Hybritech Incorporated

Hollis-eden Pharmaceuticals, Inc.

Harbor Biosciences, Inc.

Harbor Therapeutics, Inc.

Clarence Nathaniel Ahlem

James M Frincke

Christopher Reading

Ann E Huang

William Heggie

Dwight Stickney

Steven K White

Leslie D Anderson

Theodore M Page

Richard Trauger

Dominick L Auci

Charles Dowding

Mei Li

Luis D Carvalho

Jaime Flores-Riveros

Luis Daniel Dos Anjos De Carvalho

The invention relates to methods identify or characterize compounds that can be used to treat specified clinical disorders such as hyperglycemia and type 2 diabetes. Compounds that can be used in these methods include 4&#x3b1;-fluoro-17&#x3b1;-ethynylandrost-5-ene-3&#x3b2;,7&#x3b2;,17&#x3b2;-triol, 4&#x3b1;-fluoro-17&#x3b1;-ethynylandrost-5-ene-3&#x3b2;,7&#x3b1;,17&#x3b2;-triol, 4&#x3b1;-fluoro-17&#x3b1;-ethynylandrost-5-ene-3&#x3b1;,7&#x3b2;,17&#x3b2;-triol and 4&#x3b1;-fluoro-17&#x3b1;-ethynylandrost-5-ene-3&#x3b2;,17&#x3b2;-triol-7-one.

Drug screening and treatment methods

The invention provides compositions comprising formula 1 steroids, e.g., 16&#x3b1;-bromo-3&#x3b2;-hydroxy-5&#x3b1;-androstan-17-one hemihydrate and one or more excipients, typically wherein the composition comprises less than about 3% water. The compositions are useful to make improved pharmaceutical formulations. The invention also provides methods of intermittent dosing of steroid compounds such as analogs of 16&#x3b1;-bromo-3&#x3b2;-hydroxy-5&#x3b1;-androstan-17-one and compositions useful in such dosing regimens. The invention further provides compositions and methods to inhibit pathogen (viral) replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using certain steroids and steroid analogs. The invention also provides methods to make and use these immunomodulatory compositions and formulations.

Pharmaceutical compositions 3

The invention relates to the use of compounds to ameliorate or treat a condition such as a cystic fibrosis, neutropenia or other exemplified conditions. Exemplary compounds that can be used include 3&#x3b2;-hydroxy-17&#x3b2;-aminoandrost-5-ene, 3&#x3b2;-hydroxy-16&#x3b1;-fluoro-17&#x3b2;-aminoandrost-5-ene, 3&#x3b1;-hydroxy-16&#x3b1;-fluoro-17&#x3b2;-aminoandrost-5-ene, 3&#x3b2;-hydroxy-16&#x3b2;-fluoro-17&#x3b2;-aminoandrost-5-ene, 1&#x3b1;,3&#x3b2;-dihydroxy-4&#x3b1;-fluoroandrost-5-ene-17-one, 1&#x3b1;,3&#x3b2;,17&#x3b2;-trihydroxy-4&#x3b1;-fluoroandrost-5-ene, 1&#x3b2;,3&#x3b2;-dihydroxy-6&#x3b1;-bromoandrost-5-ene, 1&#x3b1;-fluoro-3&#x3b2;,12&#x3b1;-dihydroxyandrost-5-ene-17-one, 1&#x3b1;-fluoro-3&#x3b2;,4&#x3b1;-dihydroxyandrost-5-ene and 4&#x3b1;-fluoro-3&#x3b2;,6&#x3b1;,17&#x3b2;-trihydroxyandrostane.

Therapeutic treatment methods

Pharmaceutical compositions and treatment methods

The invention provides compositions comprising, 16&agr;-bromo-3&bgr;-hydroxy-5&agr;-androstan-17-one hemihydrate and one or more excipients, typically wherein the composition comprises less than about 3% water. The compositions are useful to make improved pharmaceutical formulations. The invention also provides methods of intermittent dosing of steroid compounds such as analogs of 16&agr;-bromo-3&bgr;-hydroxy-5&agr;-androstan-17-one and compositions useful in such dosing regimens. The invention further provides compositions and methods to inhibit pathogen (viral) replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using certain steroids and steroid analogs. The invention also provides methods to make and use these immunomodulatory compositions and formulations.

The present invention has multiple aspects. In its first aspect the present invention is directed to a trifunctional antibody-like compound that has tissue, organ, cell or molecule specificity and which is capable of being bifunctional when immobilized, via binding, at the tissue, organ, cell or molecule for which it has specificity. In particular, the present invention is directed to a trifunctional antibody-like compound of Formula I:

Trifunctional antibody-like compounds as a combined diagnostic and

The present invention is directed to a method for extending the length of one of the three linker arms of the compound of Formula I in the production of novel trifunctional antibody-like compounds. Formula I is defined as follows: ##STR1## wherein X is ##STR2## wherein k=1 or 0; wherein Z is ##STR3## wherein s=1 or 0; wherein n=1 or 0; wherein q=1 or 0; wherein Y is ##STR4## wherein Y' is ##STR5## wherein p or m may be the same or different and are integers ranging from 0 to 20 with the provisos that when n=0, the sum of m and p is an integer ranging from 1 to 20, whereas when n=1, p and m are each an integer that is at least 1 and the sum of p and m is an integer ranging from 2 to 20; wherein R.sup.1 is straight or branched chain lower alkyl having from 1 to 6 carbon atoms or lower alkoxy having from 1-6 carbon atoms; and wherein R.sup.2 is hydrogen, phenyl, --COOH, or straight or branched chain lower alkyl having from 1-6 carbon atoms, with the proviso that the lower alkyl moiety may be mono substituted by --NH.sub.2, --OH, or --COOH. The compound of the present invention is useful as a trivalent coupling agent for linking Fab'-like fragments to form both bifunctional and trifunctional antibody-like compounds.

Method for the synthesis of trifunctional maleimide-antibody complex

The present invention is directed to a compound for use as an intermediate in the production of novel trifunctional antibody-like compounds. More particularly, the present invention is directed to a compound of the formula: ##STR1## wherein X is ##STR2## wherein k=1 or 0;

Growing community of inventors

San Diego, CA, United States of America

Clarence Nathaniel Ahlem