Abstract: Conventionally, animal tissue from one species can only be transplanted into another species when the species are concordant; otherwise, hyperimmune rejection ensues. In this invention, donor tissue is modified, for example by being transgenic, to express or otherwise be in association with one or more substances, referred to as homologous complement restriction factors (HCRFs), which are active in the recipient species to prevent the complete activation of complement and therefore rejection. The invention is in part based on the discovery that the alternative pathway of complement activation, rather than the classical pathway, is responsible for hyperacute discordant xenograft rejection.

Abstract: Novel derivatives of rapamycin, particularly 9-deoxo-rapamycins, 26-dihydro-rapamycins, and 40-O-substituted and 28,40-O,O-disubstituted rapamycins. are found to have pharmaceutical utility, particularly as immunosuppressants.

Abstract: Fusion polypeptides and salts thereof comprising at least one IgE-binding domain fused to at least one human serum albumin component, optionally via a peptide linker, and in particular, dimeric fusion polypeptides comprising HSA protein fused, at each of its amino and carboxy termini, to an extracellular domain of the &agr;-chain of the human high affinity receptor for IgE (Fc&egr;RI&agr;); process for the preparation thereof, functionally equivalent polypeptides which are intermediates in their preparation, and polynucleotide and oligonucleotide intermediates and vectors therefor. They are indicated for use in the prevention and/or treatment of IgE-mediated allergic diseases and related disorders such as atopic dermatitis, atopic asthma and chronic urticaria.

Abstract: Polyamide conjugates comprising either (a) a xenoantigenic group; or (b) a biologically active group and a macromolecular, macro- or microscopic entity, bound to a polyamide backbone, processes for their preparation and the use of these conjugates in therapeutic compositions.

Abstract: Novel monoclonal antibodies to the CD25 antigen are characterized by the amino acid sequence of their hypervariable regions. Initially produced in murine form, they may be converted to chimeric or humanized forms, immunoconjugates or antibody fragments (generally described as binding molecules). The products are useful for the prophylaxis or treatment of transplant rejection, paticularly in combination with other antibodies to activated T-cells, for example CD7 antibodies.

Abstract: This invention relates to the use of 40-O-(2-hydroxy)ethyl-rapamycin for the prevention or treatment of neointimal proliferation and thickening, restenosis, and vascular occlusion following vascular injury.

Abstract: Transdominant repressors of viral gene phenotypic expression derived from the rev gene product of HIV-1 or the rex gene product of HTLV-1 and corresponding mutated genes, having the capability of repressing the Rev function in HIV-1 and/or the Rex function in HTLV-I and HTLV-II and, in some cases, both the Rev and the Rex function and are, therefore, active in more than one viral species. Such transdominant viral mutants are useful as anti-viral agents to, for example protect cells against the deleterious effects of viral, e.g. HIV-1, infection.

Abstract: Use of a compound of formula (I) wherein R1 is an optionally substituted straight- or branched carbon chain having 12 to 22 carbon atoms which may be optionally interrupted by an optionally substituted phenylene, and each of R2, R3, R4 and R5, independently, is H or lower alkyl, in free form or in pharmaceutically acceptable salt form, in the prevention or treatment of chronic rejection in a recipient of organ or tissue allo- or xenotransplant, or of acute rejection in a xenograft transplant recipient.

Abstract: Native complement pathway proteins modified such that the protein is capable of forming a down-regulation resistant C3 convertase. Preferably the modified protein is a modified human C3 protein. DNA sequences encoding such proteins are also provided, together with DNA constructs. Conjugates comprising such proteins and a specific binding moiety, for example an antibody, are also described, as are uses of such proteins and/or conjugates in therapy.

Abstract: Transdominant repressors of viral gene phenotypic expression derived from the rev gene product of HIV-1 or the rex gene product of HTLV-1 and corresponding mutated genes are described, having the capability of repressing the Rev function in HIV-1 and/or the Rex function in HTLV-I and HTLV-II. Transient gene expression analysis of a series of missense and deletion mutants has been used. Sane of the mutants found repress both the Rev and the Rex function and are thus active in more than one viral species. Transdominant viral mutants represent a promising new class of anti-viral agents. Cellular expression of these transdominant inhibitors may be used in such therapeutic approaches as intracellular immunization in order to protect cells against the deleterious effects of viral, e.g. HIV-1 infection.

Abstract: A synergistic combination of an IL-2 transcription inhibitor (e.g., cyclosporin A or FK506) and 40-O-(2-hydroxyethyl)-rapamycin is provided, which is useful in the treatment and prevention of transplant rejection and also certain autoimmune and inflammatory diseases, together with novel pharmaceutical compositions comprising an IL-2 transcription inhibitor in combination with a rapamycin, e.g., 40-O-(2-hydroxyethyl)-rapamycin.

Abstract: A new method of measuring blood levels of immunophilin-binding pharmaceuticals, e.g., cyclosporins, rapamycins, and FK506 compounds is provided, comprising the novel step of displacing the pharmaceutical from its immunophilin by using a binding competitor, thereby eliminating the need for an extraction step and enhancing the simplicity and accuracy of the assay. Assay kits comprising a binding competitor and a receptor, e.g., a monoclonal antibody, which binds to the pharmaceutical but not significantly to the binding competitor are also provided, as are new uses of immunophilin-binding compounds as binding competitors in such assays.

Abstract: A process for the recombinant preparation in a bacterial host of the mature form of a mammalian protein or peptide of formula X-Pro-Z, which is subject to processing by endogenous bacterial aminopeptidases is provided. In the formula X-Pro-Z, X is a single N-terminal amino acid other than proline, and Z is the remaining sequence of amino acid residues of the protein or peptide. The process comprises inserting into a cell of the bacterial host an appropriate vector containing DNA coding for Met-Y-X-Pro-Z, in which Y is a natural amino acid that is specifically cleavable in vitro from X-Pro-Z by an aminopeptidases and that imparts resistance to in vivo processing by endogenous bacterial aminopeptidases. The cell is then induced to express the expression product Met-Y-X-Pro-Z which is then treated with an appropriate aminopeptidase to cleave off Met and Y.

Abstract: Transdominant repressors of viral gene phenotypic expression derived from the rev gene product of HIV-1 or the rex gene product of HTLV-1 and corresponding mutated genes, having the capability of repressing the Rev function in HIV-1 and/or the Rex function in HTLV-I and HTLV-II. And in some cases both the Rev and the Rex function and are, active in more than one viral species. Such transdominant viral mutants are useful as anti-viral agents to, for example of these transdominant inhibitors may be used in such therapeutic approaches as intracellular immunization in order to protect cells against the deleterious effects of viral, e.g. HIV-1, infection.

Abstract: It has been found that nonimmunosuppressive, cyclophilin-binding cyclosporins are useful in the treatment and prevention of AIDS and AIDS-related disorders. Such cyclosporins include novel Ciclosporin derivatives modified at the 4- and/or 5-positions.

Abstract: Novel demethoxy derivatives of rapamycin are found to have pharmaceutical utility, particularly as an immunosuppressants.

Abstract: Quantitative reporter gene assays allowing for highly precise measurements of immunosuppressants in bodily fluids are provided, e.g., an IL-2 reporter gene assay for measuring blood levels of immunosuppressive cyclosporins and ascomycins (e.g., cyclosporin A and FK-506), and a c-jun reporter gene assay for measuring blood levels of immunosuppressive rapamycins.

Abstract: Transdominant repressors of viral gene phenotypic expression derived from the rev gene product of HIV-1 or the rex gene product of HTLV-1 and corresponding mutated genes, having the capability of repressing the Rev function in HIV-1 and/or the Rex function in HTLV-I and HTLV-II and, in some cases, both the Rev and the Rex function and are, therefore, active in more than one viral species. Such transdominant viral mutants are useful as anti-viral agents to, for example, protect cells against the deleterious effects of viral, e.g. HIV-1, infection.

Abstract: Immunoglobulin preparations, particularly liquid preparations of immunogllin G for intravenous infusion, are stabilized against dimer formation by the addition of one or more amphiphilic stabilizers. Preferred amphiphilic stabilizers are nicotinic acid derivatives, particularly nicotinamide, and naturally-occurring .alpha.-amino acids having a lipophilic side chain, for example phenylalanine, proline, leucine and isoleucine.

Abstract: Quinoline analogs of mevalonolactone of the following formula are useful as anti-cholesterol synthesis agents: ##STR1## where the substituents are as defined in the specification.