Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics

Patent metadata

Field	Value
Publication number	US-9555087-B2
Application number	US-201414469546-A
Country	US
Kind code	B2
Filing date	Aug 26, 2014
Priority date	Sep 4, 2007
Publication date	Jan 31, 2017
Grant date	Jan 31, 2017

Abstract

This invention relates to a novel target for production of immune and non-immune based therapeutics and for disease diagnosis. More particularly, the invention provides therapeutic antibodies against VSIG1, ILDR1, LOC253012, AI216611, C1ORF32 or FXYD3 antigens, which are predicted co-stimulatory family members and which are differentially expressed in cancers including, lung cancer, ovarian cancer, and colon cancer, and diagnostic and therapeutic usages. The use of these antibodies for modulating B7 costimulation and related therapies such as the treatment of autoimmunity are also provided. This invention further relates to the discovery of extracellular domains of VSIG1 and its variants, FXYD3 and its variants, ILDR1 and its variants, LOC253012 and its variants, AI216611 and its variants, and C1ORF32 and its variants awhich are suitable targets for immunotherapy, cancer therapy, and drug development.

First claim

What is claimed is:

1. An isolated polypeptide comprising the polypeptide of amino acid sequence SEQ ID NO: 299.

2. An isolated polypeptide comprising a sequence of amino acid residues having at least 95% sequence identity with amino acid residues 21-184 of SEQ ID NO:299.

3. An isolated polypeptide comprising the polypeptide of amino acid sequence SEQ ID NO: 299 and a functional group that improves stability, penetration through cellular membranes, penetration through tissue barriers, tissue localization, efficacy, or causes decreased clearance, decreased toxicity, improved selectivity, or improved resistance to expulsion by cellular pumps.

4. The isolated polypeptide of claim 3 , having at least one peptidomimetic organic moiety.

5. An isolated polypeptide comprising the polypeptide of amino acid sequence SEQ ID NO: 299, a polypeptide comprising amino acid residues 21-184 of SEQ ID NO: 299, or a polypeptide comprising a sequence of amino acid residues having at least 95% sequence identity with amino acid residues 21-184 of SEQ ID NO:299, wherein the polypeptide has been chemically modified, and wherein the chemical modification is selected from acetylation, acylation, amidation, ADP-ribosylation, glycosylation, GPI anchor formation, covalent attachment of a lipid or lipid derivative, methylation, myristylation, pegylation, prenylation, phosphorylation, and ubiquitination.

6. A fusion protein comprising an isolated polypeptide comprising the polypeptide of amino acid sequence SEQ ID NO: 299; the polypeptide of amino acid sequence SEQ ID NO: 299 and a functional group that improves stability, penetration through cellular membranes, penetration through tissue barriers, tissue localization, efficacy, or causes decreased clearance, decreased toxicity, improved selectivity, or improved resistance to expulsion by cellular pumps; or the polypeptide of amino acid sequence SEQ ID NO: 299, a polypeptide comprising amino acid residues 21-184 of SEQ ID NO: 299, or a polypeptide comprising a sequence of amino acid residues having at least 95% sequence identity with amino acid residues 21-184 of SEQ ID NO:299, wherein the polypeptide has been chemically modified, and wherein the chemical modification is selected from acetylation, acylation, amidation, ADP-ribosylation, glycosylation, GPI anchor formation, covalent attachment of a lipid or lipid derivative, methylation, myristylation, pegylation, prenylation, phosphorylation, and ubiquitination; joined to a heterologous polypeptide.

7. The fusion protein of claim 6 , comprising a sequence of amino acid residues having at least 95% sequence identity with amino acid residues 21-184 of SEQ ID NO: 299 joined to a heterologous polypeptide.

8. The fusion protein of claim 6 , wherein the heterologous sequence comprises a VASP domain.

9. The fusion protein of claim 6 , wherein the heterologous sequence comprises at least a portion of an immunoglobulin molecule.

10. The fusion protein of claim 9 , wherein said at least a portion of said immunoglobulin molecule comprises an immunoglobulin heavy chain constant region.

11. The fusion protein of claim 10 , wherein the immunoglobulin heavy chain constant region is an Fc fragment.

12. The fusion protein of claim 11 , wherein the immunoglobulin heavy chain constant region is an isotype selected from the group consisting of an IgG1, IgG2, IgG3, IgG4, IgM, IgE, IgA and IgD.

13. The fusion protein of claim 6 , wherein the fusion protein modulates lymphocyte activation in vitro or in vivo.

14. A method of producing a fusion protein according to claim 6 or a protein comprising at least one of the polypeptide of amino acid sequence SEQ ID NO: 299; the polypeptide of amino acid sequence SEQ ID NO: 299 and a functional group that improves stability, penetration through cellular membranes, penetration through tissue barriers, tissue localization, efficacy, or causes decreased clearance, decreased toxicity, improved selectivity, or improved resistance to expulsion by cellular pumps; or the polypeptide of amino acid sequence SEQ ID NO: 299, a polypeptide comprising amino acid residues 21-184 of SEQ ID NO: 299, or a polypeptide comprising a sequence of amino acid residues having at least 95% sequence identity with amino acid residues 21-184 of SEQ ID NO:299, wherein the polypeptide has been modified, and wherein the modification is selected from acetylation, acylation, amidation, ADP-ribosylation, glycosylation, GPI anchor formation, covalent attachment of a lipid or lipid derivative, methylation, myristylation, prenylation, phosphorylation, and ubiquitination; the method comprising introducing a vector comprising a polynucleotide encoding for said protein to a recombinant cell; and producing the protein with the recombinant cell.

15. The method of claim 14 , wherein the recombinant cell is a prokaryotic or eukaryotic cell.

16. The method of claim 15 , wherein the recombinant cell is a mammalian cell, yeast cell, insect cell or bacterial cell.

17. The method of claim 16 , wherein the recombinant cell is a CHO cell, a COS cell, or a 293 cell or E. coli cell.

18. A pharmaceutical composition comprising the polypeptide of amino acid sequence SEQ ID NO: 299, a polypeptide comprising amino acid residues 21-184 of SEQ ID NO: 299, or a polypeptide comprising a sequence of amino acid residues having at least 95% sequence identity with amino acid residues 21-184 of SEQ ID NO:299, and a pharmaceutically acceptable diluent or carrier.

19. A pharmaceutical composition comprising a fusion polypeptide comprising the polypeptide of amino acid sequence SEQ ID NO: 299 and a heterologous amino acid sequence, a polypeptide comprising amino acid residues 21-184 of SEQ ID NO: 299 and a heterologous amino acid sequence, or a polypeptide comprising a sequence of amino acid residues having at least 95% sequence identity with amino acid residues 21-184 of SEQ ID NO:299 and a heterologous amino acid sequence; or the polypeptide of amino acid sequence SEQ ID NO: 299 and a functional group that improves stability, penetration through cellular membranes, penetration through tissue barriers, tissue localization, efficacy, or causes decreased clearance, decreased toxicity, improved selectivity, or improved resistance to expulsion by cellular pumps and a heterologous amino acid sequence; or the polypeptide of amino acid sequence SEQ ID NO: 299, a polypeptide comprising amino acid residues 21-184 of SEQ ID NO: 299, or a polypeptide comprising a sequence of amino acid residues having at least 95% sequence identity with amino acid residues 21-184 of SEQ ID NO:299, wherein the polypeptide has been chemically modified, and wherein the chemical modification is selected from acetylation, acylation, amidation, ADP-ribosylation, glycosylation, GPI anchor formation, covalent attachment of a lipid or lipid derivative, methylation, myristylation, pegylation, prenylation, phosphorylation, and ubiquitination, and a heterologous amino acid sequence; and a pharmaceutically acceptable diluent or carrier.

20. A method for treating an autoimmune disease or preventing transplant rejection or graft versus host disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of any of polypeptide comprising the polypeptide of amino acid sequence SEQ ID NO: 299, polypeptide comprising amino acid residues 21-184 of SEQ ID NO: 299, or a polypeptide comprising a sequence of amino acid residues having at least 95% sequence identity with amino acid residues 21-184 of SEQ ID NO:299, or the pharmaceutica

Assignees

• Compugen Ltd
• Compugen Ltd

Inventors

• Toporik Amir
• Novik Amit
• Cohen-Dayag Anat
• Rosenberg Avi Yeshah
• Koifman Cynthia
• Landesman-Milo Dalit
• Montia Eve
• Rotman Galit
• Dassa Liat
• Bubis Marina
• Beiman Merav
• Levi Ofer
• Nemzer Sergey
• Pergam Tania
• Kinar Yaron
• Greenwald Shirley Sameach-
• Levine Zurit
• Walach Shira

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P7/06

  Antianaemics · CPC title

• A61P5/14

  of the thyroid hormones, e.g. T3, T4 · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title