Tanox, Inc.

Tse Wen Chang

Cecily R Y Sun

Nancy T Chang

Michael S C Fung

Bill N C Sun

Liming Yu

Disclosed is a method of using bifunctional binding molecules, such as two linked V -V single chain binding molecules, to recruit a therapeutic agent to a solid tissue site. The therapeutic agent is administered separately from the binding molecules and following the administration of a remover substance which aids in clearing free binding molecules in the circulation. In the preferred mode of the invention, the binding molecules have one specificity for antigens at the target site and one for the therapeutic agent. The binding molecules are administered and allowed time to approach a maximum concentration in the extravascular space. A remover substance, preferably a liposome conjugated with antibodies which are reactive with an antigenic epitope on the binding molecules, is then administered to remove excess binding molecules from the circulation and the extravascular space. A therapeutic agent, preferably a cytotoxic drug such as ricin A chain modified so as to enable it to enter the target cells once delivered to the target site, is then administered.

Methods and substances for recruiting therapeutic agents to solid tumors

Chimeral viral-neutralizing, particularly HIV-neutralizing, immunoglobulins made up of a non-human antigen binding region and a human constant region are described.

Chimeric viral-neutralizing immunoglobulins

A particular epitope located within the CD4-binding region of gpl20 of HIV-1, and antibodies specific for the epitope which can inhibit HIV-1 infection of human cells by diverse strains and isolates of the virus, is disclosed. The antibodies are useful for a number of purposes, including diagnosis of HIV-1 infection.

Antibodies specific for CD4-binding domain of HIV-1

Several forms of immunoregulatory substances are derived from monoclonal antibodies (MAbs) that are specific for a T cell surface antigen, such as CD3, TCR, CD4, or CD8 on T cells. The substances include: a mixture of F(ab&prime;),fragments (or other divalent binding molecules which lack Fc) which each bind noncompetitively to different monovalent antigenic epitopes on the same antigen; the F(ab&prime;),fragment (or other divalent binding molecules which lack Fc) of a bispecific antibody which has each of its binding sites derived from one of the two MAbs that bind noncompetitively to monovalent antigenic epitopes on the same antigen; a conjugate including a polymeric backbone, such as polyethylene glycol (&ldquo;PEG&rdquo;), cellulose, dextran, agarose, or an amino acid copolymer or a liposome, that is coupled with the binding molecules, e.g., Fv, Fab, or F(ab&prime;),, which bind noncompetitively to monovalent antigenic epitopes on the same antigen.

Modified binding molecules specific for T lymphocytes and their use as in vivo immune modulators in animals

Disclosed is a hybrid recombinant protein consisting of human interferon-.beta., and a human immunoglobulin Fc fragment, preferably .gamma.4 chain, joined by a peptide linker comprising the sequence Gly Gly Ser Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser (SEQ ID NO:1).

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Hsin-Chu, Taiwan

Tse Wen Chang