Interferon-λ4 (IFNL-4) protein, related nucleic acid molecules, and uses thereof

Patent metadata

Field	Value
Publication number	US-10962539-B2
Application number	US-201715597459-A
Country	US
Kind code	B2
Filing date	May 17, 2017
Priority date	Mar 28, 2012
Publication date	Mar 30, 2021
Grant date	Mar 30, 2021

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.

First claim

What is claimed:

1. A nucleic acid molecule that encodes the amino acid sequence of SEQ ID NO: 2 and at least one amino acid sequence feature selected from the group consisting of:
(a) 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, L93I, L101M, L102F, G116R, A121P, A126P, P128A, G129A, S130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, K154E, A155P, S156G, F159V, L162M, L164M, and L169F;
(b) 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, 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, V158I, F159V, L162M, L164M, and L169F; or
(d) 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.

2. The nucleic acid molecule of claim 1 , wherein the variant sequence has at least one amino acid substitution, relative to SEQ ID NO:2, selected from A10P, A11P, L13M, V15F, V19M, 120V, A21P, R26G, L28M, L35M, L40M, E52K, L55M, W57R, N61H, S63P, F64V, R65G, D69H, P71T, R72G, R78G, V92M, L931, L101M, L102F, G116R, A121P, A126P, P128A, G129A, S130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, A155P, S156G, F159V, L162M, L164M, and L169F.

3. The nucleic acid molecule of claim 1 , wherein the variant sequence has at least one amino acid substitution, relative to SEQ ID NO:2, selected from A10P, A11P, L13M, V15F, V19M, 120V, 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, F159V, L162M, L164M, and L169F.

4. The nucleic acid molecule of claim 1 , wherein the variant sequence has at least one amino acid substitution, as compared to SEQ ID NO:2, selected from A10P, A11P, L13M, V15F, V19M, I20V, A21P, R26G, L28M, L35M, L40M, G116R, A121P, A126P, P128A, G129A, 5130P, R132G, P135A, K139R, R140G, K143E, R146K, S149P, P150A, A155P, S156G, F159V, L162M, L164M, and L169F.

5. The nucleic acid molecule of claim 1 , wherein the variant sequence has at least one amino acid substitution, relative 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.

6. The nucleic acid molecule of claim 1 , wherein the variant sequence has at least one amino acid substitution, relative to SEQ ID NO:2, selected from A10P, I20V, L28M, E52K, W57R, S63P, A121P, K143E, P150A, S156G, and L162M.

7. A recombinant vector comprising the nucleic acid molecule of claim 1 .

8. A plasmid comprising the nucleic acid molecule of claim 1 .

9. The nucleic acid molecule of claim 1 , that is inserted into a vector capable of delivering the nucleic acid molecule into a host cell.

10. The nucleic acid molecule of claim 9 , operatively linked to at least one transcription control sequence capable of regulating expression of the nucleic acid molecule in a cell.

11. A recombinant vector comprising a nucleic acid sequence encoding a protein comprising a variant amino acid sequence that is 85% to 96% identical to SEQ ID NO:2, wherein the variant amino acid sequence 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.

12. The recombinant vector of claim 11 , wherein the variant amino acid sequence 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

Assignees

• The Usa As Represented By The Secretary Dept Of Health And Human Services

Inventors

• Prokunina Liudmila
• O'Brien Thomas R
• Muchmore Brian
• Donnelly Raymond P
• Porter-Gill Patricia A

Classifications

• C07K14/555 Primary

  Interferons [IFN] · CPC title

• C12Q1/707

  non-A, non-B Hepatitis, excluding hepatitis D · CPC title

• C12Q1/6883

  for diseases caused by alterations of genetic material · CPC title

• C12Q2600/158

  Expression markers · CPC title

• G01N33/56983 Primary

  Viruses · CPC title