# US 12,180,293 B2 · CD70 combination therapy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,180,293 B2 - Document ID: US12180293B2 - Status: Granted - Kind: B2 - Application number: 18/054,198 - Filed: 2022-11-10 - Published: 2024-01-04 - Granted: 2024-12-31 - Earliest claimed: 2018-01-16 - Assignees: argenx BV - Applicants: argenx BV - Inventors: Luc Van Rompaey; Mahan Moshir; Tim Delahaye; Piotr Zabrocki - Web page: https://patentgrep.com/patent/US12180293B2 ## CPC - C07K 16/2875: {against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 (against NGF C07K16/22, against TNF C07K16/241)} - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61P 35/02: specific for leukemia - C07K 16/2803: {against the immunoglobulin superfamily} - C07K 16/2866: {against receptors for cytokines, lymphokines, interferons} - A61K 2039/507: {Comprising a combination of two or more separate antibodies} - C07K 2317/22: from camelids, e.g. camel, llama or dromedary - C07K 2317/55: Fab or Fab' - C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC] - C07K 2317/734: Complement-dependent cytotoxicity [CDC] - 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 present invention relates to combination therapies for the treatment of malignancy, particularly myeloid malignancy such as acute myeloid leukemia (AML). The combination therapies may include an antibody molecule that binds to CD70 and at least one antibody molecule that binds to a leukemic stem cell target. Preferred leukemic stem cell targets are TIM-3, IL1R3/1L1RAP and CD47. ## Claims ### Claim 1 A combination comprising a first antibody molecule that binds to CD70 and a second antibody molecule that binds to IL1RAP, wherein the first antibody molecule that binds to CD70 comprises a first variable heavy chain domain (VH) comprising the heavy chain complementarity determining region (HCDR) 1 (HCDR1), HCDR2 and HCDR3 amino acid sequences set forth in SEQ ID NO: 4, and a first variable light chain domain (VL) comprising the light chain complementarity determining region (LCDR) 1 (LCDR1), LCDR2 and LCDR3 amino acid sequences set forth in SEQ ID NO: 8, and wherein the second antibody molecule that binds to IL1RAP comprises: (i) a second VH comprising the HCDR1, HCDR2 and HCDR3 amino acid sequences set forth in SEQ ID NO: 121, and a second VL comprising the LCDR1, LCDR2 and LCDR3 amino acid sequences set forth in SEQ ID NO: 122; or (ii) a second VH comprising the HCDR1, HCDR2 and HCDR3 amino acid sequences set forth in SEQ ID NO: 123, and a second VL comprising the LCDR1, LCDR2 and LCDR3 amino acid sequences set forth in SEQ ID NO: 124. ### Claim 2 (depends on 1) The combination of claim 1, wherein the first antibody molecule comprises the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences set forth in SEQ ID NOs: 1, 2, 3, 5, 6, and 7, respectively. ### Claim 3 (depends on 1) The combination of claim 1, wherein the first VH comprises an amino acid sequence at least 70% identical to SEQ ID NO: 4 and the first VL comprises an amino acid sequence at least 70% identical to SEQ ID NO: 8. ### Claim 4 (depends on 3) The combination of claim 3, wherein the first VH comprises the amino acid sequence set forth in SEQ ID NO: 4 and the first VL comprises the amino acid sequence set forth in SEQ ID NO: 8. ### Claim 5 (depends on 1) The combination of claim 1, wherein the first antibody molecule is ARGX-110. ### Claim 6 (depends on 1) The combination of claim 1, wherein the second antibody molecule comprises the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences set forth in SEQ ID NOs: 125, 126, 127, 131, 132, and 133, respectively; or SEQ ID NOs: 128, 129, 130, 134, 135, and 136, respectively. ### Claim 7 (depends on 1) The combination of claim 1, wherein: (i) the second VH comprises an amino acid sequence at least 70% identical to SEQ ID NO: 121 and the second VL comprises an amino acid sequence at least 70% identical to SEQ ID NO: 122; or (ii) the second VH comprises an amino acid sequence at least 70% identical to SEQ ID NO: 123 and the second VL comprises an amino acid sequence at least 70% identical to SEQ ID NO: 124. ### Claim 8 (depends on 7) The combination of claim 7, wherein: (i) the second VH comprises the amino acid sequence set forth in SEQ ID NO: 121 and the second VL comprises the amino acid sequence set forth in SEQ ID NO: 122; or (ii) the second VH comprises the amino acid sequence set forth in SEQ ID NO: 123 and the second VL comprises the amino acid sequence set forth in SEQ ID NO: 124. ### Claim 9 (depends on 1) The combination of claim 1, wherein the first and second antibody molecules of the combination are combined in a multispecific antibody. ### Claim 10 (depends on 9) The combination of claim 9, wherein the multispecific antibody is a bispecific antibody. ### Claim 11 (depends on 1) The combination of claim 1, wherein the first and second antibody molecules of the combination are co-formulated. ### Claim 12 (depends on 1) The combination of claim 1, wherein the first and second antibody molecules of the combination are provided separately. ### Claim 13 (depends on 1) The combination of claim 1, wherein the combination additionally comprises an agent that inhibits SIRPa signaling. ### Claim 14 (depends on 13) The combination of claim 13, wherein the agent that inhibits SIRPa signaling is selected from the group consisting of: (i) an antibody molecule that binds CD47 and inhibits interaction between CD47 and SIRPa; (ii) an antibody molecule that binds SIRPa and inhibits interaction between CD47 and SIRPa; and (iii) an SIRPa-antibody molecule fusion protein. ### Claim 15 A combination comprising a first antibody molecule that binds to CD70 and a second antibody molecule that binds to IL1RAP, wherein: (a) the first antibody molecule that binds to CD70 comprises a first VH comprising HCDR1, HCDR2 and HCDR3 regions, and a first VL comprising LCDR1, LCDR2 and LCDR3 regions, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the first VH and first VL comprise the amino acid sequences set forth in SEQ ID NOs: 1, 2, 3, 5, 6, and 7, respectively; and (b) the second antibody molecule that binds to IL1RAP comprises: (i) a second VH comprising HCDR1, HCDR2 and HCDR3 regions, and a second VL comprising LCDR1, LCDR2 and LCDR3 regions, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of the second VH and second VL comprise the amino acid sequences set forth in SEQ ID NOs: 125, 126, 127, 131, 132, and 133; or 128, 129, 130, 134, 135, and 136, respectively. ### Claim 16 (depends on 15) The combination of claim 15, wherein: (i) the first VH comprises an amino acid sequence at least 70% identical to SEQ ID NO: 4 and the first VL comprises an amino acid sequence at least 70% identical to SEQ ID NO: 8; and/or (ii) the second VH comprises an amino acid sequence at least 70% identical to SEQ ID NO: 121 and the second VL comprises an amino acid sequence at least 70% identical to SEQ ID NO: 122; or the second VH comprises an amino acid sequence at least 70% identical to SEQ ID NO: 123 and the second VL comprises an amino acid sequence at least 70% identical to SEQ ID NO: 124. ### Claim 17 (depends on 16) The combination of claim 16, wherein: (i) the first VH comprises the amino acid sequence set forth in SEQ ID NO: 4 and the first VL comprises the amino acid sequence set forth in SEQ ID NO: 8; and/or (ii) the second VH comprises the amino acid sequence set forth in SEQ ID NO: 121 and the second VL comprises the amino acid sequence set forth in SEQ ID NO: 122; or the second VH comprises the amino acid sequence set forth in SEQ ID NO: 123 and the second VL comprises the amino acid sequence set forth in SEQ ID NO: 124. ### Claim 18 (depends on 1) The combination of claim 1, wherein the second antibody molecule is an IgG1 antibody molecule.