# US 2019/0315852 A1 · Combined treatment with netrin-1 interfering drug and immune checkpoint inhibitors drugs

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- Number: US 2019/0315852 A1
- Document ID: US20190315852A1
- Status: Published application
- Kind: A1
- Application number: 16/476,239
- Filed: 2018-01-05
- Published: 2019-10-17
- Earliest claimed: 2017-01-05
- Assignees: Netris Pharma; Universite Claude Bernard Lyon 1; Centre National De La Recherche Scientifique; Centre Leon Berard; Institut National de la Sante et de la Recherche Medicale
- Applicants: Netris Pharma; Université Claude Bernard Lyon 1; Centre national de la recherche scientifique; Centre Léon-Bérard; Institut National De La Sante Et De La Recherche Medicale
- Inventors: Benjamin DUCAROUGE; David GOLDSCHNEIDER; Anna Maria Rita REDAVID; Benjamin GIBERT; Patrick MEHLEN
- Web page: https://patentgrep.com/patent/US20190315852A1

## CPC

- C07K 16/22: against growth factors {; against growth regulators}
- A61P 35/00: Antineoplastic agents
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/30: from tumour cells
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- 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
- 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 invention is the combination or combined use of (i) a compound able to disrupt or impede netrin-1/netrin-1 receptors interaction or netrin-1-mediated receptor dimerization, also called herein a NTN1 neutralizing agent, which compound may be an antibody binding to netrin-1 or anti-netrin-1 antibody, and (ii) an immune checkpoint inhibitor, in the treatment of cancer. The composition may comprise an anti-netrin-1 antibody and an immune checkpoint inhibitor, for use as an anticancerous drug with a simultaneous, separate or sequential administration of the anti-netrin-1 antibody and the immune checkpoint inhibitor to a patient.

## Claims

### Claim at position 1

1-29. (canceled)

### Claim 30

A pharmaceutical composition comprising an anti-netrin-1 antibody and an immune checkpoint inhibitor, wherein the anti-netrin-1 antibody is able to disrupt or impede netrin-1/netrin-1 receptors interaction or netrin-l-mediated receptor dimerization

### Claim 31 (depends on 30)

The composition according to claim 30, wherein the immune checkpoint inhibitor is selected from the group consisting of anti-PD1, anti-PD-L1, anti-PD-L2 and anti-CTLA-4 antibodies.

### Claim 32 (depends on 30)

The composition of claim 30, wherein the anti-netrin-1 antibody specifically binds to a polypeptide of amino acid sequence SEQ ID NO: 35, and is able to disrupt or impede netrin-1/netrin-1 receptors interaction or netrin-l-mediated receptor dimerization.

### Claim 33 (depends on 30)

The composition according to claim 30, wherein the anti-netrin-1 antibody comprises (i) a CDR1-H of sequence SEQ ID NO: 5, a CDR2-H of sequence SEQ ID NO: 6, a CDR3-H of sequence SEQ ID NO: 7, and a CDR1-L of sequence SEQ ID NO: 8, a CDR2-L of sequence YAS and a CDR3-L of sequence SEQ ID NO: 9, or (ii) a CDR1-H of sequence SEQ ID NO: 28, a CDR2-H of sequence SEQ ID NO: 29, a CDR3-H of sequence SEQ ID NO: 30, and a CDR1-L of sequence SEQ ID NO: 31, a CDR2-L of sequence SEQ ID NO: 32 and a CDR3-L of sequence SEQ ID NO: 9.

### Claim 34 (depends on 30)

The composition of claim 30, wherein the anti-netrin-1 antibody comprises an amino acid sequence SEQ ID NO: 10, 11, 12 or 13.

### Claim 35 (depends on 30)

The composition of claim 30, wherein the anti-netrin-1 antibody comprises both sequences SEQ ID NO: 10 and 11, or both sequences SEQ ID NO: 12 and 13.

### Claim 36 (depends on 30)

The composition of claim 30, wherein the anti-netrin-1 antibody comprises an amino acid sequence selected from the group of SEQ ID NO: 14 to 19.

### Claim 37 (depends on 30)

The composition of claim 30, wherein the anti-netrin-1 antibody comprises an amino acid sequence selected from the group of SEQ ID NO: 20 to 27.

### Claim 38 (depends on 30)

The composition of claim 30, wherein the anti-netrin-1 antibody comprises an amino acid sequence selected from the group of SEQ ID NO: 14 to 19 and an amino acid sequence selected from the group of SEQ ID NO: 20 to 27.

### Claim 39 (depends on 30)

The composition of claim 30, wherein the anti-netrin-1 antibody is selected from the group consisting of anti-netrin-1 antibodies comprising pairs of VH and VL amino acid sequences SEQ ID NO: 20 and 14, SEQ ID NO: 21 and 15, SEQ ID NO: 22 and 16, SEQ ID NO: 23 and 17, SEQ ID NO: 24 and 17, SEQ ID NO: 25 and 16, SEQ ID NO: 26 and 17, SEQ ID NO: 22 and 17, SEQ ID NO: 25 and 18, SEQ ID NO: 21 and 16, or SEQ ID NO: 27 and 19.

### Claim 40 (depends on 30)

The composition of claim 30, wherein the immune checkpoint inhibitor is selected from the group consisting of anti-PD1, anti-PD-L1, anti-PD-L2 and anti-CTLA-4 antibodies.

### Claim 41

A method of anti-cancer treatment comprising the administration to a patient in need thereof of an efficient amount of an anti-netrin-1 antibody and of an immune checkpoint inhibitor, wherein the anti-netrin-1 antibody is able to disrupt or impede netrin-1/netrin-1 receptors interaction or netrin-1-mediated receptor dimerization.

### Claim 42 (depends on 41)

The method according to claim 41, wherein the anti-netrin-1 antibody specifically binds to a polypeptide of amino acid sequence SEQ ID NO: 35.

### Claim 43 (depends on 41)

The method according to claim 41, wherein the anti-netrin-1 antibody comprises (i) a CDR1-H of sequence SEQ ID NO: 5, a CDR2-H of sequence SEQ ID NO: 6, a CDR3-H of sequence SEQ ID NO: 7, and a CDR1-L of sequence SEQ ID NO: 8, a CDR2-L of sequence YAS and a CDR3-L of sequence SEQ ID NO: 9, or (ii) a CDR1-H of sequence SEQ ID NO: 28, a CDR2-H of sequence SEQ ID NO: 29, a CDR3-H of sequence SEQ ID NO: 30, and a CDR1-L of sequence SEQ ID NO: 31, a CDR2-L of sequence SEQ ID NO: 32 and a CDR3-L of sequence SEQ ID NO: 9.

### Claim 44 (depends on 41)

The method of claim 41, wherein the anti-netrin-1 antibody comprises an amino acid sequence SEQ ID NO: 10, 11, 12 or 13.

### Claim 45 (depends on 41)

The method of claim 41, wherein the anti-netrin-1 antibody comprises both sequences SEQ ID NO: 10 and 11, or both sequences SEQ ID NO: 12 and 13.

### Claim 46 (depends on 41)

The method of claim 41, wherein the anti-netrin-1 antibody comprises an amino acid sequence selected from the group of SEQ ID NO: 14 to 19.

### Claim 47 (depends on 41)

The method of claim 41, wherein the anti-netrin-1 antibody comprises an amino acid sequence selected from the group of SEQ ID NO: 20 to 27.

### Claim 48 (depends on 41)

The method of claim 41, wherein the anti-netrin-1 antibody comprises an amino acid sequence selected from the group of SEQ ID NO: 14 to 19 and an amino acid sequence selected from the group of SEQ ID NO: 20 to 27.

### Claim 49 (depends on 41)

The method of claim 41, wherein the anti-netrin-1 antibody is selected from the group consisting of anti-netrin-1 antibodies comprising pairs of VH and VL amino acid sequences SEQ ID NO: 20 and 14, SEQ ID NO: 21 and 15, SEQ ID NO: 22 and 16, SEQ ID NO: 23 and 17, SEQ ID NO: 24 and 17, SEQ ID NO: 25 and 16, SEQ ID NO: 26 and 17, SEQ ID NO: 22 and 17, SEQ ID NO: 25 and 18, SEQ ID NO: 21 and 16, or SEQ ID NO: 27 and 19.

### Claim 50 (depends on 41)

The method of claim 41, wherein the immune checkpoint inhibitor is selected from the group consisting of anti-PD1, anti-PD-L1, anti-PD-L2 and anti-CTLA-4 antibodies.