Endogenous retrovirus-k (ERVK) encodes an alternate envelope protein

Patent metadata

Field	Value
Publication number	US-12064407-B2
Application number	US-201816756947-A
Country	US
Kind code	B2
Filing date	Oct 17, 2018
Priority date	Oct 17, 2017
Publication date	Aug 20, 2024
Grant date	Aug 20, 2024

Abstract

The present disclosure relates to an endogenous Retrovirus K protein (ERVK) with an alternative envelope protein titled CTXLP. Said CTXLP peptide is represented by the sequences set forth in SEQ ID NO: 1. Additionally, antibodies that specifically recognize the epitope(s) set forth in SEQ ID NO:1 are and methods of use thereof and kits comprising the peptide set forth in SEQ ID NO:1 are also included in the present disclosure.

First claim

What is claimed is:

1. A method for treating or preventing a condition or disorder associated with ω-conotoxin-like protein(CTXLP) in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of active agent optionally in a physiological carrier, or a pharmaceutically acceptable salt thereof, wherein the active agent blocks or inhibits CTXLP activity and/or CTXLP associated pathology, wherein said condition or disorder is an infectious disease or cancer,
wherein said active agent comprises a Michael acceptor electrophile (MAE), gambogic acid, celastrol, a small molecule inhibitor of HIV Tat, curcumin, rosmarinic acid, 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2), a cyclopentenone prostaglandin (CyPG), N-acetylcysteine amide (NACA), or D-penicillamine; a sulfhydryl compound with chelating properties, N-(2-Mercapto-propionyl)-glycin (MPG), 2,3-Dimercapto-propanol (DMP), 2,3-Dimercapto-propane-sulfonic acid (DMPS), Nitric oxide (NO), or a sulphated polysaccharide; or a Thioredoxin reductase 1 (TRR1) inhibitor, B5 (curcumin analog), a small molecule or antibody reversing CTXLP blockade on oligodendrocyte precursor cell maturation and oligodendrocyte myelination, clemastine fumarate, a small molecule enhancer of expression or activity of CaV2.2 or its calcium channel associated transcription regulator (CaV2.2 CCAT) of expression or activity, EGTA, or glutamate.

2. The method of claim 1 , wherein said infectious disease is herpes simplex virus (HSV) infection, human immunodeficiency virus (HIV) infection, Epstein-Barr virus (EBV) infection, human T-lymphotropic virus (HTLV) infection, Toxoplasma Gondii infection, or prion disease.

3. The method of claim 1 , wherein said cancer is breast cancer, chronic myelogenous leukemia, colon cancer, gastric cancer, a germ cell tumor, a germinogenic tongue tumor, a gonadoblastoma, hepatocellular carcinoma, adenocarcinoma, epithloid carcinoma, Acute T-cell leukemia, leukemia, lymphoma, T-cell lymphoma, Burkitt's lymphoma, neuroepithelioma, melanoma, myelodysplastic syndrome, nasopharyngeal carcinoma, ovarian cancer, pancreatic cancer, prostate cancer, testicular cancer, lung cancer, stomach cancer, skin cancer, a trophoblastic tumor, tumorigenesis, thyroid adenoma, or ERVK in a cancerous tissue.

4. The method of claim 1 , further comprising administering a human anti-Nogo-A antibody.

5. A method for treating or preventing a condition or disorder associated with endogenous retrovirus-K (ERVK) in a subject, comprising measuring an amount of CTXLP polypeptide, CTXLP activity, or CTXLP mRNA; and administering to a subject in need thereof a therapeutically effective amount of an active agent optionally in a physiological carrier or a pharmaceutically acceptable salt thereof when the amount of CTXLP polypeptide, or CTXLP activity, or CTXLP mRNA is high, optionally compared to a control, wherein the active agent blocks or inhibits the CTXLP activity and/or CTXLP associated pathology, wherein said condition or disorder is an infection disease or a cancer,
wherein said active agent comprises a Michael acceptor electrophile (MAE), gambogic acid, celastrol, a small molecule inhibitor of HIV Tat, curcumin, rosmarinic acid, 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2), a cyclopentenone prostaglandin (CyPG), N-acetylcysteine amide (NACA), or D-penicillamine; a sulfhydryl compound with chelating properties, N-(2-Mercapto-propionyl)-glycin (MPG), 2,3-Dimercapto-propanol (DMP), 2,3-Dimercapto-propane-sulfonic acid (DMPS), Nitric oxide (NO), or a sulphated polysaccharide; or a Thioredoxin reductase 1 (TRR1) inhibitor, B5 (curcumin analog), a small molecule or antibody reversing CTXLP blockade on oligodendrocyte precursor cell maturation and oligodendrocyte myelination, clemastine fumarate, a small molecule enhancer of expression or activity of CaV2.2 or its calcium channel associated transcription regulator (CaV2.2 CCAT) of expression or activity, EGTA, or glutamate.

6. A method for treating or preventing a condition or disorder associated with ERVK comprising administering to a subject in need thereof a therapeutically effective amount of an active agent optionally in a physiological carrier, or a pharmaceutically acceptable salt thereof, wherein the active agent blocks or inhibits CTXLP activity and/or CTXLP associated pathology, wherein said condition or disorder is an infectious disease or cancer,
wherein said active agent comprises a Michael acceptor electrophile (MAE), gambogic acid, celastrol, a small molecule inhibitor of HIV Tat, curcumin, rosmarinic acid, 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2), a cyclopentenone prostaglandin (CyPG), N-acetylcysteine amide (NACA), or D-penicillamine; a sulfhydryl compound with chelating properties, N-(2-Mercapto-propionyl)-glycin (MPG), 2,3-Dimercapto-propanol (DMP), 2,3-Dimercapto-propane-sulfonic acid (DMPS), Nitric oxide (NO), or a sulphated polysaccharide; or a Thioredoxin reductase 1 (TRR1) inhibitor, B5 (curcumin analog), a small molecule or antibody reversing CTXLP blockade on oligodendrocyte precursor cell maturation and oligodendrocyte myelination, clemastine fumarate, a small molecule enhancer of expression or activity of CaV2.2 or its calcium channel associated transcription regulator (CaV2.2 COAT) of expression or activity, EGTA, or glutamate.

7. The method of claim 6 , wherein said infection disease is HSV infection, HIV infection, EBV infection, HTLV infection, Toxoplasma Gondii infection, or prion disease.

8. The method of claim 6 , wherein said cancer is breast cancer, chronic myelogenous leukemia, colon cancer, gastric cancer, a germ cell tumor, a germinogenic tongue tumor, a gonadoblastoma, hepatocellular carcinoma, adenocarcinoma, epithloid carcinoma, Acute T-cell leukemia, leukemia, lymphoma, T-cell lymphoma, Burkitt's lymphoma, neuroepithelioma, melanoma, myelodysplastic syndrome, nasopharyngeal carcinoma, ovarian cancer, pancreatic cancer, prostate cancer, testicular cancer, lung cancer, stomach cancer, skin cancer, a trophoblastic tumor, tumorigenesis, thyroid adenoma, or ERVK in a cancerous tissue.

9. The method of claim 6 , further comprising administering a human anti-Nogo-A antibody.

Assignees

• Univ Manitoba
• Univ Of Winnipeg

Inventors

• Douville Renée
• Gurm Mamneet

Classifications

• C07K16/112

  Retroviridae (F), e.g. leukemia viruses · CPC title

• A61K31/192 Primary

  having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid  {(cannabinoids A61K31/658)} · CPC title

• A61K31/56

  Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids · CPC title

• A61K31/40

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• A61P35/00

  Antineoplastic agents · CPC title