Alpha interferon comprises a family of leukocyte-derived cytokines that exhibit antiviral, antiproliferative and immunomodulatory effects on many cell types. Recombinant human alpha-interferon is used to treat a variety of viral diseases and cancers and had worldwide sales in excess of $1.4 billion during 1997. We propose to create modified alpha-interferon proteins that are equal or superior to natural alpha-interferon at modulating immune responses and viral and cell proliferation in vivo, but which require less frequent dosing, on the order of once per week to once per month, rather than daily. During Phase I identified sites in alpha-interferon that can be modified without affecting the protein's in vitro bioactivity. During Phase II, we will develop manufacturing processes to produce sufficient quantities of the modified alpha-interferon proteins for testing in animal models of cancer and viral diseases. The improved characteristics of the novel alpha-interferon proteins should reduce the amount of alpha- interferon required per patient, reduce toxicity, improve parent compliance and quality of life and result in considerable cost savings to patients and healthcare providers. Alpha-interferons are members of a large family of structurally related growth factors and cytokines. Information gained from these studies will aid in creating long-acting versions of other members of this gene family for use in treating cancer, infectious disease and hematopoeitic disorders.

Proposed Commercial Applications

Recombinant human alpha-interferon is used to treat a variety of viral diseases and cancers and had worldwide sales in excess of $ 1.4 billion in 1997. The modified alpha-interferon proteins under development will require much less frequent dosing than existing alpha-interferon products, resulting in significant cost savings to patients and healthcare providers. Additional benefits may include improved drug efficacy, reduced toxicity and improved patient quality of life.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44CA079361-02
Application #
6141742
Study Section
Special Emphasis Panel (ZRG1-SSS-1 (02))
Program Officer
Muszynski, Karen
Project Start
1998-09-30
Project End
2002-02-28
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
2
Fiscal Year
2000
Total Cost
$399,339
Indirect Cost
Name
Bolder Biotechnology, Inc.
Department
Type
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80301
Bell, Stacie J; Fam, Christine M; Chlipala, Elizabeth A et al. (2008) Enhanced circulating half-life and antitumor activity of a site-specific pegylated interferon-alpha protein therapeutic. Bioconjug Chem 19:299-305
Rosendahl, Mary S; Doherty, Daniel H; Smith, Darin J et al. (2005) A long-acting, highly potent interferon alpha-2 conjugate created using site-specific PEGylation. Bioconjug Chem 16:200-7