# US 12,162,932 B2 · Combined treatment with Netrin-1 interfering drug and immune checkpoint inhibitors drugs > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,162,932 B2 - Document ID: US12162932B2 - Status: Granted - Kind: B2 - Application number: 16/476,239 - Filed: 2018-01-05 - Published: 2019-10-17 - Granted: 2024-12-10 - 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; Universite Claude Bernard Lyon 1; Centre national de la recherche scientifique; Centre Léon-Bérard; Institut National De La Sante Et De La Recherche Medicale (Inserm) - Inventors: Benjamin Ducarouge; David Goldschneider; Anna Maria Rita Redavid; Benjamin Gibert; Patrick Mehlen - Web page: https://patentgrep.com/patent/US12162932B2 ## 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 1 A method of anti-cancer treatment consisting of administering to a patient in need thereof of an effective amount of an anti-netrin-1 antibody and an immunotherapeutic agent comprising an immune checkpoint inhibitor, wherein the anti-netrin-1 antibody comprises: (i) a variable domain VH comprising 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 variable domain VL comprising 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) comprises a variable domain VH comprising 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 variable domain VL comprising 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; 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 2 (depends on 1) The method of claim 1, wherein the anti-netrin-1 antibody comprises the amino acid sequence SEQ ID NO: 10, 11, 12 or 13. ### Claim 3 (depends on 1) The method of claim 1, 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 4 (depends on 1) The method of claim 1, wherein the anti-netrin-1 antibody comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18 and SEQ ID NO: 19. ### Claim 5 (depends on 1) The method of claim 1, wherein the anti-netrin-1 antibody comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26 and SEQ ID NO: 27. ### Claim 6 (depends on 1) The method of claim 1, wherein the anti-netrin-1 antibody comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18 and SEQ ID NO: 19 and an amino acid sequence selected from the group consisting of SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26 and SEQ ID NO: 27. ### Claim 7 (depends on 1) The method of claim 1, wherein the anti-netrin-1 antibody comprises pairs of VH and VL amino acid sequences selected from the group consisting of 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, the SEQ ID NO: 27 and 19. ### Claim 8 (depends on 1) The method of claim 1, wherein the anti-netrin-1 antibody comprises a heavy chain comprising a VH having the sequence as set forth in SEQ ID NO: 22 and a Human IgG1 heavy chain constant domain, and a VL having the sequence as set forth in SEQ ID NO: 16 and a Human light chain constant domain. ### Claim 9 A method of anti-cancer treatment consisting of administering to a patient in need thereof an effective amount of an anti-netrin-1 antibody and of an immune checkpoint inhibitor, 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, and wherein the anti-netrin-1 antibody comprises: (i) a variable domain VH comprising 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 variable domain VL comprising 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 variable domain VH comprising 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 variable domain VL comprising 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 10 (depends on 9) The method of claim 9, wherein the anti-netrin-1 antibody comprises a heavy chain comprising a VH having the sequence as set forth in SEQ ID NO: 22 and a Human IgG1 heavy chain constant domain, and a VL having the sequence as set forth in SEQ ID NO: 16 and a Human light chain constant domain.