Chiron Corporation

University of California

Genetics Institute, Inc.

Gist-brocades N.v.

Novartis Vaccines & Diagnostics, Gmbh

Anthony J Brake

David J Julius

Philip J Barr

Patricia A Tekamp-Olson

Randal J Kaufman

Louise C Wasley

Michael J Caterina

Polly A Wong

Pablo D Valenzuela

Lawrence S Cousens

Mickey S Urdea

Johan A Van Den Berg

Steven Rosenberg

Robert A Hallewell

Lindley Blair

Johannes A Van Den Berg

Jeremy W Thorner

Louise Wasley

Randal J 111 Marlborough Street Kaufman

The present invention features vanilloid receptor polypeptides and vanilloid receptor-related polypeptides, specifically the capsaicin receptor subtypes VR1 and VR2 (VRRP-1), as well as the encoding polynucleotide sequences. In related aspects the invention features expression vectors and host cells comprising such polynucleotides. In other related aspects, the invention features transgenic animals having altered capsaicin receptor expression, due to, for example, the presence of an exogenous wild-type or modified capsaicin receptor-encoding polynucleotide sequence. The present invention also relates to antibodies that bind specifically to a capsaicin receptor polypeptide, and methods for producing these polypeptides. Further, the invention provides methods for using capsaicin receptor, including methods for screening candidate agents for activity as agonists or antagonists of capsaicin receptor activity, as well as assays to determine the amount of a capsaicin receptor-activating agent in a sample. In other related aspects, the invention provides methods for the use of the capsaicin receptor for the diagnosis and treatment of human disease and painful syndromes.

Nucleic acid sequences encoding capsaicin receptor and capsaicin receptor-related polypeptides and uses thereof

Nucleic acid sequences encoding capsaicin receptor and uses thereof

Compositions and methods are provided for endopeptidase production and for enhanced efficiencies of processing heterologous precursor polypeptides to mature polypeptides, including proteins requiring gamma-carboxylation for biological activity. These compositions and methods utilize recombinant PACE, a mammalian endopeptidase that is specific for dibasic amino acid sites.

Expression of pace in host cells and methods of use thereof

Expression of PACE in host cells and methods of use thereof

DNA constructs that are useful for providing secretory expression of heterologous polypeptides in yeast comprising a DNA sequence that includes a Kluyveromyces .alpha.-factor leader sequence linked to the heterologous polypeptide by a yeast processing signal. Constructs employing the K. lactis .alpha.-factor leader and processing signal sequences, with and without spacer, linked to prochymosin are exemplified.

DNA constructs containing a kluyveromyces .alpha. factor leader sequence

Methods and compositions are provided for endopeptidase production, enhanced efficiencies of processing in vivo and in vitro to provide for process polypeptides, and purified enzyme for in vitro processing of polypeptides. The endopeptidase is specific for dibasic amino acid sites, cleaving at the C-side of the dipeptide. The S. cerevisiae strain pYBCA-5 (truncated KEX2) was deposited at the A.T.C.C. on June 21, 1984 and given Accession No. 20717.

Yeast endopeptidase for basic amino-acid site cleavage, preparation and

Methods and compositions are provided for efficient production of polypeptides having insulin activity. The proinsulin gene is joined to secretion and processing signals for expression and secretion in yeast. The product may be obtained in enhanced yield in the nutrient medium. Cell line pyinse was deposited at the A.T.C.C. on Apr. 6, 1983 and given Accession No. 20670.

Hybrid DNA synthesis of insulin

DNA constructs containing a Kluyveromyces alpha factor leader sequence

Methods and compositions are provided for efficient production of polypeptides having insulin activity. The proinsulin gene is joined to secretion and processing signals for expession and secretion in yeast. The product may be obtained in enhanced yield in the nutrient medium. Cell line AB103(PYinsl) was deposited at the A.T.C.C. on Apr. 6, 1983 and given Accession No. 20,670.

Alpha factor leader sequence directed secretion of insulin

Methods and compositions are provided for producing polypeptide sequences in high yield by employing DNA constructs, wherein the DNA sequence encoding from the polypeptide of interest in preceded by a leader sequence and processing sequence for secreting and processing said polypeptide. In this manner, the mature polypeptide of interest may be isolated from the nutrient medium substantially free of major amounts of other proteins and cellular debris. The yeast strain S. cerevisiae AB103 (pYEGF8) was deposited on Jan. 5 , 1983, at the A.T.C.C. and given accession No. 20658. The plasmid pY.alpha.EGF23 (pAB114-pCl/1) was deposited at the A.T.C.C. on Aug. 12, 1983, and given Accession No. 40079.

Secretory expression in eukaryotes

Methods and compositions are provided for high level production of foreign proteins in yeast. The system is exemplified by production of .alpha..sub.1 -antitrypsin in yeast strain AB110, derived from yeast strains 2150-2-3 and AB103.1. S. carlsbergensis/S. cerevisiae hybrid strain AB110 containing plasmid pCl/1GAPATi9 was deposited at the A.T.C.C. on May 9, 1984, and given Accession No. 20709.

Expression of .alpha.-1 antitrypsin in yeast

Novel DNA constructs are provided for efficient expression of polypeptides by yeasts. The constructs employ yeast a-factor secretion leader and processing signals joined to a DNA sequence encoding a polypeptide of interest in reading frame with the a-factor signals. The constructions provide for the expression, secretion and maturation of the desired polypeptide. A strategy is provided for the isolation of the a-factor secretion leader and processing signals and the joining, by means of a relatively short adaptor, molecules of the DNA sequence encoding the polypeptide to the processing signals in proper reading frame. The bacterial cell strain E. coli HB101 (pAB163) was deposited at the A.T.C.C. on Apr. 20, 1983 and given Accession No. 39342.

a-Factor and its processing signals

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Berkeley, CA, United States of America

Anthony J Brake