368 results about "Peptide conjugate" patented technology

The present invention relates to novel peptide conjugates which have increased stability and are useful in the treatment of excess levels of blood glucose.

The present invention provides novel, water-soluble, red-emitting fluorescent rhodamine dyes and red-emitting fluorescent energy-transfer dye pairs, as well as labeled conjugates comprising the same and methods for their use. The dyes, energy-transfer dye pairs and labeled conjugates are useful in a variety of aqueous-based applications, particularly in assays involving staining of cells, protein binding, and / or analysis of nucleic acids, such as hybridization assays and nucleic acid sequencing.

Cell-penetrating peptides useful for targeting a therapeutic compound to a selected mammalian tissue, methods for their identification, methods of forming conjugate compounds containing such peptides, and conjugates formed thereby are disclosed. The cell-penetrating peptides are 8 to 30 amino acid residues in length and consist of subsequences selected from the group consisting of RXR, RX, RB, and RBR; where R is arginine, B is β-alanine, and each X is independently —C(O)—(CHR1)n—NH—, where n is 4-6 and each R1 is independently H or methyl, such that at most two R1's are methyl. In one embodiment, X is a 6-aminohexanoic acid residue.

Methods and compositions for medical imaging, evaluating intracellular processes and components, radiotherapy of intracellular targets, and drug delivery by the use of novel cell membrane-permeant peptide conjugate coordination and covalent complexes having target cell specificity are provided. Kits for conjugating radionuclides and other metals to peptide coordination complexes are also provided.

Methods and compositions for medical imaging, evaluating intracellular processes and components, radiotherapy of intracellular targets, and drug delivery by the use of novel cell membrane-permeant peptide conjugate coordination and covalent complexes having target cell specificity are provided. Kits for conjugating radionuclides and other metals to peptide coordination complexes are also provided.

The invention provides cell penetrating peptide-nucleic acid conjugates having the formula P-L-N, wherein P is a cell penetrating peptide, N is a nucleic acid, preferably an oligonucleotide and more preferably a siRNA, and L is a hydrophilic polymer, preferably a polyethylene glycol (PEG)-based linker linking P and N together. Compositions, methods of use and methods for producing such conjugates are also disclosed.

The invention relates to peptide conjugates including at least one turn inducer wherein the turn inducer comprises a 5-7 membered saturated or unsaturated nitrogen containing heterocyclic ring and methods of making the peptides. Libraries of these peptides, methods of making the libraries are also described and methods of screening the libraries for therapeutic activity are also described.

The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates, toxin-(biocompatible polymer) conjugates, antibody-(biocompatible polymer) conjugates, and bispecific antibodies) comprising acyl donor glutamine-containing tags and amine donor agents. In one aspect, the invention provides an engineered Fc-containing polypeptide conjugate comprising the formula (Fc-containing polypeptide)-T-A, wherein T is an acyl donor glutamine-containing tag engineered at a specific site or comprises an endogenous glutamine made reactive by the Fc-containing polypeptide engineering, wherein A is an amine donor agent, and wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag or the endogenous glutamine. The invention also provides methods of making engineered polypeptide conjugates using transglutaminase.

The present invention provides polypeptide conjugates wherein a modifying group such as a water-soluble polymer, a therapeutic agent or a biomolecule is covalently linked to the polypeptide through a glycosyl linking group. In one embodiment, the polypeptide includes a glycosylation consensus sequence, wherein glycosylation occurs at an aromatic amino acid residue, such as the C-2 or the N-1 position of a tryptophan side chain. Exemplary polypeptides of the invention are those in which the glycosylation consensus sequence has been introduced into the amino acid sequence of the polypeptide by mutation. In another aspect the invention provides polypeptide conjugates wherein the modifying group is covalently linked to the polypeptide via a glycosyl mimetic linking group. Also provided are methods of making and using as well as pharmaceutical compositions containing the polypeptide conjugates of the invention. Further provided are methods of treating, ameliorating or preventing diseases in mammals by administering an amount of a polypeptide conjugate of the invention sufficient to achieve the desired response.

The invention includes methods and compositions for forming peptide conjugates intracellularly having a covalent linkage between a modifying group and a glycosylated or non-glycosylated peptide. The modifying group is conjugated to the peptide via a glycosyl linking group interposed between and covalently linked to both the peptide and the modifying group.

The present invention provides methods of administering an insulinotropic peptide in an amount effective to treat a disorder or condition while reducing nausea side effect by administering to a subject in need thereof an insulinotropic peptide conjugated to albumin. The present invention also provides methods of selecting a subject for administration of a conjugated insulinotropic peptide. Exemplary disorders or conditions treatable with an insulinotropic peptide include obesity and type II diabetes.

Methods and compositions for medical imaging, evaluating intracellular processes and components, radiotherapy of intracellular targets, and drug delivery by the use of novel cell membrane-permeant peptide conjugate coordination and covalent complexes having target cell specificity are provided. Kits for conjugating radionuclides and other metals to peptide coordination complexes are also provided.

Peptide conjugates in which cytocidal and cytostatic agents, such as polyamine analogs or naphthoquinones, are conjugated to a polypeptide recognized and cleaved by enzymes such as prostate-specific antigen (PSA) and cathepsin B are provided, as well as compositions comprising these conjugates. Methods of using these conjugates in the treatment of prostate diseases are also provided.

The present invention provides peptide conjugates that are formed between a modified lipid and a glycosyl residue and / or an amino acid residue on a peptide. The modified lipid includes a modifying group and a lipid linking group. Exemplary lipid linking groups include myristoyl, palmitoyl, and isoprenyl moieties.

The present invention provides processes for the manufacturing of polypeptide conjugates. In particular, the invention provides methods for the purification of polypeptide conjugates, which include at least one polymeric modifying groups, such as a poly(alkylene oxide) moiety. Exemplary poly(alkylene oxide) moieties include poly(ethylene glycol) (PEG) and poly(propylene glycol). In an exemplary process, hydrophobic interaction chromatography (HIC) is used to resolve different glycoforms of glycoPEGylated polypeptides.

The present invention provides sequon polypeptides with an amino acid sequence including one or more exogenous O-linked glycosylation sequence of the invention. In addition, the present invention provides methods of making polypeptide conjugates as well as methods of using such conjugates and their pharmaceutical compositions. The invention further provides libraries of sequon polypeptides, wherein each member of such library includes at least one exogenous O-linked glycosylation sequence of the invention. Also provided are methods of making and using such libraries.

The invention is directed to a pharmacologically active peptide conjugate having a reduced tendency towards enzymatic cleavage comprising a pharmacologically active peptide sequence (X) and a stabilising petide sequence (Z) of 4-20 amino acid residues covalently bound to X.

Heterodimeric polypeptide conjugates exhibiting FSH activity, comprising a dimeric polypeptide comprising an FSH-.alpha. subunit and an FSH-.beta. subunit, wherein at least one of the FSH-.alpha. and FSH-.beta. subunits differs from the corresponding wildtype subunit in that at least one amino acid residue acid residue comprising an attachment group for a non-polypeptide moiety has been introduced or removed, and having at least one non-polypeptide moiety bound to an attachment group of at least one of said subunits are provided. Preferably, at least one attachment group, e.g., an N- or O-glycosylation site or an attachment site for a polymer molecule such as polyethylene glycol, has been introduced, e.g., at an N-terminal. The polypeptide conjugates exhibit improved properties, in particular an increased half-life, compared to human FSH.

The present invention relates to a composition for treating obesity-related diseases comprising an insulinotropic peptide conjugate, more particularly, to a composition for treating obesity-related diseases comprising a conjugate prepared by covalently linking the insulinotropic peptide with a carrier substance via a non-peptidyl linker, and a method for treating obesity-related diseases by using the same. In particular, the composition for treating obesity-related diseases according to the present invention remarkably improves the efficacy of suppressing food intake and its duration to reduce body weight and body fat, thereby being useful for the treatment of obesity-related diseases.

Synthetic surfaces capable of supporting culture of undifferentiated human embryonic stem cells in a chemically defined medium include a swellable (meth)acrylate layer and a peptide conjugated to the swellable (meth)acrylate layer. The swellable (meth)acrylate layer may be formed by polymerizing monomers in a composition that includes hydroxyethyl methacrylate, 2-carboxyehylacrylate, and tetra(ethylene glycol) dimethacrylate. The conjugated peptide may include an amino acid sequence of XaanProGlnValThrArgGlyAspValPheThrMetPro, where n is an integer from 0 to 3 and where Xaa is any amino acid. Further, disclosed herein is a swellable (meth)acrylate synthetic surface which can be sterilized by gamma irradiation.

The invention includes methods and compositions for forming peptide conjugates intracellularly having a covalent linkage between a modifying group and a glycosylated or non-glycosylated peptide. The modifying group is conjugated to the peptide via a glycosyl linking group interposed between and covalently linked to both the peptide and the modifying group.

The present invention relates to an insulinotropic peptide conjugate having improved in-vivo duration of efficacy and stability, comprising an insulinotropic peptide, a non-peptide polymer and an immunoglobulin Fc region, which are covalently linked to each other, and a use of the same. The insulinotropic peptide conjugate of the present invention has the in-vivo activity which is maintained relatively high, and has remarkably increased blood half-life, and thus it can be desirably employed in the development of long acting formulations of various peptide drugs.

The present invention relates to a composition for the prevention or treatment of diabetes comprising a long-acting insulin conjugate and a long-acting insulinotropic peptide conjugate, and a therapeutic method for the treatment of diabetes, and more particularly, concurrent administration of the long-acting insulin conjugate and the long-acting insulinotropic peptide conjugate inhibits weight gain caused by insulin treatment, and vomiting and nausea caused by insulinotropic peptide treatment, and reduces the required dose of insulin, thereby remarkably improving drug compliance. Moreover, each of the long-acting insulin conjugate and the long-acting insulinotropic peptide conjugate of the present invention is prepared by linking insulin or insulinotropic peptide with an immunoglobulin Fc region via a non-peptidyl linker, thereby showing improved in-vivo duration of efficacy and stability.

The present invention provides covalent conjugates between a polypeptide and a modifying group, such as a water-soluble polymer (e.g., PEG). The amino acid sequence of the polypeptide includes one or more O-linked glycosylation sequence, each being a substrate for a GIcNAc transferase. The modifying group is covalently linked to the polypeptide via a glycosyl-linking group interposed between and covalently linked to both the polypeptide and the modifying group. In one embodiment, a glucosamine linking group is directly attached to an amino acid residue of the O-linked glycosylation sequence. The invention further provides methods of making polypeptide conjugates. The present invention also provides non-naturally occurring polypeptides that include at least one O-linked linked glycosylation sequence of the invention, wherein each glycosylation sequence is a substrate for a GIcNAc transferase. The invention further provides pharmaceutical compositions that include a polypeptide conjugate of the invention.

Dye-peptide conjugates useful for diagnostic imaging and therapy are disclosed. The dye-peptide conjugates include several cyanine dyes with a variety of bis- and tetrakis(carboxylic acid) homologues. The small size of the compounds allows more favorable delivery to tumor cells as compared to larger molecular weight imaging agents. The various dyes are useful over the range of 350-1300 nm, the exact range being dependent upon the particular dye. Use of dimethylsulfoxide helps to maintain the fluorescence of the compounds. The molecules of the invention are useful for diagnostic imaging and therapy, in endoscopic applications for the detection of tumors and other abnormalities and for localized therapy, for photoacoustic tumor imaging, detection and therapy, and for sonofluorescence tumor imaging, detection and therapy.

The present invention relates to a composition for treating obesity-related diseases comprising an insulinotropic peptide conjugate, more particularly, to a composition for treating obesity-related diseases comprising a conjugate prepared by covalently linking the insulinotropic peptide with a carrier substance via a non-peptidyl linker, and a method for treating obesity-related diseases by using the same. In particular, the composition for treating obesity-related diseases according to the present invention remarkably improves the efficacy of suppressing food intake and its duration to reduce body weight and body fat, thereby being useful for the treatment of obesity-related diseases.

Conformationally constrained peptides that mimic BH3-only proteins and their conjugation to antibodies and other cell targeting compounds, compositions containing the conjugates and their use in the regulation of cell death are disclosed. The conformationally constrained peptides are capable of binding to and neutralising pro-survival Bcl-2 proteins. Processes for preparing the conformationally constrained peptides conjugated to antibodies and other cell targeting compounds and use of the conjugates in the treatment and / or prophylaxis of diseases or conditions associated with deregulation of cell death are also disclosed.