Unigene Laboratories Inc.

Enteris Biopharma, Inc.

Ugp Therapeutics, Inc.

Resother Pharma Aps

Angelo P Consalvo

Nozer M Mehta

Christopher P Meenan

Martha V L Ray

William Stern

James P Gilligan

Mauro Perretti

Jesmond P Dalli

Jesmond Dalli

Martha V Ray

Duncan A Miller

Nozar M Mehta

Martha Vl Ray

Polypeptides having homology to regions of the N-terminal 50 residues of human Annexin 1 are provided for medical use as anti-inflammatory agents. Some of the polypeptides have homology to the N-terminal 48 residues of human Annexin 1, especially to residues 2-48 and 11-48 thereof. In some embodiments, properties of these compounds are improved by at least one modification at residues corresponding to residues 11, 22, 25 and/or 36 of human Annexin 1, and/or by C-terminal amidation of the polypeptide. Analogs of amino acids 2-26 of human Annexin 1, especially acetylated at the N-terminus and/or amidated at the C-terminus and having modifications at 11 and/or 22 are also disclosed for medical use as anti-inflammatory agents.

Anti-inflammatory pharmaceutical products

Acid-containing oral pharmaceutical compositions are provided wherein the pharmaceutical active agents are peptide compounds (i.e., those that include a plurality of amino acids and at least one peptide bond in their molecular structures). Certain barrier layers and/or particulate coated acid are used to reduce any adverse interactions that might otherwise occur between the acid of the compositions and other components of the composition. Use of these barrier layers and/or use of particulate coated acid is believed to promote a more simultaneous release of the components of the composition than is achieved by prior art acid-protection techniques, thus enhancing, and making more consistent, the bioavailability of the active peptide compounds.

Peptide pharmaceutical for oral delivery

Expression systems are disclosed for the direct expression of peptide products into the culture media where genetically engineered host cells are grown. High yield was achieved with a special selection of hosts, and/or fermentation processes which include careful control of cell growth rate, and use of an inducer during growth phase. Special universal cloning vectors are provided for the preparation of expression vectors which include control regions having multiple promoters linked operably with coding regions encoding a signal peptide upstream from a coding region encoding the peptide of interest. Multiple transcription cassettes are also used to increase yield. The production of amidated peptides using the expression systems is also disclosed.

Bacterial host cell for the direct expression of peptides

Cell lines are provided for expressing peptidylglycine alpha-amidating monooxygenase (PAM), or one of its two catalytic domains. High levels of enzyme expression are achieved while utilizing a non-animal source, low protein tissue culture medium. A robust two-step downstream purification results in high enzyme purity. Resulting PAM, or its PHM catalytic domain, is used to catalyze the enzymatic conversion of X-Gly to X-alpha-hydroxy-Gly or X&#x2014;NH(X being a peptide or any chemical compound having a carbonyl group to which a glycine group can be covalently attached). Methods of preparing preferred cell lines are also set forth.

Cell lines for expressing enzyme useful in the preparation of amidated products

Conversion in vitro of X-Gly to X-alpha-hydroxy-Gly or X-NH(X being a peptide or any other compound having a carbonyl group capable of forming a covalent bond with glycine) is accomplished enzymatically in the presence of keto acids, or salts or esters thereof, to provide a good yield without the necessity of catalase or similar enzymatic reaction enhancers. Peptidylglycine &#x3b1;-amidating monooxygenase (PAM) is a preferred enzyme for catalyzing the conversion. Alternatively, peptidylglycine &#x3b1;-hydroxylating monooxygenase (PHM) is utilized to convert X-Gly to X-alpha-hydroxy-Gly which may be recovered, or optionally may be simultaneously or sequentially converted to an amide by either a Lewis base or action of the enzyme peptidyl &#x3b1;-hydroxyglycine &#x3b1;-amidating lyase (PAL). Both PHM and PAL are functional domains of PAM.

Enzymatic reactions in the presence of keto acids

Expression systems are disclosed for the direct expression of peptide products into the culture media where genetically engineered host cells are grown. High yield was achieved with novel vectors, a special selection of hosts, and/or fermentation processes which include careful control of cell growth rate, and use of an inducer during growth phase. Special vectors are provided which include control regions having multiple promoters linked operably with coding regions encoding a signal peptide upstream from a coding region encoding the peptide of interest. Multiple transcription cassettes are also used to increase yield. The production of amidated peptides using the expression systems is also disclosed.

Growing community of inventors

Monroe, NY, United States of America

Angelo P Consalvo