Abstract: Fused bicyclic amines of formula (1) are described wherein Ar is an aryl or heteroaryl group; Y is a —S(O2)— or —C(O)— group; R1 is a hydrogen or halogen atom or an alkyl, haloalkyl, alkoxy, haloalkoxy or cyano group; X is a nitrogen atom or a C(R1a) group where R1a is as defined for R1 and may be the same or different; W and Z are each a carbon atom and together with U form an optionally substituted five- or six-membered monocyclic aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the activity of Class 1 receptor tyrosine kinases and are of use in the prophylaxis and treatment of hyperproliferative disorders such as cancer, psoriasis, restenosis, atherosclerosis and fibrosis.

Abstract: CDR-grafted antibody heavy and light chains comprise acceptor framework and donor antigen binding regions, the heavy chains comprising donor residues at at least one of positions (6, 23) and/or (24, 48) and/or (49, 71) and/or (73, 75) and/or (76) and/or (78) and (88) and/or (91). The CDR-grafted light chains comprise donor residues at at least one of positions (1) and/or (3) and (46) and/or (47) or at at least one of positions (46,48, 58) and (71). The CDR-grafted antibodies arc preferably humanised antibodies, having non human, e.g. rodent, donor and human acceptor frameworks, and may be used for in vivo therapy and diagnosis.

Abstract: Alkanoic acid derivatives of formula (1) are described: Ar1(Alka)rL1Ar2CH(R1)C(Ra)(Ra?)R??(1) Ar1 is an optionally substituted aromatic or heteroarotic group; L1 is a covalent bond or a linker atom or group; Ar2 is an optionally substituted phenylene or nitrogen-containing six-membered heteroarylene group; R is a carboxylic acid (—CO2H) or a derivative thereof; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of ?4 integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders.

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: Phenylalanine derivatives of formula (1) are described: wherein L1 is a linker atom or group; X1 is a group selected from —N(R3)CO—, —N(R3)SO2—, —N(R3)C(O)O— or —N(R3)CON(R3a)—; and R is a carboxylic acid or a derivative thereof. The compounds are able to inhibit the binding of a 4 integrins to their ligands and are of use in the prophylaxis and treatment of diseases or disorders involving inflammation.

Abstract: CDR-grafted antibody heavy and light chains comprise acceptor framework and donor antigen binding regions, the heavy chains comprising donor residues at at least one of positions (6, 23) and/or (24, 48) and/or (49, 71) and/or (73, 75) and/or (76) and/or (78) and (88) and/or (91). The CDR-grafted light chains comprise donor residues at at least one of positions (1) and/or (3) and (46) and/or (47) or at at least one of positions (46, 48, 58) and (71). The CDR-grafted antibodies are preferably humanised antibodies, having non human, e.g. rodent, donor and human acceptor frameworks, and may be used for in vivo therapy and diagnosis. A generally applicable protocol is disclosed for obtaining CDR-grafted antibodies.

Abstract: CDR-grafted antibody heavy and light chains comprise acceptor framework and donor antigen binding regions, the heavy chains comprising donor residues at at least one of positions (6, 23) and/or (24, 48) and/or (49, 71) and/or (73, 75) and/or (76) and/or (78) and (88) and/or (91). The CDR-grafted light chains comprise donor residues at at least one of positions (1) and/or (3) and (46) and/or (47) or at at least one of positions (46,48, 58) and (71). The CDR-grafted antibodies are preferably humanised antibodies, having non human, e.g. rodent, donor and human acceptor frameworks, and may be used for in vivo therapy and diagnosis. A generally applicable protocol is disclosed for obtaining CDR-grafted antibodies.

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 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; X is an —O— or —S— atom or —N(R2)— group in which: Rx, Ry and Rz which may be the same or different is each a hydrogen atom or an optional substituent; or Rz is an atom or group as previously defined and Rx and Ry are joined together to form an optionally substituted spiro linked cycloaliphatic or heterocycloaliphatic group; and the salts, solvates, hydrates and N-oxides thereof.

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: Phenylalanine enamide derivatives of formula (1) are described: wherein R1 is a —CH(CH3)2, —(CH2)2CH3, —CH2C(CH3)3, —CH2CH2OH, —CH2CH2OCH3, —CH2CH2OCH2CH2OH, —CH2CH2OCH2CH2OCH3, group; and the salts, solvates and N-oxides thereof. Compounds according to the invention are potent and selective inhibitors of &agr;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: Pyrimidines of formla (1) are described: 1

Abstract: A process for the production of a chimeric antibody, comprising: a) preparing a replicable expression vector including a suitable promoter operably linked to a DNA sequence comprising a first part which encodes at least the variable region of the heavy or light chain of an Ig molecule and a second part which encodes at least part of a second protein; b) if necessary, preparing a replicable expression vector incuding a suitable promoter operably linked to a DNA sequence which encodes at least the variable region of a complementary light or heavy chain respectively of an Ig molecule; c) transforming an immortalized mammalian cell line with the or both prepared vectors; and d) culturing said transformed cell line to produce the chimeric antibody; chimeric antibodies produced by this process; and plasmids and transformed cell lines used in the process.

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: The invention provides recombinant antibody molecules comprising antigen binding regions derived from the heavy and/or light chain variable regions of a donor anti-CD3 antibody, e.g. OKT3, and which have anti-CD3 binding specificity, preferably of affinity similar to that of OKT3. The recombinant antibody is preferably a humanized antibody and may be a chimeric or CDR-grafted antibody. A method is disclosed for preparing CDR-grafted humanized antibodies in which, in addition to the CDR's non-human antibody residues are preferably used at positions 23, 24, 49, 71, 73 and 78 of the heavy chain variable region and at positions 46, 48, 58, and 71 of the light chain variable region. The recombinant, especially the humanized, anti-CD3 antibodies may be used for in vivo therapy or diagnosis.

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