The U.S. government is seeking to patent any human protein-encoding gene that includes the brain DNA sequences recentlydiscovered by government scientists, according to thecontroversial patent application by the National Institutes ofHealth.

The claims also include broad variations of the sequences,including probes, antisense oligonucleotides and vectorscontaining the gene fragments.

The application, filed in February and obtained this week byBioWorld, claims slightly more than 2,400 DNAoligonucleotides, corresponding to about 5 percent of all humangenes. However, the patent does not claim any methods toproduce or use the sequences.

The oligonucleotides, called expressed sequence tags (ESTs), aresequenced fragments isolated from human brain cDNA librariesby scientists from the National Institute of NeurologicalDisorders. More than 80 percent of the ESTs are unrelated toany sequences previously described in the scientific literature.

The claims cover 2,421 "enriched" and "isolated" DNAoligonucleotides, excluding eight ESTs that already had beenpublished and omitting nine others.

The claims also cover allelic, or alternative, forms of the ESTs,genes encoding human gene products that include the ESTs,short probes and primers corresponding to the ESTs, antisenseversions, and triple helix probes corresponding to the ESTs.

In addition, the claims contain vectors, including expressionvectors, that contain the ESTs.

The application describes a variety of potential uses for theESTS, including the identification of entire genes containing thesequences, mapping of ESTs to specific human chromosomes,identification of genetic defects, "fingerprint" identification ofindividuals, and production of proteins encoded by genes thatinclude the ESTs.

Antisense oligonucleotides and triple-helix probescorresponding to a given EST may also be used to identify thefunction of a gene that includes the sequence.

However, according to Reid Adler, director of the NIH's Office ofTechnology Transfer, the application does not claim any specificuses for the ESTs because the biological function of almost all ofthe sequences is unknown.

The application also does not provide the nucleotide sequences.However, the sequences, which total more than 765,500nucleotides, have been submitted to the GenBank computerdatabase, and the corresponding clones to the American TypeCulture Collection. As of December 1990, GenBank had fewerthan 200 human brain cDNA sequences.

As expected, the released version of the patent applicationlacks information considered proprietary, such as thelocalization of ESTs mapped to specific human chromosomesand the correlation of particular ESTs to certain diseases.

The NIH has said it has not yet decided whether to pursue thepatent to conclusion, saying the application was intended tostimulate discussion about government policy on technologytransfer and to promote U.S. competitiveness.

However, according to Adler, the process used to isolate theESTs will be made available to the public as a statutoryinvention registration, thereby preventing others frompatenting the technique.

-- Carol Talkington Verser, Ph.D. Special to BioWorld

(c) 1997 American Health Consultants. All rights reserved.