Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of...
Reexamination Certificate
2002-09-18
2004-09-14
Wax, Robert A. (Department: 1653)
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
C435S252300, C435S254110, C435S320100, C536S023100
Reexamination Certificate
active
06790660
ABSTRACT:
1.0 INTRODUCTION
The present invention relates to the discovery, identification, and characterization of novel human polynucleotides encoding proteins sharing sequence similarity with animal kielin proteins. The invention encompasses the described polynucleotides, host cell expression systems, the encoded proteins, fusion proteins, polypeptides and peptides, antibodies to the encoded proteins and peptides, and genetically engineered animals that either lack or overexpress the disclosed polynucleotides, antagonists and agonists of the proteins, and other compounds that modulate the expression or activity of the proteins encoded by the disclosed polynucleotides, which can be used for diagnosis, drug screening, clinical trial monitoring, the treatment of diseases and disorders, and cosmetic or nutriceutical applications.
2.0 BACKGROUND OF THE INVENTION
Kielins are secreted proteins that have been implicated in a number of biological processes and anomalies such as development and signal transduction. Therefore, kielins are good drug targets.
3.0 SUMMARY OF THE INVENTION
The present invention relates to the discovery, identification, and characterization of nucleotides that encode novel human proteins, and the corresponding amino acid sequences of these proteins. The novel human proteins (NHPs) described for the first time herein share structural similarity with animal kielin, zonadhesin, and chordin proteins and other animal proteins including, but not limited to, human secreted proteins. The novel human nucleic acid sequence described herein encode alternative proteins/open reading frames (ORFs) of 685 and 627 amino acids in length (see SEQ ID NOS:2 and 4, respectively).
The invention also encompasses agonists and antagonists of the described NHPs, including small molecules, large molecules, mutant NHPs, or portions thereof, that compete with native NHPs, peptides, and antibodies, as well as nucleotide sequences that can be used to inhibit the expression of the described NHPs (e.g., antisense and ribozyme molecules, and open reading frame or regulatory sequence replacement constructs) or to enhance the expression of the described NHPs (e.g., expression constructs that place the described polynucleotide under the control of a strong promoter system), and transgenic animals that express a NHP sequence, or “knock-outs” (which can be conditional) that do not express a functional NHP. Knock-out mice can be produced in several ways, one of which involves the use of mouse embryonic stem cell (“ES cell”) lines that contain gene trap mutations in a murine homolog of at least one of the described NHPs. When the unique NHP sequences described in SEQ ID NOS:1-4 are “knocked-out” they provide a method of identifying phenotypic expression of the particular gene, as well as a method of assigning function to previously unknown genes. In addition, animals in which the unique NHP sequences described in SEQ ID NOS:1-4 are “knocked-out” provide an unique source in which to elicit antibodies to homologous and orthologous proteins, which would have been previously viewed by the immune system as “self” and therefore would have failed to elicit significant antibody responses.
Additionally, the unique NHP sequences described in SEQ ID NOS:1-4 are useful for the identification of protein coding sequences, and mapping an unique gene to a particular chromosome. These sequences identify biologically verified exon splice junctions, as opposed to splice junctions that may have been bioinformatically predicted from genomic sequence alone. The sequences of the present invention are also useful as additional DNA markers for restriction fragment length polymorphism (RFLP) analysis, and in forensic biology, particularly given the presence of nucleotide polymorphisms within the described sequences.
Further, the present invention also relates to processes for identifying compounds that modulate, i.e., act as agonists or antagonists of, NHP expression and/or NHP activity that utilize purified preparations of the described NHPs and/or NHP products, or cells expressing the same. Such compounds can be used as therapeutic agents for the treatment of any of a wide variety of symptoms associated with biological disorders or imbalances.
4.0 DESCRIPTION OF THE SEQUENCE LISTING AND FIGURES
The Sequence Listing provides the sequences of NHP ORFs encoding the described NHP amino acid sequences.
REFERENCES:
patent: 4215051 (1980-07-01), Schroeder et al.
patent: 4376110 (1983-03-01), David et al.
patent: 4594595 (1986-06-01), Struckman
patent: 4631211 (1986-12-01), Houghten
patent: 4689405 (1987-08-01), Frank et al.
patent: 4713326 (1987-12-01), Dattagupta et al.
patent: 4873191 (1989-10-01), Wagner et al.
patent: 4946778 (1990-08-01), Ladner et al.
patent: 5252743 (1993-10-01), Barrett et al.
patent: 5272057 (1993-12-01), Smulson et al.
patent: 5416017 (1995-05-01), Burton et al.
patent: 5424186 (1995-06-01), Fodor et al.
patent: 5445934 (1995-08-01), Fodor et al.
patent: 5459127 (1995-10-01), Felgner et al.
patent: 5556752 (1996-09-01), Lockhart et al.
patent: 5631407 (1997-05-01), Racaniello et al.
patent: 5700637 (1997-12-01), Southern
patent: 5741957 (1998-04-01), Deboer et al.
patent: 5744305 (1998-04-01), Fodor et al.
patent: 5830721 (1998-11-01), Stemmer et al.
patent: 5837458 (1998-11-01), Minshull et al.
patent: 5869336 (1999-02-01), Meyer et al.
patent: 5877397 (1999-03-01), Lonberg et al.
patent: 5948767 (1999-09-01), Scheule et al.
patent: 6075181 (2000-06-01), Kucherlapati et al.
patent: 6110490 (2000-08-01), Thierry
patent: 6114598 (2000-09-01), Kucherlapati et al.
patent: 6150584 (2000-11-01), Kucherlapati et al.
patent: WO 96/04376 (1996-02-01), None
Milici et al., “Transcytosis of Albumin In Capillary Endothelium”, The Journal of Cell Biology, vol. 105 (No. 6, Pt. 1), Dec. 1987, pp. 2603-2612.
Schnitzer et al., “Albumin interacts specifically with a 60-kDa microvascular endothelial glycoprotein”, Proc. Natl. Acad. Sci., vol. 85, Sep. 1988, pp. 6773-6777.
Nomura, “Practical Development of Genetically Engineered Animals as Human Disease Models”, Laboratory Animal Science, vol. 47, No. 2, Apr. 1997, pp. 113-117.
Ruther et al 1983, “Easy identification of cDNA clones”, EMBO Journal 2(10):1791-1794.
Santerra et al, 1984, “Expression of prokaryotic genes for hygromycin B and G418 resistance as dominant-selection markers in mouse L cells”, Gene 30:147-156.
Sarin et al, 1988, “Inhibition of acquired Immunodeficiency syndrome virus by oligodeoxynucleoside methylphosphonates”, Proc. Natl. Acad. Sci. USA 85:7448-7451.
Smith et al, 1983, “Molecular Engineering of the Autographa californica Nuclear Polyhedrosis Virus Genome: Deletion Mutations within the Polyhedrin Gene”, J. Virol. 46(2):584-593.
Stein et al, 1988, “Physiochemical properties of phosphorothioate oligodeoxynucleotides”, Nucleic Acids Research 16(8):3209-3221.
Szybalska & Szybalski, 1962, “Genetics of Human Cell Lines, IV. DNA-Mediated Heritable Transformation of a Biochemical Trait”, Proc. Natl. Acad. Sci. USA 48:2026-2034.
Takeda et al, 1985, “Construction of Chimaeric processed immunoglobulin genes containing mouse variable and human constant region sequences”, Nature 314:452-454.
Thompson et al, 1989, “Germ Line Transmission and Expression of a Corrected HPRT Gene Produced by Gene Targeting in Embryonic Stem Cells”, Cell 56:313-321.
Van Der Putten et al, 1985, “Efficient insertion of genes into the mouse germ line via retroviral vectors”, Proc. Natl. Acad. Sci. USA 82:6148-6152.
Van Heeke et al, 1989, “Expression of Human Asparagine Synthetase inEscherichia coli”, J. Biol. Chemistry 264(10):5503-5509.
Ward et al, 1989, “Binding activities of a repertoire of single immunoglobulin variable domains secreted fromEscherichia coli”, Nature 341:544-546.
Wigler et al, 1977, “Transfer of Purified Herpes Virus Thymidine Kinase Gene to Cultured Mouse Cells”, Cell 11:223-232.
Wigler et al, 1980, “Transformation of mammalian cells with an amplifiable dominant-acting gene”, Proc. Natl. Acad. Sci. USA 77(6):3567-3570.
Bird et al, 1988, “Single-Chain Antigen-Binding Pro
Nguyen Nghi D.
Scoville John
Wilganowski Nathaniel L.
Yu Xuanchuan
Lexicon Genetics Incorporated
Wax Robert A.
LandOfFree
Human kielin-like proteins and polynucleotides encoding the... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Human kielin-like proteins and polynucleotides encoding the..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Human kielin-like proteins and polynucleotides encoding the... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3193431