NOVEL INTERFERON-(lambda)4 (IFNL-4) PROTEIN, RELATED NUCLEIC ACID MOLECULES, AND USES THEREOF
AssigneeThe USA, as represented by the Secretary, Dept. of Health and Human Services
InventorsLiudmila PROKUNINA, Thomas R. O'BRIEN, Brian MUCHMORE, Raymond P. DONNELLY, Patricia A. PORTER-GILL
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Abstract
The invention is related to identification of an interferon-analog (IFNL4) protein and genetic association with spontaneous clearance of HCV infection and response to treatment for HCV infection.
Claims38
An isolated protein that comprises at least about 30 contiguous amino acids from an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:5 and SEQ ID NO:8.
An isolated protein comprising a sequence of at least 50 contiguous amino acids, wherein the at least 50 contiguous amino acid sequence is at least 92% identical over its entire length to an at least 50 contiguous amino acid sequence from an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:5 and SEQ ID NO:8.
An variant IFNL4 polypeptide comprising an amino acid sequence having at least 90%, at least 95%, at least 97%, at least 98% or at least 99% sequence identity to IFNL4-p179, p131 and p107 (SEQ ID NO:2, SEQ ID NO:5 and SEQ ID NO:8) wherein the variant polypeptide:
- (a) has at least one amino acid substitution, as compared to SEQ ID NO:2, selected from A10P, A11P, L13M, V15F, C17Y, V19M, I20V, A21P, R26G, L28M, L35M, L40M, E52K, L55M, W57R, R60P, N61H, S63P, F64V, R65G, D69H, P70S, P71T, R72G, R78G, V92M, L931, L101M, L102F, G116R, A121P, A126P, P128A, G129A, S130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, K154E, A155P, S156G, V1581, F159V, L162M, L164M, and L169F.;
- (b) has at least one amino acid substitution as compared to SEQ ID NO:2 selected from A10P, A11P, L13M, V15F, C17Y, V19M, I20V, A21P, R26G, L28M, L35M, L40M, E52K, L55M, W57R, R60P, N61H, S63P, F64V, R65G, D69H, P70S, P71T, R72G, G116R, A121P, A126P, P128A, G129A, S130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, K154E, A155P, S156G, V1581, F159V, L162M, L164M, and L169F;
- (c) has at least one amino acid substitution as compared to SEQ ID NO:2 selected from A10P, A11P, L13M, V15F, C17Y, V19M, I20V, A21P, R26G, L28M, L35M, L40M, G116R, A121P, A126P, P128A, G129A, S130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, K154E, A155P, S156G, V1581, F159V, L162M, L164M, and L169F;
- or
- (d) has at least one amino acid substitution as compared to SEQ ID NO:2 selected from C27G, S34P, P37A, D48H, C62R, A87P, D118H, A120P, C122G, C152G, V157L, N160D, L161F, L164M, L165F, T166P, L169F, and A173P.
A method for predicting the likelihood of an individual to spontaneously clear an HCV infection, the method comprising:
- a) obtaining a biological sample from the individual;
- and,
- b) analyzing the sample to determine the presence or absence of an IFNL4 mRNA or protein of the present invention;
- wherein the presence of an IFNL4 protein of the present invention indicates the likelihood of the individual spontaneously clearing an HCV infection.
A method for predicting the likelihood that an individual will respond to a treatment for HCV infection, the method comprising:
- a) obtaining a biological sample from the individual;
- b) analyzing the sample to determine the presence or absence of an IFNL4 protein of the present invention;
- wherein the presence of an IFNL4 protein of the present invention indicates the likelihood the individual will respond to treatment for an HCV infection.
A method for predicting the likelihood of an individual to spontaneously clear an HCV infection, the method comprising:
- a) obtaining a biological sample from an individual;
- and,
- b) determining the level of IFNL4 protein present in the sample, if any;
- wherein the level of IFNL4 protein present in the sample indicates the likelihood the individual will spontaneously clear an HCV infection.
A method for treating a patient suffering from a chronic hepatitis C virus infection, the method comprising:
- a) obtaining a biological sample from the individual;
- b) analyzing the sample to determine the presence, absence or level of IFNL4 protein present in the sample;
- and,
- c) determining whether or not to administer treatment based on the presence, absence or amount of IFNL4 protein present in the sample.
A method for identifying regulators of IFNL4 protein activity, the method comprising:
- a) incubating IFNL4 protein under conditions that allow measurement of IFNL4 protein activity;
- b) measuring the resultant IFNL4 activity;
- c) incubating IFNL4 protein in the presence of a test compound under the conditions used in step (a);
- d) measuring the resultant IFNL4 activity;
- and
- e) comparing the IFNL4 activity obtained in step (b) with the IFNL4 activity obtained in step (d);
- wherein if the difference between the IFNL4 activity obtained in step (b) and the IFNL4 activity obtained in step (d) is statistically significant, identifying the test compound as a regulator of IFNL4 activity.
Dependencies are inferred from the claim text.