Cetus Corporation

Merck Patent Gmbh

Immulogic Pharmaceutical Corporation

Other

Schering Aktiengesellschaft

Berlex Laboratories, Inc.

Immulogic Pharamaceutical Corp.

Ze'ev Shaked

Mei-chang Kuo

Richard D Garman

Xian Chen

Bruce L Rogers

Julia L Greenstein

Julian F Bond

Irwin J Griffith

Mark A Exley

Stephen P Powers

Sean Evans

Susan Hershenson

Henry M Franzen

Joanne Pollock

James W Thomson

Jody Thomson

Tracy Stewart

Kirston E Koths

Robert F Halenbeck

Malcolm L Gefter

Jay Paul Morgenstern

Michael A Innis

Alice M Wang

Andrew W Brauer

Malcolm Morville

Terrance A Taforo

Sidney N Wolfe

Thomas J Briner

Thabiso M'Timkulu

Pamela Hirtzer

Richard Hsu

The present invention provides nucleic acid sequences coding for themajor pollen allergen Cry j I, Cry j II, Jun s I and Jun v I and fragments or peptides thereof. The present invention also provides purified Cry j I, Cry j II, Jun s I and Jun v I and at least one fragment thereof produced in a host cell transformed with a nucleic acid sequence coding for Cry j I, Cry j II, Jun s I and Jun v I or at least one fragment thereof, and fragments of Cry j I, Cry j II, Jun s I or Jun v I or at least one fragment thereof, and fragments of Cry j I, Cry j II, Jun s I or Jun v I prepared synthetically. Cry j I, Cry j II, Jun s I and Jun v I and fragments thereof are useful for diagnosing, treating, and preventing Japanese cedar pollinosis. The present invention also provides isolated peptides of Cry j I and Cry j II. Peptides within the scope of the invention comprise at least one T cell epitope, or preferably at least two T cell epitopes of Cry j I or Cry j II. The invention also pertains to modified peptides having similar or enhanced therapeutic properties as the corresponding naturally-occurring allergen or portion thereof but having reduced side effects. Methods of treatment or of diagnosis of sensitivity to Japanese cedar pollens in an individual and therapeutic compositions, and multipeptide formulations comprising one or more peptides of the invention are also provided.

Allergenic proteins and peptides from Japanese cedar pollen

A substantially pure, covalently linked human T cell reactive feline protein (TRFP) has been isolated from vacuum bag extract obtained by affinity purification of house dust collected from several homes with cats; DNA encoding all or a portion of the TRFP or peptide; compositions containing such a protein or peptide or portions thereof; and antibodies reactive with the TRFP or peptide are disclosed. Also disclosed are recombinant TRFP or peptide; modified or mutated TRFP peptides; their use for diagnostic or therapeutic purposes.

Human T cell reactive feline protein (TRFP) isolated from house dust and uses therefor

The present invention provides isolated peptides of the major protein allergens of the genus. Peptides within the scope of the invention comprises at least one T cell epitope, or preferably at least two T cell epitopes of a protein allergen selected from the allergens Der p I, Der p II, Der f I, or Der f II. The invention also pertains to modified peptides having similar or enhanced therapeutic properties as the corresponding, naturally-occurring allergen or portion thereof, but having reduced side effects. The invention further provides nucleic acid sequences coding for peptides of the invention. Methods of treatment or of diagnosis of sensitivity to house dust mites in an individual and therapeutic compositions comprising one or more peptides of the invention are also provided.

T cell epitopes of the major allergens from dermatophagoides (house dust mite)

The present invention provides nucleic acid sequences coding for the Cryptomeria japonica major pollen allergen Cry j I, Cry j II, Jun s I and Jun v I and fragments or peptides thereof. The present invention also provides purified Cry j I, Cry j II, Jun s I and Jun v I and at least one fragment thereof produced in a host cell transformed with a nucleic acid sequence coding for Cry j I, Cry j II, Jun s I and Jun v I or at least one fragment thereof, and fragments of Cry j I, Cry j II, Jun s I or Jun v I or at least one fragment thereof, and fragments of Cry j I, Cry j II, Jun s I or Jun v I prepared synthetically. Cry j I, Cry j II, Jun s I and Jun v I and fragments thereof are useful for diagnosing, treating, and preventing Japanese cedar pollinosis. The present invention also provides isolated peptides of Cry j I and Cry j II. Peptides within the scope of the invention comprise at least one T cell epitope, or preferably at least two T cell epitopes of Cry j I or Cry j II. The invention also pertains to modified peptides having similar or enhanced therapeutic properties as the corresponding naturally-occurring allergen or portion thereof but having reduced side effects. Methods of treatment or of diagnosis of sensitivity to Japanese cedar pollens in an individual and therapeutic compositions, and multipeptide formulations comprising one or more peptides of the invention are also provided.

T cell peptides of the CRX JII allergen

The present invention provides isolated peptides of the major protein allergens of the genus Dermatophagoides. Peptides within the scope of the invention comprises at least one T cell epitope, or preferably at least two T cell epitopes of a protein allergen selected from the allergens Der p I, Der p II, Der f I, or Der f II. The invention also pertains to modified peptides having similar or enhanced therapeutic properties as the corresponding, naturally-occurring allergen or portion thereof, but having reduced side effects. The invention further provides nucleic acid sequences coding for peptides of the invention. Methods of treatment or of diagnosis of sensitivity to house dust mites in an individual and therapeutic compositions comprising one or more peptides of the invention are also provided.

T cell epitopes of the major allergens from Dermatophagoides (house dust

T cell epitopes of the major allergens from dermatophagoides (house dust

A topical bioadhesive ointment composition comprising an aqueous mineral oil emulsion which is readily spread able and film-forming, and, upon application to moist skin or a mucosal surface, forms a stable, coherent layer thereon which resists removal therefrom by water or a body fluid associated with the mucosal surface to which the ointment composition is applied is disclosed. Also disclosed are pharmaceutical compositions containing the ointment compositions and a pharmaceutically active agent, e.g. , TGF.alpha.; and methods of using and methods of preparing the compositions.

Topical bioadhesive ointment compositions and their use in wound healing

Stable pharmaceutical compositions suitable for parenteral administration to animals or humans are prepared comprising a therapeutically effective amount of a recombinant IFN-.beta. protein dissolved in an inert carrier medium comprising as solubilizer/stabilizer(s) one or more biocompatible non-ionic polymeric detergents or a combination of one or more biocompatible non-ionic polymeric detergents with an additional solubilizing and/or stabilizing agent, such as sodium dodecyl sulfate or glycerol. The compositions are in liquid form or lyophilized.

Formulation processes for pharmaceutical compositions of recombinant .beta.

Stable pharmaceutical compositions suitable for parenteral administration to animals or humans are prepared comprising a therapeutically effective amount of a recombinant interleukin-2 (IL-2) protein dissolved in an inert carrier medium comprising one or more biocompatible non-ionic polymeric detergents which act as solubilizer/stabilizers for the claimed formulations.

Pharmaceutical compositions of recombinant interleukin-2 and formulation

An approved procedure for the purification and renaturation of biologically active, bacterially produced IFN-.beta. is described. The partially purified material obtained by solubilization of isolated refractile bodies from the recombinant cells is treated to obtain reduction of the protein in the presence of a chaotropic environment and then oxidized after removal of the reducing agent. However, the chaotropic environment is retained during the oxidation. Upon removal of the chaotropic environment, a solubilizing additive is supplied to maintain the IFN-.beta. in solution. Further purification by conventional means may also be effected.

Process for recovering microbially produced interferon-.beta.

Improved RP-HPLC methods for purifying recombinant betainterferon are disclosed. Said RP-HPLC methods employ wide pore silica gel reverse-phase columns and solvent systems containing acetonitrile as the organic modifier and either heptafluorobutyric acid or trifluoroacetic acid as the organic acid. The invention further concerns processes for purifying recombinant IFN-.beta. incorporating said improved RP-HPLC methods. The invention further concerns recombinant IFN-.beta. purified by said RP-HPLC methods, or recovered and/or purified by processes incorporating said RP-HPLC.

Purification of recombinant beta-interferon incorporating RP-HPLC

A biologically active reference therapeutic protein is protected against oxidation by a method involving substituting a conservative amino acid for each methionyl residue susceptible to chloramine T or peroxide oxidation, wherein additional, non-susceptible methionyl residues are not so substituted. The oxidation-resistant mutein so produced is preferably a human mutein of interleukin-2 or interferon-.beta., and the conservative amino acid is most preferably alanine.

Oxidation-resistant muteins

Method of oxidizing reduced cysteine-containing microbially produced synthetic proteins, such as synthetic IFN-.beta. or synthetic IL-2, in a controlled manner so that the synthetic proteins have the same disulfide bridging as their native counterparts. The oxidation employs o-iodosobenzoate as oxidizing agent and is carried out in an aqueous medium at a pH at least about one-half pH unit less than the pK.sub.a of the cysteines to be oxidized, a synthetic protein concentration of less than about 5 mg/ml, and an oxidizing agent:protein mol ratio that is at least stoichiometric, provided that the oxidizing agent is in excess in the terminal portion of the reaction.

Controlled oxidation of microbially produced cysteine-containing proteins

Growing community of inventors

Berkeley, CA, United States of America

Ze'ev Shaked