Synergen, Inc.

New York University

Andreas Sommer

Daniel B Rifkin

David A Moscatelli

Robert Z Florkiewicz

High molecular weight forms of therapeutic proteins are disclosed which are single-polypeptide-chain proteins that contain the same or similar therapeutic activity as the therapeutic protein. In particular, high molecular weight forms of the human bFGF angiogenic factor are disclosed which are single-polypeptide-chain proteins having at least one active site possessing an activity selected from the group consisting of mitogenic activity, chemotactic activity, angiogenic activity, neurotrophic activity, the ability to stimulate protease synthesis and combinations thereof. The high molecular weight angiogenic factors exhibit substantial homology to and are immunologically equivalent to the native high molecular weight forms isolatable from human hepatoma cells. The high molecular weight angiogenic factors are produced by DNA translation initiating at non-ATG codons and incorporate additional polypeptide sequences N-terminal to the human bFGF factor. The amino acid sequences of the high molecular weight angiogenic factors and the oligonucleotide sequence that translate to form the high molecular weight bFGF proteins are also disclosed. Methods for isolating the high molecular weight angiogenic factors from human hepatoma cell line SK-HEP-1 and producing the proteins by recombinant DNA techniques are also described.

High molecular weight human angiogenic basic fibroblast growth factors

High molecular weight forms of therapeutic proteins are disclosed which are single-polypeptide-chain proteins that contain the same or similar therapeutic activity as the therapeutic protein. In particular, high molecular weight forms of the human bFGF angiogenic factor are disclosed which are single-polypeptide-chain proteins having at least one active site possessing an activity selected from the group consisting of mitogenic activity, chemotactic activity, angiogenic activity, neurotrophic, activity, the ability to stimulate protease synthesis and combinations thereof. The high molecular weight angiogenic factors exhibit substantial homology to and are immunologically equivalent to the native high molecular weight forms isolatable from human hepatoma cells. The high molecular weight angiogenic factors are produced by DNA translation initiating at non-ATG codons and incorporate additional polypeptide sequences N-terminal to the human bFGF factor. The amino acid sequences of the high molecular weight angiogenic factors and the oligonucleotide sequence that translate to form the high molecular weight bFGF proteins are also disclosed. Methods for isolating the high molecular weight angiogenic factors from human hepatoma cell line SK-HEP-1 and producing the proteins by recombinant DNA techniques are also described.

Method of producing high molecular weight human fibroblast growth factors

An isolated DNA sequence encoding an angiogenic factor protein consisting of a single-polypeptide-chain protein having at least one active site possessing mitotic and chemotactic activity and the ability to stimulate protease synthesis, wherein said protein consists of the amino acid sequence: ##STR1## In a preferred embodiment, the DNA sequence encodes basic fibroblast growth factor (bFGF).

DNA encoding a basic fibroblast growth factor

An angiogenic factor is disclosed which is a purified, single-polypeptide-chain protein having at least one active site possessing an activity selected from the group consisting of mitogenic activity, chemotactic activity, the ability to stimulate protease synthesis and combinations thereof. This angiogenic factor exhibits substantial homology to and is immunologically equivalent to the native angiogenic factor isolatable from human placental tissues. The amino acid sequence of this angiogenic factor is also disclosed. In addition, a method for isolation of the purified angiogenic factor from human placental tissues is set forth. Pharmaceutical preparations incorporating this angiogenic factor are described.

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Boulder, CO, United States of America

Andreas Sommer