Identification of a family of secreted proteins in vascular endothelium
AssigneeMillennium Pharmaceuticals, Inc.
InventorsRuey-Bing Yang, Chi Kin Domingos Ng, James E. Tomlinson, Laszlo G. Komuves, James N. Topper, Keith E. Robison
Life of this patent
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Abstract
The invention relates to SCUBE molecules and generally to gene expression in vascular endothelial cells. The invention specifically relates to the discovery of a novel gene family containing the genes and proteins referred to herein as SCUBE1, SCUBE2 and SCUBE3 which can be expressed in endothelial cells. SCUBE proteins may be involved in the development of cardiovascular disease, hemostasis, thrombosis, inflammatory disease, bone metabolism disorders, urinary bladder disorders and breast disorders.
Claims19
An isolated nucleic acid molecule selected from the group consisting of:
- (a) an isolated nucleic acid molecule comprising SEQ ID NO:
- 16, 18, 3, 5, or 7;
- (b) an isolated nucleic acid molecule that encodes the amino acid sequence of SEQ ID NO:
- 17, 19, 4, 6 or 8;
- (c) an isolated nucleic acid molecule which hybridizes to the complement of a nucleic acid molecule comprising SEQ ID NO:
- 16, 18, 3, 5, or 7 and which encodes a human SCUBE protein;
- (d) an isolated nucleic acid molecule which hybridizes to the complement of a nucleic acid molecule that encodes the amino acid sequence of SEQ ID NO:
- 17, 19, 4, 6, or 8 and which encodes a human SCUBE protein;
- (e) an isolated nucleic acid molecule that encodes a protein that exhibits at least about 92% amino acid sequence identity to SEQ ID NO:
- 4;
- (f) an isolated nucleic acid molecule that encodes a protein that exhibits at least about 95% amino acid sequence identity to SEQ ID NO:
- 6;
- (g) an isolated nucleic acid molecule that encodes a protein that exhibits at least about 95% amino acid sequence identity to SEQ ID NO:
- 8;
- (h) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 17, 19, 4, 6, or 8, wherein the fragment comprises at least 10 contiguous amino acids of SEQ ID NO:
- 17, 19, 4, 6, or 8;
- and
- (i) an isolated nucleic acid molecule that encodes the amino acid sequences of SEQ ID NO:
- 4, 6 or 8 without a signal peptide sequence.
An isolated polypeptide molecule selected from the group consisting of:
- (a) an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:
- 17, 19, 6, or 8;
- (b) an isolated polypeptide comprising conservative amino acid substitutions of SEQ ID NO:
- 17, 19, 6, or 8;
- (c) a naturally occurring amino acid sequence variant of SEQ ID NO:
- 17, 19, 6, or 8;
- (d) an isolated polypeptide exhibiting at least 95% amino acid sequence identity with SEQ ID NO:
- 6;
- (e) an isolated polypeptide exhibiting at least 95% amino acid sequence identity with SEQ ID NO:
- 8;
- (f) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 17, 19, 6, or 8, wherein the fragment comprises at least 10 contiguous amino acids of SEQ ID NO:
- 17, 19, 6, or 8;
- and
- (g) an isolated polypeptide comprising SEQ ID NO:
- 6, or 8 without a signal peptide.
A method of treating a disorder from the group consisting of:
- atherosclerosis, ischemia, a coagulation disorder or thrombosis;
- in a subject by administering to the subject a compound which modulates the function of a polypeptide selected from the group consisting of:
- (a) an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:
- 17, 19, 4, 6, or 8;
- (b) an isolated polypeptide comprising conservative amino acid substitutions of SEQ ID NO:
- 17, 19, 4, 6, or 8;
- (c) a naturally occurring amino acid sequence variant of SEQ ID NO:
- 17, 19, 4, 6, or 8;
- (d) an isolated polypeptide exhibiting at least 92% amino acid sequence identity with SEQ ID NO:
- 4;
- (e) an isolated polypeptide exhibiting at least 95% amino acid sequence identity with SEQ ID NO:
- 6;
- (f) an isolated polypeptide exhibiting at least 95% amino acid sequence identity with SEQ ID NO:
- 8;
- (g) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 17, 19, 4, 6, or 8, wherein the fragment comprises at least 10 contiguous amino acids of SEQ ID NO:
- 17, 19, 4, 6, or 8;
- (h) an isolated polypeptide comprising SEQ ID NO:
- 4, 6, or 8 without a signal peptide;
- (i) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence comprising the nucleotide sequence of SEQ ID NO:
- 16, 18, 3, 5, or 7, or a complement thereof;
- (j) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 17, 19, 4, 6, or 8, wherein the fragment comprises at least 10 contiguous amino acids of SEQ ID NO:
- 17, 19, 4, 6, or 8, further comprising heterologous amino acid sequences;
- and
- (k) a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 17, 19, 4, 6, or 8, further comprising heterologous amino acid sequences.
Dependencies are inferred from the claim text.