Single-domain vhh antibodies directed to norovirus gi.1 and gii.4 and their use

Patent metadata

Field	Value
Publication number	US-2016102136-A1
Application number	US-201414889774-A
Country	US
Kind code	A1
Filing date	May 9, 2014
Priority date	May 9, 2013
Publication date	Apr 14, 2016
Grant date	—

Abstract

Isolated V H H monoclonal antibodies are disclosed that specifically bind to a Norovirus polypeptide. In some embodiments, the Norovirus is a Genogroup I Norovirus or a Genogroup II Norovirus. In other embodiments, the Norovirus is Norwalk or MD2004 virus. In some embodiments, the monoclonal antibodies specifically bind VP1. Also disclosed are compositions including the disclosed antibodies, nucleic acids encoding these antibodies, expression vectors including the nucleic acids, and isolated host cells that express the nucleic acids. The antibodies and compositions disclosed herein can be used for detecting the presence of a Norovirus in a biological sample, or detecting a Norovirus infection. Also disclosed are methods of treating and/or preventing a NoV infection.

First claim

1 . An isolated V H H monoclonal antibody comprising a heavy chain domain, wherein the heavy chain variable domain comprises a heavy chain complementarity determining region (HCDR)1, an HCDR2 and an HCDR3, wherein the CDR3 comprises the amino acid sequence set forth as one of:
a) amino acids 96-109 of SEQ ID NO: 3; b) amino acids 96-109 of SEQ ID NO: 2; c) amino acids 96-109 of SEQ ID NO: 1; d) amino acids 96-109 of SEQ ID NO: 4; e) amino acids 97-110 of SEQ ID NO: 5; f) amino acids 97-111 of SEQ ID NO: 6; g) amino acids 97-111 of SEQ ID NO: 7; h) amino acids 97-111 of SEQ ID NO: 8; i) amino acids 96-112 of SEQ ID NO: 9; j) amino acids 96-112 of SEQ ID NO: 10; k) amino acids 96-114 of SEQ ID NO: 11; l) amino acids 96-112 of SEQ ID NO: 12; m) amino acids 97-113 of SEQ ID NO: 13; n) amino acids 97-113 of SEQ ID NO: 14; o) amino acids 97-114 of SEQ ID NO: 15; p) amino acids 96-107 of SEQ ID NO: 16; q) amino acids 97-113 of SEQ ID NO: 17; r) amino acids 97-114 of SEQ ID NO: 18; s) amino acids 97-113 of SEQ ID NO: 19; t) amino acids 96-111 of SEQ ID NO: 20; u) amino acids 96-102 of SEQ ID NO: 21; v) amino acids 96-110 of SEQ ID NO: 22; w) amino acids 95-104 of SEQ ID NO: 23; x) amino acids 96-107 of SEQ ID NO: 24; y) amino acids 100-110 of SEQ ID NO: 25; z) amino acids 96-117 of SEQ ID NO: 26; aa) amino acids 97-108 of SEQ ID NO: 27; bb) amino acids 96-112of SEQ ID NO: 28; cc) amino acids 97-115 of SEQ ID NO: 29; dd) amino acids 97-121 of SEQ ID NO: 30, and wherein the V H H monoclonal antibody specifically binds a Norovirus polypeptide.

2 . The isolated V H H monoclonal antibody, or antigen binding fragment thereof of claim 1 , wherein the V H H monoclonal antibody specifically binds a Genogroup II NoV polypeptide, and wherein the CDR3 includes the amino acid sequence set forth as one of:
a) amino acids 96-109 of SEQ ID NO: 3; b) amino acids 96-109 of SEQ ID NO: 2; c) amino acids 96-109 of SEQ ID NO: 1; d) amino acids 96-109 of SEQ ID NO: 4; e) amino acids 97-110 of SEQ ID NO: 5; f) amino acids 97-111 of SEQ ID NO: 6; g) amino acids 97-111 of SEQ ID NO: 7; h) amino acids 97-111 of SEQ ID NO: 8; i) amino acids 96-112 of SEQ ID NO: 9; j) amino acids 96-112 of SEQ ID NO: 10; k) amino acids 96-114 of SEQ ID NO: 11; l) amino acids 96-112 of SEQ ID NO: 12; m) amino acids 97-113 of SEQ ID NO: 13; n) amino acids 97-113 of SEQ ID NO: 14; o) amino acids 97-114 of SEQ ID NO: 15; p) amino acids 96-107 of SEQ ID NO: 16; q) amino acids 97-113 of SEQ ID NO: 17; r) amino acids 97-114 of SEQ ID NO: 18; s) amino acids 97-113 of SEQ ID NO: 19; t) amino acids 96-111 of SEQ ID NO: 20; or u) amino acids 96-102 of SEQ ID NO: 21.

3 . The isolated V H H monoclonal antibody or antigen binding fragment of claim 1 , wherein the monoclonal antibody specifically binds a Genogroup I NoV polypeptide, and wherein the CDR3 comprises the amino acid sequence set forth as one of:
a) amino acids 96-110 of SEQ ID NO: 22 b) amino acids 95-104 of SEQ ID NO: 23; c) amino acids 96-107 of SEQ ID NO: 24; d) amino acids 100-110 of SEQ ID NO: 25; e) amino acids 96-117 of SEQ ID NO: 26; f) amino acids 97-108 of SEQ ID NO: 27; g) amino acids 96-112of SEQ ID NO: 28; h) amino acids 97-115 of SEQ ID NO: 29; or i) amino acids 97-121 of SEQ ID NO: 30.

4 . The isolated V H H monoclonal antibody of claim 2 , wherein
a) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 3, a CDR2 comprising amino acids 51-57 of SEQ ID NO: 3, and a CDR3 comprising amino acids 96-109 of SEQ ID NO: 3; b) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 2, a CDR2 comprising amino acids 51-57 of SEQ ID NO: 2, and a CDR3 comprising amino acids 96-109 of SEQ ID NO: 2; c) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 1, a CDR2 comprising amino acids 51-57 of SEQ ID NO: 1, and a CDR3 comprising amino acids 96-109 of SEQ ID NO: 1; d) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 4, a CDR2 comprising amino acids 51-57 of SEQ ID NO: 4, and a CDR3 comprising amino acids 96-109 of SEQ ID NO: 4; e) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 5, a CDR2 comprising amino acids 51-58 of SEQ ID NO: 5, and a CDR3 comprising amino acids 97-110 of SEQ ID NO: 5; f) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 6, a CDR2 comprising amino acids 51-58 of SEQ ID NO: 6, and a CDR5 comprising amino acids 97-111 of SEQ ID NO: 6; g) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 7, a CDR2 comprising amino acids 51-58 of SEQ ID NO: 7, and a CDR3 comprising amino acids 97-111 of SEQ ID NO: 7; h) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 8, a CDR2 comprising amino acids 51-58 of SEQ ID NO: 8, and a CDR3 comprising amino acids 97-111 of SEQ ID NO: 8; i) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 9, a CDR2 comprising amino acids 51-57 of SEQ ID NO: 9, and a CDR3 comprising amino acids 96-112 of SEQ ID NO: 9; j) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 10, a CDR2 comprising amino acids 51-57 of SEQ ID NO: 10, and a CDR3 comprising amino acids 96-112 of SEQ ID NO: 10; k) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 11, a CDR2 comprising amino acids 51-57, and a CDR3 comprising amino acids 96-114 of SEQ ID NO: 11; l) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 12, a CDR2 comprising amino acids 51-57 of SEQ ID NO: 12, and a CDR3 comprising amino acids 96-112 of SEQ ID NO: 12; m) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 13, a CDR2 comprising amino acids 51-58 of SEQ ID NO: 13, and a CDR3 comprising amino acids 97-113 of SEQ ID NO: 13; n) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 14, a CDR2 comprising amino acids 51-58 of SEQ ID NO: 14, and a CDR3 comprising amino acids 97-113 of SEQ ID NO: 14; o) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 15, a CDR2 comprising amino acids 51-58 of SEQ ID NO: 15, and a CDR3 comprising amino acids 97-114 of SEQ ID NO: 15; p) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 16, a CDR2 comprising amino acids 51-57 of SEQ ID NO: 16, and a CDR3 comprising amino acids 96-107 of SEQ ID NO: 16; q) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 17, a CDR2 comprising amino acids 51-58 of SEQ ID NO: 17, and a CDR3 comprising amino acids 97-113 of SEQ ID NO: 17; r) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 18, a CDR2 comprising amino acids 51-58 of SEQ ID NO: 18, and a CDR3 comprising amino acids 97-114 of SEQ ID NO: 18; s) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 19, a CDR2 comprising amino acids 51-58 of SEQ ID NO: 19, and a CDR3 comprising amino acids 97-113 of SEQ ID NO: 19; t) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 20, a CDR2 comprising amino acids 51-57 of SEQ ID NO:20, and a CDR3 comprising amino acids 96-111 of SEQ ID NO: 20; or u) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 21, a CDR2 comprising amino acids 51-57 of SEQ ID NO:21, and a CDR3 comprising amino acids 96-102 of SEQ ID NO: 21.

5 . The isolated Vi-iH monoclonal antibody of claim 3 , comprising:
a) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 22, a CDR2 comprising amino acids 51-57 of SEQ ID NO:22, and a CDR3 comprising amino acids 96-110 of SEQ ID NO: 22 b) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 23, a CDR2 comprising amino acids 50-56 of SEQ ID NO:23, and a CDR3 comprising amino acids 95-104 of SEQ ID NO: 23; c) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 24, a CDR2 comprising amino acids 51-57 of SEQ ID NO:24, and a CDR3 comprising amino acids 96-107 of SEQ ID NO: 24; d) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 25, a CDR2 comprising amino acids 51-57 of SEQ ID NO: 25, and a CDR3 comprising amino acids 100-110 of SEQ ID NO: 25; e) a CDR1 comprising amino acids 26-33 of SEQ ID NO: 26, a CDR2 comprising amino acids 50-57 of SEQ ID NO:26, and a CDR3 comprising amino acids

Assignees

• Us Health
• Inst Nac De Tecnologia Agropecuaria

Inventors

• Bok Karin
• Garaicoechea Lorena Laura
• Parreno Viviana
• Aguilar Andrea Pamela
• Bok Marina
• Green Lisbeth Kim
• Sosnovtsev Stanislav Vladimirovich

Classifications

• A61P31/12

  Antivirals · CPC title

• A61P31/14

  for RNA viruses · CPC title

• C12N2770/16034

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C12N2770/16011

  Caliciviridae · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title