La Jolla Pharmaceutical Company

Euro-celtique S.a.

La Jolla Pharmaceutial Company

Stephen M Coutts

David S Jones

Douglas Alan Livingston

Michael J Conrad

Lin Yu

John P Hachmann

T Scott Shoupe

Lloyd Jay Dolby

Paul A Barstad

G Michael Iverson

David C Baker

Elli S Hand

Chemically-defined, non-polymeric valency platform molecules and conjugates comprising chemically-defined valency platform molecules and biological or chemical molecules including polynucleotide duplexes of at least 20 base pairs that have significant binding activity for human lupus anti-dsDNA autoantibodies.

Chemically defined non-polymeric valency platform molecules and conjugates thereof

Chemically-defined non-polymeric valency platform molecules and conjugates thereof

Conjugates of nonimmunogenic valency platform molecules and analogs of immunogens that possess the specific B cell binding ability of the immunogen but lack T cell epitopes and which, when introduced into individuals, induce humoral anergy to the immunogen are disclosed. Accordingly, these conjugates are useful for treating antibody-mediated pathologies that are caused by foreign or self immunogens.

Composition for inducing humoral anergy to an immunogen comprising a T

Phosphoramidites of the formula ##STR1## where R is a base-labile protecting group, R.sup.1 and R.sup.2 are individually alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, or aryl of 6 to 20 carbon atoms or are joined together to form with the nitrogen atom a cyclic structure of 4-7 carbon atoms and 0 to 1 annular chalcogen atoms of atomic number 8 to 16, G is a hydrocarbylene group of 1 to 20 carbon atoms and Z is a hydroxy-protected vicinal diol group bound to G by one of the vicinal diol carbon atoms or a disulfide group and bound to G by one of the sulfur atoms of the disulfide group, with the proviso that G is of at least 4 carbon atoms when Z is said disulfide group are used in conventional automated oligonucleotide synthesis to introduce a functional aldehyde or thiol group on the 5' end of the oligonucleotide to thereby provide a reactive site on the oligonucleotide that may be used to conjugate the oligonucleotide to molecules that contain a free amino group or an electrophilic center reactive with a thiol group.

Modified phosphorous intermediates for providing functional groups on

Chemically-defined non-polymeric valency platform molecules and

Intermediates for providing functional groups on the 5' end of

Chemically defined conjugates of biologically stable valency platform molecules, such as copolymers of D-glutamic acid and D-lysine or polyethylene glycol, and polynucleotide duplexes of at least 20 base pairs that have significant binding activity for human lupus anti-dsDNA autoantibodies. The duplexes are preferably homogeneous in length structure and are bound to the valency platform molecule via reaction between a functional group located at or proximate a terminus of each duplex and functional groups on the valency platform molecule. These conjugates are tolerogens for human systemic lupus erythematosus.

Conjugates of biologically stable polyfunctional molecules and

Chemically defined conjugates of biologically stable polymers, such as copolymers of D-glutamic acid and D-lysine, and polynucleotide duplexes of at least 30 base pairs that have significant binding activity for human lupus anti-dsDNA autoantibodies. The duplexes are preferably homogeneous in length and structure and are bound to the polymer via reaction between an amino-reactive functional group located at or proximate a terminus of each duplex. These conjugates are tolerogens for human systemic lupus erythematosus.

Conjugates of biologically stable polymers and polynucleotides for

Novel substituted dibenzofuran compounds are disclosed. The compounds exhibit activity in antagonizing the effects of leukotriene B.sub.4 (LTB.sub.4). Pharmaceutical compositions containing the novel compounds and methods of treatment employing the same are also described.

Substituted dibenzofurans and methods of using same

Novel substituted isoquinoline compounds are disclosed together with novel 2-phenylethylamides useful as precursors or intermediates for the production of the isoquinolines. The substituted isoquinolines exhibit activity in antagonizing the effects of platelet activating factor (PAF).

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Rancho Santa Fe, CA, United States of America

Stephen M Coutts