NOVEL RECEPTOR NUCLEIC ACIDS AND POLYPEPTIDES
Disclosed are nucleic acids encoding BAFF-R polypeptides, as well as antibodies to BAFF-R polypeptides and pharmaceutical compositions including the same. Methods of treating tumorigenic and autoimmune conditions using the nucleic acids, polypeptides, antibodies and pharmaceutical compositions of this invention are also provided.
1 - 55 . (canceled)
56 . A method of detecting a BAFF-R polypeptide, said method comprising:
(a) providing a biological sample; and
(b) contacting the sample with an isolated antibody, or an antigen binding portion thereof, that specifically binds to an amino acid sequence selected from the group consisting of SEQ ID NO:5, SEQ ID NO:10, and SEQ ID NO:9.
57 . The method of claim 56 , wherein the antibody is chimeric.
58 . The method of claim 56 , wherein the antibody is humanized.
59 . The method of claim 56 , wherein the antibody is monoclonal.
60 . The method of claim 56 , wherein the antibody is a single-chain antibody.
61 . The method of claim 56 , wherein the antibody is a Fab fragment.
62 . The method of claim 56 , wherein the antibody is as produced by hybridoma clone #2.1, deposited under ATCC No. PTA-3689.
63 . The method of claim 56 , wherein the antibody is as produced by hybridoma clone #9.1, deposited under ATCC No. PTA-3688.
64 . A method of measuring BAFF-R mRNA levels, said method comprising:
(a) providing a biological sample from a subject; and
(b) determining the level of BAFF-R mRNA in the sample using a nucleic acid molecule capable of hybridizing under stringent conditions to:
(i) a nucleic acid sequence that encodes an amino acid sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:14, SEQ ID SEQ ID NO:9 and SEQ ID NO:10; or
(ii) a complement of (ii).
65 . The method of claim 64 , wherein the nucleic acid molecule is a oligonucleotide probe consisting of at least 15, 30, 50, 100, 250, or 500 consecutive nucleotides from:
(a) a complement of a nucleic acid sequence that encodes SEQ ID NO:9 or SEQ ID NO:10; or
(b) a nucleic acid sequence that encodes SEQ ID NO:9 or SEQ ID NO:10.
66 . The method of claim 65 , wherein the oligonucleotide probe is labeled.
67 . The method of claim 64 , wherein the method comprises the step of using polymerase chain reaction (PCR).
68 . The method of claim 56 or claim 64 , wherein the biological sample is a tissue, fluid or cell from a subject.
69 . The method of claim 68 , wherein the BAFF-R mRNA encodes the amino acid sequence of SEQ ID NO:13.
70 . The method of claim 69 , wherein the BAFF-R mRNA encodes the amino acid sequence of SEQ ID NO:10.
71 . The method of claim 56 or claim 64 , wherein the BAFF-R mRNA encodes the amino acid sequence of SEQ ID NO:14.
72 . The method of claim 71 , wherein the BAFF-R mRNA encodes the amino acid sequence of SEQ ID NO:9.
73 . The method of claim 56 or claim 64 , wherein the biological sample is obtained from a mammal.
74 . The method of claim 73 , wherein the mammal is human.
75 . The method of claim 73 , wherein the mammal has or is at risk of having a disease or condition selected from the group comprising a B-cell-mediated condition, an autoimmune condition, a tumorigenic condition, a plasma cell disorder, a B-cell carcinoma, leukemia, lymphoma, hypertension, a cardiovascular disorder, a renal disorder, an immunosuppressive disorder, organ transplantation, and Burkitt's lymphoma.
76 . The method of claim 75 , wherein the mammal has or is at risk for B cell carcinoma, leukemia, or lymphoma.
77 . The method of claim 75 , wherein the autoimmune condition is systemic lupus erythematosus.
78 . The method of claim 75 , wherein the autoimmune condition is rheumatoid arthritis.
79 . The method of claim 73 , wherein the mammal has or is at risk of having a disease or condition selected from multiple myeloma, Waldenstrom's macroglobulinemia, heavy-chain disease, primary or immunocyte associated amyloidosis, or monoclonal gammopathy of undetermined significance (MGUS).
80 . A method of diagnosing a disease or condition in a subject comprising the method of claim 56 , thereby diagnosing the disease or condition.
81 . A method of diagnosing a disease or condition in a subject comprising the method of claim 57 , thereby diagnosing the disease or condition.
82 . A method of diagnosing a B-cell mediated condition in a subject comprising:
(a) providing a biological sample from the subject;
(b) measuring the amount of BAFF-R polypeptide in the subject sample; and
(c) comparing the amount of BAFF-R polypeptide in the subject sample to the amount of BAFF-R polypeptide in a control sample,
wherein a difference in the amount of BAFF-R polypeptide in the subject sample as compared to the amount of BAFF-R polypeptide in the control sample indicates that the subject has a B-cell mediated condition.
83 . A method of diagnosing a B-cell-mediated condition in a subject comprising:
(a) measuring the amount of BAFF-R nucleic acid in a sample obtained from the subject; and
(b) comparing the amount of BAFF-R nucleic acid in the subject sample to the amount of BAFF-R nucleic acid in a control sample,
wherein a difference in the amount of BAFF-R nucleic acid in the subject sample as compared to the amount of BAFF-R nucleic acid in the control sample indicates that the subject has a B-cell-mediated condition.
84 . A method for identifying cells or tissues that misexpress BAFF-R comprising:
(a) contacting an oligonucleotide probe comprising at least 25 consecutive nucleotides from any one of the following: SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:6 with a biological sample of a subject; and
(b) measuring a level of a BAFF-R-encoding nucleic acid molecule in the biological sample by detecting BAFF-R mRNA levels; or alternatively,
(c) determining whether a BAFF-R nucleic acid molecule in the biological sample has been mutated or deleted.
85 . A method for determining whether a genomic BAFF-R sequence has been mutated or deleted comprising:
(a) providing a biological sample of a subject; and
(b) determining whether a BAFF-R nucleic acid molecule in the biological sample has been mutated or deleted using an nucleic acid molecule capable of hybridizing with human or mouse genomic sequence of BAFF-R.