Abstract: The present invention provides antibody Fab fragments in which the heavy chain constant region terminates at the interchain cysteine of CH1. Also provided are antibody Fab fragments in which the heavy chain constant region terminates at the interchain cysteine of CH1 to which one or more effector molecules are attached.

Abstract: Bipolar lipids are described which are able to form complexes with polyanions. The lipids comprise a cationic head linked to a hydrophobic backbone and a hydrophilic tail and are capable of self assembly to form stable complexes in aqueous solutions. The lipids are of particular use for the delivery of bioactive substances such as nucleic acids to cells in vitro and especially in vivo.

Abstract: The present invention provides a method for the treatment and/or prophylaxis of inflammatory bowel disease (IBD) comprising administering a therapeutically effective amount of an inhibitor of CSF-1 activity.

Abstract: The present invention relates to a new class of antibody fragments including antibody Fab and Fab? fragments in which the heavy chain is not covalently bonded to the light chain and two or more effector molecules are attached to the fragment, of which at least one of said molecules is attached to a cysteine in the heavy or light chain constant region.

Abstract: The invention relates to nucleic acids encoding a synthetic transmembrane region as well as to membrane associated proteins containing these synthetic transmembrane regions. The design of the synthetic transmembrane region allows various properties of a protein, such as its level of expression, and relative response to ligand binding to be tailored as required for a specific purpose.

Abstract: Compounds of the general formula (I) are described wherein R1 and R2, which may be the same or different, is each a hydrogen atom or a CF3, CF2H or CFH2 group, provided that when one of R1 and R2 is a hydrogen atom, then the other is a CF3, CF2H or CFH2 group, and the salts, solvates or hydrates thereof. Compounds of the invention are potent MMP inhibitors which advantageously do not cause tendonitis in a relevant animal model. Compounds of the invention may be expected to be of use in medicine, especially where the avoidance of side effects, such as joint pain, is desired.

Abstract: A process for the preparation of a class of phenylalanine enamide derivatives is described: wherein: Ar1 is an optionally substituted aromatic or heteroaromatic group; L2 is a linker group selected from —N(R4)— [where R4 is a hydrogen atom or an optionally substituted straight or branched C1-6alkyl group], —CON(R4)—, or —S(O)2N(R4)—; R1 is a carboxylic acid (—CO2H) or a derivative or biostere thereof; R2 is a hydrogen atom or a C1-6alkyl group; Rx, Ry and Rz which may be the same or different is each an atom or group -L1(Alk1)n(R3)v; and the salts, solvates, hydrates and N-oxides thereof; which comprises reacting a compound of formula (2): wherein: Qa is a group —N(R4)H; and the salts, solvates, hydrates and N-oxides thereof; with a compound Ar1W wherein W is a group selected from X1(wherein X1 is a leaving atom or group), —COX2 (wherein X2 is a halogen atom or a —OH group) or —SO2X3 (in which X3 is a halogen atom).

Abstract: Isolated nucleic acid molecules are provided which encode Fkhsf, as well as mutant forms thereof. Also provided are expression vectors suitable for expressing such nucleic acid molecules, and host cells containing such expression vectors. Utilizing assays based upon the nucleic acid sequences disclosed herein (as well as mutant forms thereof), numerous molecules may be identified which modulate the immune system.

Abstract: Isolated nucleic acid molecules are provided which encode Fkhsf, as well as mutant forms thereof. Also provided are expression vectors suitable for expressing such nucleic acid molecules, and host cells containing such expression vectors. Utilizing assays based upon the nucleic acid sequences disclosed herein (as well as mutant forms thereof), numerous molecules may be identified which modulate the immune system.

Abstract: Compositions and methods relating to antibodies that specifically bind to TGF-beta binding proteins are provided. These methods and compositions relate to altering bone mineral density by interfering with the interaction between a TGF-beta binding protein sclerostin and a TGF-beta superfamily member, particularly a bone morphogenic protein. Increasing bone mineral density has uses in diseases and conditions in which low bone mineral density typifies the condition, such as osteopenia, osteoporosis, and bone fractures.

Abstract: The synthesis of novel diketopiperazines, their use in inhibiting cellular events such as those involving NFK-?, NFK-? and in the treatment of inflammation events, a combinatorial library of diverse diketopiperazines and process for their synthesis as a library and as individual compounds. In particular novel diketopiperazines are disclosed including their synthesis and use in cellular events such as activation of the transcription factor, nuclear factor, TNF-?, TNF-? and also apoptosis.

Abstract: Phenylalanine enamide derivatives of formula (1) are described: wherein R1 is a —CH3, —(CH2)3CH3, —CH2CH2OH, —CH2CH2OCH3, —CH2CH2OCH2CH2OH, —CH2CH2OCH2CH2OCH3, group; and the salts, solvates and N-oxides thereof. Compounds according to the invention are potent and selective inhibitors of ?4 integrins. The compounds are of use in modulating cell adhesion and in particular are of use in the prophylaxis and treatment of diseases or disorders including inflammation in which the extravasation of leukocytes plays a role and the invention extends to such a use and to the use of the compounds for the manufacture of a medicament for treating such diseases or disorders.

Abstract: The invention provides methods for modulating the immune system using anti-CD83 antibodies that can influence CD83 function.

Abstract: Enamine derivatives of formula (1) are described: wherein R1 is a group Ar1L2Ar2Alk- in, which Ar1 is an aromatic or heteroaromatic group, L2 is a covalent bond or a linker atom or group, Ar2 is an arylene or heteroarylene group and Alk is a chain —CH2—CH(R)—, —CH═C(R)— or in which R is a carboxylic acid or a derivative or biostere thereof; R2 is a hydrogen atom or a C1-6alkyl group; Cy is a cycloaliphatic or heterocycloaliphatic ring in which X is a N atom or a C(Rw) group; Rx is a oxo, thioxo, or imino group; Rw and Rz is each a hydrogen atom or optional substituent; provided that Cy is not a cyclobutenedione group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders, or disorders involving the inappropriate growth or migration of cells.

Abstract: Squaric acid derivatives of formula (1) are described: wherein Het is an optionally substituted bicyclic fused ring heteroaromatic group; L2 is a covalent bond or an atom or group —O—, —S—, —C(O)—, —C(S)—, —S(O)—, —S(O)2, —N(R8)— or —C(R8)(R8a)—; Ar2 is an optionally substituted aromatic or heteroaromatic group; Alk is a chain  in which R is a carboxylic acid (—CO2H) or a derivative or biostere thereof; R1 is a hydrogen atom or a C1-6alkyl group; L1 is a covalent bond or a linker atom or group; Alk1 is an optionally substituted aliphatic chain; n is zero or the integer 1; R2 is a hydrogen atom or an optionally substituted heteroaliphatic, cycloaliphatic, heterocycloaliphatic, polycycloalphatic, heteropolycycloaliphatic, aromatic or heteroaromatic group other than a 2,6-naphthyridin-1-yl, isoquinolin-1-yl, 2,7-naphthyridin-1-yl or quinazolin-4-yl group; and the salt

Abstract: Bipolar lipids are described which are able to form complexes with polyanions. The lipids comprise a cationic head linked to a hydrophobic backbone and a hydrophilic tail and are capable of self assembly to form stable complexes in aqueous solutions. The lipids are of particular use for the delivery of bioactive substances such as nucleic acids to cells in vitro and especially in vivo.

Abstract: Phenylalanine derivatives of formula (1) are described: in which: Ar1 is an aromatic or heteroaromatic group; L1 is a linker atom or group; R is a carboxylic acid or a derivative thereof; Ar2 is an optionally substituted aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of &agr;4 integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders.

Abstract: Enamine derivatives of formula (1) are described: wherein R1 is a group Ar1 L2Ar2Alk- in which Ar1 is an aromatic or heteroaromatic group, L2 is a covalent bond or a linker atom or group, Ar2 is an arylene or heteroarylene group and Alk is a chain —CH2—CH(R)—, —CH═C(R)— or in which R is a carboxylic acid or a derivative or biostere thereof; R2 is a hydrogen atom or a C1-6alkyl group; Cy is a cycloaliphatic or heterocycloaliphatic ring in which X is a N atom or a C(Rw) group; Rx is a oxo, thioxo, or imino group; Rw and Rz is each a hydrogen atom or optional substituent; provided that Cy is not a cyclobutenedione group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders, or disorders involving the inappropriate growth or migration of cells.

Abstract: Enamide derivatives of formula (1) are described: wherein R1 is a group Ar1L2Ar2Alk- in which Ar1 is an optionally substituted aromatic or heteroaromatic group, L2 is a covalent bond or a linker atom or group, Ar2 is an optionally substituted arylene or heteroarylene group and Alk is a chain —CH2—CH(R)—, —CH═C(R)— or  in which R is a carboxylic acid (—CO2H) or a derivative or biostere thereof; R2 is a hydrogen atom or a C1-6alkyl group; X is an O or S atom or the group NR30 group; j and k is each zero or the integer 1 or 2 provided that the sum of j and k is zero or the integer 1 or 2; Cy1 is an optionally substituted cycloaliphatic, heterocycloaliphatic, aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof.

Abstract: Fused polycyclic 2-aminopyrimidines of formula (1): wherein Ar is an optionally substituted aromatic or heteroaromatic group; X is a carbon or nitrogen atom; Y is a carbon or nitrogen atom; Z is a linker group; A together with X and Y forms an optionally substituted monocyclic or bicyclic aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof are described. The compounds are potent and selective inhibitors of the protein tyrosine kinases p56lck and p59fyn and are of use in the prophylaxis and treatment of immune diseases, hyperproliferative disorders and other diseases in which inappropriate p56lck and/or p59fyn activity is believed to have a role.