Arrowsmith Technologies Corporation

Arrowsmith Technology Licensing LLC

Foote, Jefferson

Jefferson Foote

Carol E O'Hear

Compositions and methods are provided in embodiments directed to maintaining a desired concentration range of one or more drugs in a subject, and in particular embodiments to maintaining a desired drug concentration in a body compartment in a subject, based on the surprising discovery that antibodies persist in solution in body compartments such that antibody-antigen equilibrium principles can counteract drug clearance mechanisms. One or more antibodies are selected that have a dissociation constant Kthat is similar to the desired drug concentration, wherein Kis independent of the affinity of the drug for a specific drug target (receptor) in the subject.

Antibody buffering of a ligand in vivo

Disclosed herein are methods for humanizing antibodies based on selecting variable region framework sequences from human antibody genes by comparing canonical CDR structure types for CDR sequences of the variable region of a non-human antibody to canonical CDR structure types for corresponding CDRs from a library of human antibody sequences, preferably germline antibody gene segments. Human antibody variable regions having similar canonical CDR structure types to the non-human CDRs form a subset of member human antibody sequences from which to select human framework sequences. The subset members may be further ranked by amino acid similarity between the human and the non-human CDR sequences. Top ranking human sequences are selected to provide the framework sequences for constructing a chimeric antibody that functionally replaces human CDR sequences with the non-human CDR counterparts using the selected subset member human frameworks, thereby providing a humanized antibody of high affinity and low immunogenicity without need for comparing framework sequences between the non-human and human antibodies. Chimeric antibodies made according to the method are also disclosed.

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Seattle, WA, United States of America

Jefferson Foote