Cysteine engineered antibodies and conjugates

Patent metadata

Field	Value
Publication number	US-11873330-B2
Application number	US-202016787280-A
Country	US
Kind code	B2
Filing date	Feb 11, 2020
Priority date	Jun 8, 2010
Publication date	Jan 16, 2024
Grant date	Jan 16, 2024

Abstract

Cysteine engineered antibodies comprising a free cysteine amino acid in the heavy chain or light chain are prepared by mutagenizing a nucleic acid sequence of a parent antibody and replacing one or more amino acid residues by cysteine to encode the cysteine engineered antibody; expressing the cysteine engineered antibody; and isolating the cysteine engineered antibody. Certain highly reactive cysteine engineered antibodies were identified by the PHESELECTOR assay. Isolated cysteine engineered antibodies may be covalently attached to a capture label, a detection label, a drug moiety, or a solid support.

First claim

We claim:

1. An isolated cysteine engineered antibody comprising a free cysteine amino acid in the heavy chain located at position 200 or 212 by sequential numbering, or a free cysteine amino acid in the light chain located at position 155 by sequential numbering.

2. An isolated cysteine engineered antibody comprising a free cysteine amino acid, wherein the cysteine engineered antibody comprises a sequence in the heavy chain selected from
HC-T200C with the sequence SLGTQCYICNV (SEQ ID NO: 92) and
HC-T212C with the sequence HKPSNCKVDKK (SEQ ID NO: 95);

or a sequence in the light chain selected from
LC-Q155C with the sequence VDNALCSGNSQ (SEQ ID NO: 135) and
LC-T206C with the sequence LSSPVCKSFNR (SEQ ID NO: 146);

wherein the free cysteine amino acid is in the center of the sequence.

3. The cysteine engineered antibody of claim 1 wherein the cysteine engineered antibody is a monoclonal antibody.

4. The cysteine engineered antibody of claim 1 wherein the cysteine engineered antibody is an antibody fragment, wherein the fragment is a Fab, Fab′, F(ab′) 2 , Fv, or scFv fragment.

5. The cysteine engineered antibody of claim 1 wherein the cysteine engineered antibody is a bispecific antibody.

Assignees

• Genentech Inc

Inventors

• Bhakta Sunil
• Junutula Jagath R

Classifications

• C07K16/00 Primary

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• A61K47/6803

  Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates · CPC title

• A61K47/68033

  the drug being a maytansine · CPC title

• A61K47/68031

  the drug being an auristatin · CPC title

• A61K47/6817 Primary

  Toxins · CPC title