Abstract: In accordance with the present invention, there are provided fully human monoclonal antibodies against human cytotoxic T-lymphocyte antigen 4 (CTLA-4). Nucelotide sequences encoding and amino acid sequences comprising heavy and light chain immunoglobulin molecules, particularly contiguous heavy and light chain sequences spanning the complementarity determining regions (CDRs), specifically from within FR1 and/or CDR1 through CDR3 and/or within FR4, are provided. Further provided are antibodies having similar binding properties and antibodies (or other antagonists) having similar functionality as antibodies disclosed herein.

Abstract: There are disclosed compounds of the formula ##STR1## wherein X is O, S, SO, SO.sub.2 or CR.sup.1 R.sup.2 ;R.sup.1 and R.sup.2 are each independently hydrogen, lower alkyl, carboxyl, lower alkoxy carbonyl, lower cycloalkyl, phenyl, anphthyl, pyridyl, quinolinyl, pyrazinyl, pyridinyl, pyridazinyl, pyrimidinyl, quinoxalinyl, quinazolinyl or any of the foregoing aryl or hetaryl substituents substituted with halo, lower alkyl, lower alkyl carbonyl, benzoyl, COOR.sup.3, OR.sup.3, N(R.sup.3).sub.2, CON(R.sup.3).sub.2, SO.sub.3 R.sup.3, SO.sub.2 N(R.sup.3).sub.2, phenylsulfonyl, lower alkyl sulfonyl, cyano, nitro or trifluoromethyl;R.sup.3 is hydrogen, lower alkyl or phenyl;R.sup.4 is halo, morpholino, 4-methylpiperazino, R.sup.5 NNHR.sup.6, R.sup.5 NCH.sub.2 CH.sub.2 OCH.sub.3, or ##STR2## R.sup.5 is hydrogen or lower alkyl; R.sup.6 is hydrogen, lower alkyl, lower alkanoyl, lower cycloalkyl or phenyl; andR.sup.7 and R.sup.

Abstract: There are disclosed compounds of the formula ##STR1## wherein X is O, S, SO, SO.sub.2 or CR.sup.1 R.sup.2 ;R.sup.1 and R.sup.2 are each independently hydrogen, lower alkyl, carboxyl, lower alkoxy carbonyl, lower cycloalkyl, phenyl, naphthyl, pyridyl, quinolinyl, pyrazinyl, pyridinyl, pyridazinyl, pyrimidinyl, quinoxalinyl, quinazolinyl or any of the foregoing aryl or hetaryl substituents substituted with halo, lower alkyl, lower alkyl carbonyl, benzoyl, COOR.sup.3, OR.sup.3, N(R.sup.3).sub.2, CON(R.sup.3).sub.2, SO.sub.3 R.sup.3, SO.sub.2 N(R.sup.3).sub.2, phenylsulfonyl, lower alkyl sulfonyl, cyano, nitro or trifluoromethyl;R.sup.3 is hydrogen, lower alkyl or phenyl;R.sup.4 is halo, morpholino, 4-methylpiperazino, R.sup.5 NNHR.sup.6,R.sup.5 NCH.sub.2 CH.sub.2 OCH.sub.3, or ##STR2## R.sup.5 is hydrogen or lower alkyl; R.sup.6 is hydrogen, lower alkyl, lower alkanoyl, lower cycloalkyl or phenyl; andR.sup.7 and R.sup.

Abstract: There is disclosed a method for the treatment of inflammatory conditions and of collagenase-induced tissue destruction which comprises the administration of a therapeutically effective amount of a compound of the formula ##STR1## wherein R.sup.1 is lower alkyl or lower alkenyl or any of the foregoing optionally substituted with fluoro, carboxy, lower alkoxycarbonyl, OR.sup.2, N(R.sup.2).sub.2, SR.sup.2 CON(R.sup.2).sub.2, SO.sub.2 R.sup.2, cyano, nitro or trifluoromethyl;R.sup.2 is hydrogen, lower alkyl or phenyl;R.sup.3 is halo, morpholino, 4-methylpiperazino, R.sup.4 NNHR.sup.5, NR.sup.4 R.sup.5, OR.sup.5, SR.sup.5, ##STR2## R.sup.4 is hydrogen or lower alkyl; R.sup.5 is hydrogen, lower alkyl, lower alkanoyl, lower cycloalkyl or phenyl; andR.sup.6 and R.sup.

Abstract: There is disclosed a method for the treatment of inflammatory conditions and of collegenase-induced tissue destruction which comprises the administration of a therapeutically effective amount of a compound of the formula ##STR1## wherein R.sup.1 is phenyl or naphthyl, or phenyl or naphthyl substituted with halo, lower alkyl, lower alkyl carbonyl, benzoyl, carboxy, lower alkoxycarbonyl, OR.sup.2, N(R.sup.2).sub.2, CON(R.sup.2).sub.2, SO.sub.3 R.sup.2, SO.sub.2 N(R.sup.2).sub.2, phenylsulfonyl, lower alkylsulfonyl, cyano nitro or trifluoromethyl;R.sup.2 is hydrogen, lower alkyl or phenyl;R.sup.3 is halo, morpholino, 4-methylpiperazino R.sup.4 NNHR.sup.5, NR.sup.4 R.sup.5, OR.sup.5, SR.sup.5, ##STR2## R.sup.4 is hydrogen or lower alkyl; R.sup.5 is hydrogen, lower alkyl, lower alkanoyl, lower cycloalkyl or phenyl; andR.sup.6 and R.sup.

Abstract: There are disclosed compounds of the formula ##STR1## wherein the various substituents are defined hereinbelow, and, by virtue of their ability to inhibit interleukin 1, their use as antiinflammatory agents and in treatment of disease states involving enzymatic tissue destruction.