Cytel Corporation

Geron Corporation

Sandoz Gmbh

The Scripps Research Institute

Epimmune Inc.

Pharmexa Inc.

Federico C Gaeta

Thomas S Arrhenius

Mariano J Elices

Elaine C Stracker

Alessandro D Sette

Howard M Grey

John Sidney

Adam Antoni Galan

Zhongli Zheng

Shawn A DeFrees

Patricia A Peterli-Roth

Masaji Hayashi

John J Gaudino

Jeffrey L Alexander

Chi-Huey Wong

James C Paulson

Michael R Kozlowski

Robert M Ratcliffe

Michael Frank Powell

Jeffery L Alexander

Karen R Prowse

Shawn De Frees

Mary S Perez

The present invention provides compositions and methods of inhibiting or inducing activation of T cells in a patient. The methods comprise administering a therapeutically effective dose of pharmaceutical compositions comprising a pharmaceutically acceptable carrier and peptides of between about 4 and about 20 residues, that bind antigen binding sites on MHC molecules encoded by substantially all alleles of a DR locus. These peptides are referred to as pan DR binding peptides. The pan DR binding peptides can be used to inhibit immune responses associated with immunopathologies, such as autoimmunity, allograft rejection and allergic responses. The peptides can also be used in combination with CTL peptides to enhance a CTL response.

Alteration of immune response using pan DR-binding peptides

The present invention provides compositions and methods of inducing immune response in patients. In particular, it provides compositions useful in inducing humoral resposes against desired immunogens, particularly polysaccharides.

Induction of immune response against desired determinants

The present invention contemplates a peptide that inhibits the binding between the VLA-4 receptor expressed on inflammatory leukocytes and the fibronectin CS-1 peptide expressed on endothelial cells that are involved in immunoinflammatory disease states. Pharmaceutical compositions containing a contemplated peptide and processes for treating immunoinflammatory conditions using a binding-inhibitory peptide are also disclosed.

CS-1 peptidomimetics, compositions and methods of using the same

CS-1 peptidomimetic, compositions and methods of using the same

The present invention contemplates a compound defined by the following formula: ##STR1## that inhibits the binding between the VLA-4 and the fibronectin CS-1 compound. Pharmaceutical compositions containing a contemplated compound and methods for treating immunoinflammatory conditions using the compound are also disclosed.

Methods and compositions for treating cancer and other diseases in which inhibition of telomerase activity can ameliorate disease symptoms or prevent or treat the disease relate to compounds characterized by the following structure: ##STR1## and their pharmaceutically acceptable salts. Y is selected from the group consisting of oxygen, sulfur, sulfonyl, sulfinyl, and --NR.sub.7 --. R.sub.1 is --TR.sub.8, where T is --C(X.sub.1)-- or --SO.sub.2 --, and R.sub.8 is selected from the group consisting of --OR.sub.9, --NHNHSO.sub.2 R.sub.9, --NHNHC(X.sub.2)OR.sub.9, --NR.sub.9 R.sub.10, --NHNHC(X.sub.2)NR.sub.9 R.sub.10, --NHCR.sub.9 R.sub.10 C(X.sub.2)NR.sub.11 R.sub.12, --NHC(X.sub.2)NR.sub.9 R.sub.10, and the piperazinyl moiety shown below: ##STR2## where n is 0 or 1, and Q.sub.n, for n=1, is --SO.sub.2 --, --C(X.sub.2)-- or --C(X.sub.2)NR.sub.10 --. R.sub.2 -R.sub.6 are selected independently from the group consisting of hydrogen, alkyl, aryl, hydroxyl, alkoxyl, aryloxyl, aralkoxyl, halogen, cyano, nitro, alkylcarbamido, arylcarbamido, dialkylcarbamido, diarylcarbamido, alkylarylcarbamido, alkylthiocarbamido, arylthiocarbamido, dialkylthiocarbamido, diarylthiocarbamido, alkylarylthiocarbamido, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonylamido, arylsulfonylamido, alkylsulfonyl, arylsulfonyl, alkylsulfinyl, and arylsulfinyl. X.sub.1 and X.sub.2 are selected independently from the group consisting of oxygen, and sulfur. R.sub.7 -R.sub.12 are selected independently from the group consisting of hydrogen, alkyl, aryl, aralkyl, heterocycle, and heterocyclealkyl.

Telomerase inhibitors

CS-1 peptidomimetics, compositions and methods of using same

The present invention relates to analogues of sialyl Le.sup.x the inhibit cellular adhesion between a selectin and cell that express sialyl Le.sup.x on their surfaces, as well as methods and compositions using the same, intermediates and methods for the preparation of the celluar adhesion inhibitor compounds and their intermediates. A contemplated intermediate or inhibitor compound has a structure that corresponds to that of Formula A, ##STR1## wherein: Z is selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 acyl and ##STR2##

Sialyl Le.sup.x analogues as inhibitors of cellular adhesion

Methods and compositions for treating cancer and other diseases in which inhibition of telomerase activity can ameliorate disease symptoms or prevent or treat the disease relate to compounds that are derivatives of pyridine aldehydes, thioaldehyde, acetals, or thioacetals. Such compounds are characterized by the following structure: ##STR1## X.sub.1 is selected from the group consisting of oxygen, sulfur, sulfone, sulfinyl, and --NR-- where R is hydrogen, alkyl, aryl, and aralkyl. R.sub.1 is --Y.sub.n R.sub.6, in which n is an integer between 0 and 10 and each Y.sub.n for n greater than 0 independently is methylene, methine, or quarternary carbon. R.sub.6, for any value of n (i.e., n is zero or non-zero), is alkyl, aryl, heterocycle, heteroaryl, aralkyl, heteroaralkyl, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, heteroaralkylcarbonyl, aralkylcarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, carboxyl, alkoxycarbonyl, aryloxycarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aldehyde, sulfo, alkylsulfinyl, arylsulfinyl, alkylsulfonyl, and arylsulfonyl. R.sub.6 can also be a linker L selected from the group consisting of alkyl, aryl, aralkyl, heterocycle, and heterocyclealkyl, to which linker between 1 and 3 additional compounds having the structure shown as Compound I above are attached to form thereby homogeneous or heterogeneous poly pyridine aldehydes, acetals, or thioacetals as described in greater detail below. R.sub.2 is hydrogen, alkyl, aryl, hydroxyl, alkoxyl, aryloxyl, halogen, cyano, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, carboxyl, alkoxycarbonyl, aryloxycarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aldehyde, sulfo, alkylsulfinyl, arylsulfinyl, alkylsulfonyl, or arylsulfonyl. R.sub.3 and R.sub.4 are selected independently from the group consisting of hydrogen, halogen, hydroxyl, aryloxyl, alkoxyl, lower alkyl, aryl, heteroaryl, aralkyl, cyano, carboxyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, heteroaralkyl, nitro, amino, alkylamino, arylamino, dialkylamino, diarylamino, and arylalkylamino. Finally, R.sub.5 is selected from the group consisting of bis(alkoxy)methyl, bis(alkylthio)methyl, and --HC.dbd.X.sub.2, where X.sub.2 is oxygen or sulfur.

Compounds for treating cancer and other diseases involving telomerase activity are characterized by the following structure: ##STR1## Such compounds include those for which X.sub.1 is oxygen, sulfur, sulfone, or sulfinyl, and R.sub.1 is --Y.sub.n R.sub.6, where n is an integer between 0 and 10 and each Y.sub.n independently is methylene, methine, or quaternary carbon. R.sub.6, is alkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, alkylcarbonyl, arylcarbonyl, heteroalkylcarbonyl, heteroaralkylcarbonyl, aralkylcarbonyl, arninocarbonyl, alkylarninocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, carboxyl, carboxaldehyde, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonyl, arylsulfonyl, alkylsulfinyl, or arylsulfinyl. R.sub.6 can also be a linker selected from the group consisting of alkyl, aryl, and heterocycle. R.sub.2 is hydrogen, alkyl, aryl, hydroxyl, alkoxyl, aryloxyl, halogen, cyano, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkylcarbonyl, arylcarbonyl, alkylcarbonyloxy, arylcarbonyloxy, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonyl, or arylsulfonyl. R.sub.3 and R.sub.4 independently can be hydrogen, amino, alkylamino, arylamino, heterocycleamino, aralkylamino, dialkylamino, diarylamino, heterocylcealkylamino, alkylcarbonyl, arylcarbonyl, nitro, halogen, hydroxyl, aryloxyl, alkoxyl, lower alkyl, aryl, heteroaryl, aralkyl, cyano, carboxyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, or heteroaralkyl. R.sub.5 is selected from the group consisting of iminyl, hydroximinyl, alkyliminyl, aryliminyl, aralkyliminyl, alkoximinyl, aryloximinyl, heterocycleiminyl, and cyclic iminyl. Provided, however, that R.sub.5 is not 4-methylphenyliminyl when X.sub.1 is sulfur, n is 1, Y is methylene, R.sub.2 is cyano, R.sub.3 and R.sub.4 are hydrogen, and R.sub.6 is 4-chlorophenyl.

Methods and compositions for treating cancer and other diseases in which inhibition of telomerase activity can ameliorate disease symptoms or prevent or treat the disease relate to compounds that are derivatives of pyrido�b!thiophenes, pyrido�b!furans, pyridine ethers or pyridine thioethers. Such compounds are characterized by the following structure: ##STR1## X.sub.3 is oxygen or sulfur; and the double dashed lines between X.sub.4 and X.sub.5 indicate an optional double bond, which, when present, forms a fused, bicyclic pyrido�b!furan or pyrido�b!thiophene ring system, depending upon whether X.sub.3 is oxygen or sulfur, respectively. When the double bond is not present, the compound is a monocyclic pyridine ether or thioether, again depending upon whether X.sub.3 is oxygen or sulfur. X.sub.4 is --CH.sub.2 R.sub.21 or --CR.sub.21 --, where R.sub.21 is selected from the group consisting of aryl, heteroaryl, aralkyl, heteroaralkyl, alkylcarbonyl, arylcarbonyl, heteroalkylcarbonyl, heteroaralkylcarbonyl, aralkylcarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylarninocarbonyl, arylalkylaminocarbonyl, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonyl and arylsulfonyl; and X.sub.5 is hydrogen, alkyl, hydroxyl, alkoxyl, aryloxyl, halogen, cyano, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonyl, arylsulfonyl or --CR.sub.22 -- where R.sub.22 is selected from the group consisting of hydrogen, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, hydroxyl, halogen, cyano, carboxyl, alkoxycarbonyl and aryloxycarbonyl. When X.sub.4 is --CR.sub.21 --, X.sub.5 is --CR.sub.22 --, and X.sub.4 and X.sub.5 are joined by the above-mentioned double bond, to form thereby a fused, bicyclic pyrido�b!thiophene (X.sub.3 is sulfur) or pyrido�b!furan (X.sub.3 is oxygen) ring system. When X.sub.4 is --CH.sub.2 R.sub.21, X.sub.5 is not --CR.sub.22 --, thereby forming a pyridine ether (X.sub.3 is oxygen) or thioether (X.sub.3 is sulfur). R.sub.18 and R.sub.19 are selected independently from the group consisting of hydrogen, halogen, hydroxy, aryloxy, alkoxy, lower alkyl, aryl, heteroaryl, aralkyl and heteroaralkyl. R.sub.20 is selected from the group consisting of alkoxymethyl, dialkoxymethyl, arylalkylaminomethyl, arylaminomethyl, alkylaminomethyl, aminomethyl, diarylaminomethyl, dialkylaminomethyl, hydroximinyl, iminyl, aldehyde, alkylcarbonyl, arylcarbonyl, alkyliminyl, aryliminyl, aralkyliminyl, alkoximinyl, aryloximinyl, heterocycleimninyl, alkoxycarbonyl, aryloxycarbonyl, carboxyl, alkene, --HC.dbd.NNHR.sub.23 where R.sub.23 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, heterocycle, heterocyclealkyl, and --C(X.sub.6)NHR.sub.24 where X.sub.6 is oxygen or sulfur and R.sub.24 is selected from the group consisting of hydrogen, aryl, arylsulfonyl, aralkyl, heterocycle and heterocyclealkyl.

The present invention is directed towards compositions and methods for reducing or controlling inflammation and for treating inflammatory disease processes and other pathological conditions mediated by intercellular adhesion. The compositions of the invention include compounds that selectively bind selectin receptors, the selectin binding activity being mediated by a carbohydrate moiety. The selectin-binding moieties of the invention are derivatives of a sialylated, fucosylated N-acetyllactosamine unit of the Lewis X antigen. Compounds containing a selectin-binding moiety in both monovalent and multivalent forms are included in the invention. The compounds of the invention are provided as pharmaceutical compositions which include, for example, liposomes that carry selectin-binding moieties of the invention. The invention further includes immunoglobulins capable of selectively binding an oligosaccharide ligand that is recognized by a selectin receptor.

Intercellular adhesion mediators

Methods and compositions for treating cancer and other diseases in which inhibition of telomerase activity can ameliorate disease symptoms or prevent or treat the disease relate to compounds that are derivatives of benzo�b!thiophenes. Such compounds are characterized by the following structure: ##STR1## In this compound, R.sub.1 is selected from the group consisting of --OR.sub.7, --NR.sub.8 R.sub.9, --NHNR.sub.10 R.sub.11, --NHNHC(X.sub.2)NHR.sub.12, --NHSO.sub.2 NR.sub.8 R.sub.9, --NHNHC(O)R.sub.12, --NHNHSO.sub.2 R.sub.12 and --NHC(O)NR.sub.8 R.sub.9. R.sub.7 -R.sub.12 are selected independently from the group consisting of hydrogen, alkyl, aryl, aralkyl, heteroaryl and heteroaralkyl. X.sub.1 and X.sub.2 are selected independently from the group consisting of oxygen and sulfur. R.sub.2 is hydrogen or halogen. R.sub.3 -R.sub.6 are selected independently from the group consisting of hydrogen, halogen, hydroxyl, --NR.sub.8 R.sub.9, nitro, cyano, alkoxyl, lower alkyl, aryl and aryloxyl.

Growing community of inventors

Olivenhain, CA, United States of America

Federico C Gaeta