Appeal No. 1999-1157
Application No. 08/482,321
comprising, in phase from a first 5’ to a second 3’ end of the coding
strand thereof, the elements:
(i) a bacterial trp promoter-operator system from a bacterial trp
operon;
(ii) nucleotides coding for a ribosome binding site for translation
of element (iv);
(iii) nucleotides coding for a translation start signal for translation
of element (iv); and
(iv) a structural gene encoding the amino acid sequence of a
heterologous polypeptide;
said sequence comprising neither any trp attenuation
capability nor nucleotides coding for the trp E ribosome
binding site, provided however, that if the heterologous
polypeptide includes any polypeptide also includes
polypeptide sequence not encoded by the trp operon;
(b) placing the transformed inoculant in a fermentation vessel and
growing the same to a predetermined level in a suitable nutrient
media containing additive tryptophan sufficient in quantity to
repress said promoter-operator system; and
(c) depriving said bacteria of said additive while maintaining the viability
of said bacteria so as to derepress said system and occasion the
expression of the product encoded by said structural gene.
The references relied upon by the examiner are:
Cohen et al. (Cohen) 4,237,224 Dec. 2, 1980
Bertrand et al. (Bertrand), “Regulation of Transcription Termination in the Leader
Region of the Tryptophan Operon of Escherichia coli Involves Tryptophan or its
Metabolic Product,” J. Mol. Biol., Vol. 103, pp. 339-349 (1976)
Miozzari et al. (Miozzari (R)), “Translation of the Leader Region of the Escherichia
coli Tryptophan Operon,” J. Bacteriology, Vol. 133, No. 3, pp. 1457-1466 (1978)
Miozzari et al. (Miozzari (S)), “Tryptophan Biosynthesis in Saccharomyces
cerevisiae: Control of the Flux Through the Pathway,” J. Bacteriology, Vol. 134, No.
1, pp. 48-59 (1978)
Goeddel et al. (Goeddel), “Direct expression in Escherichia coli of a DNA sequence
coding for human growth hormone,” Nature, Vol. 281, pp. 544-548 (1979)
The reference relied upon by the Board is:
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