TALL-1 nucleic acid molecules, proteins, receptors and methods of use thereof
AssigneeNational Jewish Medical and Research Center
InventorHong-Bing Shu
Life of this patent
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Abstract
The amino acid and nucleic acid sequence of a protein expressed by monocytes and macrophages, called TALL-1, are disclosed. Homologues, mimetics and antibodies that bind to TALL-1 are disclosed. Also disclosed is the TALL-1 receptor, and homologues of such receptor. The invention includes methods for regulating the interaction between TALL-1 and its receptor and for identifying compounds capable of such regulation. The invention also includes methods for regulating B lymphocyte proliferation, activation, and/or survival.
Claims80
An isolated TALL-1 protein.
An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a protein comprising an amino acid sequence selected from the group consisting of:
- a. SEQ ID NO:2;
- and,
- b. a homologue of SEQ ID NO:2, wherein said homologue comprises an amino acid sequence selected from the group consisting of:
- (i) an amino acid sequence comprising at least 130 contiguous amino acids of SEQ ID NO:2;
- and,
- (ii) an amino acid sequence comprising at least positions 134-285 of SEQ ID NO:2.
A recombinant nucleic acid molecule comprising an expression vector operatively linked to a nucleic acid molecule comprising a nucleic acid sequence encoding a protein having TALL-1 biological activity, wherein said protein comprises an amino acid sequence selected from the group consisting of:
- a. SEQ ID NO:2;
- and,
- b. a homologue of SEQ ID NO:2, wherein said homologue comprises an amino acid sequence selected from the group consisting of:
- (i) an amino acid sequence that is at least about 40% identical to SEQ ID NO:2 over at least 175 amino acids of SEQ ID NO:2;
- and,
- (ii) an amino acid sequence that is at least about 40% identical to SEQ ID NO:2 over positions 134-285 of SEQ ID NO:2.
An isolated TALL-1 receptor homologue, wherein said homologue comprises an amino acid sequence that is:
- a. at least about 40% identical to SEQ ID NO:11 over at least 35 amino acids of SEQ ID NO:11;
- and,
- b. less than 100% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:11 and SEQ ID NO:17.
An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a TALL-1 receptor homologue, wherein said homologue comprises an amino acid sequence that is:
- a. at least about 40% identical to SEQ ID NO:11 over at least 35 amino acids of SEQ ID NO:11;
- and,
- b. less than 100% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:11 and SEQ ID NO:17.
A composition comprising:
- a. a compound selected from the group consisting of:
- (i) an isolated TALL-1 protein;
- (ii) an isolated antibody that selectively binds to said TALL-1 protein of (i);
- (iii) an isolated TALL-1 receptor;
- and,
- (iv) an isolated antibody that selectively binds to said TALL-1 receptor of (iii);
- and,
- b. a pharmaceutically acceptable carrier.
A method to activate a TALL-1 receptor, comprising contacting a TALL-1 receptor with a TALL-1 protein.
A method to regulate B lymphocyte proliferation, activation, and/or survival, comprising regulating the biological activity of a TALL-1 receptor expressed by a B lymphocyte.
A method to inhibit a B lymphocyte immune response in a patient, comprising inhibiting the interaction of TALL-1 with a TALL-1 receptor in said patient.
A method to inhibit a B lymphocyte-associated autoimmune disease in a patient, comprising inhibiting the interaction of TALL-1 with a TALL-1 receptor in said patient.
A method to identify compounds that regulate the interaction between TALL-1 and a TALL-1 receptor, comprising:
- a. contacting a TALL-i receptor with a putative regulatory compound;
- b. contacting said TALL-1 receptor with a TALL-1 protein comprising an amino acid sequence selected from the group consisting of:
- (i) SEQ ID NO:2;
- and,
- (ii) a homologue of SEQ ID NO:2, wherein said homologue comprises an amino acid sequence selected from the group consisting of:
- (1) an amino acid sequence that is at least about 40% identical to SEQ ID NO:2 over at least 175 amino acids of SEQ ID NO:2;
- and,
- (2) an amino acid sequence that is at least about 40% identical to SEQ ID NO:2 over positions 134-285 of SEQ ID NO:2 or a homologue of TALL-1;
- wherein said TALL-1 protein binds to and activates said TALL-1 receptor in the absence of said putative regulatory compound;
- and,
- c. detecting whether said putative regulatory compound regulates said TALL-1 receptor.
Dependencies are inferred from the claim text.