The Experimental
Transplantation and Immunology Branch of the National Cancer
Institute is seeking statements of capability or interest from
parties interested in forming a collaborative research alliance to
further develop, evaluate, or commercialize a new
platform technology of immunoconjugates. This technology
avoids previous challenges that have limited anti-tumor activity
and the broad application of antibody conjugates as
therapeutics. An application of interest is therapeutic agents
for hematologic malignancies, such as
leukemia, lymphoma, and myeloma.
A new class of
molecularly defined immunoconjugates exploits selenocysteine as an
engineered interface between biological and chemical
entities. The nucleophilic selenol group of selenocysteine
enables regiospecific, covalent conjugation in the presence of
the other natural amino acids. Selenocysteine, a rare
amino acid with unique chemical reactivity, is inserted into
whole antibodies (e.g., IgG) or antibody fragments (e.g., Fc, Fab,
and scFv) by recoding a stop codon from termination to
selenocysteine insertion in yields comparable to conventional
monoclonal antibodies. A derivative of a small synthetic
molecule subsequently can be regiospecifically and covalently
conjugated to the selenocysteine interface. Through this
conjugation, both biological and chemical components acquire
pharmacological advantages. Conventional
immunoconjugates, which are usually based on covalent
conjugations to amine or thiol groups, are not regiospecific
due to the abundance of lysines, cysteines, and other
reactive amino acids, and can cause substantial batch-to-batch
variability. In contrast to other technologies that utilize
unique chemical reactivities of natural or unnatural amino acids in
proteins for regiospecific covalent conjugation of small synthetic
molecules, antibody variable domains, enzymatic
modification, or artificial translational machinery are not
required.
U.S. Provisional
Application No. 60/909,665 filed April 2,
2007.
Collaborative
research and licensing opportunity: To develop small synthetic
molecules for targeting a generic Fc antibody fragment to defined
cell surface receptors; to optimize the mammalian expression of the
generic Fc antibody fragment with the C-terminal selenocysteine; to
apply the technology to whole antibodies and antibody fragments for
the conjugation of cytotoxic moieties, imaging moieties, or the
generation of defined multimers.
Contact
Information:
John D. Hewes, Ph.D., Technology
Transfer Center, NCI
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov
Reference: #466 LZ
This opportunity is also listed under the following categories:
Method For Effiecient Delivery Of Proteins Into Cells
Therapeutics To Treat Ocular Diseases
Monoclonal Antibodies Against B-Cell Chronic Lymphocytic Leukemia (B-CLL) Tumors
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