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
1998-08-06
2002-07-09
Prouty, Rebecca E. (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...
C435S183000, C435S252300, C435S320100, C435S325000, C536S023200, C536S025100
Reexamination Certificate
active
06416974
ABSTRACT:
SUMMARY OF THE INVENTION
The invention relates to the discovery and characterization of Tango-71, Tango-73, Tango-74, Tango-76, and Tango-83. Tango-71 is a human protein which is approximately 90% identical to murine ADAMTS-1. Tango-73is a human protein that is 48% identical to rate RVP.1 (Briehl et al.,
Mol. Endocrinol.
5:1381, 1991). Tango-74 is a human protein with homology to TRAIL receptor (Pan et al.,
Science
276:111, 1997). Tango-76 is a rat protein which is approximately 40% identical to murine ADAMTS-1. Tango-83 is expressed by stimulated human astrocytes.
The invention features isolated nucleic acid molecules encoding Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83 polypeptides; isolated nucleic acid molecules encoding polypeptides which are substantially similar to Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83; and isolated nucleic acid molecules which hybridize under stringent conditions to a nucleic acid molecule having the sequence of the protein coding portion of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, or SEQ ID NO:9.
The invention also features a host cell which includes an isolated nucleic acid molecule encoding Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83 and a nucleic acid vector (e.g., an expression vector; a vector which includes a regulatory element; a vector which includes a regulatory element selected from the group consisting of the cytomegalovirus hCMV immediate early gene, the early promoter of SV40 adenovirus, the late promoter of SV40 adenovirus, the lac system, the trp system, the TAC system, the TRC system, the major operator and promoter regions of phage &lgr;, the control regions of fd coat protein, the promoter for 3-phosphoglycerate kinase, the promoters of acid phosphatase, and the promoters of the yeast &agr;-mating factors; vector which includes a regulatory element which directs tissue-specific expression; a vector which includes a reporter gene; a vector which includes a reporter gene selected from the group selected from the group consisting of &bgr;-lactamase, chloramphenicol acetyltransferase (CAT), adenosine deaminase (ADA), aminoglycoside phosphotransferase (neo
r
, G418
r
), dihydrofolate reductase (DHFR), hygromycin-B-phosphotransferase (HPH), thymidine kinase (TK), lacZ (encoding &bgr;-galactosidase), and xanthine guanine phosphoribosyltransferase (XGPRT); a vector that is a plasmid, a vector that is a virus; and a vector that is a retrovirus) containing an isolated nucleic acid molecule encoding Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83.
The invention also features substantially pure Tango-71, Tango-73, Tango-74, Tango-76, and Tango-83 polypeptides; a substantially pure polypeptide which includes a first portion and a second portion, the first portion including a Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83 polypeptide and the second portion including a detectable marker.
The invention also features an antibody that selectively binds to a Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83 polypeptide (e.g., a monoclonal antibody).
The invention also features a pharmaceutical composition which includes a Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83 polypeptide.
The invention includes methods for diagnosing a disorder associated with aberrant expression of a protein of the invention (i.e., Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83), the method including obtaining a biological sample from a patient and measuring the expression of the protein in the biological sample, wherein increased or decreased expression of the protein in the biological sample compared to a control indicates that the patient suffers from a disorder associated with aberrant expression of the protein.
The invention encompasses isolated nucleic acid molecules encoding Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83 or a polypeptide fragment thereof; vectors containing these nucleic acid molecules; cells harboring recombinant DNA encoding Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83; fusion proteins which include all or a portion of Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83; transgenic animals which express Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83; and recombinant knock-out animals which fail to express Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83.
The invention encompasses nucleic acids that have a sequence that is substantially identical to a Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83 nucleic acid sequence. A nucleic acid molecule which is substantially identical to a given reference nucleic acid molecule is hereby defined as a nucleic acid molecule having a sequence that has at least 85%, preferably 90%, and more preferably 95%, 98%, 99% or more identity to the sequence of the given reference nucleic acid molecule.
The invention also includes polypeptides which are substantially identical to Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83 (e.g., polypeptides that are substantially identical to the polypeptide of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, or SEQ ID NO:10).
A polypeptide which is “substantially identical” to a given reference polypeptide molecule is a polypeptide having an amino acid sequence that has at least 85%, preferably 90%, and more preferably 95%, 98%, 99% or more identity to the amino acid sequence of the given reference polypeptide.
To determine the percent identity of two amino acid sequences or of two nucleic acids, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in the sequence of a first amino acid or nucleic acid sequence for optimal alignment with a second amino or nucleic acid sequence). The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences (i.e., % identity=# of identical positions/total # of positions (e.g., overlapping positions)×100). Preferably, the two sequences are the same length.
The determination of percent homology between two sequences can be accomplished using a mathematical algorithm. A preferred, non-limiting example of a mathematical algorithm utilized for the comparison of two sequences is the algorithm of Karlin and Altschul (1990)
Proc. Natl. Acad. Sci. USA
87:2264-2268, modified as in Karlin and Altschul (1993)
Proc. Natl. Acad. Sci. USA
90:5873-5877. Such an algorithm is incorporated into the NBLAST and XBLAST programs of Altschul, et al. (1990)
J. Mol. Biol.
215:403-410. BLAST nucleotide searches can be performed with the NBLAST program, score=100, wordlength=12 to obtain nucleotide sequences homologous to Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83 nucleic acid molecules of the invention. BLAST protein searches can be performed with the XBLAST program, score=50, wordlength=3 to obtain amino acid sequences homologous to Tango-71, Tango-73, Tango-74, Tango-76, or Tango-83 protein molecules of the invention. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al. (1997)
Nucleic Acids Res.
25:3389-3402. Alternatively, PSI-Blast can be used to perform an iterated search which detects distant relationships between molecules. Id. When utilizing BLAST, Gapped BLAST, and PSI-Blast programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used. See http://www.ncbi.nlm.nih.gov. Another preferred, non-limiting example of a mathematical algorithm utilized for the comparison of sequences is the algorithm of Myers and Miller, (1988)
CABIOS
4:11-17. Such an algorithm is incorporated into the ALIGN program (version 2.0) which is part of the GCG sequence alignment software package. When utilizing the ALIGN program for com
Goodearl Andrew D. J.
Holtzman Douglas A.
Fish & Richardson PC
Millennium Pharmaceuticals Inc.
Prouty Rebecca E.
Rao Manjunath N.
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