 Gly Val Leu Val Ala Cheese Xaa Leu Gln Xaa Phe Leu Xaa Xaa 170 Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro cheese (SEQ ID NO: 1) 184 424 where Xaa at position 1 is Thr, Ser, Arg, Tyr, or Gly; Xaa at position 2 is Pro or Leu; Xaa at position 3 is Leu, Arg, Tyr Ibb Srr; Xaa in the position b1 oonacca Phe, Ser, His, Thr or Pro; Xaa for knowledge of b (5 characters Lys, Pro, Ser, Thr lulb His; Xcc at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg; Xaa in the cognition of the symbol of Leu, Thr, Pro, His, II b ^ b yys; Xaa in knowledge of b 2 Dose of Arg, Tyr, Ser, Thr or Ala; Xaa in position 2 2 born ^ z Ile, Pro, Tyr or eur; Xcc in position! 2 2 bornaca Asp or Gly; Xaa at position 33 bornaca Ala, Ile, Leu or GC ;; Xaa in position! 33 bom Lys, ll! ber; Xaa at position 36 is Cys or Ser; Xaa at position 42 is Cys or Ser; Xaa at position 43 is Hśs, Thr, GCy, Va1, Lys, Trp, Ala, Arg, Cys or Leu; Xaa at position 00 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln or Thr; Xaa in the fate of Glu, Arg, Phe, Ar, and Ile or Ala; Xaa at pooonCj and 0 3 Leu nomination Thr; Xaa in demand 0 bornace Leu, Phe, Arg or Ser; Xaa at position i5 bynaαca Leu, I1v bii, Pro or Tyr; 184 424 Xaa in item i 554 means Leu or His; Xaa in item i 64 means Cys or Cheese; Xaa in item i 7 means Gln, Lys, Leu or Cys; Xaa in position 70 means Gln, Pizo, Leu, Arglub Xaa in item i 74 means Cys or Cheese; Xaa in position 104 stands for Asp , Gly or Val; Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly; Xaa in item i 115 means Thr, His, Leu poured Ala; Xaa in position 120 means Gln, Gly, Arg, Lys or His; Xaa in position 123 means Glu, Arg, Phh luu Thr; Xaa in position 144 means Phe, His, Arg, Pro, Leu, Gln or Glu; Xuu in item j 146 is Arg or Gln; Xaa in position ΐ 147 is Arg IuŁ »(yIu; Xaa in position 1156 means His, Gly or eer; Xaa in item i 159 means Cheese, Arg, hhr, Tyr, Val or Gly; Xaa in item i H32 stands for Glu, Leu, Gly (uu Tr ^ r ^^ Xuu in position i 113 means VuU, Gly, Arr (uL · Ma; Xaa in position i 169 is Arg, Ser, Leu, Arg or Cys Xaa at position 170 is His Arg or Ser; 184,424 where optionally 1-11 amino acids may be removed from the N-terminus 1-5 from the C-terminus; and where the N terminus joins the C terminus directly or via a linker, permitting joining of the N terminus to the C terminus and having new C and N terminus on the amino acids: 38-39 62-63 123-124 39-40 63-64 124-125 40-41 64-65 125-126 41-42 65-66 126-127 42-43 66-67 128-129 43-44 67-68 128-129 45-46 68-69 129-130 48-49 69-70 130-131 49-50 70-71 131-132 52-53 71-72 132-133 53-54 91-92 133-134 54-55 92-93 134-135 55-56 93-94 135-136 56-57 94-95 136-137 57-58 95-96 137-138 58-59 96-97 138-139 59-60 97-98 139-140 60-61 98-99 140-141 61-62 99-100 141-142 or 142-143; (II) a polypeptide comprising: a modified hIL-3 sequence of the formula: Ala Pro Met Thr Gin Thr Thr Ser Leu Lys Thr Ser Trp Val Asn 15 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa XXa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa XXa Xxx Xaa Xaa Xaa Xaa Xaa XXa Xaa Xaa Xaa Xaa 50 55 60 Xaa Xaa Xaa Xxx Xxx Xaa Xxa Xax Xxa Xaa Xxx Xaa Xaa Xaa Xaa 65 70 75 Xaa Xaa Xaa Xxx XXa Xaa Xaa Xaa Xxa Xaa Xxx Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xxx Xxx Xaa Xaa Xxa Xaa Xaa Xxx Xaa Xaa Xax Xaa 95 100 105 Xaa Phe Xaa Xxx Xxx Xaa Xaa Xaa Xxx Xaa Xxx Xaa Xaa Xaa Xaa 110 115 120 Xxx Xxx Xxx iln iln Thr Thr Leu Ser Leu Ala Ile Phe 125 130 (XEQ # Xr: 2); 184 424 where Xaa at position 17 is Cheese, Lys, Gly Asp, Underworld, Main or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg llb Gln; Xaa in position 19 means Met, Phe, Ile, Arg, Gly, Ala llb Cys; Xaa in position twenty means Ile, Cys, Gln, Glu, Arg, Ppo How many Ala; Xaa in position 21 stands for Asp), Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Cheese or Val; Xaa in item i 22 Means Glu, Top, Pro, Ser ?, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa in item i 23 stands for Ile, Val, Ala, Gly, Top, Lys, Phe, Leu, Ser or Arg; Xaa in position 24 is Ile, Gly, Val, Arg, SSr, PPh llb Leu; Xaa in position 25 means Tho, His, Gly, dl, AA6g, Ppo llb Ala; Xaa in you 26 is His, Thr, Phe, dL /, Aao, AA and How many » Trp; Xaa in position 27 is Leu, Gly, Arg, Tho, Ser or Ala Xaa in position 28 is Lys, Arg, Leu, Gln, Gly, hro, Val or Trp; 184 424 Xaa at position 29 is Gln, Asn, Leu, Pro, Arg or Val; Xaa in position 30 means Pro, His, Thr, Gyy, Asp, Gln, Ssr, Leu or ubo; Xaa in position 31 is Pro, Asp, Gly, Ala, Arg, Leu or Gln; Xaa p items 02 means Leu, Val, Arg, Gln, Asn, Gly, Ala or Glu; Xaa in position 33 is Pro, Leu, G1, Ala, Thr or Glu; Xaa in position 3 0 means Leu, Val, Gly, Se,, LLy, du, GGu, Thr, Arg, Ala, Ple,, Ile or Met; Xaa in position 35 is Leu, Ala, Gly, Asn, Pro, Gln or Val; Xaa p items 36 is Asp, Leu or Val; Xaa p will live and 37 is Phe, Ser, Pro, Trp or Ile; Xaa p items 08 means. As, lu, Ala; Xaa p items 40 is Leu, Trp or Arg; Xaa in position 41 is Asn, Cys, Arg, Leu, His, Met or Pro; Xaa p items 42 means Gly, Asp), Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa p items 43 means Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa p items 44 means Asp, Ser, Leu, Arg, Lys, Thr, Underworld, Trp, Glu, Asn, Gln, Ala or Pro; 184 424 Xaa at position 05 means Gln, Pro, Phe, VzV, Met, Leu, Thr, Lys, Thp, Asp, Asn, Arg, Cheese, Ala, Ile, Glu or His; Xaa w b ^ zyccΐ 06 distinctive Asp, Ph,, Se,, Th ,, Cys, Gi ,, An ,, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa in position 7b he marks I! e, G1 y, Va 1 , he r, arg, obo or His; Xaa in boyncja 08 means Leu, Se,, Cy, At ,, Ile, His, Rh ,, Glu, Lys, Thr ^, AAa, Met, Val or Asn; Xaa at position 09 means Met, Arg, Ala, Gly, Pro, Asn, His or Asp; Xaa at position 50 means Glu, Leu, Thr ^, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa in position 51 means Asn, Arg, e ^^ t, hro,! er, hhb] .bb His; Xaa in bpyycja 52 means Asn, hs,, hg,, Iu, lC, erb Ha Thr; Xaa in position 53 Means Leu, Thry Ala, Gly, Glu, Pro, Lys, Cheese or Met; Xaa in position 50 means Arg, Asp, Ile, Ser, Val, Thh, Gln, Asn, Lys, His, Ala or Leu; Xaa in position 55 is Arg, Thr, VzV, Si ;, Leu or Gly; Xaa in position 56 Means Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr1, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; 184 424 Xaa in position 58 is Leu, Ser, Asp), Arg, Gln, Val or Cys; Xaa in position 59 is Glu, Tyr, His, Leu, Pro or Arg Xuu in position 60 is Al.a, Ser, Pro, Tyr®, Asn or Thr Xaa in position 61 means Phe, Asn, Glu, Pro, Lys, Arg or Cheese; Xuu in position 62 means Asn, His, Val, Arg, Pro, Thr, Asp or How much; Xaa in position 63 means Arg, Tyr, Trp, Lys, Ser, His, Pro or Val; Xaa in position 64 is Ala, Asn, Pro, Ser or Lys; Xaa in position 65 is Val, Thr, Pro, His, Leu, Phe or Cheese; Xaa in position 66 means Lys, Ile, Arg, Val, Asn, Glu or Cheese; Xaa in position 67 stands for Ser, Ala, Phe, Val, Gly /, Asn, How much, Pro or His; Xaa in position 68 Means Leu, Val, Trp, Cheese, Ile, Phe, Thr or His; Xaa in position 69 means Gln, Ala, Pro, Thr, Glu, Arg, Trpn, Gly or Leu; Xuu in position 70 is Asn, Leu, Val, Trp, Pro or Ala Xuu in position 71 means Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp or Asn; 184 424 Xaa at X <in entry 722 means Cheese, Glu, Met, Ala, His, Asn, Arg or Asp; Xax in position 77 means Ala, Glu x Ao, x Mou, Ser, Giy, Thr or Arg; Xxx in position 74 Xznnac How much, Met, Thr, Pro, Arg, ily, Ali; Xxx in position 74 Xznnxca Bullfinch, Lys, Gl, x Asp, Prr, Thp, Arg, Cheese, iln or Leu; Xaa in position 46 means Cheese, Val, Ala, Asn, Trp), how many, Pro, how many or Asp; Xax in position 77 means How much, Ser, Arg, Thr or Leu; Xxx in position 78 means Leu, Ala, Ser, ilu, Phe, ily or Arg; Xai in X position 77 means Lys, Th, x Asn, Me, x Arg, How much, Gly or Asp; Xx in X position 80 means Asn, Tr, ya, dyX Thr, Leu, Glu or Arg; Xx in X position 88 means Leu, G ^ AI,, Trp, -Arg, Incl or Lys; Xai in position 82 means Leu, iln, Lys, Trp, Arg, Asp, how many Asn, His, Thr, Cheese Ali Tire, Phe, Ile, Met or Val; Xaa in position 83 means Pro, Ala, Thr, Trp, Arg or Met 184 424 Λ7 _ _ Xaa at position 84 is Cys, Glu, Gly, Arg, Met or Val; \ ζ__ Xaa at position 855 is Leu, Asn, VaI How many GGl; - * Xaa at position 86 is Pro, Cys, Ar1A11lb Lys; Xaa at position 87 is Leu, Cheese, Trp Ilu GGl; Xaa at position 88 is Ala, Lys, Ag ,, Val Ilto Trp; Xaa at position 89 is Thr. Asp, Cyv, Luv, VlV, Gu ,, His, Asn How many Isr; Xaa at position 90 is Ala, Pro, . Ser, Thr, Gly, Asp, Ile or Underworld; 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, Ile or Leu; Xaa v position i 93 is Tiar, 7 \ - - ^rs P ^, Cheese, Asn, Pro, Ala, Leu or Arg; Xaa at position 94 is Arg, How much, Sof, Guv, Luf, VlV, GGl, Lys, His, Ala or Pro; Xaa at position 95 is His, Bullfinch, Pof, Ag,, 1iV, euv, GGi,;, Thr, Asn, Lys, Ser, Ala, TrT, V ha, Ile or Tyr; Xaa at position 96 means Pro, f ys, Tyo, Gly, Ile or Thr; Xaa in position 97 it means Ile, Va! L Lys, Ala, or Ass; Xaa at position 98 is His, How much, Asf, Łev, Ap ,, A1f, Thr, Glu, Gln, Cheese, Phe, Met, Val, Lys, Arg, Tyr, or Pro; 184 424 Xaa at position 99 is how many, Leu, Arg A ^ s ^p , Val, Pro, Gln, Gly, Ser, Phe or His; Xaa at position 100 is Lys, Tyr, Leu r His, Arg, He, Cheese, Gln or Pro; Xaa at position 101 is Asp), Pro, Underworld, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser, Ala, Gly, Ile, Leu or Gln; Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr or Pro; Xaa at position 103 is Asp or Ser; Xaa at heading 104 means Trp, Val, Cys, Tyr, Thr, Mee, Pro, Leu, Gln, Lys, Ala, Phe or Gly; Xaa in fire protection 105 stands for Asn, Pro, Ala, Phe, Cheese, Tt ,, Gln, Tyr, Leu, Lys, Ile, Asp or His; Xaa at position 106 is Glu, Ser, Ala, Lys, Th!?, Ile, Gly or Pro; Xaa in pzzcision 108 means .Arg, Lys, Asp, Leu, Thr, IIu, Gln, His, Ser, Ala or Pro; Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr4, Leu, See or Gly; Xaa in pzzcision 110 means Lys, Ala, Asn, TTh, Llu, Arg, Gln, His, Glu, Ser or Trp; Xaa at position 111 is Leu, Ile, Arg, Asp or Met; Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser or Phe; 184 424 Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp®, Lys, Leu, Ille, Va 1 or Ass; Xaa at position 114 is Τ i and Cys, iis, Ser, Trp, Nrg or Leu; Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, iis, Thr, Trp or Met; Xaa at position 116 onaccai Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gin or How much; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys or Pro; Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp or Tyr; Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr or Arg; Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val or Gln; Xaa at position 1 ^ 3. means Ma, Ser, Ile, AatI; Ppo, Lls, Asp or Gly; Xaa at position 122 is Gln, Ser, Met, Top, Arg, Phe, Pro, His, Ile, Tyo or Cys; Xaa at position 123 is Ala, Met, Glu, His, Sio, Pro, Tyo or Leu; Where optionally 1 to 14 amino acids can be deleted from the N-terminus and / or 1 to 15 amino acids can be removed from the C-terminus; and where 0 to 44 amino acids designated Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; and where the N-terminus joins the C-terminus directly or via a linker (L2) allowing the joining of the N-terminus to the C-terminus and having C and N terminus at 15 amino acids: 26-27 49-50, 83-84 27-28 50-51 84-85 28-29 51-52 85-86 29-30 52-53 86-87 30-31 53-54 87-88 31-32 54-55 88-89 32-33 64-65 89-90 33-34 65-66 90-91 34-35 66-67 91-92 35-36 67-68 92-93 36-37 68-69 97-98 37-38 69-70 98-99 38-39 70-71 99-100 39-40 71-72 100-101 40-41 72-73 101-102 41-42 82-83 102-103 or 103-104; or (III) a polypeptide, comprising: a modified amino acid sequence. human c-mpl ligand of formula: SerProAnaProProAlaCysAspLeιArgValLeuSerLysLeuLeuArgAspSer 15 10 15 HisValLeuHisSerArgLelSerlnsCysProlluValHisProLeuProThrPro 20 25 30 35 VanLelLelProAlaVanAspPheSerLelGlylnllrpLyslhrGnnMetlllGnu 40 45 50 55 lhrLysAnalnnAspIneLellnyAlaVanlhrLelLeuLelGnlGnyValMetAna 60 65 70 75 snaArglnyGlnLeuGnyProlhrCysLelSerSerLe ^ iLeuGnyGlsLeuSerGny 80 85 90 95 lnsVanArgLelLeuLellnyAnaLeyGnsSerLeuneuGnylhrGnnXaaXaaXaa 100 105 110 184 424 aαl11yAgghhrThgA1αHisLysAsoPgoAsnA1αIlMrheLeuSerPhe11nHis 115 120 125 130 LelLeuAggGnyLysVa1ArgrheLelMetLeuVa111y11ySegThrLeuCysVa1 135 140 145 110 AggrggA1aProPgoThrThrrlaVa1PgoSerrrgThrSerLeuVa1LeuThrLeu 155 160 165 170 Asnl1lLMlProrsnrrgThgSer11yLeuLel11uThrAsnrheThgrlaSegA1a 175 180 185 190 AggThrhhg11ySMr11yeMuLeuLysTrp11n11n11yPheArgrlaeysIlePro 195 200 205 11yLMuLelAsn11nThrSerAggSMgLelurspi1nI1erro11yTygLMursnArg 210 215 220 222 I1eHisGluLeuLeuAsnGlyTyrArgGlyLeuPhePro11yProSerAggAggThg 230 235 220 225 Lel11yA1argoAspI1eSerSeg11yThgSegAspThg11ySereeuProPgoAsn 250 255 260 265 eeu11nPgoG1yTyrSerProSerrgoThrHisrroProThg11yi1n1TyrhhrLel 270 275 280 285 PheProLeuProProThrLellProThrProValVa111nLeuHίsrroLelLeuPgo 290 295 300 AspPgoSerA1lPgoThrProThrrgoThreerrgoLMueeuAsnThgSMrTygThg 305 310 331 332 Hiseer11nAsneeleer11n11l11y (SEQ ID NO: 3) 325 330 332 153 184 424 where Xaa at position 112 is removed or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met; Xaa at position 113 removes ss or Ρπ \ Phr, A and p Val, Leu, Ile, Trp, or Met; Xaa at position 114 removes the iubPrOl PhpAir, Val. Teu. ΙΑ, ΊΙρ orMet; Xaa at position 115 is removed or Gln, Gly, Ser, Thr ·, Tyr or Asn; and where the N terminus joins the C terminus directly or via a linker (I2) um ^ t ^ zWwiajscy joining the N terminus to the C terminus and having C and N terminus at the amino acids: 26-27 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 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; or (IV) a polypeptide, comprising: a modified hIL-3 amino acid sequence of the formula: Ala Pro Underworld Thr Main hhb TTl ^ r Cheese Leu Lys Thr Cheese Trp Val Asn 1 5 10 15 Cys Xzz Xzz Xaa Xaa Xab Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xzz twenty 25 33 Xaa Xzz Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 00 45 Xzz Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xzz Xaa Xaa Xaa Xaa Xaa 50 55 60 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65 70 75 Xzz Xzz Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 184 424 Xaa Xaa Xar Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa X aa 105 95 100 Xaa Phe Xaa raa Xar Xaa Xaa Xaa Xoa Xxo Xxx Xxx Xox X oa Xxx 110 115 122 Xxx Xaa Xxx 01n lira Thn TTh 0er Arr eer Air iuA a0i 125 30 0 (SE0 ID No. at 2; vol where Xxx at position 17 is Cheese, yys, , <^ 21, o Az, o Underworld, Main or Arg; Xxx in position 18 is Asn, His, Leu , Ile, Phe, Arg or Gln; Xaa in item i 19 is Met, Pile, How many , Arg, Gly, Ala or Cys; Xaa in position 20 is Ile, Cys, Gln , Glu, Arg, PPA or AAx; Xaa in position 21 means Asp, Phe, Lys, Ag, o αχ, o AC, o Glu, Gln, Asn, Thr, Cheese or VxI; Xaa in position 22 means Glu, Trp, Pro, Cheese, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa in position 23 means Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser or Arg; Xaa in position 24 is Ile, Gly, Vx1 , Arg, Cheese, Phh flax? Leu; Xaa in position 25 stands for The, His, Gly , Gln, Arg, PPA or Ala; 184 424 Xaa in position 26 means His, Thr, Phe, Gly, Arg, Ala or Trp; Xaa in position 27 means Leu, Gly, Arg, Tho, Ser or Ala Xaa in position 28 means Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa in position 29 is Gln, Ass, Leu, Pro, Arg or Val Xaa in position thirty means Pro, His, Tho, Gly, Asp, Gls,: Cheese, Leu or Lys; Xaa in position 31 means Pro, Asp, Gly, Ala, Arg, Leu or Gln; Xaa in position 32 means Leu, Val, Arg, Gln, Asn, Gly, Ala or Glu; Xaa in position 33 is Pro, Leu, Gls, Ala, Thr or Glu with Xaa in position 34 means Leu, Val, Gly, Ser, Lys, Glu, < iln, Tho, Arg, Ala, Phe, Ile or Met; Xaa in position 35 means Leu, Ala, Gly, Ass, Pro, Main or Val; Xaa in position 36 consacai Asp, Leu or Val; Xaa in position 3Ί oonsaca Phe, Sev, Prv, Trp or He; Xaa in position 31 is Asn or Ala; Xaa in position 4 0 Leu oorisaza, Τη? or Arg; Xaa in position 41 means Asr, Cys, Arg, Leu, His, Underworld or Pro; 184 424 Xaa in position 42 means Gly, Asp, Sio, Cys, Asn, Lyi, Tho, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa in position 43 means Glu, Asn, Tyo, Leu, Phe, Asp), Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa in position 44 means Asp, Ser, Leu, Arg, Lys, Tho, Underworld, Top, Glu, Asn, Gln, Ala or Pro; Xaa in position 45 means Gln, Poo, Phe, Val, Met, Leu, Tho, Lys, Trp, Asp, Asn, Arg, Ser, Ala, How much, Glu or His; Xaa in position 46 means Asp, Phe, Seo, Tho, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa in position 71 is H, Gl, Val , Ser , Arg, Pito or His; Xaa in position 48 means Leu, Ser, Cys, Arg, How many, Hii, Phe, Glu, Lys, Tho, Ala, Met, Val or Asn; Xaa in position 49 is Met, Arg, Ala, Gly, Poo, Asn, His or Asp; Xaa in position 50 means Glu, Leu, Tho, Aip, Tyo, Lys, Asn, Cheese, Ala, Ile, Va, and Hi, and Ptei Met or Gln; Xaa in position 511 is An, and Arg, Underworld , Pro, , Seo, TTr or His; Xaa in position 52 is As, and H ± Si Arg , Llu, , Gly, Ser or Thr; 184 424 Xaa in position 53 means Leu, Thr, Ala, Gly, Glu, Pro, Lys, Cheese or Met; Xaa in position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa in position 55 is Arg, Thr, Val, Ser, Leu or Gly Xaa in position 56 Means Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa in position 57 is Asn or Gly; Xaa in position 58 is Leu, Ser, Asp), Arg, Gln, Val or Cys; Xaa in position 59 is Glu, Tyr :, His, Leu, Pro or Arg Xaa in position 60 is Ala, Ser, Pro, Tyr, Asn or Thr ; Xaa in position 61 is Phe, Asn, Glu, Pro, Lys, Arg or Cheese; Xaa in position 62 means Asn, His, Val, Arg, Pro, Thr, Asp or How many; Xaa in position 63 means Arg, Tyr, Trp, Lys, Ser, His, Pro or Val; Xaa in position 64 is Ala, Asn, Pro, Ser or Lys; Xaa in position 65 is Val, Thr, Pro, His, Leu, Phe or Cheese; Xaa in position 66 means Lys, Ile, Arg, Val, Asn, Glu or Cheese; 184 424 Xaa in position 67 ozz ^ i ^ z ^ a Cheese Al, Phe, Vvl, Giy, Am, How much, Pro or His; Xaa in position 68 means Leu, Ca,, ro, Cheese, Ile, Phe, Thr or His; Xaa in position 69 oozer iin, Al, Pro, Thg, Ginu AAg, Th ,, how many or Leu; Xxx in position 70 Go ^ acs Asn, Lmu, ^ æ ^ l. Trp, Pro luo Ma; Xaa in position 71 He can Ala, Me ,, Leu, Aa ,, Giu, Thr, iln, Trp, or Asn; aaa in position 72 means Cheese :, IAu, Met, Mc, His, Asn, Agg or Asp; Xcc in position 73 means Ala, Glu, Ap,, Mu,, Mr,, Μ,, h, r or Arg; Xcc in position 74 ozaaαca Ile, Met, Thr, Pro, Arg, Gly, Ala; aαa in position 75 coiiaGca ilu, Ly,, Gly, AAs, Poro Trg, AAg, Cheese, iln or Len; aαx in position 76 means Ser, Vcl, Ala, Asn, Trp, ilu, Oro, how many or Asp; aaa in position 77 means Ile, Ser, Arg, Thg, or Leu; acα in position 78 means Leu, Alc, Ser, ilu, Phe, ily or Agg; Xcc in position 79 means Lys, Thr, Asn, Met, Arg, Ile, how many or Asp; 184 424 Xaa in position 80 stands for Asn, Trrp, Val, Gly, The, Leu, Glu or Arg; Xaa p items 81 means Leu, Gln, Gly, Ala, Trp, Arg, VaU or Lys; Xaa in position 82 means Leu, GUs., Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa p items 83 means Pro, AA a, Thr, Trp, Arg or Met Xaa p items 84 means Cys, ,] ^ u, Gly /, Arg, Met or Val Xaa p items 85 means Leu, Asn, Val or Gln; Xaa p items 86 means Pro, , ys, Arg, AULa, or Lys; Xaa p items 87 stands for LeUu , er, Trp or Gl ;; Xaa p items 88 stands for Alu, , ys, Arg, Val, or Trp; Xaa p items 89 means Thr, Asp, Cys, Leu, Val, Glu, His, Asn or Ssr; Xaa p items 90 means Ala, Po ,, Sr,, Thr, G ^ ly /, TAsp, IIe or Met; Xaa p items 91 means Ala, Pr, Se, Thr, Phe, Leu, AAsp or His; Xaa p items 92 means Pro, Phe, Arg, Cheese, Lys, His, Ala, Gly, How many Uub Leu; Xaa p items 93 means Thr, Asp, Se, Asn, Pro, TALa, Llu or Arg; Xaa p items 94 means Arg, How much, Cheese, GUu, Val, Gln, Lys, His, Ala or Pro; 184 424 Xaa at position 95 is His, (Sin, roo, Ar,, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile or Tyjc; Xaa at position 99 is Pro, Lys, Tyr, Gly, Ile or Thr; Xaa at position 99 is PIe, Val, Lys, Ala or Asn; Xaa at position 98 is His, ILs, As, L20, Asp, Ma, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg, Tyr, or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe or His; Xaa in position 100 means Lys, Tire, Leo, His, Arg, How much, Cheese, Gln or Pro; Xaa in position 101 means Asp, Pro, MtO, Lys, His, Thr, Val, Tyr, Glu, Asn, Cheese, Ala, Gly, How much, Leu or Gln; Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr or Pro; Xaa at position 103 is Asp or Ser; Xaa at position 104 on Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 105, it is Asn, Pro, Ais, Phe, Ser, Τιρ, Gln, Tyr, Leu, Lys, Ile, Asp or His; Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly or Pro; Xaa at position 108 of the plug -Arg, Lys, asp], Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; 184 424 Xxx in position 109 means .Arg, TTr, Pry, Glu, Tg, o Leu, Ser or Gly; Xxx in the pose 0 10 is Lys , Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Cheese or Tep; Xxx in ροζγ ^ Ι 13.1. CyZllαj.c Leu, Ι1θ, A.rg, Asp or Met; Xxx in position 112 of the thrower, VaX, Gln, Tyr, Gu, o His, SSr or PIi; Xxx in posit 0 11 Phe , Cheese, Cys, Hii, Gly, Trp, Tire, Asp, Lys, Leu, Ile, VaU or Asn Xxx in position 114 is Tire, Cys, His, eero Ar,, Arg Feb :) Leu; Xaa in posit 0 11 for Leu , Asn, VaU, Pito, Arg, Ala, His, Thr, Tep. Uub Met; Xxx in position 0 11 ozzacc ^ Lys , Leu, Pro, TTh, Mer, Asp, Val, GUu, Aeg, Trp, See, Asn, His, Ala, Tyr, Phe, Gln luu How much; Xxx in position 117 is Thr, Cheese, Asn, Uleo Arp, Lys luu Pro; Xaa in position 118 mark; Leu, Cheese, Pro, Ala, du ^, Ccc, Asp or Tire; Xxx in position 119 is Glu, Cheese, Lys, Pro, Lee, TTr, Trr or Aeg; 184 424 Xaa at position 11 ^ 0 means An, i la, i Oro, 1u,, Hi, i Vi and lrnb Gln; Xaa at position 122 is Ala, Se, i ie, and Asn, Pr, and L ^ y ^^ and Asp or Gly; Xaa at position 12 2 select Gli, Sei, Mei, Trp, Ari, Phe, Poo, His, Ile, Tyo or Cys; Xaa at the H 2 position is Aleja, Met, Gl,, Hi, and Se, and PrOi Tyr or Leu; where optionally from 1 to 14 amino acids can be removed from the N-terminus and / or from 1 to 15 amino acids can be removed from the C-terminus; and wherein 1 to 44 amino acids designated Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3; or (V) a colony stimulating factor; and wherein L: is a linker that allows R to be linked to R5 provided that at least R: or R is selected from polypeptides of formula (I), (II) or (III); and said hematopoietic protein may be immediately preceded by (methionine ' ¹ ), (alanine' ¹ ) or (methionine ', alanine' ¹ ). The more recommended breakpoints at which a new C-terminus and N-terminus are made in the above pollpeptide (() are: 38-39, 39-40. 40-41, 41-42, 48-49, 54-55, 55-56, 56-57, 57-58, 55-59, 59-60, 60-6E 61-62, 62-63, 64-65, 6 ^ - ^^, 66-67, 67 -68, 68-69, 69-70, 96-97, ^ 25-126, ^^ 6-127, 127-128, 128-129, 129-130, 1905131, 131-132, 132133, 133-134,134- 135,135-136, 136-137, 137-138, 138-139, 139-140, 140-141 and 141-145. The most preferred breakpoints at which a new C-terminus and N-terminus are made in the above polypeptide (I) are: 38-39.48-49.96-97. 125-126,132-133 and 24-142. The more preferred breakpoints at which a new C-terminus and N-terminus are made in the polypeptides I (II, above, are: 28-29, 29-30, 30-31, 31-32, HH, 33-34, 94-35). , 35-36, 36-37, 37-38, 33-9, 39-40, 6 ^ - ^^, 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 101-105. The most preferred breakpoints at which a new C-terminus and N-terminus are made in the above polypeptide (II) are: 34-35, 69-70 and 90-91. The more preferred point and steps in which a new C and N-terminus is performed, in which the polyp of the cpUd (ΠΪ) or the acid sequence (SEQ ID NO: 256) is made are: 80-81, 81-82, 82 -83, 83-84, 84-85, 85-86, 86-87, 108-109, 109-110, 110-111, 111-112, 112-113, 1-3-114, 114-1-9 , 115-116, 116-117, 117-118, 118-119, 119-120, 120-151, 121-122, 122-123, 123-124, 154-159, 125-156, and 126-127. The most preferred breakpoints at which a new C-terminus is made and a N kum in the above polypeptide: th (1U) or in the aminoPevao gull in SEQ ID NO: 2556 are; S - 82, 108-11) 0, 115-1165 119-I21, 122-123 and H 51 59.U-a \ wjioneeo egoisto of the multifunctional receptor may also represent the following formula: (Y ^, ) a- (L ¹ ) b - X ¹ - (L) cX ² - (L ² ) d- (T ² ) e X '^) _c -X ² X) AfL (L) _c -Y ² wherein: χ1 is a peptide containing an amino acid sequence corresponding to residues n + 1 to J of the original protein having the amino acid residues numbered 1 to J followed by the amino acid at residue 1; L is an optional linker; χ2 is a peptide containing an amino acid sequence of residues 1 to n of the original protein; γ1 is a peptide containing the amino acid sequence containing the sequence 184,424 with residues n = 1 to K of the original protein having the amino acid residues sequentially numbered 1 to K with the amino terminus at residue 1; Y ² is a peptide containing an amino acid sequence of residues 1 to n of the original protein; L ¹ and L 2 are possible manifolds peptide: n is an integer ranging from 1 to J-1; a and e are either 0 or 1, provided that both a and and e cannot be simultaneously 0; and T ¹ and T2 are proteins. The disclosure also relates to recombinant expression vectors containing nucleotide sequences encoding multi-functional hematopoietic receptor agonists, related microbial expression systems, and methods for producing a multi-functional hematopoietic receptor agonist. Also disclosed are pharmaceutical compositions containing multi-functional hematopoietic receptor agonists and methods of using the multi-functional hematopoietic receptor agonists. In addition to the use of multi-functional hematopoietic receptor agonists in vivo, it is apparent that in vitro uses will include the ability to stimulate bone marrow and activate blood cells and growth before infecting a patient.