Patent classifications
A61K38/03
Formulation for oral delivery of proteins, peptides and small molecules with poor permeability
The present disclosure is directed to a pharmaceutical formulation intended for oral delivery of synthetic or natural poorly permeable molecules or salts/solvates thereof having a therapeutic activity. The pharmaceutical formulation can include a synthetic or natural poorly permeable molecule or salt or solvate thereof in an amount 0.01-10 wt. % of the total weight of the formulation; a lipophilic phase comprising triglycerides of fatty acids in an amount of 50-80 wt. % of the total weight of the formulation; and at least one lipophilic surfactant comprising partial esters of polyol and fatty acids in an amount of about 10-50 wt. % of the total weight of the formulation.
METHODS FOR DISRUPTING BIOFILMS
The present invention provides methods for disrupting biofilms and/or preventing the formation of biofilms along with medical items that contain a coating or covering made of compositions for achieving such disruption or prevention. In particular, the compositions of the present invention provide random-sequence peptide mixtures for use in disrupting bacterial biofilms; the random-sequence peptides having hydrophobic and/or cationic amino acids, wherein the ratio of the total hydrophobic and cationic amino acids in the mixture is predefined.
METHODS FOR DISRUPTING BIOFILMS
The present invention provides methods for disrupting biofilms and/or preventing the formation of biofilms along with medical items that contain a coating or covering made of compositions for achieving such disruption or prevention. In particular, the compositions of the present invention provide random-sequence peptide mixtures for use in disrupting bacterial biofilms; the random-sequence peptides having hydrophobic and/or cationic amino acids, wherein the ratio of the total hydrophobic and cationic amino acids in the mixture is predefined.
PEPTIDOMIMETIC MACROCYCLES
Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.
PEPTIDOMIMETIC MACROCYCLES
Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.
Peptidic TGF-beta antagonists
The present invention provides peptidic TGF-β antagonists capable of inhibiting TGF-β signaling and disrupting the biochemical events that promote fibrosis and the epithelial-mesenchymal transition. The peptidic TGF-β antagonist may contain from 11 to 28 amino acid residues (for instance, may consist of from 12 to 16 amino acid residues) and may have the following structure (II):
NH.sub.2′ETWIWLDTNMG-Xaa.sub.1-Y′COOH (II)
wherein Xaa.sub.1 is any amino acid and Y is a peptide having from 0 to 9 amino acids. The peptidic TGF-β antagonists can advantageously be used for the prevention, treatment, and/or alleviation of the symptoms of a condition associated with an increase in TGF-β activity, including fibrosis (such as fibrosis of the skin, liver, lungs, and heart, among others) and cancer (including various carcinomas, such as squamous cell carcinoma, sarcomas, and metastatic cancers).
Peptidic TGF-beta antagonists
The present invention provides peptidic TGF-β antagonists capable of inhibiting TGF-β signaling and disrupting the biochemical events that promote fibrosis and the epithelial-mesenchymal transition. The peptidic TGF-β antagonist may contain from 11 to 28 amino acid residues (for instance, may consist of from 12 to 16 amino acid residues) and may have the following structure (II):
NH.sub.2′ETWIWLDTNMG-Xaa.sub.1-Y′COOH (II)
wherein Xaa.sub.1 is any amino acid and Y is a peptide having from 0 to 9 amino acids. The peptidic TGF-β antagonists can advantageously be used for the prevention, treatment, and/or alleviation of the symptoms of a condition associated with an increase in TGF-β activity, including fibrosis (such as fibrosis of the skin, liver, lungs, and heart, among others) and cancer (including various carcinomas, such as squamous cell carcinoma, sarcomas, and metastatic cancers).
PEPTIDES DERIVED FROM KITA-KYUSHU LUNG CANCER ANTIGEN (KKLC1, CT83, CXORF61) AND COMPLEXES COMPRISING SUCH PEPTIDES BOUND TO MHC MOLECULES
The present invention relates to novel peptides derived from Kita-kyushu lung cancer antigen 1 (CT83), complexes comprising such peptides bound to recombinant MHC molecules, and cells presenting said peptide in complex with MHC molecules. Also provided by the present invention are binding moieties that bind to the peptides and/or complexes of the invention. Such moieties are useful for the development of immunotherapeutic reagents for the treatment of diseases such as cancer.
PEPTIDES DERIVED FROM KITA-KYUSHU LUNG CANCER ANTIGEN (KKLC1, CT83, CXORF61) AND COMPLEXES COMPRISING SUCH PEPTIDES BOUND TO MHC MOLECULES
The present invention relates to novel peptides derived from Kita-kyushu lung cancer antigen 1 (CT83), complexes comprising such peptides bound to recombinant MHC molecules, and cells presenting said peptide in complex with MHC molecules. Also provided by the present invention are binding moieties that bind to the peptides and/or complexes of the invention. Such moieties are useful for the development of immunotherapeutic reagents for the treatment of diseases such as cancer.
METHODS FOR PREVENTING OR TREATING MITOCHONDRIAL PERMEABILITY TRANSITION
The invention provides a method of reducing or preventing mitochondrial permeability transitioning. The method comprises administering an effective amount of an aromatic-cationic peptide having at least one net positive charge; a minimum of four amino acids; a maximum of about twenty amino acids; a relationship between the minimum number of net positive charges (p.sub.m) and the total number of amino acid residues (r) wherein 3p.sub.m is the largest number that is less than or equal to r+1; and a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (p.sub.t) wherein 2 a is the largest number that is less than or equal to p.sub.t+1, except that when a is 1, p.sub.t may also be 1.