Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Hydrolase
Reexamination Certificate
1998-12-14
2001-08-07
Prouty, Rebecca E. (Department: 1652)
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
Hydrolase
C435S189000, C435S219000, C530S350000, C536S023200
Reexamination Certificate
active
06271014
ABSTRACT:
FIELD OF THE INVENTION
The present invention contemplates compositions related to proteins from animals, e.g., mammals, which function as proteinases. In particular, it provides nucleic acids which encode the proteinases, antibodies to, and proteins which exhibit biological functions, e.g., capacity to degrade proteinaceous substrates.
BACKGROUND OF THE INVENTION
The proteases are a very broad group of enzymes which carry out an enzymatic function of hydrolyzing a peptide bond. See, e.g., Beynon (ed. 1989)
Proteolytic Enzymes: A Practical Approach
IRL Press, Oxford;
Methods in Enzymology
vols. 244 and 248. Within the group, there is a wide range of substrate specificities for the amino acids adjacent the cleavage sites. Proteases are typically categorized on the basis of their catalytic mechanisms, e.g., based upon studies of their active sites, or by the effects of pH. Four main categories of proteases are serine proteinases, sulfhydryl proteases, acid proteases, and metalloproteases. They may also be classified according to their sites of substrate cleavage, e.g., endoproteases, amino peptidases, or carboxy peptidases.
Proteases have traditionally held a large share of the industrial enzyme market. Proteases are used in many industrial processes, including in detergents and cleaning products, e.g., to degrade protein materials such as blood and stains, in leather production, e.g., to remove hair, in baking, e.g., to break down glutens, in flavorings, e.g., soy sauce, in meat tenderizing, e.g., to break down collagen, in gelatin or food supplement production, in the textile industry, in waste treatment, and in the photographic industry. See, e.g., Gusek (1991)
Inform
1:14-18; Zamost, et al. (1996)
J. Industrial Microbiol.
8:71-82; James and Simpson (1996)
CRC Critical Reviews in Food Science and Nutrition
36:437-463; Teichgraeber, et al. (1993)
Trends in Food Science and Technology
4:145-149; Tjwan, et al. (1993)
J. Dairy Research
60:269-286; Haard (1992)
J. Aquatic Food Product Technology
1:17-35; van Dijk (1995)
Laundry and Cleaning News
21:32-33; Nolte, et al. (1996)
J. Textile Institute
87:212-226; Chikkodi, et al. (1995)
Textile Res. J.
65:564-569; and Shih (1993)
Poultry Science
72:1617-1620.
Matrix metalloproteinases (MMPs) are a family of enzymes whose main physiological function is degradation of the extracellular matrix. See, e.g., Parsons, et al. (1997)
Br. J. Surgery
84:160-166. These enzymes are present in normal healthy individuals and have been shown to have an important role in processes such as wound healing (see Wolf, et al. (1992)
J. Invest. Dermatol.
99:870-872; and Wysocki, et al. (1993)
J. Invest. Dermatol.
101:64-68), pregnancy and parturition (see Jeffrey (1991)
Seminars Perinatol.
15:118-126), bone resorption (see Delaisse and Vaes, pp. 290-314 in Rifkin and Gay (eds. 1992)
Biology and Physiology of the Osteoclast
CRC Press, Ratan, Fla.), and mammary involution (Talhouk, et al. (1992)
J. Cell Biol.
118:1271-1282). See also Nagase (1996) in Hooper (ed.)
Zinc Metalloproteinases in Health and Disease
Taylor and Francis, London. A recent focus on the MMPs is on their role in certain disease states in which breakdown of the extracellular matrix is a key feature, e.g., in rheumatoid arthritis (see Harris (1990)
NEJ Med.
322:1277-1289), periodontal disease (see Page (1991)
J. Periodont. Res.
26:230-242), and cancer (see Brown (1997)
Medical Oncology
14:1-10; Chambers and Matisian (1997)
J. NCI
89:1260-1270; Yu, et al. (1997)
Drugs and Aging
11:229-244; Yu, et al. (1997)
Clinical Pharmacology
11:229-244; Wojtowicz-Praga, et al. (1997)
Invest. New Drugs
15:61-75; Coussens and Werb (1996)
Chem. Biol.
3:895-904; and Talbot and Brown (1996)
Eur. J. Cancer
32A:2528-2533).
While there are many uses for proteases, there is always the need for a more active or specific protease under various specific conditions. Alternatively, the distribution of these gene products may be useful as markers for specific cell or tissue types. There is a need for new proteinases of differing properties, specificities, and activities.
SUMMARY OF THE INVENTION
In a search for DC restricted molecules, a novel member of the MMP family of proteolytic enzymes was identified which belongs to the Membrane-type Matrix Metalloproteinase (MT-MMP) subclass. This fifth MT-MMP proteinase, located on chromosome 16p13.3, is present in spleen, lymph node, thymus, appendix, PBL, and bone marrow, and strongly expressed by DC and weakly by granulocytes and effector T cells. Interestingly, the mRNA expression of this gene is down-regulated by CD40L activation of CD34
+
- and monocyte-derived DC. According to its cellular expression and putative membrane localization, a role is proposed for this novel Membrane-type Matrix Metalloproteinase gene in degradation of the extracellular matrix during DC migration.
The present invention provides a binding compound comprising an antibody binding site which specifically binds to primate F06B09 protein; a nucleic acid comprising sequence encoding at least 12 amino acids of primate F06B09 protein; a substantially pure protein which is specifically recognized by the above antibody binding site; a substantially pure primate F06B09 protein or peptide thereof; and a fusion protein comprising a 30 amino acid sequence portion of primate F06B09 protein sequence.
In certain binding compound embodiments, the antibody binding site is specifically immunoreactive with a protein selected from polypeptides of SEQ ID NO: 4; is raised against a purified or recombinantly produced primate F06B09 protein; is immunoselected on a substantially purified or recombinantly produced primate F06B09 protein; is in a monoclonal antibody, Fab, or F(ab)2; is detectably labeled; is attached to a solid substrate; is from a rabbit or mouse; binds with a Kd of at least about 300 &mgr;M; is fused to another protein segment; is in a chimeric antibody; or is coupled to another chemical moiety.
The invention also provides a method of making an antigen-antibody complex, comprising a step of contacting a primate biological sample to a specific binding antibody described. In preferred embodiments, the method further includes steps to purify the antigen or antibody.
Alternative embodiments provide an antibody binding site wherein the binding site is detected in a biological sample by a method comprising the steps of contacting a binding agent having an affinity for F06B09 protein with the biological sample; incubating the binding agent with the biological sample to form a binding agent:F06B09 protein complex; and detecting the complex. In certain embodiments, the biological sample is human, and the binding agent is an antibody.
The invention also provides kits containing a composition described above and instructional material for the use of the composition; or segregation of the composition into a container. Typically, the kit is used to make a qualitative or quantitative analysis.
The invention also embraces a cell comprising an antibody described above; a cell transfected with a nucleic acid described above; or a cell comprising a fusion protein described above.
In nucleic acid embodiments, the nucleic acid may encode a polypeptide which specifically binds an antibody generated against an immunogen selected from the group consisting of the mature polypeptides of SEQ ID NO: 4. Alternatively, the nucleic acid may encode at least 12 amino acids of SEQ ID NO: 4; comprise sequence of at least about 39 nucleotides selected from protein coding portions of SEQ ID NO: 1 or 3; hybridize to SEQ ID NO: 1 or 3 under stringent wash conditions of at least 45° C. and less than about 150 mM salt; comprise sequence made by a synthetic method; be an expression vector; be detectably labeled; be attached to a solid substrate; be from human; bind with a Kd of at least about 300 &mgr;M; be fused to another nucleic acid segment; be coupled to another chemical moiety; be operably associated with promoter, ribosome binding site, or poly-A addition site; be a PCR product; b
Caux Christophe
de Saint-Vis Blandine Marie
Fossiez Francois
Lebecque Serge J. E.
Ching Edwin P.
Dow Karen B.
Hutson Richard
Prouty Rebecca E.
Schering-Plough
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