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AssigneeSeagen Inc.
InventorsAndrew WAIGHT, Chris LEISKE, Travis BIECHELE, Django SUSSMAN, Patrick BURKE, Jocelyn LEISKE
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The invention provides modified heavy chain constant regions including a cysteine at position 295 by EU numbering and optionally at position 239 by EU numbering. These cysteine residues provide sites for conjugation to a drug or label. When both cysteines are present in a normal heterodimeric antibody format, there are four such sites per molecule of antibody allowing a stoichiometry of one molecule of antibody to four of drug or label. Selection of the cysteine at position 295 with or without cysteine at position 239 is advantageous over cysteines at many other positions due to ease of expression, stability and cytotoxicity.
An antibody comprising a heavy chain constant region in which position 295 by EU numbering is occupied by cysteine.
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An antibody drug conjugate comprising an antibody comprising a heavy chain constant region in which position 239 by EU numbering is occupied by cysteine, which cysteine is conjugated to tubulysin M.
A method of producing an antibody comprising a heavy chain constant region in which positions 239 and 295 by EU numbering are occupied by cysteines, the method comprising:
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An antibody or fusion protein comprising a heavy chain constant region in which any of positions 246, 294, 296, 303, 334, 336, 337, 301, 243, 262, 264, or 267 is occupied by cysteine.
The antibody or fusion protein of claim 21, wherein any of positions 246, 294, 296, 303, 334, 336, or 337 is occupied by cysteine.
The antibody or fusion protein of claim 23, wherein position 239 by EU numbering is occupied by cysteine.
An antibody or fusion protein comprising a heavy chain constant region in which any of positions 246, 294, 296, 303, 334, 336, 337, 301, 243, 262, 264, or 267 conjugated to a drug or label via the cysteine.
A method of producing an antibody of or fusion protein conjugated to a drug, the method comprising:
An antibody drug conjugate comprising an antibody comprising a heavy chain constant region in which position 295 by EU numbering is occupied by cysteine conjugated to a drug via the cysteine.
A method of producing an antibody drug conjugate comprising an antibody comprising a heavy chain constant region in which positions 239 and 295 by EU numbering are occupied by cysteines, the method comprising:
A fusion protein comprising a heavy chain constant region in which position 295 by EU numbering is occupied by cysteine.
Dependencies are inferred from the claim text.