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)p I where p is 1 to 4. Diagnostic and therapeutic uses for cysteine engineered antibody drug compounds and compositions are disclosed.

Cysteine engineered antibodies and conjugates

Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.

Monomethylvaline compounds capable of conjugation to ligands

The present invention relates to antibody-drug conjugate compounds of Formula I: Ab-(L-D)p where one or more maytansinoid drug moieties (D) are covalently linked by L to an antibody (Ab) which binds to an ErbB receptor, or which binds to one or more tumor-associated antigens or cell-surface receptors. These compounds may be used in methods of diagnosis or treatment of cancer, and other diseases and disorders.

Antibody-drug conjugates and methods

Methods for the targeted integration of nucleotide sequences into a plant are provided. Transfer cassettes comprising nucleotide sequences of interest flanked by non-identical recombination sites are used to transform a plant comprising a target site. The target site contains at least a set of non-identical recombination sites corresponding to those on the transfer cassette. Exchange of the nucleotide sequences flanked by the recombination sites is effected by a recombinase.

Compositions and methods for genetic modification of plants

Conjugates and compounds for making conjugates which are PBD molecules linked via the N10 position are disclosed, along with the use of the conjugates for treating proliferative diseases, including cancer

Pyrrolobenzodiazepines and conjugates thereof

Recombinant expression of Coleoptera luciferase

DNA compositions and methods of constructing and using the same consisting of DNA sequences encoding luciferase activity, or DNA sequences encoding hybrid molecules exhibiting luciferase activity and a second biological activity that are useful in performing biological assays

DNA sequences encoding coleoptera luciferase activity

This invention provides methods for obtaining specific and stable integration of nucleic acids into eukaryotic cells. The invention makes use of site-specific recombination systems that use prokaryotic recombinase polypeptides, such as the ΦC31 integrase, that can mediate recombination between the recombination sites, but not between hybrid recombination sites that are formed upon the recombination. Thus, the recombination is irreversible in the absence of additional factors. Eukaryotic cells that contain the recombinase polypeptides, or genes that encode the recombinases, are also provided.

Dna recombination in eukaryotic cells by the bacteriophage phic31 recombination system

The present invention provides methods for producing a transgenic cell having a stably integrated, single copy of an exogenous polynucleotide sequence. The method, which resolves repeated insertions of the introduced polynucleotide sequence into a single copy, involves introducing into a genetic locus of a cell a polynucleotide sequence flanked on each end by a recombination site. The recombination sites are oriented such that contact with a recombinase would not result in deletion of the polynucleotide sequence from the construct. The multiple, tandem copies of the introduced polynucleotide locus are then contacted with a recombinase that catalyzes recombination among the recombination sites. As a result of this method, the multiple, tandem copies are resolved to a single copy.

Resolution of complex integration patterns to obtain single copy transgenes

Genetic transformation of plants often re- sults in multiple copies of the introduced DNA at a single locus. To ensure that only a single copy of a foreign gene resides in the plant genome, we used a strategy based on site-specific recombination. The transformation vector con- sists of a transgene f lanked by recombination sites in an inverted orientation. Regardless of the number of copies integrated between the outermost transgenes, recombination between the outermost sites resolves the integrated molecules into a single copy. An example of this strategy has been demonstrated with wheat transformation, where four of four multiple-copy loci were resolved successfully into single-copy transgenes.

Single-copy transgenic wheat generated through the resolution of complex integration patterns (wheat transformationysite-specific recombinationyCre-lox)

David W. Ow

Papers

Recombinant expression of Coleoptera luciferase

DNA sequences encoding coleoptera luciferase activity

Dna recombination in eukaryotic cells by the bacteriophage phic31 recombination system

Resolution of complex integration patterns to obtain single copy transgenes

Single-copy transgenic wheat generated through the resolution of complex integration patterns (wheat transformationysite-specific recombinationyCre-lox)