University of California

Regeneron Pharmaceuticals, Inc.

Other

Richard M Harland

William C Smith

George D Yancopoulos

David M Valenzuela

Neil E Stahl

Aris N Economides

Nancy Y Ip

Teresa Lamb

Henryk D Cudny

Anne Knecht

David Hsu

Henryk Cudny

Described are modified Noggin muteins, compositions comprising the muteins, and DNA or RNA sequences comprising coding (sense) or antisense sequences for the muteins.

Nucleic acid molecules encoding modified dorsal tissue affecting factor

DAN (Differential-screening-selected gene Aberrative in Neuroblastoma) and gremlin proteins and related nucleic acids are provided. Included are natural DAN and gremlin homologs from several species and proteins comprising a DAN or gremlin domain having specific activity, particularly the ability to antagonize a bone morphogenic protein. The proteins may be produced recombinantly from transformed host cells with the subject nucleic acids. Also provided are isolated hybridization probes and primers capable of specifically hybridizing with the disclosed genes, specific binding agents and methods of making and using the subject compositions.

Morphogenic proteins

Novel dorsal growth inducing factors, complexes including the factors, and DNA or RNA coding sequences for the factors are described.

Dorsal tissue affecting factor and compositions

Modified noggin polypeptide and compositions

A functional peptide is encoded by SEQ ID NO:1. This peptide is capable of inducing dorsal and neural tissue development in vertebrates. The peptide is a member of the TGF-.beta. superfamily, and can be prepared in therapeutic applications to treat congenital conditions or degenerative disorders of the nervous system and in compositions useful for inducing growth of bone.

Nucleic acids encoding a neural tissue affecting factor

Human dorsal tissue affecting factor (noggin) and nucleic acids encoding

Novel dorsal growth inducing factors, complexes including the factors, and DNA or RNA coding sequences for the factors are described. Hybridoma cell lines and antibodies that bind to the dorsal growth inducing factor noggin, having the amino acid sequence set forth in SEQ ID NO:2, are also described.

Hybridoma cell lines and antibodies that bind noggin

A novel and soluble polypeptide that is highly conserved among vertebrates has been discovered, which is designated 'noggin.' The properties of noggin include dorsal growth inducing activity. Noggin and activin act synergistically to produce dorsal mesoderm. Noggin's cDNA has been cloned. Several expression systems have been successfully used to express biologically active noggin. Amino acid sequences representing completely conserved portions as between frog noggin and mouse noggin are:

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Moraga, CA, United States of America

Richard M Harland