ImClone Systems Inc. is in line for an exclusive, worldwide license toa pending patent that energizes blood-forming stem cells to multiply.
Late last week, the National Institutes of Health Office of TechnologyTransfer forwarded a notice to the Federal Register that it intends togrant such royalty-bearing rights to the company, covering anapplied-for patent on a "delta-like gene expressed in neuroendocrinetissue." Molecular oncologist Jorge Laborda, of the FDA's Center forBiologics Evaluation and Research, is the discovery's lead inventor.
He and Larry Witte, ImClone's director of molecular and cellularbiology, have been collaborating on developing the gene, which fitssnugly into the company's intellectual property portfolio. Just oneyear ago, ImClone of New York City secured from Rhone-PoulencRorer rights to a monoclonal antibody against an epidermal growth-factor receptor (EGFr). That tumor antigen studs the cell surfaces ofmany malignancies, and is a target for ImClone's antibody-deliveredchemotherapy. (See BioWorld Today, July 7, 1994, p. 2.)
Last May, the company launched two Phase I/II trials of its EGFrantagonist, targeting a spectrum of solid tumors. The delta-like gene,dlk, object of its pending license to Laborda's pending patent,encodes a 42-kiloDalton, 383-amino-acid protein "that appears to bea novel member of the family of neurogenic genes."
As an embryo develops in utero, ImClone's chief operating officer,Harlan Waksal, explained to BioWorld Today, its forked cellularroads most traveled are the neurogenic _ generating the futurenervous system _ and the epidermal. As these growing paths divergeand divide, each branch, twig and bud gives rise to specific organsand tissues, each sired by clones of cells derived from thedifferentiation of single stem-cell ancestors.
Laborda found that dlk can detect certain human tumors, specifically,neuroblastomas, pheochromocytomas and small cell lung cancers,with which the gene has much in common at the molecular level. TheFDA scientist made this discovery, Witte recalled, "pretty muchthrough serendipity."
After cloning the sequence in mice, "he ran it through the gene banks,which showed it had considerable homology with the Delta gene ofDrosophila melanogaster, the fruit fly. Hence the "d" in dlk.
Witte requested a license to Laborda's patent, and sees "its simplestapplication by ImClone as ex vivo experiments for expansion ofhematopoietic stem cells, functioning to maintain them in anundifferentiated state."
By exploring "the common pathways behind these tumor cells andthe dlk protein," Waksal suggested, various treatment modalitiesmight be found that may be in common."
Putting a bit in the mouths of these totipotent progenitor cells, Witteexplained, "would allow them to proliferate and expand their ownpopulations, for return to the original cancer patient during bonemarrow transplantation."
The adult bone marrow, Laborda points out, is the site where bloodcells are formed. An estimated one in 10,000 such cells are stromal_ that is, structural. They are thought to produce factors that helpkeep the stem cells uncommitted.
Stromal cells flourish in tumors, such as neurocrine malignancies,which are highly homologous to the delta-like EGFr. One such issmall cell lung carcinoma. n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.