Celltech Limited

Celltech Therapeutics Limited

University of Durham

Celltech R&d Limited

Centre National De La Recherche Scientifique

Johannes Gutenberg-universität Mainz

Ecole Normale Superieure De Lyon

Cookson Group Plc

Sensors for Medicine & Science, Inc.

Mds Analytical Technologies (us) Inc.

Cisbio Bioassays

Cisbo Bioassays

Mds Analytical Technologies

David Parker

Thomas A Millican

Nigel Robert Beeley

Terence Seward Baker

Timothy John Norman

Laurent Lamarque

Robert Pal

Michael Anthony William Eaton

Filip Kielar

Andrew Neil Charles Weir

Catherine Fiona Catterall

Edwin F Ullman

Poopathy Kathirgamanathan

George Y Daniloff

J Richard Sportsman

Michael Anthony Eaton

Jurriaan Zwier

Arthur E Colvin

Olivier Maury

Aristotle G Kalivretenos

Annegret Boge

Frank Rösch

Alexandre V Nikolaitchik

Elizabeth Gaudet

George G Yi

Robert Anthony Poole

Andre D Chissel

Martin R Bryce

Stephen J Butler

Martina Delbianco

Nigel R Smith

Bradley Peter Waldron

James W Walton

Paul Atkinson

Adrien Bourdolle

Aristole G Kalivretenos

Edwin E Ullman

A compound for radio metal complexation includes a chelator and one or more biological targeting vectors TV conjugated to said chelator, wherein the chelator has structure (A) or (B) or (C), based on 1,4-diazepine with groups R, R, R, R, X, X, X. The compound is particularly suited for complexation of radio-isotopic metals, such asGa(III),Ga(III) andGa(III).

Bifunctional chelating agents based on the 1,4-diazepine scaffold (DAZA) for non-invasive molecular imaging

The invention relates to complexing agents of formula (I): in which A, chrom1, chrom2 and chrom3 are as defined in the description. The invention also relates to the lanthanide complexes obtained from these complexing agents.

Water-soluble complexing agents and corresponding lanthanide complexes

The invention provides a compound of formula (I): (wherein:

Responsive luminescent lathanide complexes

The present invention concerns complexing agents of formula (I) in which a, b, c, chrom, chrom, chrom, R, Rand Rare as defined in the description. The invention also concerns lanthanide complexes comprising said complexing agents, as well as a method for synthesizing said agents.

Complexing agents and corresponding lanthanide complexes

Responsive luminescent lanthanide complexes

The invention provides a method of determining the amount of an analyte having an oxidation potential, for a one electron oxidation process, of about +0.10 to about +1.20 volts at pH 7, relative to the normal hydrogen electrode at 298K, said method comprising measuring the emission intensity or emission lifetime, at two or more wavelengths, from a sample comprising said analyte and two or more different macrocyclic lanthanide (III) complexes, wherein each of said macrocyclic lanthanide (III) complexes comprises a different lanthanide ion but the same macrocyclic ligand, and using a ratio of emission intensities or emission lifetimes measured at two different wavelengths to calculate the amount of analyte in said sample.

Luminescence assay using macrocyclic lanthanide (III) complexes

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.

Lipids

Systems, including compositions, kits, and methods, particularly for photoluminescence applications. The systems may include, among others, (1) organic chelators, (2) complexes between the chelators and lanthanide ions, and (3) precursors, derivatives, and uses thereof. The chelators may include a 1,4,7,10-tetraazacyclododecane ring system, for example, having the formula: Here, R, R, and Rare substituents of the tetraazacyclododecane ring system, that is further substituted at the 10-position by a sensitizer Z that is typically a polyheterocyclic ring system. The organic chelator may be capable of forming a luminescent complex with a lanthanide ion, and is optionally further substituted by a reactive functional group or a conjugated substance. The resulting lanthanide complex may be useful in luminescence-based assays, such as energy transfer assays, among others.

Luminescent lanthanide complexes

1,4,7,10-Tetrazacyclododecanes carrying a side chain terminating in a group capable of reacting with an antibody, and their complexes with a di- or tripositive metal having a coordination number of 6 or more can be used to prepare imaging agents. Typical metals are indium, copper, lead, bismuth, yttrium, terbium, gadolinium, and scandium. The compounds can be reacted with a monoclonal or polyclonal antibody or antibody fragment to target the metal to a specific type of tissue.

Tetra-aza macrocycles and metal complexes thereof

Compositions and methods for determining the presence or concentration of an analyte in a sample by exposing the sample to an indicator molecule comprising a fluorescent lanthanide metal chelate complex. The presence or concentration of the analyte in the sample is determined by observing and/or measuring the change in intensity of fluorescence emitted by the lanthanide metal chelate complex upon binding of the analyte to one or more recognition elements in the complex. The fluorescent indicator molecules can be used in various types of fluorescent sensing devices and are useful in various fields, including energy, medicine and agriculture.

Detection of analytes by fluorescent lanthanide metal chelate complexes containing substituted ligands

##STR1## Conjugate compounds are described comprising a compound of formula (1), wherein A is a group --Alk.sup.3 -- or --Alk.sup.3 N(R.sup.4)Alk.sup.1 --, Alk.sup.2, Alk.sup.3 and Alk.sup.4 which may be the same or different is each a C.sub.1-4 alkylene chain optionally substituted by one or more C.sub.1-6 alkyl groups; and R.sup.1, R.sup.2, R.sup.3 and R.sup.4, which may be the same or different, is each a hydrogen atom or a group--AlkR.sup.5 where Alk is an optionally substituted straight or branched C.sub.1-6 alkyl group and R.sup.5 is a hydrogen atom or a --CO.sub.2 H, --CONR.sup.6 R.sup.7 (where R.sup.6 and R.sup.7, which may be the same or different is each a hydrogen atom or an alkyl group) or --P(X.sup.1)(X.sup.2 R.sup.8)L group where X.sup.1 and X.sup.2 is each an oxygen or sulphur atom. R.sup.8 is a hydrogen atom or an alkyl group and L is an aliphatic, aromatic, or heteroaromatic group or a linker group with the proviso that at least one of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is a group AlkP(X.sup.1)(X.sup.2 R.sup.8)L where L is a linker group; and a metal complexes and/or salts thereof, coupled to a protein, peptide or carbohydrate. The conjugates are useful for imaging and in the treatment of abnormal cell disorders, such as in the treatment of tumours.

Conjugate compounds containing aza-macro-cycles and processes for their

##STR1## Metal complex of tetra-aza macrocycles of formula (1) wherein Alk.sup.1, Alk.sup.2, Alk.sup.3 and Alk.sup.4, which may be the same or different, is each a C.sub.1-4 alkylene chain optionally substituted by one or more optionally substituted C.sub.1-6 alkyl groups; and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 which may be the same or different is each a hydrogen atom or a group AlkR.sup.5 where Alk is an optionally substituted straight or branched C.sub.1-6 alkyl group and R.sup.5 is a hydrogen atom or a --CO.sub.2 H,--CONR.sup.6 R.sup.7 [where R.sup.6 and R.sup.7, which may be the same or different, is each a hydrogen atom or a C.sub.1-6 alkyl group] or --P(X.sup.1)(X.sup.2 R.sup.8)R.sup.9 group where X.sup.1 and X.sup.2, which may be the same or different is each an oxygen or sulphur atom, R.sup.8 is a hydrogen atom or an alkyl group and R.sup.9 is an aliphatic, aromatic or heteroaromatic group, with the proviso that at least two of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is a group -AlkP(X.sup.1)(X.sup.2 R.sup.8)R.sup.9 or one or R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is a group -AlkP(X.sup.1)(X.sup.2 R.sup.8)R.sup.9 and at least one of the remaining groups R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is a group -AlkCO.sub.2 H or -AlkCONR.sup.6 R.sup.7, or a salt thereof, for use as contrast agents in nuclear magnetic resonance imaging are described.

Tetra-aza macrocycles, processes for their preparation and their use in

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.

Triaza macrocycles

Ti-aza macrocycles of formula (1), wherein m and n, which may be the same or different, is each zero or an integer 1, 2, or 3; p is zero or an integer 1 or 2; q is zero or an integer from 1 to 6 inclusive; R.sup.1, R.sup.2 and R.sup.3, which may be the same or different, is each a hydrogen atom or an alkyl, alkoxyalkyl, --CO.sub.2 H, --SO.sub.3 H, PO.sub.3 H.sub.2 or aryl group; L is a covalent bond or linker group; Z is a hydrogen atom or a reactive functional group, with the proviso that when L is a covalent bond Z is a reactive functional group; and metal complexes and/or salts thereof are described together with processes for their preparation and compositions containing them. The compounds are useful for imaging and in the treatment of abnormal cell disorders, such as in the treatment of tumours, and are particularly suitable for coupling to other molecules such as proteins for use in diagnosis and therapy.

Tri-aza macrocycles and metal complexes thereof

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Durham, United Kingdom

David Parker