The General Hospital Corporation

Chugai Pharmaceutical Co.

Bristol-myers Squibb Compnay

Chugai Seiyaku Kabushiki Kaisha

John T Potts, Jr

Thomas J Gardella

Henry M Kronenberg

Harald T Juppner

Harald Jüppner

Abdul-Badi Abou-Samra

Ernestina Schipani

Gino V Segre

Naoto Shimizu

F Richard Bringhurst

Hisashi Takasu

Makoto Okazaki

Mark C Poznansky

Masaru Shimizu

Fabrizio Vianello

Fumihiko Ichikawa

Natalia Papeta

David M Slovik

Robert M Neer

Harald J&uuml;ppner

Michael Rosenblatt

Harald Jueppner

This invention provides methods and compositions for modulating movement of eukaryotic cells with migratory capacity. More specifically, the invention provides anti-fugetactic agents and methods for the use thereof in enhancing an immune response.

Antifugetactic agents for the treatment of cancers

Anti-fugetactic agents for the treatment of ovarian cancer

Disclosed are two PTH analog ligands, SP-PTH-AAK and Aib-SP-PTH-AAK, that have long-acting activity at the PTH receptor, as demonstrated both in vitro and in vivo. These polypeptides are thus particularly useful in the treatment of diseases, such as hypoparathyroidism, in which long-acting activity is desired. The method of making the analog polypeptides is also disclosed.

Parathyroid hormone analogs and uses thereof

The present invention provides screening methods for GPCRs based on the discovery that the affinity of a receptor agonist for a GPCR (such as the parathyroid hormone receptor) when not bound to a G-protein is correlated with the length of time over which the agonist is effective, independently of its pharmacokinetic properties. The invention also provides PTH- and PTHrP-derived polypeptides.

Screening methods using G-protein coupled receptors and related compositions

The present invention relates to conformationally constrained parathyroid hormone (PTH) analogs, and methods of preparing and using the PTH analogs. The invention provides novel PTH polypeptide derivatives containing amino acid substitutions at selected positions in the polypeptides. The invention provides derivatives of PTH(1-34), PTH(1-21), PTH(1-20), PTH(1-19), PTH(1-18), PTH(1-17), PTH(1-16), PTH(1-15), PTH(1-14), PTH(1-13), PTH(1-12), PTH(1-11), and PTH(1-10) polypeptides, wherein at least one residue in each polypeptide is a helix, preferably an &#x3b1;-helix, stabilizing residue. The invention also provides methods of making such peptides. Further, the invention encompasses compositions and methods for use in limiting undesired bone loss in a vertebrate at risk of such bone loss, in treating conditions that are characterized by undesired bone loss or by the need for bone growth, e.g., in treating fractures or cartilage disorders and for raising cAMP levels in cells where deemed necessary.

Conformationally constrained parathyroid hormone (PTH) analogs

Novel parathyroid hormone (PTH) polypeptide derivatives are disclosed, as are pharmaceutical compositions containing said polypeptides, and synthetic and recombinant methods for producing said polypeptides. Also disclosed are methods for treating mammalian conditions characterized by decreases in bone mass using therapeutically effective pharmaceutical compositions containing said polypeptides. Also disclosed are methods for screening candidate compounds of the invention for antagonistic or agonistic effects on parathyroid hormone receptor action. Also disclosed are diagnostic and therapeutic methods of said compounds.

Polypeptide derivatives of parathyroid hormone (PTH)

The present invention is related to novel parathyroid hormone polypeptide derivatives, and to pharmaceutical composition containing the polypeptides, as well as synthetic and recombinant methods for producing the polypeptides. Also disclosed are methods for treating mammalian conditions characterized by decreases in bone mass using therapeutically effective pharmaceutical compositions containing the polypeptides of the present invention. The present invention further provides diagnostic and therapeutic methods using the polypeptide derivatives.

Novel parathyroid hormone peptide (PTH) and parathyroid hormone related peptide (PTHrP) or derivatives thereof which are biologically active are disclosed, as are pharmaceutical compositions containing such peptides, and synthetic and recombinant methods for producing such peptides. Also disclosed are methods for treating mammalian conditions characterized by decreases in bone mass using therapeutically effective pharmaceutical compositions containing such peptides. Also disclosed are methods for screening candidate compounds of the invention for antagonistic or agonistic effects on parathyroid hormone receptor action. Also disclosed are diagnostic and therapeutic methods of such compounds.

Bioactive peptides and peptide derivatives of parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP)

The invention provides novel P1R polypeptide antagonists. These antagonists contain amino acid substitutions at selected positions in truncated PTH and PRHrP polypeptides and function by binding selectively to the juxtamembrane ('J') domain of the receptor. The J domain is the region of the receptor that spans the seven transmembrane domain and the extracellular loops.

Conformationally constrained parthyroid hormone (PTH) analogs

The present invention relates to conformationally constrained parathyroid hormone (PTH) analogs and derivatives of those analogs. The invention also provides methods of preparing and using the PTH analogs. Further, the invention encompasses compositions and methods for use in limiting undesired bone loss in a vertebrate at risk of such bone loss, in treating conditions that are characterized by undesired bone loss or by the need for bone growth, e.g. in treating fractures or cartilage disorders and for raising camp levels in cells where deemed necessary.

Conformationally constrained parathyroid hormones with alpha-helix stabilizers

The present invention is related to synthetic and/or recombinant biologically active peptide derivatives of PTH(1-28). Some of the peptides of the invention are at least 90% identical to a peptide consisting essentially of the amino acid sequence XValSerGluIleGlnLeuMetHis AsnLeuGlyLysHisLeuAsnSer MetXArgValGluTrpLeuArgLysLysLeu (SEQ ID NO:1), wherein Xis Ser, Ala or Gly; and Xis Glu or Arg.

Human parathyroid hormone modifications, preparation and use

Parathyroid hormone(PTH) polypeptide derivatives are disclosed, as are pharmaceutical compositions containing said polypeptides, and synthetic and recombinant methods for producing said polypeptides. Also disclosed are methods for treating mammalian conditions characterized by decreases in bone mass using therapeutically effective pharmaceutical compositions containing said polypeptides. Also disclosed are methods for screening candidate compounds of the invention for antagonistic or agonistic effects on parathyroid hormone receptor action. Also disclosed are diagnostic and therapeutic methods of said compounds.

Nucleic acids encoding parathyroid hormone (PTH) derivatives

Novel parathyroid hormone (PTH) peptides and analogs thereof of the PTH(1&#x2013;34) fragment are disclosed that combine the N-terminal signaling domain (residues 1&#x2013;9) and the C-terminal binding domain (residues 15&#x2013;31) via a linker. Nucleic acid molecules and peptides for PTH(1&#x2013;9)-(Gly)5-PTH(15&#x2013;31) (PG5) and PTH(1&#x2013;9)-(Gly)7-PTH(15&#x2013;31) and a novel PTH receptor are disclosed. Additionally, methods of screening for PTH agonists, pharmaceutical compositions and methods of treatment are disclosed.

Nucleic acids encoding PTH functional domain conjugate peptides

The invention provides a novel PTH receptor polypeptide, r&#x394;Nt, characterized by a deletion of the extracellular amino-terminus, ligand binding domain of the receptor. Additionally disclosed are nucleic acid molecules encoding the receptor. The receptor has a minimal domain for ligand binding and is useful in screening assays designed for the identification of agonists and antagonists of PTH receptor activity.

Growing community of inventors

Newton, MA, United States of America

John T Potts, Jr