Antibodies are engineered by replacing one or more amino acids of a parent
antibody with non cross-linked, highly reactive cysteine amino acids.
Antibody fragments may also be engineered with one or more cysteine amino
acids to form cysteine engineered antibody fragments (ThioFab). Methods
of design, preparation, screening, and selection of the cysteine
engineered antibodies are provided. Cysteine engineered antibodies (Ab),
optionally with an albumin-binding peptide (ABP) sequence, are conjugated
with one or more drug moieties (D) through a linker (L) to form cysteine
engineered antibody-drug conjugates having Formula I: Ab-(L-D).sub.p I
where p is 1 to 4. Diagnostic and therapeutic uses for cysteine
engineered antibody drug compounds and compositions are disclosed.