Amgen Inc.

Amylin Pharmaceuticals, Inc.

Michael B Mann

Christopher Francis Toombs

Mary Ann Pelleymounter

Randy Ira Hecht

Thomas Charles Boone

Huimin Li

Hsieng Sen Lu

Larry B Tsai

Dennis M Fenton

Por-Hsiung Lai

Mary Ann Pellymounter

The present invention relates to Fc-OB fusion protein compositions, methods of preparation of such compositions and uses thereof. In particular, the present invention relates to a genetic or chemical fusion protein comprising the Fc immunoglobulin region, derivative or analog fused to the N-terminal portion of the OB protein, derivative or analog.

OB fusion protein compositions and methods

DNA sequences comprising nucleic acids encoding fusion proteins comprising an Fc portion of an antibody attached at the N-terminus of an OB protein moiety, vectors comprising such DNA sequences, host cells comprising such vectors or DNA sequences, and processes for preparing such fusion proteins, and pharmaceutical compositions comprising such fusion proteins, are described. The DNA sequences, vectors comprising such DNA sequences, host cells comprising such vectors or DNA sequences, and processes for preparing such fusion proteins, and pharmaceutical compositions comprising such fusion proteins are useful, for example, in providing therapeutically effective amounts of compositions useful for, for example, increasing insulin sensitivity, decreasing the dose of insulin required for the treatment of diabetes, controlling serum glucose levels, increasing lean tissue mass, increasing overall body strength, or regulating bone resorption, or effecting any combination of such, in subjects in need or desirous thereof to which the compositions are administered.

Methods of increasing lean tissue mass using OB protein compositions

The present invention provides methods and compositions for treating excess weight by administering OB protein in a form for constant supply, at a dosage of less than or equal to about 1 mg protein/kg body weight/day. Compositions and methods used for production of recombinant murine and human OB protein are also provided. Compositions and methods for preparing recombinant murine methionyl OB protein and recombinant human methionyl OB protein, including DNA sequences, vectors, host cells, methods of fermentation, and methods of purification are provided herein.

OB protein compositions and methods

The present invention provides methods of creating and using OB protein compositions with an antibody constant region or portion thereof fused to an OB protein. The fusion protein is created by attaching the polyamino acids to the OB protein moiety. The fusion proteins can then be used for various therapeutic uses.

A fibrinolytically active metalloproteinase polypeptide (called 'novel acting thrombolytic') which is useful for blood clot lysis in vivo and methods and materials for its production by recombinant expression are described.

Methods for the treatment of thrombosis

A fibrinolytically active metalloproteinase polypeptide (called &ldquo;novel acting thrombolytic&rdquo;) which is useful for blood clot lysis in vivo and methods and materials for its production by recombinant expression are described.

DNA molecules encoding fibrinolytically active polypeptide

Fibronolytically active polypeptide

Norleucine incorporation into recombinant gene products may be inhibited by culturing the cells expressing the gene products in media comprising a high level of leucine and/or methionine, or by expressing the gene products in a leu mutant. Norleucine incorporation in recombinant gene products may be promoted by culturing the cells expressing the gene products in media comprising norleucine or deficient in leucine and/or methionine. For example, norleucine analogs of IL-2, GCSF, .gamma.-interferon and .alpha.-consensus interferon may be produced in this way.

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Thousand Oaks, CA, United States of America

Michael B Mann