Tanox Biosystems, Inc.

Tanox, Inc.

Centocor, Inc.

Tse W Chang

Nancy T Chang

Cecily R Sun

Bill N Sun

Michael S Fung

Jan T Vilcek

Junming Le

Victor D Liu

Liming Yu

Patrick C Kung

Pranab Chanda

Ikunoshin Kato

Disclosed are conjugates including a polymer backbone or microbead and binding molecules, such as Fv, Fab, or F(ab').sub.2 fragments of monoclonal antibodies or whole antibodies that are bound through their Fc carbohydrate moieties or have their Fc portion modified so that they cannot effect ADCC or complement-mediated cytolysis, and that are specific for a T cell surface antigen, such as CD3, TCR, CD4, CD8, or CD28 on T cells. The polymer or microbead is preferably made of cross-linked dextran, ficoll, latex, or agarose. The microbeads are preferably of 1 to 10 .mu.m in size, so that they can be suspended in in vivo fluids. These conjugates can be used to induce proliferation of T cells and immune stimulation, and to increase the antibody response against an administered antigen.

Method of Increasing activation on proliferation of T cells using

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').sub.2 fragments (or other divalent binding molecules which lack Fc) which each bind noncompetitively to different monovalent antigenic epitopes on the same antigen; a conjugate including a polymer molecule, such as dextran, ficoll, or agarose, that is coupled with the binding molecules, e.g., Fv, Fab, or F(ab').sub.2, which bind to monovalent antigenic epitopes on the same antigen on T cells; a conjugate including a liposome or microbead that is coupled with the same binding molecules specific for a T cell surface antigen.

Conjugates of microbeads and antibodies specific for T lymphocytes and

Several forms of immunoregulatory substances are derived from monoclonal antibodies (MAbs) that are specific for a T or B cell surface antigen, such as CD3, TCR, CD4, or CD8 on T cells or membrane-bound immunoglobulins on B cells. The substances include: a mixture of F(ab').sub.2 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').sub.2 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 ('PEG'), 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').sub.2, which bind noncompetitively to monovalent antigenic epitopes on the same antigen.

Modified binding molecules specific for T or B lymphocytes and their use

Disclosed are conjugates including a substantially nonimmunogenic polymer backbone or microbead and binding molecules, such as Fv, Fab, or F(ab').sub.2 fragments of monoclonal antibodies or whole antibodies that are bound through their Fc carbohydrate moieties or have their Fc portion modified so that they cannot effect ADCC or complement-mediated cytolysis, and that are specific for a T cell surface antigen, such as CD3, TCR, CD4, CD8, or CD28 on T cells. The polymer or microbead is preferably made of cross-linked dextran, ficoll, latex, or agarose, and is preferably of 0.1 to 10 .mu.m in size, so that it can be suspended in fluids for in vivo applications. These conjugates can be used as adjuvants to enhance the antibody response against an administered immunogen.

Conjugates of polymers and antibodies specific for T lymphocytes, and

The invention relates to a method of using a peptide which has the sequence of epitopes which are present on B cell-bound but not secreted IgA. This induces production of the antibody itself. These extracellular peptide segments form, entirely or in part, antigenic epitopes unique to membrane-bound but not secreted IgA.

Method of producing an antibody with a peptide corresponding to

Murine monoclonal antibodies and related products such as antibody fragments, immunotoxins, human and humanized antibodies are disclosed, all of which bind to the gp120 protein on the envelope of HIV-1. These antibodies and related products neutralize HIV-1. They inhibit the infection of T cells, and also inhibit syncytium formation. Further, the antibodies are preferably group-specific and neutralize various strains and isolates of HIV-1. These antibodies have a variety of uses, including the treatment of AIDS and ARC, the prevention of HIV-1 infection, as well as a diagnostic application, in that they can be used for assaying of unknown fluid samples for HIV-1.

Monoclonal antibodies which neutralize HIV-1 infection

Disclosed is a hybrid recombinant protein consisting of human interferon, preferably interferon-.alpha. (IFN.alpha.), and 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).

Hybrid with interferon-alpha and an immunoglobulin Fc linked through a

The invention relates to unique extracellular peptide segments present on B cell-bound but not secreted IgA. These extracellular peptide segments form, entirely or in part, antigenic epitopes unique to membrane-bound but not secreted IgA, and thereby provide a unique epitope on the IgA-bearing B cells to which membrane-bound IgA is attached. These peptide segments can be used as immunogens to generate antibodies which specifically target membrane-bound IgA and IgA-bearing B cells.

Peptides relating to the extracellular membrane-bound segment of human

Disclosed are pharmaceutical preparations containing human monoclonal IgA antibodies specific for major allergenic proteins found in ragweed, house dust mites, and cat and dog dander. Also disclosed are constructs comprising physiological compatible polymer backbones or microbeads and a plurality of covalently conjugated allergen-specific binding molecules. Such binding molecules are IgG or IgA, or their F(ab').sub.2, Fab, or Fv fragments, specific to the major allergenic proteins mentioned above. Also disclosed are methods for treating a patient with allergic rhinitis, asthma, or conjunctivitis by applying a pharmaceutical preparation containing the antibodies specific for the allergenic molecules, to which the patient is sensitized, to the patient's affected mucosal tissues, such as the nasal linings, the respiratory tract, or the eyes.

Allergen-specific human IgA monoclonal antibodies for mucosal

Unique antigenic epitopes of IgE (designated ige.bl) which are present on IgE-bearing B lymphocytes but not basophils are described. Monoclonal antibodies which bind to the epitopes are useful to treat IgE-mediated allergy. The monoclonal antibodies, either alone or as cytotoxin-conjugated immunotoxins, can be used to reduce or deplete IgE-producing B cells in allergy sufferers. The antibodies may also have the additional therapeutical effects of clearing IgE from circulation by forming immune complexes. Monoclonal antibodies against the paratope of the antibody can be used to actively immunize allergy sufferers to attain the same results of administering the monoclonal antibody.

Humanized monoclonal antibodies binding to IgE-bearing B cells but not

The invention relates to methods of treating allergic reactions and of reducing circulating IgE using antibodies which bind to secreted IgE and membrane-bound IgE on the surface of IgE-producing B cells but not to IgE on basophils or mast cells.

Treating hypersensitivities with anti-IGE monoclonal antibodies which

Antigenic epitopes associated with the extracellular segment of the domain which anchors dog immunoglobulin-.epsilon. to the B cell membrane are disclosed. The epitopes are present on dog IgE-bearing B cells but not basophils or the secreted, soluble form of dog IgE. The peptides representing the epitopes associated with the anchor domain of dog IgE can be used to generate antibodies against these regions.

Peptides representing antigenic epitopes of dog IgE present on B cell

The invention relates to epitopes which are present on B cell-bound but not secreted IgA, peptide segments which represent such epitopes, and DNA coding for these peptides. These extracellular peptide segments form, entirely or in part, antigenic epitopes unique to membrane-bound but not secreted IgA.

Nucleotides coding for the extracellular membrane-bound segment of IgA

The invention relates to antibodies which immunologically bind epitopes present on B cell-bound but not secreted IgA. This is accomplished by targeting extracellular epitopes on the membrane anchoring peptide of the .alpha. chain which form, entirely or in part, antigenic epitopes unique to membrane-bound but not secreted IgA.

Antibodies to epitopes present on membrane-bound but not secreted IGA

Antigenic epitopes associated with the extracellular segment of the domain which anchors immunoglobulins to the B cell membrane are disclosed. For IgE, the epitopes are present on IgE-bearing B cells but not basophils or the secreted, soluble form of IgE. Three different isoforms of the C-terminal segment of the human .epsilon. chain resulting from alternative mRNA splicings in the membrane exon region are disclosed, one of which is secreted and not membrane-bound.

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Houston, TX, United States of America

Tse W Chang