Abstract: The present invention relates to an insulin analog that has reduced insulin receptor binding affinity for the purpose of increasing the blood half-life of insulin, and long-acting insulin, a conjugate, and a method of preparing long-acting insulin using the same.

Abstract: Novel photocleavable drug conjugates for forming drug depots comprise drugs attached to photocleavable groups. In one embodiment, the drug is linked via photocleavable group(s) to a polymer chain to form a photocleavable drug-polymer conjugate that generally forms the depot matrix. In another embodiment, the drug is crosslinked via photocleavable group(s) to themselves to form a photocleavable drug conjugate that generally forms the depot.

Abstract: The present invention provides methods for detecting insulin autoantibody. Such methods can be used, for example, to predict susceptibility of and/or diagnose the presence of Type 1 diabetes in a subject. Some aspects of the invention also provide kits adapted for use in such methods. In particular, some aspects of the invention use proinsulin to detect the presence of insulin autoantibody.

Abstract: The disclosure provides for peptide-based bolaamphiphile vectors that are capable of encapsulating a variety of agents, including peptides, proteins, nucleic acids, and drugs. The disclosure further provides for delivering these agents across biological membranes using the peptide-based bolaamphiphile vectors.

Abstract: An acylated insulin analogue wherein the insulin analogue comprises a lysine residue connected C-terminally to the A21 amino acid residue or a peptide residue of up to 4 amino acid residues comprising a lysine residue which peptide residue is connected C-terminally to the A21 amino acid residue, characterized in that an acyl moiety comprising an alkylene glycol moiety is attached to the lysine residue in the A22 position or attached to a lysine residue present in the peptide residue that is attached to the C terminal end of the A21 amino acid residue and wherein there is only one lysine (K, Lys) in the insulin analogue, can conveniently be administered pulmonary.

Abstract: The invention is related to a method for making human insulin analogs by culturing an fungi cell comprising a DNA vector encoding a precursor for human insulin analog, wherein the said precursor comprises a connecting peptide flanked with cleavage sites at both junctions with the A- and the B-chain of the insulin peptide, respectively said cleavage sites being cleaved within the fungi cell allowing the cell to secrete high amount of correctly processed, mature two chain human insulin analog to the culture media.

Abstract: Conjugates which comprise a drug and a ligand which includes a first saccharide; wherein the conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic or pharmacodynamic property of the conjugate is sensitive to serum concentration of a second saccharide. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

Abstract: The present invention relates to novel insulin analogues exhibiting resistance towards protease, wherein at least two amino acids are substituted and/or deleted relative to the parent insulin molecule. A method for the preparation of such insulin analogues, insulin preparations containing the insulin analogues of the invention and a method of treating diabetes mellitus using these insulin analogues is also provided.

Abstract: Novel PEGylated insulin analogs exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogs contain B25H and A14E or A14H. The PEGylation is at B29K.

Abstract: A pharmaceutical composition comprising a mixture of carboxylated oligopeptides, derived by hydrolysis of eukaryotic or prokaryotic cells and their subsequent partial carboxylation through acylation or alkylation of the amino acid and basic amino acid residues in the amino terminal structure of the oligopeptides. The resulting pharmaceutical composition can be used in production of medical drugs effective in the treatment of cancer, pancreatitis, viral infection, for the development of vaccines.

Abstract: The present invention relates to PEGylated C-peptide derivatives comprising at least one PEG group attached to the N-terminus, which exhibit improved pharmacokinetic and biological activity in vivo.

Abstract: Single chain insulin analogs are provided having high potency and specificity for the insulin receptor. As disclosed herein optimally sized linking moieties can be used to link human insulin A and B chains, or analogs or derivatives thereof, wherein the carboxy terminus of the B25 amino acid of the B chain is linked to the amino terminus of the A1 amino acid of the A chain via the intervening linking moiety. In on embodiment the linking moiety comprises a polyethylene glycol of 6-16 monomer units and in an alternative embodiment the linking moiety comprises a non-native amino acid sequence derived form the IGF-1 C-peptide and comprising at least 8 amino acids and no more than 12 amino acid in length. Also disclosed are prodrug and conjugate derivatives of the single chain insulin analogs.

Abstract: The present invention is related to human insulin containing additional disulfide bonds and methods of making such.

Abstract: The present invention is related to insulin derivatives containing additional disulfide bonds and methods of making such.

Abstract: The present invention is related to insulin derivatives having a side chain attached to an ?-amino group of a Lys residue present in the A-chain or to an ?-amino group of a Lys residue in the B-chain.

Abstract: An insulin analogue comprises a B-chain polypeptide incorporating a halogenated phenylalanine at position B24, B25 or B26. The halogenated phenylalanine may be ortho-monofluoro-phenylalanine, ortho-monobromo-phenylalanine, ortho-monochloro-phenylalanine, or para-monochloro-phenylalanine or penta-fluoro-Phenylalanine at position B24 alone or in combination with an acidic substitution (Aspartic Acid or Glutamic Acid) at position B10. The analogue may be of a mammalian insulin, such as human insulin. A nucleic acid encodes such an insulin analogue. The halogenated insulin analogues retain significant activity. A method of treating a patient comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient. Halogen substitution-based stabilization of insulin may enhance the treatment of diabetes mellitus in regions of the developing world lacking refrigeration.

Abstract: The present invention relates to human insulin analogues containing a substituting cysteine, to human insulin derivatives containing a PEGylated substituting cysteine and methods of making such. The compounds of the invention may be useful for the treatment of diabetes.

Abstract: New biosynthetic analogues of recombined human insulin of prolonged therapeutical activity, which can find place in prophylactic and treatment of diabetes.

Abstract: The invention is related to fast acting insulin analogues which can form soluble mix-tures (pre-mixed or self-mixed) with long acting insulin analogues. The fast action is achieved through monomerizing substitutions/deletions in the C-terminus of the B-chain of human insulin and the mixability with long acting insulin analogues is achieved through a substitution of the Zn-binding His in position B10 of human insulin with a Gln amino acid residue. In one embodiment the invention is related to fast acting insulin analogues in which at least one of the natural amino acid residues in position B22-B30 in the human B-chain has been substituted with another amino acid residue having the effect of promoting formation of the monomeric form of insulin, the His amino acid residue in position 10 in the B-chain is substituted with a Gln and wherein further one or more of the amino acid residues in position B22-B30 optionally have been deleted.

Abstract: The present invention provides therapeutic agents and compositions comprising elastin-like peptides (ELPs) and therapeutic proteins. In some embodiments, the therapeutic protein is a GLP-1 receptor agonist, insulin, or Factor VII/VIIa, including functional analogs. The present invention further provides encoding polynucleotides, as well as methods of making and using the therapeutic agents. The therapeutic agents have improvements in relation to their use as therapeutics, including, inter alia, one or more of half-life, clearance and/or persistence in the body, solubility, and bioavailability.

Abstract: Provided are methods for continuous subcutaneous insulin infusion (CSII) that employ a hyaluronan-degrading enzyme, including a recombinant human PH20 (rHuPH20). The methods can be used to more consistently control blood glucose during the course of CSII. The methods can be used to treat subjects having diabetes or other insulin-associated disease or condition.

Abstract: Insulin-like growth factor analogs are disclosed wherein substitution of the IGF native amino acids, at positions corresponding to positions B16 and B17 of native insulin, with tyrosine and leucine, respectively, increases potency of the resulting analog at the insulin receptor by tenfold. Also disclosed are prodrug and depot formulations of the IGF analogs, wherein the IGF analog has been modified by the linkage of a dipeptide to the analog through an amide bond linkage. The prodrug and depot formulations disclosed herein have extended half lives of at least 2 hours, 10 hours, and more typically greater than 2 are converted to the active form at physiological conditions through a non-enzymatic reaction driven by chemical instability.

Abstract: The invention relates to methods of inducing smooth muscle relaxation, for example, a method of inducing relaxation of a vascular or a non-vascular muscle or a method of inducing relaxation of the microvasculature, in a subject in need thereof by promoting the accumulation of protoporphyrin IX in the smooth muscle.

Abstract: The invention is related to fast acting insulin analogues which can form soluble mix-tures (pre-mixed or self-mixed) with long acting insulin analogues. The fast action is achieved through monomerizing substitutions/deletions in the C-terminus of the B-chain of human insulin and the mixability with long acting insulin analogues is achieved through a substitution of the Zn-binding His in position B10 of human insulin with a Gln amino acid residue. In one embodiment the invention is related to fast acting insulin analogues in which at least one of the natural amino acid residues in position B22-B30 in the human B-chain has been substituted with another amino acid residue having the effect of promoting formation of the monomeric form of insulin, the His amino acid residue in position 10 in the B-chain is substituted with a Gln and wherein further one or more of the amino acid residues in position B22-B30 optionally have been deleted.

Abstract: The present invention is related to fast acting single-chain insulin comprising a modified B-chain and the A-chain of human insulin or an analogue thereof connected by a connecting peptide wherein one or more of the amino acid residues in position B25, B26 or B27 in the human B-chain are Glu or Asp or are deleted and/or B28 is Glu, Asp, Lys or is deleted, and the amino acid residue in position B10 in the human insulin B-chain is Gln, Ala, Val, Thr or Ser. The invention is also related to pharmaceutical compositions being a mixture of the rapid acting single-chain insulin and the protracted acylated insulin.