Abstract: The present invention provides antisera that specifically recognize peptides containing methylated arginines. The present invention also provides peptides for producing the antisera. Also provided is a method for the detection of methylation status of proteins and peptides, and compositions that affect the methylation status.

Abstract: A stable, aqueous insulin formulation suitable for pulmonary delivery is disclosed. The formulation has increased convenience for the patient and improved bioavailability of insulin.

Abstract: The present invention relates to insulin derivatives in which a lipophilic group having from 12 to 40 carbon atoms is attached to the &agr;-amino group of the N-terminal amino acid in the B-chain or to the carboxy group of the C-terminal amino acid in the B-chain have a protracted profile of action.

Abstract: Disclosed is a method for producing seeding microcrystals for the production of human insulin, the microcrystals being free of non-human pancreatic insulin, the method comprising providing an unseeded suspension of human insulin, the suspension being free of non-human pancreatic insulin, and homogenizing the insulin suspension under pressure to result in human insulin microcrystals suitable for use as seeding microcrystals for the production of zinc insulin products. The method of homogenization under pressure may also be used for the production of seeding mnicrocrystals for other peptides and proteins, in particular pharmaceutical peptides or proteins such as insulin, GLP-1, glucagon and growth hormones.

Abstract: The present invention provides a monomeric insulin analog formulation stabilized against aggregation in which the buffering agent is either TRIS or arginine. The stable formulations of the present invention are useful for treating diabetes, and are particularly advantageous in treatment regimes requiring lengthy chemical and physical stability, such as, in continuous infusion systems.

Abstract: The present invention relates to insoluble compositions comprising a protein selected from the group consisting of insulin, insulin analogs, and proinsulins; a derivatized protein selected from the group consisting of derivatized insulin, derivatized insulin analog, and derivatized proinsulin; a complexing compound; a hexamer-stabilizing compound; and a divalent metal cation. Formulations of the insoluble composition are suitable for both parenteral and non-parenteral delivery for treating hyperglycemia and diabetes. Microcrystal forms of the insoluble precipitate are pharmaceutically analogous to the neutral protamine Hagedorn (NPH) insulin crystal form. Surprisingly, it has been discovered that suspension formulations of such insoluble compositions possess unique and controllable dissolution properties that provide therapeutically advantageous glucodynamics compared with insulin NPH formulations.

Abstract: Large cobalt and nickel complexes that may be linked to antibodies and other molecules are described. These may be useful in applications benefiting from their magnetic properties.

Abstract: The present invention is directed to a composition which is used to enhance the elasticity and/or appearance of tissue. Specifically, the present invention is directed to a composition formulated from peptides having low molecular weights and which substantially correspond to sequences found in elastin More preferably, the present invention corresponds to the general formula R1-Leucine-Glycine-Alanine-Glycine-Glycine-Alanine-Glycine-R2.

Abstract: Stable, aqueous insulin formulations without phenol and m-cresol which are suitable for pulmonary delivery and for delivery when phenol and m-cresol are undesirable are disclosed. The formulations provide increased convenience for the patient.

Abstract: The present invention relates to insoluble compositions containing acylated proteins selected from the group consisting of acylated insulin, acylated insulin analog, and acylated proinsulin, and formulations thereof. The formulations are suitable for parenteral delivery or other means of delivery, to a patient for extended control of blood glucose levels. More particularly, the present invention relates to compositions comprised of an acylated protein complexed with zinc, protamine, and a phenolic compound such that the resulting microcrystal is analogous to the neutral protamine Hagedorn (NPH) insulin crystal form. Surprisingly, it has been discovered that compositions of such acylated proteins have therapeutically superior subcutaneous release pharmacokinetics, and more extended and flatter glucodynamics, than presently available commercial preparations of NPH insulin.

Abstract: The present invention relates-to protracted acting, water-soluble aggregates of derivatives of human insulin, derivatives of human insulin capable of forming such aggregates, pharmaceutical compositions containing them, and to the use of such aggregates in the treatment of diabetes.

Abstract: This invention is directed to cytochrome c551 polypeptides and polynucleotides encoding the polypeptides.

Abstract: The present invention relates to a process for the preparation of a product of blood coagulation factors II, VII, IX and X which is virtually free of virus, the process comprising heating an aqueous liquid containing these factors in the presence of calcium ions and a chelating agent and, optionally, an amino acid, a saccharide or sugar alcohol, antithrombin III and/or heparin. The product can be used for the treatment of blood coagulation disorders.

Abstract: The present invention relates to insoluble compositions containing acylated proteins selected from the group consisting of acylated insulin, acylated insulin analog, and acylated proinsulin, and formulations thereof. The formulations are suitable for parenteral delivery or other means of delivery, to a patient for extended control of blood glucose levels. More particularly, the present invention relates to compositions comprised of an acylated protein complexed with zinc, protamine, and a phenolic compound such that the resulting microcrystal is analogous to the neutral protamine Hagedorn (NPH) insulin crystal form. Surprisingly, it has been discovered that compositions of such acylated proteins have therapeutically superior subcutaneous release pharmacokinetics, and more extended and flatter glucodynamics, than presently available commercial preparations of NPH insulin.

Abstract: The present invention relates to insulin derivatives in which a lipophilic group having from 12 to 40 carbon atoms is attached to the &agr;-amino group of the N-terminal amino acid in the B-chain or to the carboxy group of the C-terminal amino acid in the B-chain have a protracted profile of action.

Abstract: Insulin derivatives with increased zinc binding where Z is a histidine residue or a peptide having 2 to 35 genetically encodable amino acid residues, having 1 to 5 histidine residues, are suitable for the production of pharmaceutical preparations for the treatment of diabetes. Insulins of the formula I form complexes with zinc++, comprising an insulin hexamer and approximately 5 to 9 mol of zinc++ per hexamer.

Abstract: An aqueous insulin composition with improved chemical and physical stability comprising human insulin or an analogue or derivative thereof, a buffer selected from glycylglycine, citrate or TRIS, in particular glycylglycine, and metal ions, in particular calcium or magnesium ions.

Abstract: Divalent cation crystals of human growth factor (hGH) or derivatives thereof, and pharmaceutical preparations comprising divalent cation crystals of hGH. In specific embodiments, the divalent cation is Zn++ and the molar ration Zn++ and hGH is about 0.2 to about 10.

Abstract: New insulin derivatives of the formula II with an iso-electric point between 5 and 8.5, with improved stability in weakly acid aqueous medium and with a special action profile, and the physiologically tolerated salts of these insulin derivatives, for the treatment of diabetes mellitus; formula II is: ##STR1## in which R.sup.1 denotes H or H-Phe,R.sup.2 denotes a genetically encodable L-amino acid which contains no amide group,R.sup.30 represents the residue of a neutral genetically encodable L-amino acid,R.sup.31 represents a physiologically acceptable organic group which is basic in nature and has up to 50 carbon atoms, in whose structure 0 to 3 .alpha.-amino acids are involved and whose terminal carboxyl group which is present where appropriate can be free, in the form of an ester functionality, an amide functionality, a lactone or reduced to CH.sub.2 0H, andX represents a genetically encodable L-amino acid.

Abstract: A chemical complex comprising divalent metal ions, preferably Ca.sup.+2 ions, and peptide-peptoid trimers in a fixed ratio and having a centrosymmetric crystalline structure wherein three divalent metal ions at the interior of the complex are coordinated with the peptide carboxylate and urethane oxygen atoms. The globular complex has a hydrophobic outer surface and is useful as an ionophore.

Abstract: The invention relates to libraries of synthetic test compound attached to separate phase synthesis supports. In particular, the invention relates to libraries of synthetic test compound attached to separate phase synthesis supports that also contain coding molecules that encode the structure of the synthetic test compound. The molecules may be polymers or multiple nonpolymeric molecules. Each of the solid phase synthesis support beads contains a single type of synthetic test compound. The synthetic test compound can have backbone structures with linkages such as amide, urea, carbamate (i.e., urethane), ester, amino, sulfide, disulfide, or carbon--carbon, such as alkane and alkene, or any combination thereof. Examples of subunits suited for the different linkage chemistries are provided.

Abstract: The present invention provides a monomeric insulin analog formulation stabilized against aggregation in which the buffering agent is either TRIS or arginine. The stable formulations of the present invention are useful for treating diabetes, and are particularly advantageous in treatment regimes requiring lengthy chemical and physical stability, such as, in continuous infusion systems.

Abstract: This invention provides a method for treating a condition associated with oxidative stress in a subject which comprises administering to the subject an amount of a heme-peptide effective to treat the condition associated with oxidative stress in the subject. The subject may be a mammal. The mammal may be a human being. The condition associated with oxidative stress may be an inflammatory condition, an allergic condition or an auto-immune condition.

Abstract: The present invention relates to protracted human insulin derivatives in which the A21 and the B3 amino acid residues are, independently, any amino acid residue which can be coded for by the genetic code except Lys, Arg and Cys; Phe.sup.B1 may be deleted; the B30 amino acid residue is (a) a non-codable, lipophilic amino acid having from 10 to 24 carbon atoms, in which case an acyl group of a carboxylic acid with up to 5 carbon atoms is bound to the .epsilon.-amino group of Lys.sup.B29 ; or (b) the B30 amino acid residue is deleted or is any amino acid residue which can be coded for by the genetic code except Lys, Arg and Cys, in any of which cases the .epsilon.-amino group of Lys.sup.B29 has a lipophilic substituent; and any Zn.sup.2+ complexes thereof with the proviso that when B30 is Thr or Ala and A21 and B3 are both Asn, and Phe.sup.B1 is present, then the insulin derivative is always present as a Zn.sup.2+ complex.

Abstract: The present invention provides a method of treating or preventing the clinical manifestation of an autoimmune disease having the symptoms of uveoretinitis in a mammal in need of such treatment comprising orally administering to said mammal an effective amount of an autoantigen, e.g., S antigen (S-Ag), and/or biologically active fragments, or analogs thereof specific for uveoretinitis.Also provided is a pharmaceutical formulation useful for treating or preventing uveoretinitis in mammals comprising an effective amount of one or more of the foregoing autoantigen, fragments or analogs.

Abstract: The present invention provides a human metallothionein (HMBP-I) and polynucleotides which identify and encode HMBP-I. The invention also provides genetically engineered expression vectors and host cells comprising the nucleic acid sequences encoding HMBP-I and a method for producing HMBP-I. The invention also provides for agonists, antibodies, or antagonists specifically binding HMBP-I, and their use, in the prevention and treatment of diseases associated with expression of HMBP-I. Additionally, the invention provides for the use of antisense molecules to polynucleotides encoding HMBP-I for the treatment of diseases associated with the expression of HMBP-I. The invention also provides diagnostic assays which utilize the polynucleotide, or fragments or the complement thereof, and antibodies specifically binding HMBP-I.

Abstract: The present invention relates to a process for preparing human proinsulin which is represented as a following chemical formula(I): ##STR1## wherein, R is an amino acid residue or a peptide which is degradable enzymatically or chemically; and, X is a linkage of an amino group of A-1 in insulin A chain and a carboxyl group of B-30 in insulin B chain which can be separated from the A chain or the B chain enzymatically or chemically, provided that a region from A-1 to A-21 is the insulin A chain and a region from B-1 to B-30 is the insulin B chain. In accordance with the present invention, human recombinant insulin precursor can be simply manufactured with a good reproducibility, since dissolution, sulfonation, concentration, desalting and purification are remarkably simplified, while increasing the yield of refolding reaction.

Abstract: The present invention relates to the field of diabetes. More particularly, the invention relates to a monomeric insulin analog wherein the A chain is the naturally occurring sequence of the human insulin A chain and the B chain is modified at either position B28 and B29 or both. The analog is mono-acylated at the N-terminal of the A chain or B chain or at the lysine. The acylated insulin analogs have an extended duration of action.

Abstract: This invention relates to a radiodiagnostic agent to image arterial and venous thrombi, pulmonary emboli and lesions of atherosclerosis. A composition for a thrombus imaging agent, a method and kit for preparing a thrombus imaging agent, and a radiolabeling reagent for preparing the thrombus imaging agent are provided. Methods of using the thrombus imaging agent to detect thrombi are also provided.

Abstract: Insulin preparations of superior chemical stability, comprising human insulin or an analogue or derivative thereof, glycerol and/or mannitol, and 5 to 100 mM of a halogenide are disclosed.

Abstract: The present invention relates to insulin crystals comprising ASP.sup.B28 and protamine, and pharmaceutical preparations containing same. The crystals and preparations exhibit rapid onset and prolonged activity when administered in vivo.

Abstract: The present invention relates to insulin crystals comprising ASP.sup.B28 and protamine, and pharmaceutical preparations containing same, The crystals and preparations exhibit rapid onset and prolonged activity when administered in vivo.

Abstract: Insulin formulations containing ligands for the insulin hexamer which bind several orders of magnitude more tightly to the hexamer than chlorine ion or acetate ion. These ligands are aliphatic and aromatic carboxylates having a dissociation constant (K.sub.D) of less than about 5 mM, and preferably less than about 1 mM. The increased tightness of binding conveys additional stability to the insulin hexamers, improving their usefulness in slow release and fast acting formulations (for example, for the treatment of diabetics).

Abstract: Methods and devices for dissociating multimeric proteins and their delivery to patients, along with resultant compositions, are provided. A monomeric protein delivery device is also provided, comprising a supply of a multimeric protein 4, complex, comprising multimeric protein and an aggregating agent; a flow path having a subcutaneous exit 8, fluidly coupling the multimeric protein supply to the exit; a porous surface assembly situated along the flow path comprising a porous surface 10; and an aggregating agent binding partner carried by the surface 12; whereby the aggregating agent of the multimeric protein complex passing along the surface is bound to the binding partner on the surface to create a monomeric protein flow through the subcutaneous exit.

Abstract: A method of producing chemically stable and biologically active growth hormone crystals and processes for production of pharmaceutical preparations containing these growth hormone crystals.

Abstract: Somatostatin peptides bearing at least one chelating group for a detectable element, said chelating group being linked to an amino group of said peptide, and said amino group having no significant binding affinity for somatostatin receptors, in free or salt form, are complexed with a detectable element and are useful as a pharmaceutical, e.g. a radiopharmaceutical for in vivo imaging of somatostatin receptor positive tumors or for therapy.

Abstract: Peptide derivatives usable as zinc endopeptidase 24-15 inhibitors.These peptide derivatives have the following amino acid sequence:-Phe.psi.(PO.sub.2 CH.sub.2)-.sub.(L,D) Xaa'-Yaa'-Zaa'-in which .psi.(PO.sub.2 CH.sub.2) indicates that the peptide bond (CONH) has been replaced by the phosphine bond (PO.sub.2 CH.sub.2), Xaa' and Zaa', which can be the same or different, in each case represent a natural amino acid or an amino pseudo-acid and Yaa' represents Arg or Lys.As examples of such derivatives, reference can be made to those of formula:Z-.sub.(L,D) Phe.psi.(PO.sub.2 CH.sub.2)-.sub.(L,D) -Gly-Arg-MetOHZ-.sub.(L,D) Phe.psi.(PO.sub.2 CH.sub.2)-.sub.(L,D) -Ala-Arg-MetOHZ-.sub.(L,D) Phe.psi.(PO.sub.2 CH.sub.2)-.sub.(L,D) -Ala-Arg-PheOHwith Z representing the benzyloxycarbonyl group.

Abstract: Somatostatin peptides bearing at least one chelating group for a detectable element, said chelating group being linked to an amino group of said peptide, and said amino group having no significant binding affinity for somatostatin receptors, in free or salt form, are complexed with a detectable element and are useful as a pharmaceutical, e.g. a radiopharmaceutical for in vivo imaging of somatostatin receptor positive tumors or for therapy.

Abstract: The present invention relates to human insulin derivatives having a protracted profile of action in which the A21 and B3 amino acid residues are, independently, any amino acid residue which can be coded for by the genetic code except Lys, Arg and Cys; Phe.sup.B1 may be deleted; the B30 amino acid residue is (a) a non-codable, lipophilic amino acid having from 10 to 24 carbon atoms in which case an acyl group of a carboxylic acid with up to 5 carbon atoms is bound to the E-amino group of Lys.sup.B29 ; (b) any amino acid residue which can be coded by the genetic code except Lys, Arg and Cys, in which case a lipophilic substituent is bound to the E-amino group of Lys.sup.B29 ; or (c) deleted, in which case a lipophilic substituent is bound to the E-amino group of LyS.sup.B29 ; and any Zn.sup.2+ complexes thereof; provided that when the B30 amino acid residue is Thr or Ala, the A21 and B3 amino acid residues are both Asn and Phe.sup.B1 is present, then the insulin derivative is a Zn.sup.2 + complex.

Abstract: The invention relates to a stabilized feed additive, more particularly containing zinc bacitracin, and processes for the preparation thereof.

Abstract: The present invention discloses various parenteral pharmaceutical formulations, which comprise: a monomeric insulin analog, zinc, protamine, and phenolic derivative. The analog formulations provide a prolonged duration of action. A process for preparing insulin analog-protamine formulations is also described.

Abstract: New insulin derivatives, the use thereof, and a pharmaceutical composition containing themInsulin derivatives having an isoelectric point between 5 and 8.5, or physiologically tolerated salts thereof, of the Formula II ##STR1## in which: R.sup.1 at position B1 denotes H or H-Phe;R.sup.2 at position A21 denotes a genetically encodable L-amino acid selected from the group consisting of Gly, Ala, Val, Leu, Ile, Pro, Phe, Trp, Met, Ser, Thr, Cys, Tyr, Asp, and Glu;R.sup.30 represents the residue of a neutral genetically encodable L-amino acid selected from the group consisting of Ala, Thr, and Ser;R.sup.31 represents 1, 2, or 3 neutral or basic alpha amino acids, wherein at least one of the alpha amino acids is selected from the group consisting of Arg, Lys, Hyl, Orn, Cit, and His;X represents His at position B10; andthe sequences A1 to A20 and B1 to B29 in Formula II correspond to a mammalian insulin;excluding those insulin derivatives in which simultaneously:R.sup.1 at position B1 denotes Phe; andR.sup.

Abstract: The present invention discloses various parenteral pharmaceutical formulations, which comprise: a monomeric insulin analog, zinc, protamine, and phenolic derivative. The analog formulations provide a prolonged duration of action. A process for preparing insulin analog-protamine formulations is also described.

Abstract: Methods and reagents for the in vivo tagging of leukocytes, and in particular lymphocytes, with a leukostimulatory agent and a linked medically useful metal ion, including a radioisotope, and subsequent detection of leukocyte or lymphocyte trafficking and sites of concentrated leukocytes or lymphocytes within the patient by radiodetection or paramagnetic means are disclosed.

Abstract: A process is described for obtaining insulin, which is virtually free from proteases and/or insulin acetylated at position A9, by chromatography in aqueous, buffered solvents which contain water-miscible organic solvents, on lipophilically modified silica gel, wherein the dissolving buffer contains acetone or acetonitrile.

Abstract: The present invention discloses a process of preparing a crystalline alkali metal or ammonium salt of Lys.sup.B28 Pro.sup.B29 -human insulin. The process is useful in the purification and manufacture of Lys.sup.B28 Pro.sup.B29 -human insulin. Lys.sup.B28 Pro.sup.B29 -human insulin is useful in the treatment of diabetes.

Abstract: Analogs of human insulin containing an aspartic acid at position 1 of the B chain (Asp.sup.B1), and optionally, having a gln modification at position 13 (Gln.sup.B13), display modified physico-chemical and pharmacokinetic properties which enable them to be long acting. These analogs are useful in the treatment of hyperglycemia because they are soluble and display an increased tendency to self-associate.

Abstract: The present invention discloses various parenteral pharmaceutical formulations, which comprise a mixture of a monomeric insulin analog and insulin-NPH. The analog formulations provide a rapid onset and a prolonged duration of action.

Abstract: The present invention relates to insulin crystals comprising ASP.sup.B28 and protamine, and pharmaceutical preparations containing same. The crystals and preparations exhibit rapid onset and prolonged activity when administered in vivo.

Abstract: Peptide-copper complexes are disclosed which stimulate the growth of hair on warm-blooded animals. In one aspect of this invention, the peptide-copper complexes are dipeptides or tripeptides chelated to copper at a molar ratio ranging from about 1:1 to 3:1, with the second position of the peptide from the amino terminus being histidine, arginine or a derivative thereof. The peptide-copper complexes may be formulated for administration by, for example, topical application or injection. Any affliction associate with hair loss, including hair loss associated with both androgenetic and secondary alopecia, may be treated with the peptide-copper complexes of this invention.