Multi-functional hematopoietic fusion proteins between sequence rearranged G-CSF receptor agonists and other hematopoietic factors

A hematopoietic protein comprising;

• an amino acid sequence of the formula:
• R1-L1-R2, R2-L1-R1, R1-R2, or R2-R1
• wherein R1 and R2 are independently selected from the group consisting of:
• (I) A polypeptide comprising;
• a modified human G-CSF amino acid sequence of the formula:
• 26 1 10 (SEQ ID NO:
• 1) Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa 20 Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly 30 40 Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa 50 Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp 60 70 Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly 80 Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu 90 100 Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu 110 Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp 120 130 Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr 140 Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala 150 160 Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa 170 Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro
• wherein
• 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 or Ser;
• Xaa at position 13 is Phe, Ser, His, Thr or Pro;
• Xaa at position 16 is Lys, Pro, Ser, Thr or His;
• Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg;
• Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys;
• Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala;
• Xaa at position 24 is Ile, Pro, Tyr or Leu;
• Xaa at position 27 is Asp, or Gly;
• Xaa at position 30 is Ala, Ile, Leu or Gly;
• Xaa at position 34 is Lys or Ser;
• Xaa at position 36 is Cys or Ser;
• Xaa at position 42 is Cys or Ser;
• Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu;
• Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr;
• Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala;
• Xaa at position 47 is Leu or Thr;
• Xaa at position 49 is Leu, Phe, Arg or Ser;
• Xaa at position 50 is Leu, Ile, His, Pro or Tyr;
• Xaa at position 54 is Leu or His;
• Xaa at position 64 is Cys or Ser;
• Xaa at position 67 is Gln, Lys, Leu or Cys;
• Xaa at position 70 is Gln, Pro, Leu, Arg or Ser;
• Xaa at position 74 is Cys or Ser;
• Xaa at position 104 is Asp, Gly or Val;
• Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly;
• Xaa at position 115 is Thr, His, Leu or Ala;
• Xaa at position 120 is Gln, Gly, Arg, Lys or His
• Xaa at position 123 is Glu, Arg, Phe or Thr
• Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu;
• Xaa at position 146 is Arg or Gln;
• Xaa at position 147 is Arg or Gln;
• Xaa at position 156 is His, Gly or Ser;
• Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly;
• Xaa at position 162 is Glu, Leu, Gly or Trp;
• Xaa at position 163 is Val, Gly, Arg or Ala;
• Xaa at position 169 is Arg, Ser, Leu, Arg or Cys;
• Xaa at position 170 is His, Arg or Ser,
• wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can optionally be deleted from said modified human G-CSF amino acid sequence;
• and
• wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids;
• 27 38-39 39-40 40-41 41-42 42-43 43-44 45-46 48-49 49-50 52-53 53-54 54-55 55-56 56-57 57-58 58-59 59-60 60-61 61-62 62-63 63-64 64-65 65-66 66-67 67-68 68-69 69-70 70-71 71-72 91-92 92-93 93-94 94-95 95-96 96-97 97-98 98-99 99-100 123-124 124-125 125-126 126-127 128-129 128-129 129-130 130-131 131-132 132-133 133-134 134-135 135-136 136-137 137-138 138-139 139-140 140-141 141-142 or 142-143 respectively;
• (II) A polypeptide comprising;
• a modified human IL-3 amino acid sequence of the formula:
• 28 Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO:
• 2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 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 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130
• wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe;
• Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• 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 Leu;
• Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, 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 at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp, Pro, Met, 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 position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, 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 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, 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;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;
• 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 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu,
• wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human IL-3 amino acid sequence;
• wherein from 0 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
• and
• wherein the N-terminus is joined to the C-terminus directly or through a linker (L2), capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids:
• 29 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 respectively;
• (III) A polypeptide comprising;
• a modified human c-mpl ligand amino acid sequence of the formula:
• 30 SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer (SEQ ID NO:
• 256) 1 5 10 15 HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 25 30 35 ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 60 65 70 75 AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95 GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110 XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis 115 120 125 130 LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150 Arg 153
• wherein
• Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met;
• Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
• Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
• Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn,
• wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids:
• 31 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 respectively;
• (IV) A polypeptide comprising;
• a modified human IL-3 amino acid sequence of the formula:
• 32 Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO:
• 2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 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 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130
• wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• 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 at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, 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 at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp, Pro, Met, 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 position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, 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 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, 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;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;
• 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 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;
• wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human IL-3 amino acid sequence;
• and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
• and
• (V) a colony stimulating factor
• wherein L1 is a linker capable of linking R1 to R2
• with the proviso that at least R1 or R2 is selected from the polypeptide of formula (I), (II), or (III) and
• said hematopoietic protein can optionally be immediately preceded by (methionine−1), (alanine−1) or (methionine−2, alanine−1).

A hematopoietic protein comprising an amino acid sequence of the formula:

• R1-L1-R2, R2-L1-R1, R1-R2, or R2-R1
• wherein R1 and R2 are independently selected from the group consisting of:
• (I) A polypeptide comprising;
• a modified human G-CSF amino acid sequence of the formula:
• 33 1 10 Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa (SEQ ID NO:
• 1) 20 Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly 30 40 Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa 50 Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp 60 70 Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly 80 Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu 90 100 Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu 110 Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp 120 130 Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr 140 Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala 150 160 Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa 170 Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro
• wherein
• 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 or Ser;
• Xaa at position 13 is Phe, Ser, His, Thr or Pro;
• Xaa at position 16 is Lys, Pro, Ser, Thr or His;
• Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg;
• Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys;
• Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala;
• Xaa at position 24 is Ile, Pro, Tyr or Leu;
• Xaa at position 27 is Asp, or Gly;
• Xaa at position 30 is Ala, Ile, Leu or Gly;
• Xaa at position 34 is Lys or Ser;
• Xaa at position 36 is Cys or Ser;
• Xaa at position 42 is Cys or Ser;
• Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu;
• Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr;
• Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala;
• Xaa at position 47 is Leu or Thr;
• Xaa at position 49 is Leu, Phe, Arg or Ser;
• Xaa at position 50 is Leu, Ile, His, Pro or Tyr;
• Xaa at position 54 is Leu or His;
• Xaa at position 64 is Cys or Ser;
• Xaa at position 67 is Gln, Lys, Leu or Cys;
• Xaa at position 70 is Gln, Pro, Leu, Arg or Ser;
• Xaa at position 74 is Cys or Ser;
• Xaa at position 104 is Asp, Gly or Val;
• Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly;
• Xaa at position 115 is Thr, His, Leu or Ala;
• Xaa at position 120 is Gln, Gly, Arg, Lys or His
• Xaa at position 123 is Glu, Arg, Phe or Thr
• Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu;
• Xaa at position 146 is Arg or Gln;
• Xaa at position 147 is Arg or Gln;
• Xaa at position 156 is His, Gly or Ser;
• Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly;
• Xaa at position 162 is Glu, Leu, Gly or Trp;
• Xaa at position 163 is Val, Gly, Arg or Ala;
• Xaa at position 169 is Arg, Ser, Leu, Arg or Cys;
• Xaa at position 170 is His, Arg or Ser,
• wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted from said modified human G-CSF amino acid sequence;
• and
• wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids:
• 34 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 respectively;
• (II) A polypeptide comprising;
• a modified human IL-3 amino acid sequence of the formula:
• 35 Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO:
• 2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 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 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130
• wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• 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 at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, 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 at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp, Pro, Met, 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 position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, 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 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, 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;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;
• 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 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu,
• wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human IL-3 amino acid sequence;
• and wherein from 0 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
• and
• wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids:
• 36 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 respectively;
• (III) A polypeptide comprising;
• a modified human c-mpl ligand amino acid sequence of the formula:
• 37 SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer (SEQ ID NO:
• 256) 1 5 10 15 HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 25 30 35 ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 60 65 70 75 AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95 GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110 XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis 115 120 125 130 LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150 Arg 153
• wherein
• Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met;
• Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
• Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
• Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn;
• and
• wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids:
• 38 52-53 108-109 53-54 109-110 54-55 110-111 55-56 111-112 56-57 112-113 57-58 113-114 58-59 114-115 59-60 115-116 78-79 116-117 79-80 117-118 80-81 118-119 81-82 119-120 82-83 120-121 83-84 121-122 84-85 122-123 85-86 123-124 86-87 124-125 87-88 125-126 88-89 126-127 or 127-128 respectively;
• (IV) A polypeptide comprising;
• a modified human IL-3 amino acid sequence of the formula:
• 39 Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO:
• 2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 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 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130
• wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• 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 at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, 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 at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp, Pro, Met, 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 position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, 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 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, 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;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;
• 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 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu,
• wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human IL-3 amino acid sequence;
• and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3, and
• (V) a colony stimulating factor;
• and wherein L1 is a linker capable of linking R1 to R2
• with the proviso that at least R1 or R2 is selected from the polypeptide of formula (I), (II), or (III);
• and
• said hematopoietic protein can optionally be immediately preceded by (methionine−1), (alanine−1) or (methionine−2, alanine−1).

A hematopoietic protein comprising;

• an amino acid sequence of the formula:
• R1-L1-R2, R2-L1-R1, R1-R2, or R2-R1
• wherein R1 is a polypeptide comprising;
• a modified human G-CSF amino acid sequence of the formula:
• 43 1 10 Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa (SEQ ID NO:
• 1) 20 Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly 30 40 Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa 50 Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp 60 70 Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly 80 Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu 90 100 Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu 110 Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp 120 130 Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr 140 Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala 150 160 Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa 170 Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro
• wherein
• 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 or Ser;
• Xaa at position 13 is Phe, Ser, His, Thr or Pro;
• Xaa at position 16 is Lys, Pro, Ser, Thr or His;
• Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg;
• Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys;
• Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala;
• Xaa at position 24 is Ile, Pro, Tyr or Leu;
• Xaa at position 27 is Asp, or Gly;
• Xaa at position 30 is Ala, Ile, Leu or Gly;
• Xaa at position 34 is Lys or Ser;
• Xaa at position 36 is Cys or Ser;
• Xaa at position 42 is Cys or Ser;
• Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu;
• Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr;
• Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala;
• Xaa at position 47 is Leu or Thr;
• Xaa at position 49 is Leu, Phe, Arg or Ser;
• Xaa at position 50 is Leu, Ile, His, Pro or Tyr;
• Xaa at position 54 is Leu or His;
• Xaa at position 64 is Cys or Ser;
• Xaa at position 67 is Gln, Lys, Leu or Cys;
• Xaa at position 70 is Gln, Pro, Leu, Arg or Ser;
• Xaa at position 74 is Cys or Ser;
• Xaa at position 104 is Asp, Gly or Val;
• Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly;
• Xaa at position 115 is Thr, His, Leu or Ala;
• Xaa at position 120 is Gln, Gly, Arg, Lys or His
• Xaa at position 123 is Glu, Arg, Phe or Thr
• Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu;
• Xaa at position 146 is Arg or Gln;
• Xaa at position 147 is Arg or Gln;
• Xaa at position 156 is His, Gly or Ser;
• Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly;
• Xaa at position 162 is Glu, Leu, Gly or Trp;
• Xaa at position 163 is Val, Gly, Arg or Ala;
• Xaa at position 169 is Arg, Ser, Leu, Arg or Cys;
• Xaa at position 170 is His, Arg or Ser,
• wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted from said modified human G-CSF amino acid sequence;
• and
• wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids:
• 44 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 respectively,
• wherein R2 is a polypeptide comprising;
• a modified human IL-3 amino acid sequence of the formula:
• 45 Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO:
• 2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 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 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130
• wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• 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 at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, 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 at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp, Pro, Met, 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 position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, 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 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, 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;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;
• 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 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu,
• wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human interleukin-3 amino acid sequence;
• and wherein from 0 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3 and
• wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids:
• 46 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 respectively;
• wherein L1 is a linker capable of linking R1 to R2 and
• said hematopoietic protein can optionally be immediately preceded by (methionine−1), (alanine−1) or (methionine−2, alanine−1).

A hematopoietic protein comprising;

• an amino acid sequence of the formula:
• R1-L1-R2, R2-L1-R1, R1-R2, or R2-R1
• wherein R1 is a polypeptide comprising;
• a modified human G-CSF amino acid sequence of the formula:
• 47 1 10 Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa (SEQ ID NO:
• 1) 20 Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly 30 40 Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa 50 Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp 60 70 Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly 80 Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu 90 100 Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu 110 Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp 120 130 Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr 140 Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala 150 160 Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa 170 Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro
• wherein
• 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 or Ser;
• Xaa at position 13 is Phe, Ser, His, Thr or Pro;
• Xaa at position 16 is Lys, Pro, Ser, Thr or His;
• Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg;
• Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys;
• Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala;
• Xaa at position 24 is Ile, Pro, Tyr or Leu;
• Xaa at position 27 is Asp, or Gly;
• Xaa at position 30 is Ala, Ile, Leu or Gly;
• Xaa at position 34 is Lys or Ser;
• Xaa at position 36 is Cys or Ser;
• Xaa at position 42 is Cys or Ser;
• Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu;
• Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr;
• Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala;
• Xaa at position 47 is Leu or Thr;
• Xaa at position 49 is Leu, Phe, Arg or Ser;
• Xaa at position 50 is Leu, Ile, His, Pro or Tyr;
• Xaa at position 54 is Leu or His;
• Xaa at position 64 is Cys or Ser;
• Xaa at position 67 is Gln, Lys, Leu or Cys;
• Xaa at position 70 is Gln, Pro, Leu, Arg or Ser;
• Xaa at position 74 is Cys or Ser;
• Xaa at position 104 is Asp, Gly or Val;
• Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly;
• Xaa at position 115 is Thr, His, Leu or Ala;
• Xaa at position 120 is Gln, Gly, Arg, Lys or His
• Xaa at position 123 is Glu, Arg, Phe or Thr
• Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu;
• Xaa at position 146 is Arg or Gln;
• Xaa at position 147 is Arg or Gln;
• Xaa at position 156 is His, Gly or Ser;
• Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly;
• Xaa at position 162 is Glu, Leu, Gly or Trp;
• Xaa at position 163 is Val, Gly, Arg or Ala;
• Xaa at position 169 is Arg, Ser, Leu, Arg or Cys;
• Xaa at position 170 is His, Arg or Ser;
• wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted from said modified human G-CSF amino acid sequence and
• wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids:
• 48 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 respectively;
• R2 is a polypeptide comprising a modified human IL-3 amino acid sequence of the formula:
• 49 Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO:2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 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 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130
• wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• 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 at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, 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 at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp, Pro, Met, 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 position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, 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 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, 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;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;
• 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 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu,
• wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus;
• and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3 and
• L1 is a linker capable of linking R1 to R2 and
• additionally said hematopoietic protein can be immediately preceded by (methionine−1), (alanine−1) or (methionine−2, alanine−1).

A hematopoietic protein comprising an amino acid sequence of the formula:

• R1-L1-R2, R2-L1-R1, R1-R2, or R2-R1
• wherein R1 is a polypeptide comprising;
• a modified human G-CSF amino acid sequence of the formula:
• 50 1 10 (SEQ ID NO:1) Xaa Xaa Xaa Gly Pro Ala Ser Ser Leu Pro Gln Ser Xaa 20 Leu Leu Xaa Xaa Xaa Glu Gln Val Xaa Lys Xaa Gln Gly Xaa Gly 30 40 Ala Xaa Leu Gln Glu Xaa Leu Xaa Ala Thr Tyr Lys Leu Xaa Xaa 50 Xaa Glu Xaa Xaa Val Xaa Xaa Gly His Ser Xaa Gly Ile Pro Trp 60 70 Ala Pro Leu Ser Ser Xaa Pro Ser Xaa Ala Leu Xaa Leu Ala Gly 80 Xaa Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu 90 100 Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu 110 Xaa Thr Leu Gln Xaa Asp Val Ala Asp Phe Ala Xaa Thr Ile Trp 120 130 Gln Gln Met Glu Xaa Xaa Gly Met Ala Pro Ala Leu Gln Pro Thr 140 Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Xaa Gln Xaa Xaa Ala 150 160 Gly Gly Val Leu Val Ala Ser Xaa Leu Gln Xaa Phe Leu Xaa Xaa 170 Ser Tyr Arg Val Leu Xaa Xaa Leu Ala Gln Pro
• wherein
• 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 or Ser;
• Xaa at position 13 is Phe, Ser, His, Thr or Pro;
• Xaa at position 16 is Lys, Pro, Ser, Thr or His;
• Xaa at position 17 is Cys, Ser, Gly, Ala, Ile, Tyr or Arg;
• Xaa at position 18 is Leu, Thr, Pro, His, Ile or Cys;
• Xaa at position 22 is Arg, Tyr, Ser, Thr or Ala;
• Xaa at position 24 is Ile, Pro, Tyr or Leu;
• Xaa at position 27 is Asp, or Gly;
• Xaa at position 30 is Ala, Ile, Leu or Gly;
• Xaa at position 34 is Lys or Ser;
• Xaa at position 36 is Cys or Ser;
• Xaa at position 42 is Cys or Ser;
• Xaa at position 43 is His, Thr, Gly, Val, Lys, Trp, Ala, Arg, Cys, or Leu;
• Xaa at position 44 is Pro, Gly, Arg, Asp, Val, Ala, His, Trp, Gln, or Thr;
• Xaa at position 46 is Glu, Arg, Phe, Arg, Ile or Ala;
• Xaa at position 47 is Leu or Thr;
• Xaa at position 49 is Leu, Phe, Arg or Ser;
• Xaa at position 50 is Leu, Ile, His, Pro or Tyr;
• Xaa at position 54 is Leu or His;
• Xaa at position 64 is Cys or Ser;
• Xaa at position 67 is Gln, Lys, Leu or Cys;
• Xaa at position 70 is Gln, Pro, Leu, Arg or Ser;
• Xaa at position 74 is Cys or Ser;
• Xaa at position 104 is Asp, Gly or Val;
• Xaa at position 108 is Leu, Ala, Val, Arg, Trp, Gln or Gly;
• Xaa at position 115 is Thr, His, Leu or Ala;
• Xaa at position 120 is Gln, Gly, Arg, Lys or His
• Xaa at position 123 is Glu, Arg, Phe or Thr
• Xaa at position 144 is Phe, His, Arg, Pro, Leu, Gln or Glu;
• Xaa at position 146 is Arg or Gln;
• Xaa at position 147 is Arg or Gln;
• Xaa at position 156 is His, Gly or Ser;
• Xaa at position 159 is Ser, Arg, Thr, Tyr, Val or Gly;
• Xaa at position 162 is Glu, Leu, Gly or Trp;
• Xaa at position 163 is Val, Gly, Arg or Ala;
• Xaa at position 169 is Arg, Ser, Leu, Arg or Cys;
• Xaa at position 170 is His, Arg or Ser,
• wherein optionally 1-11 amino acids from the N-terminus and 1-5 from the C-terminus can be deleted from said modified human G-CSF amino acid sequence and
• wherein the N-terminus is joined to the C-terminus directly or through a linker capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids:
• 51 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 respectively;
• R2 is a polypeptide comprising a modified human c-mpl ligand amino acid sequence of the formula:
• 52 SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer (SEQ ID NO:256) 1 5 10 15 HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 25 30 35 ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 60 65 70 75 AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95 GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110 XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis 115 120 125 130 LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150 Arg
• wherein
• Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met;
• Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
• Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
• Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn, and
• wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids:
• 53 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;
• wherein L1 is a linker capable of linking R1 to R2 and
• additionally said hematopoietic protein can be immediately preceded by (methionine−1), (alanine−1) or (methionine−2, alanine−1).

A hematopoietic protein comprising;

• an amino acid sequence of the formula:
• R1—L1—R2, R2—L1—R1, R1—R2, or R2—R1
• wherein R1 is a polypeptide comprising a modified human c-mpl ligand amino acid sequence of the formula:
• 54 SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer (SEQ ID NO:256) 1 5 10 15 HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 25 30 35 ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 60 65 70 75 AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95 GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110 XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis 115 120 125 130 LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150 Arg 153
• wherein
• Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met;
• Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
• Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
• Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn, and
• wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids:
• 55 26-27 27-28 28-29 29-30 30-31 32-33 33-34 34-35 36-37 37-38 38-39 40-41 41-42 42-43 43-44 44-45 46-47 47-48 48-49 50-51 51-52 52-53 53-54 54-55 55-56 56-57 57-58 58-59 59-60 78-79 79-80 80-81 81-82 82-83 83-84 84-85 85-86 86-87 87-88 88-89 108-109 109-110 110-111 111-112 112-113 113-114 114-115 115-116 116-117 117-118 118-119 119-120 120-121 121-122 122-123 123-124 124-125 125-126 126-127 or 127-128;
• wherein R2 is a polypeptide comprising a modified human IL-3 amino acid sequence of the formula:
• 56 Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn (SEQ ID NO:2) 1 5 10 15 Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 20 25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 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 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 80 85 90 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 95 100 105 Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 110 115 120 Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe 125 130
• wherein Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;
• Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;
• Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;
• Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;
• Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val;
• Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly;
• Xaa at position 23 is Ile, Val, Ala, Gly, Trp, Lys, Phe, Leu, Ser, or Arg;
• Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;
• Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;
• Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;
• Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;
• Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;
• Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;
• Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;
• Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;
• Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;
• Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;
• Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met;
• Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;
• Xaa at position 36 is Asp, Leu, or Val;
• Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;
• Xaa at position 38 is Asn, or Ala;
• Xaa at position 40 is Leu, Trp, or Arg;
• Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;
• Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala;
• Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser;
• Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;
• Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;
• Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly;
• Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;
• Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn;
• Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;
• Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln;
• Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;
• Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;
• Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;
• Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu;
• Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;
• Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys;
• Xaa at position 57 is Asn or Gly;
• Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;
• Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;
• Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;
• Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;
• Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;
• Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;
• Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;
• Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;
• Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;
• Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;
• Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;
• Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;
• Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;
• Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn;
• Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;
• Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;
• Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;
• Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu;
• Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;
• Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;
• Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;
• Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;
• Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;
• Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;
• Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;
• Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;
• Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;
• Xaa at position 85 is Leu, Asn, Val, or Gln;
• Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;
• Xaa at position 87 is Leu, Ser, Trp, or Gly;
• Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;
• Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;
• Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;
• 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 at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;
• Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro;
• Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, or Tyr;
• Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;
• Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;
• Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, 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 at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;
• Xaa at position 101 is Asp, Pro, Met, 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 position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly;
• Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, 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 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro;
• Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;
• Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, 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;
• Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn;
• Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;
• Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met;
• Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp, Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;
• 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 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;
• Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys;
• Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu,
• wherein from 1 to 14 amino acids can optionally be deleted from the N-terminus and/or from 1 to 15 amino acids can optionally be deleted from the C-terminus of said modified human interleukin-3 amino acid sequence;
• and wherein from 1 to 44 of the amino acids designated by Xaa are different from the corresponding amino acids of native (1-133) human interleukin-3;
• wherein L1 is a linker capable of linking R1 to R2;
• and
• said hematopoietic protein can optionally be immediately preceded by (methionine−1), (alanine−1) or (methionine−2, alanine−1).

A hematopoietic protein comprising;

• an amino acid sequence of the formula:
• R1-L1-R2, R2-L1-R1, R1-R2, or R2-R1
• wherein R1 is a polypeptide comprising;
• a modified human c-mpl ligand amino acid sequence of the formula:
• 58 SerProAlaProProAlaCysAspLeuArgValLeuSerLysLeuLeuArgAspSer (SEQ ID NO:256) 1 5 10 15 HisValLeuHisSerArgLeuSerGlnCysProGluValHisProLeuProThrPro 20 25 30 35 ValLeuLeuProAlaValAspPheSerLeuGlyGluTrpLysThrGlnMetGluGlu 40 45 50 55 ThrLysAlaGlnAspIleLeuGlyAlaValThrLeuLeuLeuGluGlyValMetAla 60 65 70 75 AlaArgGlyGlnLeuGlyProThrCysLeuSerSerLeuLeuGlyGlnLeuSerGly 80 85 90 95 GlnValArgLeuLeuLeuGlyAlaLeuGlnSerLeuLeuGlyThrGlnXaaXaaXaa 100 105 110 XaaGlyArgThrThrAlaHisLysAspProAsnAlaIlePheLeuSerPheGlnHis 115 120 125 130 LeuLeuArgGlyLysValArgPheLeuMetLeuValGlyGlySerThrLeuCysVal 135 140 145 150 Arg 153
• wherein
• Xaa at position 112 is deleted or Leu, Ala, Val, Ile, Pro, Phe, Trp, or Met;
• Xaa at position 113 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
• Xaa at position 114 is deleted or Pro, Phe, Ala, Val, Leu, Ile, Trp, or Met;
• Xaa at position 115 is deleted or Gln, Gly, Ser, Thr, Tyr, or Asn;
• and
• wherein the N-terminus is joined to the C-terminus directly or through a linker (L2) capable of joining the N-terminus to the C-terminus and having new C- and N-termini at amino acids:
• 59 26-27 27-28 28-29 29-30 30-31 32-33 33-34 34-35 36-37 37-38 38-39 40-41 41-42 42-43 43-44 44-45 46-47 47-48 48-49 50-51 51-52 52-53 53-54 54-55 55-56 56-57 57-58 58-59 59-60 78-79 79-80 80-81 81-82 82-83 83-84 84-85 85-86 86-87 87-88 88-89 108-109 109-110 110-111 111-112 112-113 113-114 114-115 115-116 116-117 117-118 118-119 119-120 120-121 121-122 122-123 123-124 124-125 125-126 126-127 or 127-128 respectively;
• wherein R2 is G-CSF or G-CSF Ser17
• wherein L1 is a linker capable of linking R1 to R2;
• and
• said hematopoietic protein can optionally be immediately preceded by (methionine−1), (alanine−1) or (methionine−2, alanine−1).