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AssigneeChiron Corporation
InventorsJayvardhan Pandit, Jarmila Jancarik, Sung-Hou Kim, Kirston Koths, Robert Halenbeck, Anna Lisa Fear, Eric Taylor, Ralph Yamamoto, Andrew Bohm
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The present invention is directed to methods for crystallizing macrophage colony stimulating factor (M-CSF) and to a crystalline M-CSF produced thereby. The present invention is also directed to methods for designing and producing M-CSF agonists and antagonists using information derived from the crystallographic structure of M-CSF. The invention is also directed to methods for screening M-CSF agonists and antagonists. In addition, the present invention is directed to an isolated, purified, soluble and functional M-CSF receptor.
Crystalline macrophage colony stimulating factor .alpha. (M-CSF.alpha.), the M-CSF.alpha. being a dimer of two M-CSF.alpha. polypeptide monomers, said monomers being the same or different and having the same amino acid sequence as a mature M-CSF.alpha. polypeptide, and when said monomers are different, said monomers differing from one another by at least one but less than five amino acid residues.
A method of crystallizing a macrophage colony stimulating factor .alpha. (M-CSF.alpha.) dimer having two M-CSF.alpha. polypeptide monomers which may be the same or different, each monomer containing 146 to 162 amino acids, when said monomers are different, said monomers differing from one another by at least one but less than five amino acid residues, the method comprising the steps of:
Crystalline macrophage colony stimulating factor .alpha. (M-CSF.alpha.) comprising amino acids 4-158 of a mature M-CSF.alpha..
A method for determining a three-dimensional stucture of an M-CSF dimer containing two M-CSF.alpha. polypeptide monomers that may be the same or different, each monomer having between about 146 and 162 amino acids beginning from about residue 1 to about residue 5 of mature M-CSF.alpha., when said monomers are different, said monomers differing from one another by at least one but less than five amino acid residues, the method comprising:
A composition comprising:
A crystalline M-CSF.alpha. (4-158) comprising at least one but less than five amino acid substitutions at a residue or residues selected from the group consisting of His 15, Gln 17, Gln 79, Arg 86, Glu 115, Lys 93, Asp 99, Leu 55, Ser 18, Gln 20, Arg 21, Ile 75, Val 78, Leu 85, Asp 69, Asn 70, His 9, Asn 63 and Thr 34.
A crystalline M-CSF.alpha. wherein the M-CSF.alpha. is a dimer of two M-CSF.alpha. polypeptide monomers.
A crystalline M-CSF wherein the M-CSF is a dimer of two M-CSF polypeptide monomers that are the same or different, having a length up to residue position 158 as measured from the N-terminus of mature M-CSF, and are selected from the group consisting of M-CSF.alpha., M-CSF.beta. and M-CSF.gamma., when said monomers are different, said monomers differing from one another by at least one but less than five amino acid residues.
Dependencies are inferred from the claim text.