C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
530/13, 195/1.2,
C12N 1/16 (2006.01) A61K 38/18 (2006.01) A61L 15/32 (2006.01) C07K 14/15 (2006.01) C07K 14/49 (2006.01) C07K 19/00 (2006.01) C12N 15/18 (2006.01) C12N 15/62 (2006.01) C12N 15/81 (2006.01) C12P 21/00 (2006.01) C12Q 1/00 (2006.01) A61K 38/00 (2006.01)
Patent
CA 1341398
Methods for expressing a variety of biologically active PDGF analogs in eucaryotic cells are disclosed. The methods generally comprise introducing into a eucaryotic host cell a DNA construct capable of directing the expression and secretion of biologically active PDGF analogs in eucaryotic cells. The DNA construct contains a transcriptional promoter followed downstream by a suitable DNA sequence. The DNA sequence may encode a protein substantially homologous or identical to the A-chain or the B-chain of PDGF, or a portion thereof, or an A-B heterodimer. In addition, a portion of the DNA sequence may encode at least a portion of the a chain, while another portion encodes ate least a portion of the B-chain of PDGF. Eucaryotic cells transformed with these DNA con- structs are also disclosed Methods of promoting the growth of mammalian cells, comprising incubating the cells with a biologi- cally active PDGF analog expressed by are eucaryotic host cell transformed with such a DNA construct, are also disclosed. Dimeric proteins having substantially the same biological activity as PDGF are also disclosed. More specifi- cally, the proteins may have two polypeptide chains, one of the chains being a mosaic of amino acid sequences substantially identical to portions of the A- ar B-chains of PDGF, the second of the chains being substantially homologous to either the A-cha in or the B-chain to PDGF, or each of the chains may be substantially identical to the A-chain of PDGF. Alternatively, each of the two polypeptide chains may be a mosaic of amino acid sequences as described above. In addition, proteins comprising polypeptides that are variante, or derivatives of the A- or B-chains of PDGF arcs also disclosed. Therapeutic compositions containing these proteins and methods for enhancing the wound-healing process in warm-blooded animals are also disclosed.
544480
Kelly James D.
Murray Mark J.
Osler Hoskin & Harcourt Llp
Zymogenetics Inc.
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