Human lymphoid protein tyrosine phosphatases
AssigneeHSC Research and Development Limited Partnership
InventorChaim M. Roifman
Life of this patent
Estimating the term…
Abstract
The invention provides a human gene encoding two new cytoplasmic phosphatases, Lyp1 and Lyp2, as well as the proteins and methods for preparing and using the described gene and proteins.
Claims39
An isolated polynucleotide comprising a nucleotide sequence encoding a Lyp protein.
An isolated polynucleotide which encodes a Lyp protein having an amino acid sequence of greater than 70% overall identity to the amino acid sequence of Table 2.
An isolated polynucleotide which encodes a Lyp protein having an amino acid sequence of greater than 70% overall identity to the amino acid sequence of Table 4.
An isolated polynucleotide which encodes a Lyp protein having an amino acid sequence with at least 80% overall identity, preferably at least 90% overall identity to the amino acid sequence of Table 2.
An isolated polynucleotide which encodes a Lyp protein having an amino acid sequence with at least 80% overall identity, preferably at least 90% overall identity to the amino acid sequence of Table 4.
A nucleotide sequence comprising at least 10, preferably 15 and more preferably 20 consecutive nucleotides of Sequence ID NO:1 or Sequence ID NO:3.
A substantially purified Lyp protein.
A substantially purified protein having an amino acid sequence of greater than 70% overall identity to the amino acid sequence of Table 2.
A substantially purified protein having an amino acid sequence of greater than 70% overall identity to the amino acid sequence of Table 4.
A substantially purified protein having an amino acid sequence with at least 80% overall identity, preferably at least 90% overall identity, to the amino acid sequence of Table 2.
A substantially purified protein having an amino acid sequence with at least 80% overall identity, preferably at least 90% overall identity, to the amino acid sequence of Table 4.
A peptide comprising at least 5, preferably 10, more preferably 20 consecutive amino acids of Sequence ID NO:2 or Sequence ID NO:4.
A peptide comprising at least one functional domain of a Lyp protein.
A peptide comprising at least one antigenic determinant of a Lyp protein.
An antibody which binds specifically to a Lyp protein.
A method for screening a candidate compound for an ability to increase or decrease the phosphatase activity of a Lyp protein comprising
- (a) providing an assay system for assaying Lyp phosphatase activity;
- (b) assaying Lyp phosphatase activity in the presence or absence of the candidate compound;
- and
- (c) determining whether the Lyp phosphatase activity was higher or lower in the presence of the candidate compound than in its absence.
A method for screening a candidate compound for ability to modulate expression of a Lyp gene comprising
- contacting a cell with a candidate compound, wherein the cell includes a regulatory region of a Lyp gene operably joined to a coding region;
- and
- detecting a change in expression of the coding region.
A non-human animal wherein a genome of said animal, or of an ancestor thereof, has been modified by a modification selected from the group consisting of:
- (a) knockout of a Lyp gene;
- and
- (b) insertion of a polynucleotide encoding a heterologous Lyp gene.
A pharmaceutical composition comprising an active ingredient selected from the group consisting of:
- (a) an isolated nucleotide sequence encoding a Lyp protein;
- (b) a substantially purified Lyp protein;
- (c) a substantially purified antibody which binds specifically to a Lyp protein
- and a pharmaceutically acceptable carrier.
A method for treating a subject having a deficiency of Lyp activity comprising administering to the subject an effective amount of an agent selected from the group consisting of:
- (a) an isolated nucleotide sequence encoding a Lyp protein;
- (b) a substantially purified Lyp protein.
A method for modulating signalling mediated by the T cell receptor, the method comprising administering to a T cell an agent which increases Lyp phosphatase activity or increases Lyp expression in the T cell.
A method for reducing or preventing T cell activation and/or proliferation, the method comprising administering to the T cell an agent which increases Lyp phosphatase activity or increases Lyp expression in the T cell.
A method for treating a disorder which requires immunosuppression, the method comprising administering to the subject in need of treatment an immunosuppression-effective amount of an agent which increases Lyp phosphatase activity or increases Lyp expression.
A method for treating lymphoma in a subject, the method comprising administering to the subject an agent which increases Lyp phosphatase activity or increases Lyp expression in an amount effective to reduce or prevent lymphoma cell proliferation.
A method for preventing or treating a disorder characterised by an abnormality in the T cell receptor signalling pathway or the IL2-mediated signalling pathway, comprising modulating signalling by administration of an agent which increases Lyp phosphatase activity or Lyp expression.
Dependencies are inferred from the claim text.