652 results about "Amino terminal" patented technology

The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

This invention relates to compounds, compositions, and methods useful for modulating mitogen activated protein kinase (MAP kinase) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of MAP kinase gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of MAP kinase genes, such as Jun amino-terminal kinase (e.g., JNK-1, JNK-2), p38 (MAPK 14), ERK (e.g., ERK-1, ERK-2) and/or c-Jun.

Use of a growth hormone protein and polynucleotides encoding same comprising an amino-terminal carboxy-terminal peptide (CTP) of chorionic gonadotrophin and two carboxy-terminal chorionic gonadotrophin CTPs attached to the growth hormone in methods of inducing growth or weight gain, method of increasing insulin-like growth factor (IGF-1) levels, and methods of reducing the dosing frequency of a growth hormone in a human subject are disclosed. Pharmaceutical compositions comprising the growth hormone and polynucleotides encoding the growth hormone of the invention and methods of using same are also disclosed.

Nucleic acid sequences of truncated or mutated alternansucrases, vectors containing these nucleic acids sequences, host cells transformed with the nucleic acid sequences encoding truncated or mutated alternansucrases are provided. Furthermore, a process to recombinantly alternansucrase with a high level of expression, while retaining the enzymatic activity is described.

The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

The present invention provides modified therapeutic polypeptides or peptides partially or completely protected from DPP activity. The modified polypeptides or peptides comprise at least one additional amino acid at the amino terminus. The modified therapeutic polypeptides or peptides are useful in the treatment of diseases such as diabetes.

Disclosed are peptide agents and uses thereof that are analogs of biologically active peptides such as somatostatin and bombesin. The compounds of the invention have the general formula X-Y-Z-Q, where X is a cytotoxic agent, therapeutic agent, detectable label or chelating group, and Q is a biologically active peptide. In peptide agents of the invention Y is optionally a hydrophilic polymer or peptide, and Z is a linking peptide bonded to Q at the amino terminus of Q, having two, three, four, or five, amino acid residues selected to link X to Q, while retaining the biological activity of Q. Methods of using these peptide agents in the diagnosis and treatment of diseases are also disclosed.

The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGP's), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

The invention relates to targeted post translational modifi-cation of metallo-beta-lactamase by truncation and inser-tion of a dipeptide at the amino terminal end to reduce amino terminal heterogeneity in a recombinant DNA pro-duction system. A protein K-T-E-ΔBL is expressed, and modified by host proteases to E-ΔBL. Appropriate nucleotide molecules, vectors and hosts are also de-scribed. E-ΔBL is useful in a pharmaceutical composition for treating antibiotic induced adverse effects in the intes-tine of patients treated with beta-lactam antibiotics.

An immunoglobulin binding peptide having the general formula, from amino terminus to carboxy terminus, of Z-R¹—R²—R³—R⁴—R⁵—R⁶—X, is described, wherein: R¹ is H or Y; R² is a hydrophobic, preferentially aromatic, amino acid (for example W, F, Y, V); R³ is a positively charged or aromatic amino acid (for example R, H, F, W); R⁴ is a hydrophobic or positively charged amino acid (for example G, Y, R, K, L); R⁵ is a positively charged or aromatic amino acid (for example W, F, R, H, Y); R⁶ a random amino acid but preferably hydrophobic or negatively charged (for example V, W, L, D, H); X is present or absent and when present is a linking group; and Z is present or absent and when present is a capping group bonded to the N terminus of R¹; and wherein the amino acids of said peptide are in D form, L form, or a combination thereof. Methods of using such peptides for the purification of Immunoglobulins are also described

Antibodies or fragments thereof having CDR regions replaced or fused with biologically active peptides are described. Flanking sequences may optionally be attached at one or both the carboxy-terminal and amino-terminal ends of the peptide in covalent association with adjacent framework regions. Compositions containing such antibodies or fragments thereof are useful in therapeutic and diagnostic modalities.

An object of the present invention is to provide a novel protein having the following amino acid sequence altered for specifically and efficiently binding a protein to an immobilization carrier via the carboxy terminus. The protein is used for immobilizing a portion represented by R1-R2 on an immobilization carrier, comprising the amino acid sequence represented by the general formula R1-R2-R3-R4-R5 [wherein:

• • the sequences are oriented from the amino terminal side to the carboxy terminal side;
  • the sequence of the R1 portion is the sequence of a subject protein to be immobilized and contains neither a lysine residue nor a cysteine residue;
  • the sequence of the R2 portion may be absent, but when the sequence of the R2 portion is present, the sequence of the R2 portion is a spacer sequence composed of amino acid residues other than lysine and cysteine residues;
  • the sequence of the R3 portion is composed of two residues of amino acid represented by cysteine-X (where X denotes an amino acid residue other than lysine or cysteine);
  • the sequence of the R4 portion may be absent, but when the sequence of the R4 portion is present, the sequence of the R4 portion contains neither a lysine residue nor a cysteine residue, but contains an acidic amino acid residue capable of acidifying the isoelectric point of the entire protein comprising the amino acid sequence represented by the general formula R1-R2-R3-R4-R5; and
  • the sequence of an R5 portion is an affinity tag sequence for protein purification.

A means of measuring and monitoring skeletal growth rate using a plasma analyte, amino-terminal C-type natriuretic peptide (NT-CNP). Plasma NT-CNP concentrations reflect the potential for further growth of the immature skeleton. Measurement of plasma NT-CNP in a subject, when related to the mean of an appropriate age and gender matched set of control subjects, provides an index of the severity of a growth disorder not otherwise available and facilitates diagnosis in children with undetected osteo-chondrodysplasias or other intrinsic disorders of the growth plate. The invention also provides a means of detecting and monitoring potentially harmful effects of drugs and other factors on skeletal growth long before they are evident using current methods in clinical practice.

The present invention concerns a family of nucleic acids, polypeptides and cloning vectors which direct expression of fusion proteins that can mimic aggregated IgG (AIG) and immune complex function with respect to their interactions with FcγR and which allow for the inclusion and targeting of a second protein domain to cells expressing FcγR. This was accomplished by expressing multiple linear copies of the hinge and CH2 domains (HCH2) of human IgG₁ fused to the framework region of human IgG₁. Convenient restriction sites allow for the facile introduction of additional amino-terminal domains. Methods for treating patients using fusion proteins are also disclosed. The HCH2 polymers described here represent a new strategy in the design of recombinant proteins for the therapeutic targeting of FcγR in autoimmune disorders.

A method of treating chronic hepatitis B is disclosed that comprises administering a T cell-stimulating amount of a vaccine to a patient. The vaccine comprises an immunogenic amount of chimeric, carboxy-terminal truncated hepatitis B virus nucleocapsid (core) protein (HBc) that is engineered for both enhanced stability of self-assembled particles and the substantial absence of nucleic acid binding by those particles. The chimeric protein molecule can include one or more immunogenic epitopes peptide-bonded to one or more of the N-terminus, the immunogenic loop or the C-terminus of HBc. The enhanced stability of self-assembled particles is obtained by the presence of at least one heterologous cysteine residue near one or both of the amino-terminus and carboxy-terminus of the chimer molecule.

A single-chain probe of the present invention for detecting a ligand, comprises: a ligand binding protein for binding the ligand; a recognition protein for recognizing that the ligand is bound by the ligand binding protein; and C— and N-terminal fragments, generated by dissecting an enzyme, between the ligand binding protein and the recognition protein, wherein a carboxy terminal end of the C-terminal fragment is located upstream of an amino terminal end of the N-terminal fragment, and the C— and N-terminal fragments vary the enzyme activity via complementation in case where the recognition protein recognizes that the ligand is bound by the ligand binding protein. This makes it possible to achieve detection of a target protein-specific ligand using the single chain with a high efficiency.