Tetz-proteins and prion-like proteins and associated methods
OwnerViktor Veniaminovich TETS, Georgy Viktorovich TETSinventors
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Abstract
The invention relates to diagnosis, prevention, and treatment of diseases and conditions associated with the functions of prion-like or Tetz-proteins.
Claims129
A method of diagnosing a disease in a subject, which method comprises:
- a) heating a sample collected from the subject for 10 seconds to 48 hours at a temperature from 43° C. to 200° C.,
- b) isolating a protein fraction in the sample after the completion of the heating,
- c) determining the level of one or more polypeptides in the protein fraction isolated in step (b),
- d) comparing the level of the one or more polypeptides identified in step (c) with a control level(s) of said polypeptide(s), and
- e) (i) identifying the subject as being afflicted with the disease when the level(s) of said one or more polypeptides is different by 10% or more from the control level(s), or (ii) identifying that the subject is not afflicted with the disease if the level(s) of said one or more polypeptides differs from the control level(s) by less than 10%.
A method of monitoring changes in development of a disease in a subject, which method comprises:
- a) heating a first sample collected from the subject for 10 seconds to 48 hours at a temperature from 43° C. to 200° C.,
- b) isolating a protein fraction in the first sample after the completion of the heating,
- c) determining the level of one or more polypeptides in the protein fraction isolated in step (b),
- d) repeating steps (a)-(c) for one or more additional samples, wherein said additional samples have been collected from the subject at later time points than the first sample,
- e) comparing the levels of the one or more polypeptides identified in step (c) with the level(s) of said polypeptide(s) identified in step (d), and
- f) (i) determining that the disease has progressed when the level(s) of the one or more polypeptides identified in step (d) is higher than the level(s) of said polypeptide(s) identified in step (c), or (ii) determining that the disease has not progressed when the level(s) of the one or more polypeptides identified in step (d) is not higher than the level(s) of said polypeptide(s) identified in step (c).
A method of monitoring the effect of a treatment on development of a disease in a subject who had been previously diagnosed with the disease, which method comprises:
- a) heating a first sample collected from the subject for 10 seconds to 48 hours at a temperature from 43° C. to 200° C., wherein said first sample has been collected from the subject prior to initiation of the treatment,
- b) isolating a protein fraction in the first sample after the completion of the heating,
- c) determining the level of one or more polypeptides in the protein fraction isolated in step (b),
- d) repeating steps (a)-(c) for one or more additional samples, wherein said additional samples have been collected from the subject after initiation of the treatment,
- e) comparing the levels of the one or more polypeptides identified in step (c) with the level(s) of said polypeptide(s) identified in step (d), and
- f) (i) determining that the treatment is effective when the level(s) of the one or more polypeptides identified in step (d) is the same or lower than the level(s) of said polypeptide(s) identified in step (c), or (ii) determining that treatment is not effective when the level(s) of the one or more polypeptides identified in step (d) is higher than the level(s) of said polypeptide(s) identified in step (c).
A method for identifying a compound useful for slowing down the progression or treating a disease in a subject who had been previously diagnosed with the disease, which method comprises:
- a) heating a first sample collected from the subject for 10 seconds to 48 hours at a temperature from 43° C. to 200° C., wherein said first sample has been collected from the subject prior to administration of a test compound,
- b) isolating a protein fraction in the first sample after the completion of the heating,
- c) determining the level of one or more polypeptides in the protein fraction isolated in step (b),
- d) repeating steps (a)-(c) for one or more additional samples, wherein said additional samples have been collected from the subject after administration of the test compound,
- e) comparing the levels of the one or more polypeptides identified in step (c) with the level(s) of said polypeptide(s) identified in step (d), and
- f) (i) determining that the test compound is useful for slowing down the progression or treating the disease when the level(s) of the one or more polypeptides identified in step (d) is the same or lower than the level(s) of said polypeptide(s) identified in step (c), or (ii) determining that the test compound is not useful for slowing down the progression or treating the disease when the level(s) of the one or more polypeptides identified in step (d) is higher than the level(s) of said polypeptide(s) identified in step (c).
A method of diagnosing a disease in a subject, which method comprises:
- a) adding to a sample collected from the subject a polynucleotide molecule and incubating the sample with said polynucleotide molecule,
- b) isolating a protein fraction in the sample,
- c) determining the level of one or more polypeptides in the protein fraction isolated in step (b),
- d) comparing the level of the one or more polypeptides identified in step (c) with a control level(s) of said polypeptide(s), and
- e) (i) identifying the subject as being afflicted with the disease when the level of said one or more polypeptides is different by 10% or more from the control level, or (ii) identifying that the subject is not afflicted with the disease if the level of said one or more polypeptides differs from the control level by less than 10%.
A method of monitoring changes in development of a disease in a subject, which method comprises:
- a) adding to a first sample collected from the subject a polynucleotide molecule and incubating the sample with said polynucleotide molecule,
- b) isolating a protein fraction in the first sample after the completion of the heating,
- c) determining the level of one or more polypeptides in the protein fraction isolated in step (b),
- d) repeating steps (a)-(c) for one or more additional samples, wherein said additional samples have been collected from the subject at later time points than the first sample,
- e) comparing the levels of the one or more polypeptides identified in step (c) with the level(s) of said polypeptide(s) identified in step (d), and
- f) (i) determining that the disease has progressed when the level(s) of the one or more polypeptides identified in step (d) is higher than the level(s) of said polypeptide(s) identified in step (c), or (ii) determining that the disease has not progressed when the level(s) of the one or more polypeptides identified in step (d) is not higher than the level(s) of said polypeptide(s) identified in step (c).
A method of monitoring the effect of a treatment on development of a disease in a subject who had been previously diagnosed with the disease, which method comprises:
- a) adding to a first sample collected from the subject a polynucleotide molecule and incubating the sample with said polynucleotide molecule, wherein said first sample has been collected from the subject prior to initiation of the treatment,
- b) isolating a protein fraction in the first sample after the completion of the heating,
- c) determining the level of one or more polypeptides in the protein fraction isolated in step (b),
- d) repeating steps (a)-(c) for one or more additional samples, wherein said additional samples have been collected from the subject after initiation of the treatment,
- e) comparing the levels of the one or more polypeptides identified in step (c) with the level(s) of said polypeptide(s) identified in step (d), and
- f) (i) determining that the treatment is effective when the level(s) of the one or more polypeptides identified in step (d) is the same or lower than the level(s) of said polypeptide(s) identified in step (c), or (ii) determining that treatment is not effective when the level(s) of the one or more polypeptides identified in step (d) is higher than the level(s) of said polypeptide(s) identified in step (c).
A method for identifying a compound useful for slowing down the progression or treating a disease in a subject who had been previously diagnosed with the disease, which method comprises:
- a) adding to a first sample collected from the subject a polynucleotide molecule and incubating the sample with said polynucleotide molecule, wherein said first sample has been collected from the subject prior to administration of a test compound,
- b) isolating a protein fraction in the first sample after the completion of the heating,
- c) determining the level of one or more polypeptides in the protein fraction isolated in step (b),
- d) repeating steps (a)-(c) for one or more additional samples, wherein said additional samples have been collected from the subject after administration of the test compound,
- e) comparing the levels of the one or more polypeptides identified in step (c) with the level(s) of said polypeptide(s) identified in step (d), and
- f) (i) determining that the test compound is useful for slowing down the progression or treating the disease when the level(s) of the one or more polypeptides identified in step (d) is the same or lower than the level(s) of said polypeptide(s) identified in step (c), or (ii) determining that the test compound is not useful for slowing down the progression or treating the disease when the level(s) of the one or more polypeptides identified in step (d) is higher than the level(s) of said polypeptide(s) identified in step (c).
A method of diagnosing a disease in a subject, which method comprises:
- a) adding to a sample collected from the subject a protease and incubating the sample with said protease,
- b) isolating a protein fraction in the sample,
- c) determining the level of one or more polypeptides in the protein fraction isolated in step (b),
- d) comparing the level of the one or more polypeptides identified in step (c) with a control level(s) of said polypeptide(s), and
- e) (i) identifying the subject as being afflicted with the disease when the level of said one or more polypeptides is different by 10% or more from the control level, or (ii) identifying that the subject is not afflicted with the disease if the level of said one or more polypeptides differs from the control level by less than 10%.
A method of monitoring changes in development of a disease in a subject, which method comprises:
- a) adding to a first sample collected from the subject a protease and incubating the sample with said protease,
- b) isolating a protein fraction in the first sample after the completion of the heating,
- c) determining the level of one or more polypeptides in the protein fraction isolated in step (b),
- d) repeating steps (a)-(c) for one or more additional samples, wherein said additional samples have been collected from the subject at later time points than the first sample,
- e) comparing the levels of the one or more polypeptides identified in step (c) with the level(s) of said polypeptide(s) identified in step (d), and
- f) (i) determining that the disease has progressed when the level(s) of the one or more polypeptides identified in step (d) is higher than the level(s) of said polypeptide(s) identified in step (c), or (ii) determining that the disease has not progressed when the level(s) of the one or more polypeptides identified in step (d) is not higher than the level(s) of said polypeptide(s) identified in step (c).
A method of monitoring the effect of a treatment on development of a disease in a subject who had been previously diagnosed with the disease, which method comprises:
- a) adding to a first sample collected from the subject a protease and incubating the sample with said protease, wherein said first sample has been collected from the subject prior to initiation of the treatment,
- b) isolating a protein fraction in the first sample after the completion of the heating,
- c) determining the level of one or more polypeptides in the protein fraction isolated in step (b),
- d) repeating steps (a)-(c) for one or more additional samples, wherein said additional samples have been collected from the subject after initiation of the treatment,
- e) comparing the levels of the one or more polypeptides identified in step (c) with the level(s) of said polypeptide(s) identified in step (d), and
- f) (i) determining that the treatment is effective when the level(s) of the one or more polypeptides identified in step (d) is the same or lower than the level(s) of said polypeptide(s) identified in step (c), or (ii) determining that treatment is not effective when the level(s) of the one or more polypeptides identified in step (d) is higher than the level(s) of said polypeptide(s) identified in step (c).
A method for identifying a compound useful for slowing down the progression or treating a disease in a subject who had been previously diagnosed with the disease, which method comprises:
- a) adding to a first sample collected from the subject a protease and incubating the sample with said protease, wherein said first sample has been collected from the subject prior to administration of a test compound,
- b) isolating a protein fraction in the first sample after the completion of the heating,
- c) determining the level of one or more polypeptides in the protein fraction isolated in step (b),
- d) repeating steps (a)-(c) for one or more additional samples, wherein said additional samples have been collected from the subject after administration of the test compound,
- e) comparing the levels of the one or more polypeptides identified in step (c) with the level(s) of said polypeptide(s) identified in step (d), and
- f) (i) determining that the test compound is useful for slowing down the progression or treating the disease when the level(s) of the one or more polypeptides identified in step (d) is the same or lower than the level(s) of said polypeptide(s) identified in step (c), or (ii) determining that the test compound is not useful for slowing down the progression or treating the disease when the level(s) of the one or more polypeptides identified in step (d) is higher than the level(s) of said polypeptide(s) identified in step (c).
A method of diagnosing a viral infection in a subject, which method comprises:
- a) treating a sample collected from the subject with an antibody against a prion-like domain (PrD) or a protein comprising a PrD, wherein said PrD or protein is present in said virus, and
- b) identifying the subject as being afflicted with the viral infection when an increased reactivity of the antibody to the PrD or the protein comprising the PrD is detected in the sample collected from the subject as compared to the antibody reactivity in a control.
A method of treating a disease in a subject in need thereof, comprising administering to the subject an effective amount of a compound which inhibits expression or activity of one or more polypeptides selected from thermostable Tetz-proteins, non-thermostable disease-associated Tetz-proteins, proteins comprising PrDs, prion-like proteins, and fragments thereof.
A method of treating a cancer in a subject in need thereof, comprising administering to the subject an effective amount of a compound which inhibits expression or activity of one or more proteins listed in Tables 4, 5, 6, 7, 8, 9, 10, 11, 19, 23, or 24.
A method of treating a cancer in a subject in need thereof, comprising administering to the subject an effective amount of a compound which inhibits expression or activity of one or more proteins selected from serum albumin, Fibronectin, Complement factor B, Vitamin D-binding protein, Immunoglobulin heavy constant gamma 2, Plasminogen, Inter-alpha-trypsin inhibitor heavy chain H4, Inter-alpha-trypsin inhibitor heavy chain H2, Apolipoprotein B-100, Apolipoprotein L1, Alpha-1-acid glycoprotein 2, C4b-binding protein beta chain, Immunoglobulin heavy constant gamma 1, Apolipoprotein A-II, Alpha-1-acid glycoprotein 2, Apolipoprotein B-100, Hemoglobin subunit alpha, CD5 antigen-like, Selenoprotein P, Immunoglobulin lambda constant 3, Eukaryotic translation initiation factor 5A-1, Cluster of Keratin, type II cytoskeletal 1, Keratin, type I cytoskeletal 9, Keratin, type I cytoskeletal 10, Immunoglobulin kappa variable 1-27, Chromodomain-helicase-DNA-binding protein 7, Fetuin-B, Immunoglobulin heavy constant gamma 1, Immunoglobulin heavy constant gamma 4, Immunoglobulin lambda variable 3-27, Kallikrein-2, N-lysine methyltransferase SETD6, Protein SON, Reversion-inducing cysteine-rich protein with Kazal motifs, CON_Q2UVX4, Serotransferrin, Gelsolin, Complement C2, Complement factor H-related protein 1, Pigment epithelium-derived factor, Hemoglobin subunit alpha, Complement C5, Complement C1q, Immunoglobulin lambda constant 7, Actin, cytoplasmic 1, Coagulation factor XII, Complement component C6, Calmodulin-1, Tropomyosin alpha-4, Tropomyosin beta Epididymis luminal protein 189, Tropomyosin alpha-1, and Tropomyosin alpha-3.
The method of treating a cancer in a subject in need thereof, comprising administering to the subject an effective amount of a compound which inhibits expression or activity of one or more proteins selected from serum albumin, Fibronectin, Complement factor B, Vitamin D-binding protein, Immunoglobulin heavy constant gamma 2, Plasminogen, Inter-alpha-trypsin inhibitor heavy chain H4, Inter-alpha-trypsin inhibitor heavy chain H2, Apolipoprotein B-100, Apolipoprotein L1, Alpha-1-acid glycoprotein 2, C4b-binding protein beta chain, Immunoglobulin heavy constant gamma 1, Apolipoprotein A-II, Alpha-1-acid glycoprotein 2, Apolipoprotein B-100, Hemoglobin subunit alpha, CD5 antigen-like, Selenoprotein P, Immunoglobulin lambda constant 3, Eukaryotic translation initiation factor 5A-1, Cluster of Keratin, type II cytoskeletal 1, Keratin, type I cytoskeletal 9, Keratin, type I cytoskeletal 10, Immunoglobulin kappa variable 1-27, Chromodomain-helicase-DNA-binding protein 7, Fetuin-B, Immunoglobulin heavy constant gamma 1, Immunoglobulin heavy constant gamma 4, Immunoglobulin lambda variable 3-27, Kallikrein-2, N-lysine methyltransferase SETD6, Protein SON, Reversion-inducing cysteine-rich protein with Kazal motifs, CON_Q2UVX4, Serotransferrin, Complement factor H-related protein 1, Pigment epithelium-derived factor, Cluster of Hemoglobin subunit alpha, Hemoglobin subunit alpha, CON_P01966, Complement C5, and Immunoglobulin lambda constant 7.
The method of treating a cancer in a subject in need thereof, comprising administering to the subject an effective amount of a compound which inhibits expression or activity of one or more proteins selected from serum albumin, Fibronectin, Complement factor B, Vitamin D-binding protein, Immunoglobulin heavy constant gamma 2, Plasminogen, Inter-alpha-trypsin inhibitor heavy chain H4, Inter-alpha-trypsin inhibitor heavy chain H2, Apolipoprotein B-100, Apolipoprotein L1, Alpha-1-acid glycoprotein 2, C4b-binding protein beta chain, Immunoglobulin heavy constant gamma 1, Apolipoprotein A-II, Alpha-1-acid glycoprotein 2, Apolipoprotein B-100, Hemoglobin subunit alpha, CD5 antigen-like, Selenoprotein P, Immunoglobulin lambda constant 3, Eukaryotic translation initiation factor 5A-1, Cluster of Keratin, type II cytoskeletal 1, Keratin, type I cytoskeletal 9, Keratin, type I cytoskeletal 10, Immunoglobulin kappa variable 1-27, Chromodomain-helicase-DNA-binding protein 7, Fetuin-B, Immunoglobulin heavy constant gamma 1, Immunoglobulin heavy constant gamma 4, Immunoglobulin lambda variable 3-27, Kallikrein-2, N-lysine methyltransferase SETD6, Protein SON, Reversion-inducing cysteine-rich protein with Kazal motifs, Complement C3, CON_Q2UVX4, Serotransferrin, Gelsolin, Immunoglobulin lambda constant 7, and Inter-alpha-trypsin inhibitor heavy chain H3.
A method of treating a disease in a human subject comprising administering to the subject an effective amount of a compound that inhibits a human cell or a human protein from interacting with a viral protein comprising a prion-like domain.
A method of treating a disease in a human subject comprising administering to the subject an effective amount of a compound that prevents a human cell or a human protein from interacting with a viral protein comprising a prion-like domain.
Dependencies are inferred from the claim text.