Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Reexamination Certificate
1999-08-31
2002-07-30
Achutamurthy, Ponnathapu (Department: 1652)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
C435S023000, C435S226000, C435S252300, C435S320100, C536S023200, C536S023400
Reexamination Certificate
active
06426199
ABSTRACT:
BACKGROUND OF THE INVENTION
The members of the trypsin/chymotrypsin-like (S1) serine protease family are gaining recognition due to the increased awareness that these enzymes play pivotal roles in a multitude of diverse physiological processes. In addition to the classical functions the proteases trypsin and chymotrypsin perform during the digestive process, serine proteases also participate in regulating key amplification cascades through the proteolytic activation of inactive zymogen precursors. Thus, in many instances the protease substrates within these cascades are themselves the inactive form, or zymogen, of a “downstream” serine protease. Well-known examples of this serine protease-mediated regulation include blood coagulation, (Davie et al. (1991).
Biochemistry
30:10363-70), kinin formation (Proud and Kaplan (1988).
Annu. Rev. Immunol.
6:49-83) and the complement system (Reid and Porter (1981).
Annual Review of Biochemistry
50:433-464). Although these proteolytic pathways have been known for sometime, it is likely that the discovery of novel serine protease genes and their products will enhance our understanding of the regulation within these existing cascades, and possibly lead to the elucidation of entirely distinct protease networks.
Proteases are used in non-natural environments for various commercial purposes including laundry detergents, food processing, fabric processing and skin care products. In laundry detergents, the protease is employed to break down organic, poorly soluble compounds to more soluble forms that can be more easily dissolved in detergent and water. In this capacity the protease acts as a “stain remover.” Examples of food processing include tenderizing meats and producing cheese. Proteases are used in fabric processing, for example, to treat wool in order prevent fabric shrinkage. Proteases may be included in skin care products to remove scales on the skin surface that build up due to an imbalance in the rate of desquamation. Unfortunately use of some proteases is limited by their potential to cause allergic reactions in sensitive individuals or by reduced efficiency when used in a non-natural environment. Because of these limitations, there is a need for alternative proteases that are less immunogenic to sensitive individuals and/or provides efficient proteolytic activity in a non-natural environment.
SUMMARY OF THE INVENTION
Here we describe the molecular identification of a cDNA encoding a novel serine protease we have termed protease C-E. The protease C-E cDNA sequence predicts a preproC-E polypeptide of 317 amino acids, and its alignment with other well-characterized serine proteases clearly indicates that it is a member of the S1 serine protease family.
Enzymatically active protease C-E is amenable to further biochemical analyses for the identification of physiological substrates and specific modulators. Modulators identified in the chromogenic assay disclosed herein are potentially useful as therapeutic agents in the treatment of diseases associated with certain regions of the brain, but not limited to neurodegeneration. In addition, expression of protease C-E in fibroblasts and epidermis suggests that modulators of protease C-E function could be used to treat disorders effecting skin as well. Since this novel human serine protease is also expressed in pancreas, prostate, small intestine, stomach and spleen where it may function in normal physiology or during various pathological states, modulators of protease C-E function could likewise be used to treat disorders effecting these tissues.
The recombinant DNA molecules coding for C-E, and portions thereof, are useful for isolating homologues of the DNA molecules, identifying and isolating genomic equivalents of the DNA molecules, and identifying, detecting or isolating mutant forms of the DNA molecules.
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Andrade-Grodon Patricia
Darrow Andrew
Qi Jenson
Achutamurthy Ponnathapu
Moore William W.
Ortho-McNeil Pharmaceutical , Inc.
Wallen III John W.
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