Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2000-01-18
2004-06-01
Gambel, Phillip (Department: 1644)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C435S069100, C435S455000, C435S471000, C435S252300, C435S320100, C435S810000, C435S006120
Reexamination Certificate
active
06743903
ABSTRACT:
FIELD OF THE INVENTION
This invention generally pertains to the fields of medicine and medical diagnostics. In particular, this invention provides novel genes and polypeptides and methods for making and using them. Specifically, the compositions and methods of the invention are used to diagnose and treat Giant Cell Arteritis (GCA).
BACKGROUND OF THE INVENTION
Giant cell arteritis (GCA) is a systemic vasculitis that is a serious and potentially blinding rheumatologic disease of the elderly. Current treatment of GCA requires systemic immunosuppression with profound morbidity in the affected elderly population. GCA is widely believed to be immune-mediated; however, the etiology and pathogenesis of this systemic vasculitis remains unidentified. Furthermore, diagnosis of GCA is difficult because it relies on a constellation of nonspecific signs and symptoms and a diagnostic arterial biopsy. Significantly, blindness may be the first symptom of GCA. Thus, if a way were found to better diagnose or even screen for early onset or predisposition for GCA at an earlier stage of the disease, many cases of blindness and many lives would be saved.
Currently, corticosteroids are critical in the treatment of giant cell arteritis; they reduce the incidence of blindness and rapidly relieve symptoms. However, the amounts of steroids (e.g., prednisone) needed are significant and not without side effects, particularly as they usually must be given over an extended period of time, usually about two years. Steroid treatment is not unformly effective and causes significant morbidity in up to 40% of patients because of hypertension, osteoporosis, infection, glucose dysregulation, fluid overload, and aseptic necrosis of the hip or shoulder. Alternative use of nonsteroidal anti-inflammatory drugs (NSAIDs) will lessen the painful symptoms, but they do not prevent the blindness or vascular problems. Accordingly, new methods of treating GCA are needed. The present invention addresses these and other needs.
SUMMARY OF THE INVENTION
The present invention provides novel compositions and methods in the screening for, diagnosis of and treatment of GCA.
The invention provides an isolated or recombinant nucleic acid comprising a nucleic acid sequence having at least 75% sequence identity to SEQ ID NO:1 or a nucleic acid encoding a polypeptide, wherein the polypeptide has a sequence as set forth in SEQ ID NO:2; or a nucleic acid sequence having at least 75% sequence identity to SEQ ID NO:3 or a nucleic acid encoding a polypeptide, wherein the polypeptide has a sequence as set forth in SEQ ID NO:4; or a nucleic acid sequence having at least 85% sequence identity to SEQ ID NO:5 or a nucleic acid encoding a polypeptide, wherein the polypeptide has a sequence as set forth in SEQ ID NO:6; or a nucleic acid sequence having at least 75% sequence identity to SEQ ID NO:7 or a nucleic acid encoding a polypeptide, wherein the polypeptide has a sequence as set forth in SEQ ID NO:8. In various embodiments, the sequence identity to SEQ ID NO:1 is at least 80%, 85%, 90%, 95%, and 98%; the sequence identity to SEQ ID NO:3 is at least 80%, 85%, 90%, 95%, and 98%; the sequence 8 identity to SEQ ID NO:5 is at least 900%, 95%, and 98%; and, the sequence identity to SEQ ID NO:7 is at least 80%, 85%, 90%, 95%, and 98%. The nucleic acid can also comprises a sequence as set forth in SEQ ID NO:1; SEQ ID NO:3; SEQ ID NO:5; or SEQ ID NO:7.
The invention also provides an isolated or recombinant nucleic acid comprising a nucleic acid sequence having at least 75% sequence identity to SEQ ID NO:9, SEQ ID NO:10; SEQ ID NO:11; SEQ ID NO:13; SEQ ID NO:14, SEQ ID NO:15 or SEQ ID NO:16; or has a sequence as set forth in SEQ ID NO:12. In alternative embodiments, the sequence identity to SEQ ID NO:9, SEQ ID NO:10; SEQ ID NO:11; SEQ ID NO:13; SEQ ID NO:14, SEQ ID NO:15 or SEQ ID NO:16 is at least 80%, 85%, 90%, 95%, and 98%. The nucleic acid can also have a sequence as set forth in SEQ ID NO:9, SEQ ID NO:10; SEQ ID NO:11; SEQ ID NO:13; SEQ ID NO:14, SEQ ID NO:15 or SEQ ID NO:16.
The invention provides an isolated or recombinant nucleic acid which specifically hybridizes to a nucleic acid comprising a sequence as set forth in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15 or SEQ ID NO:16 under stringent conditions, wherein the stringent conditions include a wash step comprising a wash in 0.2×SSC at a temperature of about 65° C. for about 15 minutes. The nucleic acid can be between about 15 and about 200 residues in length; between about 25 and about 100 residues in length; or between about 35 and about 75 residues in length.
The invention provides an expression vector comprising at least one nucleic acid operably linked to a promoter, wherein the nucleic acid comprises a nucleic acid sequence of the invention. In the expression vector, the nucleic acid can be operably linked to the promoter in the sense orientation or the antisense orientation. Also provided is a transformed cell comprising the nucleic acids and/or expression vectors of the invention.
The invention provides a polymerase chain reaction (PCR) primer pair that can amplify a nucleic acid sequence of the invention, or a subsequence thereo, under in situ or in vitro conditions.
The invention provides an isolated or recombinantly expressed polypeptide, said polypeptide encoded by nucleic acid which specifically hybridizes to a nucleic acid comprising a sequence as set forth in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15 or SEQ ID NO:16 under stringent conditions, wherein the stringent conditions include a wash step comprising a wash in 0.2×SSC at a temperature of about 65° C. for about 15 minutes.
The invention provides a polypeptide encoded by SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15 or SEQ ID NO:16 in any reading frame on either strand (e.g., coding strand or complementary strand); such exemplary polypeptide and peptide sequences of the invention are set forth herein.
The invention provides an isolated or recombinantly expressed polypeptide having 75% sequence identity to SEQ ID NO:2, 75% sequence identity to SEQ ID NO:4, having 85% sequence to SEQ ID NO:6 or 75% sequence identity to SEQ ID NO:8. In alternative embodiments, the polypeptide has 80%, 85%, 90%, 95%, and 98% sequence identity to an amino acid sequence as set forth in SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:8; and, 90%, 95%, and 98% sequence identity to an amino acid sequence as set forth in SEQ ID NO:6. The isolated or recombinantly expressed polypeptide of the invention can have an amino acid sequence as set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, or SEQ ID NO:8. The isolated or recombinantly expressed polypeptide can be between about 15 and about 200 residues in length; between about 25 and about 100 residues in length; or between about 35 and about 75 residues in length.
The invention further provides an immunogenic peptide comprising a subsequence of a polypeptide of the invention, exemplary sequences of which are provided herein. For example, the immunogenic peptide can have a sequence as set forth from about residue 1 to residue 92 of SEQ ID NO:2; about residue 1 to 124 of SEQ ID NO:4; about residue 1 to 48 of SEQ ID NO:6; or about residue 1 to 81 of SEQ ID NO:8. The invention also provides a fusion protein comprising a polypeptide, particularly an immunogenic peptide, and a heterologous sequence. The heterologous sequence can be any sequence not GCA-associated; for example, a sequence that aids in the expression, isolation/purification of the fusion protein.
The invention provides an isolated or recombinant antibody or binding fragment thereof which specifically binds to a polypeptide or peptide or an immunogenic fragment thereof, of the invention. The antibody can be a monoclonal antibody or a polyclonal antibody or binding
Goldman Melissa
Goodglick Lee
Gordon Lynn K.
Gambel Phillip
Roark Jessica H.
Smith , Gambrell & Russell, LLP
Sundby Suzannah K.
The Regents of the University of California
LandOfFree
Nucleic acids for the diagnosis and treatment of giant cell... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Nucleic acids for the diagnosis and treatment of giant cell..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nucleic acids for the diagnosis and treatment of giant cell... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3350668