Abstract: Peptidyl derivatives are disclosed that are orally active metalloproteinase inhibitors. The peptidyl derivatives have a selective gelatinase action, have a long duration of action, and are useful in the prophylaxis or treatment of diseases or disorders in which stromelysis, collagenase or gelatinase have a role, for example, in the treatment of cancer to control the development of tumor metastases.

Abstract: Compounds of general formula (1) are described: ##STR1## wherein .dbd.W-- is (1) .dbd.C(Y)-- where Y is a halogen atom, or an alkyl or --XR.sup.a group where X is --O--, --S(O).sub.m -- ?where m is zero or an integer of value 1 or 2!, or --N(R.sup.b)-- ?where R.sup.b is a hydrogen atom or an optionally substituted alkyl group! and R.sup.a is a hydrogen atom or an optionally substituted alkyl group or, (2) .dbd.N--; L is a --XR, ?where R is an optionally substituted alkyl, alkenyl, cycloalkyl or cyloalkenyl group!, --C(R.sup.5).dbd.C(R.sup.1)(R.sup.2) or ?--CH(R.sup.5)!.sub.n CH(R.sup.1)(R.sup.2) group where R.sup.5 is a hydrogen or a fluorine atom or a methyl group, and R.sup.1 and R.sup.2, which may be the same or different, is each a hydrogen or fluorine atom or an optionally substituted alkyl, alkenyl, alkynyl, alkoxy, alkylthio, --CO.sub.2 R.sup.6, ?where R.sup.6 is a hydrogen atom or an optionally substituted alkyl, aralkyl, or aryl group!, --CONR.sup.7 R.sup.8 ?where R.sup.7 and R.sup.

Abstract: The present invention provides an altered antibody molecule (AAM) having a hinge region which has a different number of cysteine residues from that found in the hinge region normally associated with the CH1 domain of the antibody molecule and a process for producing the same using recombinant DNA technology.

Abstract: Compounds of formula (1) ##STR1## are described wherein Y represents a halogen atom or a group --OR.sup.1, where R.sup.1 is an optionally substituted alkyl group; R.sup.2 represents an optionally substituted cycloalkyl or cycloalkenyl group; R.sup.3 is a monocyclic or bicyclic aryl group optionally containing one or more heteroatoms selected from oxygen or sulphur atoms or a group --N(R.sup.4)-- where R.sup.4 is a hydrogen atom or an alkyl group; X is --O--, --S--, or --N(R.sup.4)--, where R.sup.5 is a hydrogen or an alkyl group; with the proviso that when X is --O-- then R.sup.3 is not a 3-cyanamino-6-pyridazinyl or a 3-chloro-6-pyridazinyl group; and the salts, solvates, hydrates and N-oxides thereof.The compounds are selective and potent inhibitors of phosphodiesterase IV and are useful for the prophylaxis and treatment of inflammatory diseases and the alleviation of conditions associated with central nervous malfunction.

Abstract: Process for the fed-batch culture of animal cells comprises culturing the cells in nutrient medium characterized in that during the culture the medium is supplemented with a combined feed of one or more energy sources and one or more animo acids, and culturing is continued into the decline phase of the culture to provide the product(s) of the cells. The process is particularly applicable to genetically modified cells, especially hybridoma cell cultures to produce monoclonal antibodies. Preferably, the supplemental feed is fed to the culture at a slow rate over a prolonged period. Very significant enhancement of overall product yield may be obtained.

Abstract: This invention relates to a process for obtaining antibodies in soluble and correctly folded and assembled form. It comprises a step to raise the temperature at a time in the process selected to facilitate the subsequent isolation of soluble, correctly folded and assembled antibody, substantially free of other antibody-related material. The operating temperature may be raised at any stage in the microbial fermentation or eukaryotic cell culture, or at any stage during extraction and purification of the antibodies.

Abstract: A device for performing an enzyme-labelled binding assay comprises an absorbent material and a developing solution containing a substrate for said enzyme, wherein the absorbent material is provided with a plurality of reagent zones including an indicator reagent zone and is capable of transporting the developing solution by capillary action sequentially through the reagent zones, and wherein the indicator reagent zone includes a reagent capable, directly or indirectly, of immobilising an enzyme-labelled reagent in an amount dependent on the assay result, characterized in that the absorbent material includes a reagent that prevents a signal formation except where enzyme-labelled reagent is immobilised at the indicator reagent zone. The absorbent material is suitably in the form of an elongate strip provided with transverse reagent zones. The device is useful for performing immunoassays, including immunometric assays and dual analyte assays.

Abstract: Compounds of general formula (1) ##STR1## are described wherein Y is a halogen atom or a group --OR.sup.1, wherein R.sup.1 is an optionally substituted alkyl group; X is --O--, --S--, or --N(R.sup.6), wherein R.sup.6 is a hydrogen atom or an optionally substituted alkyl group; R.sup.2 is an optionally substituted cycloalkyl or cycloalkenyl group; R.sup.3 and R.sup.4, which may be the same or different, is each a hydrogen atom or an optionally substituted alkyl, --CO.sub.2 R.sup.7 (wherein R.sup.7 is a hydrogen atom, am optionally substituted alkyl, aralkyl, aryl, aryloxyalkyl, alkanoyloxyalkyl or aroyloxyalkyl group), --CONR.sup.8 R.sup.9 (where R.sup.8 and R.sup.9, which may be the same or different, is as defined for R.sup.7), --CSNR.sup.8 R.sup.9, --CN or --CH.sub.2 CN group; Z is --(CH.sub.2).sub.n -- where n is zero or an integer 1, 2 or 3; R.sup.

Abstract: Compounds of the general formula (1) ##STR1## are described wherein Y is halogen or --OR.sup.1, where R.sup.1 is a substituted or unsubstituted alkyl; X is --O--, --S-- or --N(R.sup.8)--, where R.sup.8 is hydrogen or alkyl; R.sup.2 is substituted or unsubstituted alkyl, alkenyl, cycloalkyl or cycloalkenyl; R.sup.3 is hydrogen, halogen or --OR.sup.9, where R.sup.9 is hydrogen or substituted or unsubstituted alkyl, alkenyl, alkoxyalkyl, or alkanoyl, or formyl, carboxamido or thiocarboxamido; R.sup.4 and R.sup.5, which may be the same or different, are each --(CH.sub.2).sub.n Ar, where Ar is a monocyclic or bicyclic aryl group or monocyclic or bicyclic heteroaryl and n is integer of 0 to 3; R.sup.6 is hydrogen or substituted or unsubstituted alkyl; R.sup.7 is hydrogen or substituted or unsubstituted alkyl; and the salts, solvates, hydrates and N-oxides thereof.

Abstract: An enantioselective multi-stage process is described which uses as a starting material an .alpha.,.beta.-unsaturated olefin of formula (1):Ar--CH.dbd.C(R.sup.4)COAux (1)where Ar and R.sup.4, which may be the same or different, is each a monocyclic or bicyclic aryl group optionally containing one or more heteroatoms selected from oxygen, sulphur or nitrogen atoms; and Aux is the residue of a chiral (R- or S-) auxiliary.In the process, the olefin is converted to a chiral triarylethane which is of use in medicine.

Abstract: Compounds of general formula (1) ##STR1## are described wherein Y is a halogen atom or a group --OR.sup.1, wherein R.sup.1 is an optionally substituted alkyl group; X is --O--, --S-- or --N(R.sup.6)--, where R.sup.6 is a hydrogen atom or an alkyl group; R.sup.2 is an optionally substituted alkyl, alkenyl, cycloalkyl or cycloalkenyl group; R.sup.3 and R.sup.4, which may be the same or different, is each a group --(CH.sup.2).sub.n Ar, where Ar is a monocyclic or bicyclic aryl group optionally containing one or more heteroatoms selected from oxygen, sulphur or nitrogen atoms and n is zero or an integer 1, 2 or 3; R.sup.5 is a hydrogen atom or an optionally substituted alkyl group; and the salts, solvates, hydrates and N-oxides. Compounds according to the invention are potent, selective and orally active PDE IV inhibitors and are useful in the prophylaxis and treatment of asthma.

Abstract: Triaza macrocycles carrying a -CH.sub.2 COOH, -CH.sub.2 CONR.sup.6 R.sup.7, --CH.sub.2 P(R.sup.5)O.sub.2 H, or --CH.sub.2 PO.sub.3 H.sub.2 group on two of the three ring nitrogen atoms and a --CH(L--Z)COOH, --CH(L--Z)CONR.sup.6 R.sup.7, --CH(L--Z)P(R.sup.5)O.sub.2 H, or --CH(L--Z)PO.sub.3 H.sub.2 group on the third ring nitrogen atom, in which L is an organic linking radical and Z is any group capable of reacting with a thiol, amino, carboxy, hydroxyl, aldehyde, aromatic, or heteroaromatic group, and metal complexes thereof, are useful for imaging, diagnosis, and therapy. A typical embodiment is N-[5-carboxy-5-{4,7-bis-(carboxymethyl)-1,4,7-triazacyclonon-1-yl}pentyl] 3-maleimidopropionamide.

Abstract: Compounds of formula (1) are described wherein R represents a --CONHOH, carboxyl, carboxyl ester, or --P(O)(X.sup.1 R.sup.8)X.sup.2 R.sup.9, where X.sup.1 and X.sup.2 are the same or different and each is oxygen or sulphur, R.sup.8 and R.sup.9 are the same or different and each represents hydrogen or an optionally substituted alkyl, aryl or aralkylthioalkyl group; R.sup.2 represents an optionally substituted alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkoxy, or aralkylthio group, or an amino, substituted amino, carboxyl, or carboxyl ester group; R.sup.3 represents hydrogen or alkyl; R.sup.4 represents hydrogen or alkyl; R.sup.5 represents an optionally substituted alkyl or alkenyl group optionally interrupted by one or more --O-- or --S-- atoms or --N(R.sup.7)-- groups, where R.sup.7 is a hydrogen atom or a C.sub.1-6 alkyl group, or --(Alk).sub.n R.sup.6 where Alk is an alkyl or alkenyl group optionally interrupted by one or more --O-- or --S-- atoms or --N(R.sup.