Neutralizing anti-influenza binding molecules and uses thereof

Patent metadata

Field	Value
Publication number	US-10442854-B2
Application number	US-201615577799-A
Country	US
Kind code	B2
Filing date	May 31, 2016
Priority date	Jun 1, 2015
Publication date	Oct 15, 2019
Grant date	Oct 15, 2019

Abstract

Binding molecules, including bispecific antibodies that include at least two anti-influenza binding domains are disclosed, including binding molecules having a first binding domain that specifically binds influenza A virus and a second binding domain that specifically binds influenza B virus.

First claim

What is claimed is:

1. An isolated binding molecule which specifically binds to influenza A virus and influenza B virus, comprising:
(a) a first binding domain comprising an Fv domain of a first antibody that is capable of binding to influenza A virus hemagglutinin (HA) and neutralizing at least one group 1 subtype and at least 1 group 2 subtype of influenza A virus, wherein the first antibody comprises a VH and a VL selected from:
(i) a VH of SEQ ID NO.: 7 and a VL of SEQ ID NO.: 2; and
(ii) a VH of SEQ ID NO.: 17 and a VL of SEQ ID NO.: 12; and
(b) a second binding domain comprising an scFv of a second antibody that is capable of binding to influenza B virus hemagglutinin (HA) and neutralizing influenza B virus in at least two phylogenetically distinct lineages, wherein the second antibody comprises a VH and a VL selected from:
(i) a VH of SEQ ID NO.: 27 and a VL of SEQ ID NO.: 22;
(ii) a VH of SEQ ID NO.: 33 and a VL of SEQ ID NO.: 32;
(iii) a VH of SEQ ID NO.: 36 and a VL of SEQ ID NO.: 35;
(iv) a VH of SEQ ID NO.: 43 and a VL of SEQ ID NO.: 38;
(v) a VH of SEQ ID NO.: 49 and a VL of SEQ ID NO.: 48;
(vi) a VH of SEQ ID NO.: 52 and a VL of SEQ ID NO.: 51;
(vii) a VH of SEQ ID NO.: 59 and a VL of SEQ ID NO.: 54; and
(viii) a VH of SEQ ID NO.: 65 and a VL of SEQ ID NO.: 64.

2. The isolated binding molecule according to claim 1 , wherein the first binding domain is capable of neutralizing one or more influenza A virus group 1 subtypes selected from: H1, H2, H5, H6, H8, H9, H11, H12, H13, H16, H17, and H18; and one or more influenza A virus group 2 subtypes selected from: H3, H4, H7, H10, H14 and H15.

3. The isolated binding molecule according to claim 1 , wherein the second binding domain is capable of neutralizing influenza B virus in both Yamagata and Victoria lineages.

4. The isolated binding molecule according to claim 1 , wherein the binding molecule is a bispecific antibody.

5. The isolated binding molecule according to claim 1 , wherein the Fv domain of the first binding domain comprises a heavy chain (HC) comprising a polypeptide chain having an amino terminus and a carboxy terminus and a light chain (LC) comprising a polypeptide chain having an amino terminus and a carboxy terminus, and
(a) the second binding domain is covalently linked to the carboxy-terminus of the HC of the first binding domain;
(b) the second binding domain is covalently linked to the amino-terminus of the HC of the first binding domain;
(c) the second binding domain is covalently linked to the amino-terminus of the LC of the first binding domain; or
(d) the second binding domain is covalently intercalated in the polypeptide chain of the HC of the first binding domain.

6. An isolated polynucleotide comprising a nucleic acid which encodes the isolated binding molecule according to claim 1 .

7. A vector comprising the polynucleotide of claim 6 .

8. A host cell comprising the polynucleotide of claim 6 .

9. A composition comprising the isolated binding molecule according to claim 1 and a pharmaceutically acceptable carrier.

10. A method for manufacturing an isolated binding molecule according to claim 1 , comprising culturing a host cell under conditions suitable for expression of the binding molecule.

11. A method for prophylaxis or treatment of influenza A infection, influenza B infection, or a combination thereof in a subject comprising administering an effective amount of an isolated binding molecule according to claim 1 to the subject.

Assignees

• Medimmune Llc

Inventors

• Kallewaard-Lelay Nicole
• Zhu Qing
• Rainey Godfrey Jonah
• Gao Cuihua
• Kasturirangan Srinath
• Gao Changshou

Classifications

• C07K16/108 Primary

  Orthomyxoviridae (F), e.g. influenza virus · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• A61K38/00 Primary

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K2317/31

  multispecific · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title