Novel notch-like polypeptides
AssigneeApplied Research Systems ARS Holding N.V.
InventorsJadwiga Bienkowska, Gregg Macallister
Life of this patent
Estimating the term…
Abstract
The present invention discloses open reading frames (ORFs) in human genome encoding for novel notch-like polypeptides, and reagents related thereto including variants, mutants and fragments of said polypeptides, as well as ligands and antagonists directed against them. The invention provides methods for identifying and making these molecules, for preparing pharmaceutical compositions containing them, and for using them in the diagnosis, prevention and treatment of diseases.
Claims16
1-41. (canceled)
A composition of matter comprising:
- a) an isolated polypeptide having notch-like activity selected from the group consisting of:
- 1) the amino acid sequence recited in SEQ ID NO:
- 2;
- 2) the mature form of the polypeptide whose sequence is recited in SEQ ID NO:
- 2 (SEQ ID NO:4);
- 3) active variants of the amino acid sequence of SEQ ID NO:
- 2, wherein any amino acid specified in the chosen sequence is non-conservatively substituted, provided that no more than 15% of the amino acid residues in the sequence are so changed;
- and 4) the active fragment, precursor, salt, or derivative of the amino acid sequences given in 1), 2), or 3);
- b) an isolated polypeptide that is a naturally occurring allelic variant of the sequence given by SEQ ID NO:
- 2 or SEQ ID NO:4;
- c) an isolated polypeptide that is a naturally occurring allelic variant of the sequence given by SEQ ID NO:
- 2 or SEQ ID NO:4, wherein the variant is the translation of a single nucleotide polymorphism;
- d) a polypeptide as set forth in a) or b) or c), wherein the polypeptide binds specifically an antibody or a binding protein generated against SEQ ID NO:
- 2 or SEQ ID NO:4 or a fragment thereof;
- e) a fusion protein comprising a polypeptide as set forth in a) or b) or c) or d);
- f) an antagonist of a polypeptide as set forth in a) or b) or c) or d), wherein said antagonist comprises an amino acid sequence resulting from the non-conservative substitution, the deletion or both the non-conservative substitution and deletion of one or more residues into the corresponding polypeptide;
- g) a ligand which binds specifically to a polypeptide a) or b) or c) or d);
- h) a polypeptide a) or b) or c) or d) or e), wherein said polypeptides are in the form of active conjugates or complexes with a molecule chosen amongst radioactive labels, fluorescent labels, biotin, or cytotoxic agents;
- i) a peptide mimetic designed on the sequence or the structure or the sequence and structure of a polypeptide as set forth in a) or b) or c) or d);
- j) an isolated nucleic acid encoding for an isolated polypeptide selected from the group consisting of:
- 1) polypeptides as set forth in a) or b) or c) or d);
- 2) a fusion protein comprising a polypeptide as set forth in a) or b) or c) or d);
- or
- 3) an antagonist of a polypeptide as set forth in a) or b) or c) or d), wherein said antagonist comprises an amino acid sequence resulting from the non-conservative substitution, the deletion or both the non-conservative substitution and deletion of one or more residues into the corresponding polypeptide;
- k) an isolated nucleic acid sequence consisting of SEQ ID NO:
- 1, or the complement of said DNA sequence;
- l) a purified nucleic acid which:
- 1) hybridizes under high stringency conditions;
- or
- 2) exhibits at least about 85% identity over a stretch of at least about 30 nucleotides with a nucleic acid selected from the group consisting of SEQ ID NO:
- 1, or a complement of said DNA sequence;
- m) a vector comprising a nucleic acid as set forth in j) or k) or l);
- n) a polypeptide encoded by the nucleic acid of j) or k) or l);
- o) a host cell comprising a vector or nucleic acid as set forth in j) or k) or l) or m);
- p) a transgenic animal cell comprising a vector or nucleic acid as set forth in j) or k) or l) or m) and having enhanced or reduced expression levels of a polypeptide as set forth in a) or b) or c) or d);
- q) a transgenic non-human animal that has been transformed to have enhanced or reduced expression levels of a polypeptide as set forth in a) or b) or c) or d);
- r) a compound that enhances the expression level of a polypeptide as set forth in a) or b) or c) or d) in a cell or animal;
- or
- s) a compound that reduces the expression level of a polypeptide as set forth in a) or b) or c) or d) in a cell or animal.
A method for determining the activity and/or the presence of a notch-like polypeptide in a sample comprising:
- a) providing a protein-containing sample;
- b) contacting said sample with a ligand that specifically binds to a polypeptide comprising:
- 1) an isolated polypeptide having notch-like activity selected from the group consisting of:
- i) the amino acid sequence recited in SEQ ID NO:
- 2;
- ii) the mature form of the polypeptide whose sequence is recited in SEQ ID NO:
- 2 (SEQ ID NO:4);
- iii) active variants of the amino acid sequence of SEQ ID NO:
- 2, wherein any amino acid specified in the chosen sequence is non-conservatively substituted, provided that no more than 15% of the amino acid residues in the sequence are so changed;
- and iv) the active fragment, precursor, salt, or derivative of the amino acid sequences given in i), ii), or iii);
- 2) an isolated polypeptide that is a naturally occurring allelic variant of the sequence given by SEQ ID NO:
- 2 or SEQ ID NO:4;
- 3) an isolated polypeptide that is a naturally occurring allelic variant of the sequence given by SEQ ID NO:
- 2 or SEQ ID NO:4, wherein the variant is the translation of a single nucleotide polymorphism;
- or
- 4) a polypeptide as set forth in a) or b) or c), wherein the polypeptide binds specifically an antibody or a binding protein generated against SEQ ID NO:
- 2 or SEQ ID NO:4 or a fragment thereof;
- and
- c) determining the presence or said ligand bound to said polypeptide.
Dependencies are inferred from the claim text.