# US 12,006,360 B2 · Dual specific antibodies for binding interleukin 4 (IL4) and interleukin 5 (IL5)

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- Number: US 12,006,360 B2
- Document ID: US12006360B2
- Status: Granted
- Kind: B2
- Application number: 16/860,891
- Filed: 2020-04-28
- Published: 2020-08-13
- Granted: 2024-06-11
- Earliest claimed: 2013-12-20
- Assignees: Genentech, Inc.
- Applicants: Genentech, Inc.
- Inventors: Germaine Fuh; Chingwei V. Lee; Patrick Koenig
- Web page: https://patentgrep.com/patent/US12006360B2

## CPC

- C07K 16/244: {Interleukins [IL]}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 11/06: Antiasthmatics
- A61P 35/00: Antineoplastic agents
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/247: {IL-4}
- C07K 16/468: {Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/14: Specific host cells or culture conditions, e.g. components, pH or temperature
- C07K 2317/21: from primates, e.g. man
- C07K 2317/31: multispecific
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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 VL residues that are electrostatic or hydrophobic and altering the nucleic acid sequence encoding one or more solvent accessible residues in the VH of the antibody either alone or in combination with alteration of the nucleic acid sequence encoding the VL of the antibody. The altered VH and the VL are expressed and dual specific antibodies, or antigen-binding fragments thereof, are selected.

## Claims

### Claim 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).

### Claim 2 (depends on 1)

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 GRX1TITX2DX3STSTX4 (SEQ ID NO: 26), wherein X1 is Val or Phe, X2 is Arg or Ile, X3 is Thr, Phe, Met, or Pro, and X4 is Ala or Val.

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

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).

### Claim 6 (depends on 1)

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.

### Claim 7 (depends on 1)

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

### Claim 8 (depends on 1)

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

### Claim 9 (depends on 1)

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

### Claim 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.

### Claim 11 (depends on 10)

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