Magainin Pharmaceuticals, Inc.

Alliedsignal Inc.

Allied Corporation

Genetics Institute, Inc.

Enichem S.p.a

Genaera Corporation

Ohr Pharmaceutical Inc.

Jon I Williams

Michael A Zasloff

Mark L Anderson

William Alvin Kinney

Michael D Swerdloff

Edward F Fritsch

Michael McLane

Mary Collins

Steven E Diamond

Himangshu R Bhattacharjee

Marian S Ellwood

Nicholas P Everett

Joseph G Brewen

W Lee Maloy

John P Sibilia

Yash P Khanna

Morris B Berenbaum

U Prasad Kari

Ann Shinnar

William T McAllister

Rakesh Kumar

G Mark Anderson

Newell F Bascomb

Ina Goldberg

James C Pierce

Mitchell H Sokoloff

Anthony J Salerno

Prasad Kari

A pharmaceutical composition includes, as an active ingredient, a compound according to formula 1436 as shown in FIG., or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. Various pharmaceutical products may be produced including this pharmaceutical composition. Such pharmaceutical products may be used for the treatment of obesity or diabetes. Methods for using the pharmaceutical compositions also are described. In these methods, various diseases are treated or other body functions are activated or inhibited by administering an effective amount of the pharmaceutical composition. For example, diabetes and obesity may be treated by administering an effective amount of the pharmaceutical compositions. Weight gain and growth factor production can be inhibited by administering an effective amount of these pharmaceutical compositions. Appetite can be suppressed by administering an effective amount of the pharmaceutical compositions, and a diuretic effect can be produced.

Therapeutic uses for an aminosterol compound

A pharmaceutical composition includes, as an active ingredient, a compound according to formula 1436 as shown in FIG., or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. Various pharmaceutical products may be produced including this pharmaceutical composition. Such pharmaceutical products may be used for the treatment of obesity or diabetes. Methods for using the pharmaceutical compositions also are described. In these methods, various diseases are treated or other body functions are activated or inhibited by administering an effective amount of the pharmaceutical composition. For example, diabetes and obesity may be treated by administering an effective amount of the pharmaceutical compositions. Weight gain, and growth factor production can be inhibited by administering an effective amount of these pharmaceutical compositions. Appetite can be suppressed by administering an effective amount of the pharmaceutical compositions, and a diuretic effect can be produced.

Therapeutic uses for aminosterol compounds

A method for treating a tumor includes a first treatment procedure using a conventional cancer treatment technique, and a second treatment procedure which includes administering an effective amount of squalamine. Synergistically effective amounts are preferred. The first treatment procedure may be a treatment with one or more conventional cytotoxic chemical compounds. As examples, the cytotoxic chemical compound may be a nitrosourea (such as BCNU), cyclophosphamide, doxorubicin, 5-fluorouracil, paclitaxel and its derivatives, cisplatin or other platinum containing cancer treating agents. Alternatively, the first treatment may be a treatment with one or more conventional anti-hormonal agents. As examples, the anti-hormonal agents may be a LHRH (luteinizing hormone releasing hormone) agonist or an anti-androgen such as flutamide, biclutamide, nilutamide, and luprolide. These conventional cancer treatments compounds and the squalamine may be administered by any suitable route. The first treatment procedure may take place prior to the second treatment procedure, after the second treatment procedure, or the two treatment procedures may take place simultaneously. As an alternative, the first treatment procedure may be a conventional radiation treatment regimen. As a further alternative the first treatment procedure may be a combination of treatment with one or more conventional cytotoxic chemical compounds and a conventional radiation treatment regimen.

Treatment of carcinomas using squalamine in combination with other anti-cancer agents or modalities

A method for treating a tumor includes a first treatment procedure using a conventional cancer treatment technique, and a second treatment procedure which includes administering an effective amount of squalamine. The first treatment procedure may be a treatment with one or more conventional cytotoxic chemical compounds. As examples, the cytotoxic chemical compound may be a nitrosourea (such as BCNU), cyclophosphamide, adriamycin, 5-fluorouracil, paclitaxel and its derivatives, cisplatin or other platinum containing cancer treating agents. The cytotoxic chemical compound and the squalamine may be administered by any suitable route. The first treatment procedure may take place prior to the second treatment procedure, after the second treatment procedure, or the two treatment procedures may take place simultaneously. In one example, the first treatment procedure (e.g., a one time intravenous dosage of BCNU) is completed before the second treatment procedure with squalamine begins. As an alternative, the first treatment procedure may be a conventional radiation treatment regimen.

Treatment of carcinomas using squalamine in combination with other

Aminosterol compounds are described that are useful as inhibitors of the sodium/proton exchanger (NHE). Methods of using such aminosterols compounds are also disclosed, including those employing compounds that are inhibitors of a spectrum of NHEs as well as those using compounds that are inhibitors of only one specific NHE. Advantageous screening techniques and assays for evaluating a compound's therapeutic activity are also disclosed.

Method of inhibiting profileration of cells by administering an

The present invention relates to the recombinant production of amphiphilic peptides with biologically and therapeutically significant activities. In one embodiment, this invention relates to recombinantly producing an amphiphilic peptide by providing a protease-deficient microbial host transformed with an expression vector containing DNA that encodes the amphiphilic peptide under the control of a regulatory sequence operable in the microbial host and expressing the amphiphilic peptide in the transformed microbial host. In another embodiment, this invention relates to providing an E. coli protease-deficient K-12 cell transformed with a vector that expresses a cleavable fusion protein comprising at least part of a carbohydrate binding protein and the amphiphilic peptide in the cell, expressing the fusion protein in the cell, and cleaving the fusion protein to obtain the amphiphilic peptide substantially free of carbohydrate binding protein residues. The biologically active amphiphilic peptide so produced can be further treated chemically or enzymatically to obtain a chemically distinct amphiphilic peptide with improved biological and therapeutic properties.

Recombinant production of biologically active peptides and proteins

The present invention relates to several types of antimicrobial peptides including reverse antimicrobial peptides, antimicrobial oligopeptides and other antimicrobial compositions, such as cecropin P1. The present invention also relates to the use of these antimicrobial peptides to provide organisms, and, in particular, plants, with protection from microbial pathogens. Finally, the present invention relates to a screening method which may be useful for determining the phytotoxity of an antimicrobial peptide.

Reverse antimicrobial peptides

Biologically active amphiphilic peptides including one of the following basic structures: I. R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.1 --R.sub.1 ; II. R.sub.2 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.2 --R.sub.2 ; III. R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.3 ; IV. R.sub.1 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.4 ; V. R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.3 ; or VI. R.sub.1 --R.sub. 1 --R.sub.3 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.1 --R.sub.1 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.1 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1. R.sub.1 is a hydrophobic amino acid and R.sub.2 is a basic hydrophilic or neutral hydrophilic amino acid, R.sub.3 is a neutral hydrophilic amino acid, and R.sub.4 is a neutral hydrophilic amino acid or proline.

Biologically active amphiphilic peptide compositions and uses therefor

The present invention relates to a number of peptides which have antimicrobial activity and which are useful in retarding plant pathogens. In addition, compounds in accordance with the present invention may have improved resistance to degradation by plant proteases, and/or sufficiently low phytotoxicity to render them likely candidates for use in conjunction with plants. The present invention also relates to oligonucleotides which are capable of expressing the aforementioned peptides. Also provided hereby is a process of retarding the growth of plant pathogens using the compounds of the present invention as well as a screening method and screening reagent useful in determining the proteolytic degradation resistance of a known compound.

Antimicrobial peptides active against plant pathogens

This invention relates to processes for the microbial production of peptide oligomers, to polypeptide products resulting from application of any of these processes, and to microbes for use in such production. Another aspect of this invention relates to processes for genetically engineering such microbes and to plasmid vectors for use in such engineering.

Method of producing a gene cassette coding for polypeptides with

A process for preparing a co-poly(amide/peptide) by reacting polymeric or oligomeric polypeptides and polymeric or oligomeric polyamides in the presence of an effective amount of one or more aryl phosphoryl azide compounds.

Process for preparing co-poly(amides/peptides)

This invention relates to a process for blow molding polyamide compositions where the molten polyamide includes an effective amount of one or more aryl phosphoryl azide compounds.

Method of blow molding polyamides

A diagnostic reagent is disclosed containing a complex of a probe polynucleotide (P) bound via purine/pyrimidine hydrogen bonding to a labeled polynucleotide (L). The probe (P) contains a target binding region (TBR) capable of binding to a target nucleotide sequence (G) of a biological sample. A method is disclosed in which contact with a sample containing the target nucleotide sequence (G) causes binding, initially between G and a single-stranded portion (IBR) of the target binding region (TBR). Thereafter the labeled polynucleotide (L) is displaced from the complex by branch migration of (G) into the (P)/(L) binding region. A volume excluding polymeric agent such as poly(ethylene oxide) (PEO or PEG) or other polyethers enhances the rate of appearance of displaced labeled polynucleotide. Determination of displaced labeled polynucleotide (L) gives a value which is a function of the presence and concentration of target nucleotide sequence (G) in the sample.

Displacement polynucleotide assay employing polyether and diagnostic kit

A diagnostic reagent is disclosed containing a complex of a probe polynucleotide (P) bound via purine/pyrimidine hydrogen bonding to a labeled polynucleotide (L). The probe (P) contains a target binding region (TBR) capable of binding to a target nucleotide sequence (G) of a biological sample. A method is disclosed in which contact with a sample containing the target nucleotide sequence (G) causes binding, initially between G and a single-stranded portion (IBR) of the target binding region (TBR). Thereafter the labeled polynucleotide (L) is displaced from the complex by branch migration of (G) into the (P)/(L) binding region. Determination of displaced labeled polynucleotide (L) gives a value which is a function of the presence and concentration of target nucleotide sequence (G) in the sample.

Displacement polynucleotide assay method and polynucleotide complex

A target nucleotide sequence having a half-restriction site is determined in the nucleic acid of a biological sample. It is contacted with a reagent complex of:

Growing community of inventors

Robbinsville, NJ, United States of America

Jon I Williams