Dual specific antibodies for binding interleukin 4 (IL4) and interleukin 5 (IL5)

Patent metadata

Field	Value
Publication number	US-12006360-B2
Application number	US-202016860891-A
Country	US
Kind code	B2
Filing date	Apr 28, 2020
Priority date	Dec 20, 2013
Publication date	Jun 11, 2024
Grant date	Jun 11, 2024

Abstract

The invention provides dual specific antibodies capable of binding interleukin 4 (IL4) and interleukin 5 (IL5) and methods of making and using such antibodies. In general, the dual specific antibodies capable of binding IL4 and IL5 are generated by identification of a monospecific antibody having light chain variable region V L residues that are electrostatic or hydrophobic and altering the nucleic acid sequence encoding one or more solvent accessible residues in the V H of the antibody either alone or in combination with alteration of the nucleic acid sequence encoding the V L of the antibody. The altered V H and the V L are expressed and dual specific antibodies, or antigen-binding fragments thereof, are selected.

First claim

What is claimed is:

1. An isolated dual specific antibody, or antigen-binding fragment thereof, capable of binding interleukin 4 (IL4) and interleukin 5 (IL5), comprising the following six CDRs:
(i) a CDRL1 comprising the amino acid sequence of KASQSVINDAA (SEQ ID NO: 9);
(ii) a CDRL2 comprising the amino acid sequence of YTSHRYT (SEQ ID NO: 10);
(iii) a CDRL3 comprising the amino acid sequence of QQDYKHPWTF (SEQ ID NO: 31);
(iv) a CDRH1 comprising the amino acid sequence of DYFIH (SEQ ID NO: 15);
(v) a CDRH2 comprising the amino acid sequence of AGIVYDATGFTVYADDFK (SEQ ID NO: 32); and
(vi) a CDRH3 comprising the amino acid sequence of GGIFYGMDY (SEQ ID NO: 20).

2. The isolated dual specific antibody, or antigen-binding fragment thereof, of claim 1 , further comprising a framework region 3 (FR3) comprising the amino acid sequence of GRX 1 TITX 2 DX 3 STSTX 4 (SEQ ID NO: 26), wherein X 1 is Val or Phe, X 2 is Arg or Ile, X 3 is Thr, Phe, Met, or Pro, and X 4 is Ala or Val.

3. The isolated dual specific antibody, or antigen-binding fragment thereof, of claim 1 , wherein said antibody binds IL4 with a Kd of 10 nM or lower and IL5 with a Kd of about 50 nM or lower.

4. The isolated dual specific antibody, or antigen-binding fragment thereof, of claim 1 , wherein said antibody is an IgG antibody.

5. The isolated dual specific antibody, or antigen-binding fragment thereof, of claim 1 , wherein said fragment is a Fab fragment or a single chain variable fragment (scFv).

6. The isolated dual specific antibody, or antigen-binding fragment thereof, of claim 1 , wherein at least a portion of the framework sequence is a human consensus framework sequence.

7. The isolated dual specific antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody is a chimeric antibody.

8. The isolated dual specific antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody is a humanized antibody.

9. A pharmaceutical composition comprising the isolated dual specific antibody, or antigen-binding fragment thereof, of claim 1 , and a pharmaceutically acceptable excipient.

10. An isolated dual specific antibody, or antigen-binding fragment thereof, capable of binding IL4 and IL5, comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO: 33 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 34.

11. A pharmaceutical composition comprising the isolated dual specific antibody, or antigen-binding fragment thereof, of claim 10 , and a pharmaceutically acceptable excipient.

Assignees

• Genentech Inc

Inventors

• Fuh Germaine
• Lee Chingwei V
• Koenig Patrick

Classifications

• C07K2317/31

  multispecific · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• C07K2317/56

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

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K2317/14

  Specific host cells or culture conditions, e.g. components, pH or temperature · CPC title