US2020292546A1PendingUtilityA1

A NOVEL INTERFERON-(lambda)4 (IFNL-4) PROTEIN, RELATED NUCLEIC ACID MOLECULES, AND USES THEREOF

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Assignee: THE USA AS REPRESENTED BY THE SECRETARY DEPT OF HEALTH AND HUMAN SERVICESPriority: Mar 28, 2012Filed: Jan 24, 2020Published: Sep 17, 2020
Est. expiryMar 28, 2032(~5.7 yrs left)· nominal 20-yr term from priority
Inventors:Liudmila ProkuninaThomas R. O'BrienBrian MuchmoreRaymond P. DonnellyPatricia A. Porter-Gill
C07K 14/555C12Q 1/707C12Q 1/6883C12Q 2600/158C07K 16/249G01N 2800/52G01N 33/56983C12Q 2600/156C07K 2317/76
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Claims

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.

Claims

exact text as granted — not AI-modified
1 - 38 . (canceled) 
     
     
         39 . A variant IFNL4 protein comprising an amino acid sequence that is between 90% and 96% identical over its entire length to SEQ ID NO: 2, where the variant IFNL4 protein comprises at least one sequence feature selected from the group consisting of:
 a. a cysteine residue at the position corresponding to position 27 of SEQ ID NO:2;   b. a leucine residue at the position corresponding to position 29 of SEQ ID NO:2   c. a serine residue at the position corresponding to position 30 of SEQ ID NO:2   d. a tyrosine residue at the position corresponding to position 32 of SEQ ID NO:2   e. a serine residue at the position corresponding to position 34 of SEQ ID NO:2   f. a proline residue at the position corresponding to position 37 of SEQ ID NO:2;   g. a leucine residue at the position corresponding to position 40 of SEQ ID NO:2;   h. an alanine residue at the position corresponding to position 42 of SEQ ID NO:2;   i. a lysine residue at the position corresponding to position 44 of SEQ ID NO:2;   j. an aspartic acid residue at the position corresponding to position 48 of SEQ ID NO:2;   k. a tyrosine residue at the position corresponding to position 50 of SEQ ID NO:2;   l. a leucine residue at the position corresponding to position 111 of SEQ ID NO:2;   m. a leucine residue at the position corresponding to position 112 of SEQ ID NO:2;   n. an aspartic acid residue at the position corresponding to position 118 of SEQ ID NO:2;   o. an alanine residue at the position corresponding to position 120 of SEQ ID NO:2;   p. a cysteine residue at the position corresponding to position 122 of SEQ ID NO:2;   q. a cysteine residue at the position corresponding to position 152 of SEQ ID NO:2;   r. a valine residue at the position corresponding to position 157 of SEQ ID NO:2;   s. an asparagine residue at the position corresponding to position 160 of SEQ ID NO:2;   t. a leucine residue at the position corresponding to position 161 of SEQ ID NO:2;   u. an arginine residue at the position corresponding to position 163 of SEQ ID NO:2   v. a leucine residue at the position corresponding to position 165 of SEQ ID NO:2;   w. a threonine residue at the position corresponding to position 166 of SEQ ID NO:2;   x. an alanine residue at the position corresponding to position 173 of SEQ ID NO:2; and   y. a cysteine residue at the position corresponding to position 178 of SEQ ID NO:2.   
     
     
         40 . The variant IFNL4 protein of  claim 39 , wherein the protein comprises:
 a. a cysteine residue at the position corresponding to position 27 of SEQ ID NO:2;   b. a leucine residue at the position corresponding to position 29 of SEQ ID NO:2   c. a serine residue at the position corresponding to position 30 of SEQ ID NO:2   d. a tyrosine residue at the position corresponding to position 32 of SEQ ID NO:2   e. a serine residue at the position corresponding to position 34 of SEQ ID NO:2   f. a proline residue at the position corresponding to position 37 of SEQ ID NO:2;   g. a leucine residue at the position corresponding to position 40 of SEQ ID NO:2;   h. an alanine residue at the position corresponding to position 42 of SEQ ID NO:2;   i. a lysine residue at the position corresponding to position 44 of SEQ ID NO:2;   j. an aspartic acid residue at the position corresponding to position 48 of SEQ ID NO:2;   k. a tyrosine residue at the position corresponding to position 50 of SEQ ID NO:2;   l. a leucine residue at the position corresponding to position 111 of SEQ ID NO:2;   m. a leucine residue at the position corresponding to position 112 of SEQ ID NO:2;   n. an aspartic acid residue at the position corresponding to position 118 of SEQ ID NO:2;   o. an alanine residue at the position corresponding to position 120 of SEQ ID NO:2;   p. a cysteine residue at the position corresponding to position 122 of SEQ ID NO:2;   q. a cysteine residue at the position corresponding to position 152 of SEQ ID NO:2;   r. a valine residue at the position corresponding to position 157 of SEQ ID NO:2;   s. an asparagine residue at the position corresponding to position 160 of SEQ ID NO:2;   t. a leucine residue at the position corresponding to position 161 of SEQ ID NO:2;   u. an arginine residue at the position corresponding to position 163 of SEQ ID NO:2   v. a leucine residue at the position corresponding to position 165 of SEQ ID NO:2;   w. a threonine residue at the position corresponding to position 166 of SEQ ID NO:2;   x. an alanine residue at the position corresponding to position 173 of SEQ ID NO:2; and   y. a cysteine residue at the position corresponding to position 178 of SEQ ID NO:2.   
     
     
         41 . The isolated protein of  claim 39 , wherein the isolated protein comprises at least one amino acid substitution, relative to SEQ ID NO:2, selected from the group consisting of A10P, A11P, L13M, V15F, V19M, I20V, A21P, R26G, L28M, L35M, L40M, E52K, L55M, W57R, N61H, S63P, F64V, R65G, D69H, P71T, R72G, R78G, V92M, L93I, L101M, L102F, G116R, A121P, A126P, P128A, G129A, S130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, A155P, S156G, V158I, F159V, L162M, L164M, and L169F. 
     
     
         42 . The isolated protein of  claim 39 , wherein the isolated protein comprises at least one amino acid substitution relative to SEQ ID NO:2, selected from the group consisting of A10P, A11P, L13M, V15F, V19M, I20V, A21P, R26G, L28M, L35M, L40M, E52K, L55M, W57R, N61H, S63P, F64V, R65G, D69H, P71T, R72G, G116R, A121P, A126P, P128A, G129A, S130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, A155P, S156G, V158I, F159V, L162M, L164M, and L169F. 
     
     
         43 . The isolated protein of  claim 39 , wherein the isolated protein comprises at least one amino acid substitution relative to SEQ ID NO:2, selected from the group consisting of A10P, A11P, L13M, V15F, V19M, I20V, A21P, R26G, L28M, L35M, L40M, G116R, A121P, A126P, P128A, G129A, S130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, A155P, S156G, V158I, F159V, L162M, L164M, and L169F. 
     
     
         44 . The isolated protein of  claim 39 , wherein the isolated protein comprises at least one amino acid substitution relative to SEQ ID NO:2, C27G, S34P, P37A, D48H, C62R, A87P, D118H, A120P, C122G, C152G, V157L, N160D, L161F, L164M, L165F, T166P, L169F, and A173P. 
     
     
         45 . The isolated protein of  claim 39 , wherein the isolated protein has at least one activity selected from the group consisting of eliciting an antibody that selectively binds a protein consisting of SEQ ID NO:2, selectively binding a compound that binds to a protein consisting of SEQ ID NO:2, activating expression of the JAK/STAT pathway, and inducing expression of at least one ISG listed in  FIG. 15 . 
     
     
         46 . A kit comprising the variant IFNL4 protein of  claim 39 . 
     
     
         47 . Use of the variant IFNL4 protein of  claim 39  in a method of determining the presence or absence of IFNL4 protein in a sample. 
     
     
         48 . An isolated protein comprising the amino acid sequence of SEQ ID NO: 2, wherein the isolated protein comprises at least one amino acid substitution, as compared to SEQ ID NO:2, selected from the group consisting of A10P, A11P, L13M, V15F, V19M, I20V, A21P, R26G, L28M, L35M, L40M, E52K, L55M, W57R, N61H, S63P, F64V, R65G, D69H, P71T, R72G, R78G, V92M, L93I, L101M, L102F, G116R, A121P, A126P, P128A, G129A, S130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, K154E, A155P, S156G, V158I, F159V, L162M, L164M, and L169F. 
     
     
         49 . The isolated protein of  claim 48 , wherein the isolated protein comprises at least one amino acid substitution, as compared to SEQ ID NO:2, selected from the group consisting of A10P, A11P, L13M, V15F, V19M, I20V, A21P, R26G, L28M, L35M, L40M, E52K, L55M, W57R, N61H, S63P, F64V, R65G, D69H, P71T, R72G, G116R, A121P, A126P, P128A, G129A, S130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, K154E, A155P, S156G, V158I, F159V, L162M, L164M, and L169F. 
     
     
         50 . The isolated protein of  claim 48 , wherein the isolated protein comprises at least one amino acid substitution, as compared to SEQ ID NO:2, selected from the group consisting of A10P, A11P, L13M, V15F, V19M, I20V, A21P, R26G, L28M, L35M, L40M, G116R, A121P, A126P, P128A, G129A, S130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, K154E, A155P, S156G, V158I, F159V, L162M, L164M, and L169F. 
     
     
         51 . The isolated protein of  claim 48 , wherein the isolated protein comprises at least one amino acid substitution, as compared to SEQ ID NO:2, selected from the group consisting of C27G, S34P, P37A, D48H, C62R, A87P, D118H, A120P, C122G, C152G, V157L, N160D, L161F, L164M, L165F, T166P, L169F, and A173P. 
     
     
         52 . The isolated protein of  claim 48 , wherein the isolated protein has at least one activity selected from the group consisting of eliciting an antibody that selectively binds a protein consisting of SEQ ID NO:2, selectively binding a compound that binds to a protein consisting of SEQ ID NO:2, activating expression of the JAK/STAT pathway, and inducing expression of at least one ISG listed in  FIG. 15 . 
     
     
         53 . A kit comprising the isolated protein of  claim 47 . 
     
     
         54 . Use of the isolated protein of  claim 47  in a method of determining the presence or absence of IFNL4 protein in a sample. 
     
     
         55 . An isolated protein comprising the amino acid sequence of SEQ ID NO: 2, where in the isolated protein has been modified to increase the stability, solubility, or absorbability of the protein. 
     
     
         56 . The isolated protein of  claim 55 , wherein the modification is selected from the group consisting of pegylation, phosphorylation, acetylation, myristylation, palmitoylation, and amidation. 
     
     
         57 . The isolated protein of  claim 55 , wherein the isolated protein has at least one activity selected from the group consisting of eliciting an antibody that selectively binds a protein consisting of SEQ ID NO:2, selectively binding a compound that binds to a protein consisting of SEQ ID NO:2, activating expression of the JAK/STAT pathway, and inducing expression of at least one ISG listed in  FIG. 15 . 
     
     
         58 . The isolated protein of  claim 55 , wherein the modification is pegylation.

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