# US 2019/0169277 A1 · Modified anti-tenascin antibodies and methods of use

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- Number: US 2019/0169277 A1
- Document ID: US20190169277A1
- Status: Published application
- Kind: A1
- Application number: 16/186,418
- Filed: 2018-11-09
- Published: 2019-06-06
- Earliest claimed: 2016-05-11
- Assignees: Hoffmann-La Roche Inc.
- Applicants: Hoffmann-La Roche Inc.
- Inventors: Ralf HOSSE; Ekkehard MOESSNER; Pablo UMANA
- Web page: https://patentgrep.com/patent/US20190169277A1

## CPC

- C07K 16/18: against material from animals or humans
- A61P 35/00: Antineoplastic agents
- C12N 15/85: for animal cells
- A61K 38/00: 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)
- C07K 2317/21: from primates, e.g. man
- C07K 2317/31: multispecific
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C12N 2015/8518: {expressing industrially exogenous proteins, e.g. for pharmaceutical use, human insulin, blood factors, immunoglobulins, pseudoparticles}
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)

## Abstract

The present invention relates to improved antibodies specific for Tenascin-C (TnC), in particular domain specific anti-TnC antibodies with improved cross-species reactivity. In addition, the invention relates to polynuleotides encoding such antibodies, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the antibodies and methods of using them in the treatment of disease.

## Claims

### Claim 1

An antibody that specifically binds to Tenascin-C (TnC), wherein said antibody comprises:
(i) a heavy chain variable region comprising a heavy chain CDR1 of SEQ ID NO: 49, a heavy chain CDR2 of SEQ ID NO: 50 and a heavy chain CDR3 of SEQ ID NO:51; and a light chain variable region comprising a light chain CDR1 of SEQ ID NO: 37, a light chain CDR2 of SEQ ID NO: 38 and a light chain CDR3 of SEQ ID NO: 39; or
(ii) a heavy chain variable region comprising a heavy chain CDR1 of SEQ ID NO: 52, a heavy chain CDR2 of SEQ ID NO: 53 and a heavy chain CDR3 of SEQ ID NO: 54; and a light chain variable region comprising a light chain CDR1 of SEQ ID NO: 40, a light chain CDR2 of SEQ ID NO:41 and a light chain CDR3 of SEQ ID NO: 42; wherein said antibody has cross-species reactivity.

### Claim 2 (depends on 1)

The antibody of claim 1, wherein said antibody comprises a heavy chain variable region comprising
(a) the heavy chain CDR1 of SEQ ID NO: 49;
(b) the heavy chain CDR2 of SEQ ID NO: 50;
(c) the heavy chain CDR3 of SEQ ID NO: 51,
and a light chain variable region comprising
(a) the light chain CDR1 of SEQ ID NO: 37;
(b) the light chain CDR2 of SEQ ID NO: 38, and
(c) the light chain CDR3 of SEQ ID NO: 39.

### Claim 3 (depends on 1)

The antibody of claim 1, wherein said antibody comprises a heavy chain variable region comprising
(a) the heavy chain CDR1 of SEQ ID NO: 52;
(b) the heavy chain CDR2 of SEQ ID NO: 53;
(c) the heavy chain CDR3 of SEQ ID NO: 54,
and a light chain variable region comprising
(a) the light chain CDR1 of SEQ ID NO: 40;
(b) the light chain CDR2 of SEQ ID NO: 41, and
(c) the light chain CDR3 of SEQ ID NO: 42.

### Claim 4 (depends on 1)

The antibody of claim 1, wherein said antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 28 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 27.

### Claim 5 (depends on 1)

The antibody of claim 1, wherein said antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 30 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 29.

### Claim 6 (depends on 1)

The antibody of claim 1, wherein said antibody comprises an Fc region or a region equivalent to the Fc region of an immunoglobulin.

### Claim 7 (depends on 1)

The antibody of claim 1, wherein said Fc region is an IgG1 Fc region.

### Claim 8 (depends on 1)

The antibody of claim 1, wherein said antibody is a human antibody.

### Claim 9

The antibody of laim 1, wherein said antibody has an improved affinity.

### Claim 10 (depends on 1)

The antibody of claim 1, wherein said antibody binds to at least one of human, mouse and cynomolgus TnC with a KD value lower than about 2 nM.

### Claim 11 (depends on 1)

The antibody of claim 1, wherein the antibody binds to human, mouse and cynomolgus TnC.

### Claim 12 (depends on 1)

The antibody of claim 1, wherein said antibody binds to the target antigen from all indicated species with similar affinity.

### Claim 13 (depends on 12)

The antibody of claim 12, wherein said antibody binds to the target antigen from all indicated species with similar affinity, in particular within a KD range of a factor of 10.

### Claim 14 (depends on 1)

The antibody of claim 1, wherein the antibody is a multispecific antibody.

### Claim 15 (depends on 1)

The antibody of claim 1, wherein the antibody is a bispecific antibody.

### Claim 16

A pharmaceutical formulation comprising an antibody that specifically binds to Tenascin-C (TnC), wherein said antibody comprises:
(i) a heavy chain variable region comprising a heavy chain CDR1 of SEQ ID NO: 49, a heavy chain CDR2 of SEQ ID NO: 50 and a heavy chain CDR3 of SEQ ID NO:51; and a light chain variable region comprising a light chain CDR1 of SEQ ID NO: 37, a light chain CDR2 of SEQ ID NO: 38 and a light chain CDR3 of SEQ ID NO: 39; or
(ii) a heavy chain variable region combrising a heavy chain CDR1 of SEQ ID NO: 52, a heavy chain CDR2 of SEQ ID NO: 53 and a heavy chain CDR3 of SEQ ID NO: 54; and a light chain variable region comprising a light chain CDR1 of SEQ ID NO: 40, a light chain CDR2 of SEQ ID NO:41 and a light chain CDR3 of SEQ ID NO: 42; wherein said antibody has cross-species reactivity.

### Claim 17 (depends on 1)

The antibody of claim 1 for use as a medicament.

### Claim 18

A method of treating an individual having a disease characterized by expression of TnC, the method comprising administering to a patient in need thereof an antibody that specifically binds to Tenascin-C (TnC), wherein said antibody comprises:
(i) a heavy chain variable region comprising a heavy chain CDR1 of SEQ ID NO: 49, a heavy chain CDR2 of SEQ ID NO: 50 and a heavy chain CDR3 of SEQ ID NO:51; and a light chain variable region comprising a light chain CDR1 of SEQ ID NO: 37, a light chain CDR2 of SEQ ID NO: 38 and a light chain CDR3 of SEQ ID NO: 39; or
(ii) a heavy chain variable region combrising a heavy chain CDR1 of SEQ ID NO: 52, a heavy chain CDR2 of SEQ ID NO: 53 and a heavy chain CDR3 of SEQ ID NO: 54; and a light chain variable region comprising a light chain CDR1 of SEQ ID NO: 40, a light chain CDR2 of SEQ ID NO:41 and a light chain CDR3 of SEQ ID NO: 42; wherein said antibody has cross-species reactivity.

### Claim 19 (depends on 18)

The method of claim 18, wherein said disease is cancer.

### Claim 20

The method of manufacturing an antibody that specifically binds to Tenascin-C (TnC) for treating cancer, wherein said antibody comprises:
(i) a heavy chain variable region comprising a heavy chain CDR1 of SEQ ID NO: 49, a heavy chain CDR2 of SEQ ID NO: 50 and a heavy chain CDR3 of SEQ ID NO:51; and a light chain variable region comprising a light chain CDR1 of SEQ ID NO: 37, a light chain CDR2 of SEQ ID NO: 38 and a light chain CDR3 of SEQ ID NO: 39; or (ii) a heavy chain variable region combrising a heavy chain CDR1 of SEQ ID NO: 52, a heavy chain CDR2 of SEQ ID NO: 53 and a heavy chain CDR3 of SEQ ID NO: 54; and a light chain variable region comprising a light chain CDR1 of SEQ ID NO: 40, a light chain CDR2 of SEQ ID NO:41 and a light chain CDR3 of SEQ ID NO: 42; wherein said antibody has cross-species reactivity.

### Claim 21 (depends on 20)

The method of claim 20 wherein the antibody is for inducing lysis of a tumor cell or a stromal cell of a tumor.

### Claim 22 (depends on 1, 16)

A method of treating an individual having a disease characterized by TnC expression, comprising administering to the individual an effective amount of the antibody of claim 1, or the pharmaceutical formulation of claim 16.

### Claim 23 (depends on 22)

The method of claim 22, wherein said disease is cancer.

### Claim 24 (depends on 18)

The method of claim 18 wherein the antibody is for inducing lysis of a tumor cell or a stromal cell of a tumor.