Novel Shc-binding protein
AssigneeAmgen Canada Inc.
InventorsJane McGlade, Rosemary Schmandt
Life of this patent
Estimating the term…
Abstract
Novel Shc-binding protein, oligonucleotides encoding the same, methods of producing and use thereof are disclosed.
Claims46
An isolated polynucleotide encoding a PAL polypeptide comprising the amino acid sequence set out in SEQ ID NO.:
- 2 or SEQ ID NO.:
- 4, and variants including conserved variants, allelic variants, and analogs including biologically active fragments thereof.
An isolated polynucleotide encoding a PAL polypeptide the polynucleotide being selected from the group consisting of:
- (a) the DNA molecules set out as SEQ ID NOs.:
- 1 or 3, DNA molecules encoding variants including conserved variants, allelic variants, analogs, and fragments thereof;
- (b) DNA molecules which hybridize to the DNA molecules defined in a) or hybridizable fragments thereof;
- and
- (c) DNA molecules that code an expression for the amino acids encoded by any of the foregoing DNA molecules.
A mammalian cell containing a PAL polypeptide encoding DNA modified so as to permit higher expression of PAL polypeptide by means of a homologous recombinational event consisting of inserting an expression regulatory sequence in functional proximity to the PAL encoding DNA.
A purified PAL polypeptide comprising the PAL amino acid sequence of SEQ ID NO.:
- 2, and variants including conserved variants, allelic variants, and analogs including biologically active fragments thereof.
A substantially purified and isolated polypeptide comprising of the PAL amino acid sequence of SEQ ID NO.:
- 4, and variants including conserved variants, allelic variants, and analogs including biologically active fragments thereof.
An isolated nucleic acid encoding an analog of a PAL polypeptide comprising the amino acid sequence set out as SEQ ID NOs.:
- 2 or 4 wherein one or more amino acids selected from the group consisting of amino acids 4, 5, 6, 7, 10, 13, 14, 17, 19, 21, 22, 23, 25, 27, 29, 32, 33, 34, 38, 40, 42, 46, 47, 49, 50, 51, 54, 55, 56, 57, 58, 59, 60, 66, 69, 71, 75, 99 103, 104, 116, 125, 130, 132, 136, 137, 148, 149, 150, 151, 153, 154, 159, 160, 161, 162, 171, 172, 182, 186, 187, 189, 191, 203, 241, 288, 292, 321, 324, 326, 327, 331, 332, 340, 341, 348, 349, 352, 354, 356, 357, 358, 361, 364, 369, 372, 377, 378, 384, 395, 429, 431, 439, 443, 450, 452, 477, 478, 484, 499, 503, 532, 535, 553, 559, 560, 562, 563, 564, 565, 570, 571, 573, 574, 575, 577, 580, 582, 583, 588, 589, 590, 592, 593, 594, 598, 599, 601, 602, 604, 605, 608, 609, 615, 619, 621, 623, 627, 628, 645, 652, 653, 655, and 672 is substituted with another amino acid.
An antibody which specifically binds human PAL.
An antibody which specifically binds murine PAL.
A derivative of PAL polypeptide having one or more chemical moieties attached thereto optionally in a pharmaceutically acceptable carrier wherein the polypeptide is selected from the group consisting of PAL variants including variants, conserved variants, allelic variants, and analogs including biologically active fragments thereof.
A method for determining the presence of PAL protein in a biological sample comprising the steps of:
- (a) obtaining a biological sample;
- (b) exposing said biological sample to a PAL specific antibody;
- and
- (c) detecting the binding of PAL specific antibody in said biological sample.
A diagnostic reagent comprising a detectably labeled polynucleotide encoding part or all of the PAL amino acid sequences set out in SEQ ID NO.:
- 2, including conserved variants, allelic variants, fragments and analogs.
A diagnostic reagent comprising detectably labeled polynucleotide encoding all or part of the PAL amino acids set out in SEQ ID NO.:
- 4, including conserved variants, allelic variants, fragments and analogs.
A method of identifying a candidate inhibitor of PAL binding to a PAL binding protein comprising the steps of:
- (a). exposing PAL to a PAL binding protein under conditions which permit binding of PAL to the PAL binding protein in the presence or absence of a candidate inhibitor;
- (b) measuring the binding of PAL to the PAL binding protein in the presence or absence of the candidate inhibitor;
- (c) comparing the level of binding observed in step (a);
- and
- (d) identifying the compound as an inhibitor of PAL binding by its ability to prevent binding of PAL to the PAL binding protein.
A method of stimulating hematopoietic progenitor cell proliferation in a mammal, the method comprising administering to the mammal a hematopoietically effective dose of a PAL, the PAL polypeptide selected from the polypeptides set out in SEQ ID NO.:
- 2 or 4 including conserved variants, allelic variants and analogs including biologically active fragments thereof;
- thereby stimulating proliferation of said hematopoietic progenitor cells.
A method of stimulating hematopoietic progenitor cell proliferation the method comprising the steps of:
- (a) obtaining hematopoietic progenitor cells from a mammal;
- (b) culturing the cells obtained in step (a) in vitro;
- (c) introducing PAL polynucleotides in an eukaryotic expression vector into the hematopoietic progenitor cells in culture;
- (d) selecting producer cells expressing the PAL molecule prepared in step (b);
- (e) expanding PAL producing cells in vitro;
- and
- (f) introducing said PAL producing hematopoietic progenitor cells into a mammal.
A method of stimulating hematopoietic progenitor cell proliferation in vitro with PAL protein comprising:
- (a) obtaining hematopoietic progenitor cells from a donor;
- (b) exposing the hematopoietic progenitor cells obtained in step (a) to hematopoietically effective dose of PAL polypeptide, the PAL polypeptide selected from the polypeptide set out in SEQ ID NO. 2 and including conserved variants, allelic variants, and analogs including biologically active fragments thereof;
- and
- (c) administering to said donor the early hematopoietic progenitor cells obtained in step (b).
A method of stimulating hematopoietic progenitor cell proliferation in vitro with PAL protein comprising:
- (a) obtaining hematopoietic progenitor cells from a donor;
- (b) exposing the hematopoietic progenitor cells obtained in step (a) to a hematopoietically effective dose of PAL polypeptide, the PAL polypeptide selected from polypeptide set out in SEQ ID NO. 4 and including conserved variants, allelic variants, and analogs including biologically active fragments thereof, and
- (c) administering to said donor the early hematopoietic progenitor cells obtained in step (b).
Dependencies are inferred from the claim text.