Centocor, Inc.

Other

Mallinckrodt Medical, Inc.

Mallinckrodt, Inc.

Centecor, Inc.

Robert W Weber

Richard T Dean

Raymond H Boutin

George A Heavner

David H White

Muthunadar P Periasamy

Youlin Lin

Marian Kruszynski

Miljenko Mervic

Peptides which consist of 4-25 amino acids and which bind to tumor necrosis factor-alpha, prevent tumor necrosis factor-alpha from binding to its receptors and inhibit tumor necrosis factor-alpha activity are disclosed. Methods of inhibiting tumor necrosis factor-alpha activity and of treating individuals suffering from tumor necrosis factor-alpha-mediated diseases and disorders are disclosed.

Tumor necrosis factor inhibitors

A bifunctional coupling agent for joining a sulfhydryl-containing protein or peptide and a metallic radionuclide comprising a sulfhydryl selective electrophile, a chelator containing at least one protected thiol and a organic linking radical which serves to join said electrophile and said chelator is disclosed. A radiodiagnostic precursor comprising an antibody or antibody fragment and the specified bifunctional coupling agent bound to a sulfhydryl group on the antibody or antibody fragment is also disclosed.

Bifunctional coupling agents and radionuclide labeled compositions

A bifunctional coupling agent for joining a sulfhydryl containing protein or peptide and a metallic radionuclide comprising a sulfhydryl selective electrophile, a chelator containing at least one protected thiol and a organic linking radical containing at least one cleavable site which serves to join said electrophile and said chelator is disclosed. A radiodiagnostic or radiotherapeutic precursor comprising an antibody or antibody fragment and the specified bifunctional coupling agent bound to a sulfhydryl group on the antibody or antibody fragment and a radiodiagnostic or radiotherapeutic agent comprising such precursor having a metallic radionuclide bound thereto are also disclosed.

Cleavable bifunctional coupling agents

Novel magnetic resonance imaging agents methods utilize complexes of paramagnetic ions with alkoxyalkylamide deriviatives of diethylenetriaminepentaacetic acid ('DTPA') or ethylenediaminetetyraacetic acid ('EDTA'). These novel imaging agents are characterized by excellent NMR image-contrasting properties and by high solubilities in physiological solutions. The complexes are represented by the following formula: ##STR1## wherein A is --CH.sub.2 CH.sub.2 -- or ##STR2## and M.sup.+Z is a paramagnetic ion of an element with an atomic number of 21-29, 42-44 or 58-70, and a valence number, Z, of 2 or 3; R.sup.1 is --O.sup.- or R.sup.3 --N--R.sup.2, R.sup.2 is --(CH.sub.2 CH.sub.2 O).sub.n --R.sup.4, n is 1-10, R.sup.4 is alkyl or aryl, R.sup.3 is H, R.sup.2, alkyl, hydroxy, alkoxy, cycloalkyl or aryl, wherein Z of the R.sup.1 groups are --O.sup.- and the remainder of the R.sup.1 groups are R.sup.2 -N--R.sup.3 groups.

Paramagnetic DTPA and EDTA alkoxyalkylamide complexes as MRI agents

Novel magnetic resonance imaging agents and methods which utilize complexes of paramagnetic ions with alkoxyalkylamide derivatives of diethylenetriaminepentaacetic acid ('DTPA') or ethylenediaminetetraacetic acid ('EDTA'). These novel imaging agents are characterized by excellent NMR image-contrasting properties and by high solubilities in physiological solutions. The complexes are represented by the following formula: ##STR1## wherein A is --CH.sub.2 CH.sub.2 -- or ##STR2## and M.sup.+z is a paramagnetic ion of an element with an atomic number of 21-29, 42-44 or 58-70, and a valence, Z, of 2 or 3; the R groups may be the same or different and are selected from the group consisting of -O.sup..crclbar. and lower alkoxyalkylamino groups having from 2 to about 6 carbon atoms, wherein the number of R groups -O.sup..crclbar. equals Z and the remaining R groups are lower alkoxyalkylamino, equal to 4-Z when A is --CH.sub.2 CH.sub.2 --, or 5-Z when A ##STR3##

A bifunctional chelating agent for joining an antibody or antibody fragment and a metallic radionuclide is disclosed. The agent consists of a derivative of 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid or a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, an organic linking radical which optionally contains a cleavable group, and a function capable of reacting with a site on a protein. Radiodiagnostic or radiotherapeutic precursors comprising an antibody or antibody fragment and the above-described bifunctional chelating agent and radiodiagnostic or radiotherapeutic agent comprising a metallic radionuclide and the above mentioned precursor are also disclosed.

Chelating agents

The disclosure is directed to compounds of the formula: ##STR1## wherein n=0, 1, 2, 3 or 4, and R.sub.1 and R.sub.2 may be the sam e or different and are selected from the group consisting of hydrogen and lower alkyl and hydroxy lower alkyl groups containing between 1 and 6 carbon atoms. Complexes of iron(II), iron(III), manganese(II), manganese(III), gadolinium(III), chromium(III), cobalt(II), and nickel(II) and such compounds are useful for enhancing magnetic resonance images of body organs and tissues. Illustrative complexes include (N,N'-bis[N-(2,3-dihydroxypropyl) carbamoylmethyl]diethylenetriamine-N,N',N'-triaceto)-iron(III), (N,N'-bis[N-(2,3-dihydroxypropyl)carbamoylmethyl]diethylenetriamine-N,N',N '-triaceto)manganese(II), (N,N'-bis[N-(2,3-dihydroxypropyl) )carbamoylmethyl]diethylenetriamine-N,N',N'-triaceto)gadolinium(III) and (N,N'-bis[N-(2,3-dihydroxypropyl)-carbamoylmethyl]ethylenediamine-N,N'-dia ceto)manganese(II).

Methods and compositions for enhancing magnetic resonance imaging

A dual load trailer for simultaneously transporting a first vehicle in an upper position and a second vehicle in a lower position, with the upper vehicle inclined towards the front end of the trailer and with at least a portion of the first vehicle below the top of the second vehicle.

Dual load trailer

A fishing net having a handle supporting a frame defining an opening and a net mounted to the perimeter of the frame. A guide member is pivotally mounted in a gap in the frame and connected to the net. The guide member is adapted to receive a fishing line on which a fish is caught. The fishing line is pulled upwards through the guide member and pulls the fish into engagement with the net. The fishing net is then inverted with the fish captured in the net. Preferably, the guide member includes a latch member for securing the fishing line within the guide member.

Growing community of inventors

Downingtown, PA, United States of America

Robert W Weber