Modified forms of reproductive hormones
AssigneeWashington University
InventorsIrving Boime, Martin M. Matzuk
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Abstract
The invention provides recombinant native and mutein forms of human reproductive hormones with characteristic glycosylation patterns which are influential in the metabolic activity of the protein. The invention also provides recombinant mutant forms of the human alpha subunit common to FSH, LH, CG, and TSH, to obtain hormones which also have unique glycosylation patterns. Also provided are recombinant materials to produce these subunits separately or together to obtain complete heterodimeric hormones of regulated glycosylation pattern and activity. Modified forms of LH and FSH beta subunits which enhance the rate of dimerization and secretion of the dimers or individual chains are also disclosed.
Claims7
A modified LH beta subunit having enhanced ability to dimerize with alpha subunit and enhanced secretion as a dimer from mammalian recombinant host cells, as compared to wild-type LH beta subunit, wherein said subunit is a modified wild-type beta subunit wherein the 7-amino acid hydrophobic sequence at positions 115-121 is deleted or replaced by a hydrophilic sequence, and at least one residue selected from the group consisting of trp.sup.8, ile.sup.15, and met.sup.42 is replaced by a hydrophilic amino acid or thr.sup.58 is replaced by asn.
Dependencies are inferred from the claim text.