# US 10,766,956 B2 · Antagonist antibodies that bind to human TGFB1, TGFB2 and to TGFB3 and their use for the treatment of lung fibrosis

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- Number: US 10,766,956 B2
- Document ID: US10766956B2
- Status: Granted
- Kind: B2
- Application number: 16/307,444
- Filed: 2017-06-07
- Published: 2019-10-31
- Granted: 2020-09-08
- Earliest claimed: 2016-06-08
- Assignees: Ucb Biopharma Srl
- Applicants: Ucb Biopharma Sprl
- Inventors: Helene Bon; Joanne Elizabeth Compson; Kate Louise Dixon; Carl Brendan Doyle; Mark Ellis; Maria Margarida Gouveia Sancho; Raymond Anthony Jupp; Lara Kevorkian; Daniel John Lightwood; Diane Marshall; Andrew Charles Payne; Joseph Michael David Rastrick; Monika-Sarah Schulze; Alison Turner; Kerry Louise Tyson
- Web page: https://patentgrep.com/patent/US10766956B2

## CPC

- C07K 16/22: against growth factors {; against growth regulators}
- A61K 9/0075: {for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles}
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 39/39533: {against materials from animals}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/544: {to the airways}
- A61P 11/12: Mucolytics
- C07K 2317/31: multispecific
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- 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 present disclosure relates to TGF-beta antibodies and binding fragments thereof, DNA encoding the same, host cells comprising said DNA and methods of expressing the antibody or binding fragment in a host cell. The disclosure also extends to pharmaceutical compositions comprising the antibody or a binding fragment thereof and use of the antibody, binding fragment and compositions comprising the same in treatment of various diseases including fibrosis.

## Claims

### Claim 1

An antagonistic antibody, or a binding fragment thereof, which binds human TGF-beta 1, human TGF-beta 2 and human TGF-beta 3 comprising a heavy chain and a light chain wherein the variable domain of the heavy chain comprises a CDR having the sequence given in SEQ ID NO:4 for CDR-H1, a CDR having the sequence given in SEQ ID NO:5 for CDR-H2 and a CDR having the sequence given in SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8 or SEQ ID NO:9 for CDR-H3, and wherein the variable domain of the light chain comprises a CDR having the sequence given in SEQ ID NO:1 for CDR-L1, a CDR having the sequence given in SEQ ID NO:2 for CDR-L2 and a CDR having the sequence given in SEQ ID NO:3 for CDR-L3.

### Claim 2 (depends on 1)

The antibody, or a binding fragment thereof, according to claim 1, wherein the antibody comprises a heavy chain comprising the sequence given in SEQ ID NO:52, SEQ ID NO:66, SEQ ID NO:80 or SEQ ID NO:94.

### Claim 3 (depends on 1)

The antibody, or a binding fragment thereof, according to claim 1, wherein the antibody comprises a light chain comprising the sequence given in SEQ ID NO:38.

### Claim 4 (depends on 1)

The antibody, or a binding fragment thereof, according to claim 1, selected from the group consisting of a complete antibody molecule having full length heavy and light chains, a Fab, modified Fab′, Fab′, F(ab′)2, Fv, and scFv.

### Claim 5 (depends on 1)

The antibody, or a binding fragment thereof, according to claim 1, having a binding affinity for human TGF-beta 1 of 200 pM or better, a binding affinity for human TGF-beta 2 of 300 pM or better and a binding affinity for human TGF-beta 3 of 2500 pM or better.

### Claim 6 (depends on 1)

The antibody, or a binding fragment thereof, according to claim 1, that is a monoclonal humanized antibody.

### Claim 7 (depends on 1)

A pharmaceutical composition comprising an antibody, or a binding fragment thereof, according to claim 1 in combination with one or more of a pharmaceutically acceptable excipient, diluent or carrier.

### Claim 8 (depends on 1)

A method for the treatment of a human subject suffering from kidney fibrosis or pulmonary fibrosis, the method comprising administering to the subject an effective amount of an antibody, or a binding fragment thereof, according to claim 1, wherein extracellular matrix (ECM) deposition is inhibited.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the binding fragment thereof is a Fab or Fab′ fragment which binds human TGF-beta 1, human TGF-beta 2 and human TGF-beta 3 and is administered by inhalation.

### Claim 10

An antagonistic antibody, or a binding fragment thereof, which binds human TGF-beta 1, human TGF-beta 2 and human TGF-beta 3, having a heavy chain comprising the sequence given in SEQ ID NO:52, SEQ ID NO:59, SEQ ID NO:66, SEQ ID NO:73, SEQ ID NO:80, SEQ ID NO:87, SEQ ID NO:94, or SEQ ID NO:101 and a light chain comprising the sequence given in SEQ ID NO:38 or SEQ ID NO:45.

### Claim 11

A process for the production of an antagonistic antibody, or a binding fragment thereof, which binds human TGF-beta 1, human TGF-beta 2 and human TGF-beta 3 comprising a heavy chain and a light chain, wherein the variable domain of the heavy chain comprises a CDR having the sequence given in SEQ ID NO:4 for CDR-H1, a CDR having the sequence given in SEQ ID NO:5 for CDR-H2 and a CDR having the sequence given in SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8 or SEQ ID NO:9 for CDR-H3, and wherein the variable domain of the light chain comprises a CDR having the sequence given in SEQ ID NO:1 for CDR-L1, a CDR having the sequence given in SEQ ID NO:2 for CDR-L2 and a CDR having the sequence given in SEQ ID NO:3 for CDR-L3, comprising culturing a host cell expressing said antibody and isolating said antibody.