Patent classifications
A61K51/1051
Compositions for therapeutics, targeted PET imaging and methods of their use
Described herein is a chelator for radiolabels (e.g., .sup.89Zr) for targeted PET imaging that is an alternative to DFO. In certain embodiments, the chelator for .sup.89Zr is the ligand, 3,4,3-(LI-1,2-HOPO) (HOPO), which exhibits equal or superior stability compared to DFO in chemical and biological assays across a period of several days in vivo. As shown in FIG. 1, the HOPO is an octadentate chelator that stabilizes chelation of radiolabels (e.g., .sup.89Zr). A bifunctional ligand comprising p-SCN-Bn-HOPO is shown in FIG. 4 and FIG. 5. Such a bifunctional ligand can eliminate (e.g., .sup.89Zr) loss from the chelate in vivo and reduce uptake in bone and non-target tissue. Therefore, the bifunctional HOPO ligand can facilitate safer and improved PET imaging with radiolabeled antibodies.
Cysteine Engineered Antibodies and Conjugates
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.
ANTI-HER2 NANOBODY AND CODING SEQUENCE AND USE THEREOF
Provided are an anti-Her2 nanobody and a coding sequence and the use thereof. In particular, provided is a nanobody combating human epidermal growth factor receptor-2 (Her2/ERBB2). Disclosed are the nanobody and the a gene sequence encoding the nanobody, a corresponding expression vector and a host cell capable of expressing the nanobody, and a method for producing the nanobody of the present invention and the related use thereof. The present invention may also provide an immunoconjugate of the nanobody and the use thereof, especially the use in the diagnosis and treatment of Her2 positive tumor.
RADIO-LABELLED ANTIBODY FRAGMENTS FOR USE IN THE PROGNOSIS, DIAGNOSIS OF CANCER AS WELL AS FOR THE PREDICTION OF CANCER THERAPY RESPONSE
The application provides polypeptides comprising or essentially consisting of at least one heavy chain variable domain of a heavy chain antibody (V.sub.HH) or a functional fragment thereof, wherein said V.sub.HH or a functional fragment thereof specifically binds to a target protein that is present on and/or specific for a solid tumor, e.g. HER2. The application further provides nucleic acids encoding such polypeptides; methods for preparing such polypeptides; host cells expressing or capable of expressing such polypeptides; compositions, and in particular to pharmaceutical compositions, that comprise such polypeptides, nucleic acids and/or host cells. The application further provides such polypeptides, nucleic acids, host cells and/or compositions, for use in methods for detection, imaging, prognosis and diagnosis of cancer as well as for predicting patient response(s) to therapeutics.
NOVEL ANTI-HUMAN MUC1 ANTIBODY FAB FRAGMENT
The problem to be solved is to provide an anti-human MUC1 antibody Fab fragment that is expected to be useful in the diagnosis and/or treatment of a cancer, particularly, the diagnosis and/or treatment of breast cancer or bladder cancer, and a diagnosis approach and/or a treatment approach using a conjugate comprising the Fab fragment. The solution is an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment comprising a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 8 or 10, and a light chain comprising a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 12, and a conjugate comprising the Fab fragment.
NOVEL IMAGING COMPOSITION AND USES THEREOF
The invention discussed in this application relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours.
RADIOLABELED BIOMOLECULES AND THEIR USE
The application is drawn to radiolabeled biomolecules and methods for radiolabeling biomolecules with radioactive halogen atoms that minimizes loss of the radioactive halogen due to dehalogenation in vivo, preserves the biological activity of the biomolecule, maximizes retention of radioactivity in cancer cells, and minimizes the retention of radioactivity in normal tissues after in vivo administration. Some such radiolabeled biomolecules comprise a radioactive metal atom in place of, or in addition to the radioactive halogen. The biomolecules have an affinity for particular types of cells and may specifically bind a certain cell, such as cancer cells. Relevant biomolecules include antibodies, monoclonal antibodies, antibody fragments, peptides, other proteins, nanoparticles and aptamers.
Alpha-emitting complexes
The present invention provides a tissue-targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand and the ion of an alpha-emitting thorium radionuclide. The invention additionally provides therapeutic methods employing such complexes, methods of their production and use, and kits and pharmaceutical compositions comprising such complexes.
SITE-SPECIFIC RADIOISOTOPE-LABELED ANTIBODY USING IgG-BINDING PEPTIDE
The present invention relates to an IgG-binding peptide comprising a ligand capable of binding to a radioactive metal nuclide, an IgG-binding peptide labeled with a radioactive metal nuclide, a conjugate of the IgG-binding peptide and IgG, and a radionuclide imaging agent or a diagnostic agent for cancer comprising the IgG-binding peptide or the conjugate, etc.
NOVEL ANTI-HUMAN MUC1 ANTIBODY FAB FRAGMENT
The problem to be solved is to provide an anti-human MUC1 antibody Fab fragment that is expected to be useful in the diagnosis and/or treatment of a cancer, particularly, the diagnosis and/or treatment of breast cancer or bladder cancer, and a diagnosis approach and/or a treatment approach using a conjugate comprising the Fab fragment. The solution is an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment comprising a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 8 or 10, and a light chain comprising a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 12, and a conjugate comprising the Fab fragment.