# US 11,897,948 B2 · Treatment of chronic kidney disease and other renal dysfunction using a GDF15 modulator > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,897,948 B2 - Document ID: US11897948B2 - Status: Granted - Kind: B2 - Application number: 16/179,166 - Filed: 2018-11-02 - Published: 2019-09-26 - Granted: 2024-02-13 - Earliest claimed: 2014-06-20 - Assignees: AVEO Pharmaceuticals, Inc. - Applicants: AVEO Pharmaceuticals, Inc. - Inventors: Jeno Gyuris; Lorena Lerner - Web page: https://patentgrep.com/patent/US11897948B2 ## CPC - C07K 16/22: against growth factors {; against growth regulators} - A61P 13/12: of the kidneys - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 14/475: Growth factors; Growth regulators - A61K 2039/505: {comprising antibodies} - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto - 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 provides methods and compositions for treating a subject having a renal-related disorder, such as chronic kidney disease (CKD), end stage renal failure, diabetes, insulin resistance, kidney hypertrophy, kidney hypotrophy, polycystic kidney disease, proteinuria, hyperglycemia, hyperuricemia, gout, kidney stones, hypertension or hypertensive nephropathy, dyslipidemia, anemia and/or reduced erythropoietin production, iron deficiency or hyperfiltration. The methods and compositions use or contain a composition that reduces or inhibits GDF15 activity. ## Claims ### Claim 1 A method of decreasing blood urea nitrogen (BUN) levels in a subject with hyperuricemia, the method comprising administering an effective amount of an anti-GDF15 antibody that decreases or inhibits GDF15 activity in the subject, wherein the anti-GDF15 antibody is selected from: a) an antibody comprising the heavy chain sequence of SEQ ID NO:47 or 49 and the light chain sequence of SEQ ID NO:30; b) an antibody comprising the heavy chain sequence of SEQ ID NO:41, 42, 43, 44, 45, 46, 48, or 49 and the light chain sequence of SEQ ID NO:29; c) an antibody comprising the heavy chain sequence of SEQ ID NO:41, 42, 43, 44, or 45 and the light chain sequence of SEQ ID NO:28; d) an antibody comprising the heavy chain sequence of SEQ ID NO:39, 40, 41, 42, 43, 44, or 45 and the light chain sequence of SEQ ID NO:27; e) an antibody comprising the heavy chain sequence of SEQ ID NO:38 and the light chain sequence of SEQ ID NO:26; f) an antibody comprising the heavy chain sequence of SEQ ID NO:37 and the light chain sequence of SEQ ID NO:25; g) an antibody comprising a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO:7, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:22; h) an antibody comprising a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO:9, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:22; i) an antibody comprising a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO:4, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:21; j) an antibody comprising a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO:5, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:21; k) an antibody comprising a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO:6, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:21; l) an antibody comprising a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO:8, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:21; and m) an antibody comprising a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO:9, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:21. ### Claim 2 (depends on 1) The method of claim 1, wherein the subject has an elevated blood level of GDF15. ### Claim 3 (depends on 1) The method of claim 1, wherein the subject exhibits a glomerular filtration rate (GFR) below 90 ml creatinine/minute/1.73 m2 body-surface area. ### Claim 4 (depends on 1) The method of claim 1, wherein the subject exhibits albuminuria. ### Claim 5 (depends on 1) The method of claim 1, wherein the subject exhibits urinary excretion of albumin in excess of 30 mg per day, 30 mg per liter of urine, and/or 30 pg/mg of creatinine in urine. ### Claim 6 (depends on 1) The method of claim 1, wherein the subject exhibits a serum uric acid level of at least 6.3 mg/dL. ### Claim 7 (depends on 1) The method of claim 1, wherein the subject exhibits iron deficiency. ### Claim 8 (depends on 1) The method of claim 1, wherein the subject exhibits transferrin saturation of below 25% and a low ferritin level. ### Claim 9 (depends on 1) The method of claim 1, wherein the anti-GDF15 antibody is humanized or human. ### Claim 10 (depends on 1) The method of claim 1, wherein the anti-GDF15 antibody comprises the heavy chain sequence of SEQ ID NO:47 and the light chain sequence of SEQ ID NO:30. ### Claim 11 (depends on 1) The method of claim 1, wherein the anti-GDF15 antibody comprises a heavy chain CDRH3 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO: 7, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:22. ### Claim 12 (depends on 1) The method of claim 1, wherein the anti-GDF15 antibody comprises the heavy chain sequence of SEQ ID NO:48 and the light chain sequence of SEQ ID NO:29. ### Claim 13 (depends on 1) The method of claim 1, wherein the anti-GDF15 antibody comprises a heavy chain CDRH3 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO: 8, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:21. ### Claim 14 A method of increasing renal function in a subject suffering from chronic kidney disease (CKD), the method comprising administering an effective amount of an anti-GDF15 antibody that decreases or inhibits GDF15 activity to increase renal function in the subject, wherein the anti-GDF15 antibody is selected from: a) an antibody comprising the heavy chain sequence of SEQ ID NO:47 or 49 and the light chain sequence of SEQ ID NO:30; b) an antibody comprising the heavy chain sequence of SEQ ID NO:41, 42, 43, 44, 45, 46, 48, or 49 and the light chain sequence of SEQ ID NO:29; c) an antibody comprising the heavy chain sequence of SEQ ID NO:41, 42, 43, 44, or 45 and the light chain sequence of SEQ ID NO:28; d) an antibody comprising the heavy chain sequence of SEQ ID NO:39, 40, 41, 42, 43, 44, or 45 and the light chain sequence of SEQ ID NO:27; e) an antibody comprising the heavy chain sequence of SEQ ID NO:38 and the light chain sequence of SEQ ID NO:26; f) an antibody comprising the heavy chain sequence of SEQ ID NO:37 and the light chain sequence of SEQ ID NO:25; g) an antibody comprising a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO:7, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:22; h) an antibody comprising a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO:9, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:22; i) an antibody comprising a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO:4, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:21; j) an antibody comprising a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO:5, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:21; k) an antibody comprising a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO:6, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:21; l) an antibody comprising a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO:8, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:21; and m) an antibody comprising a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO:9, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:21; wherein the subject does not exhibit cachexia. ### Claim 15 (depends on 14) The method of claim 14, wherein the subject has an elevated blood level of GDF15. ### Claim 16 (depends on 14) The method of claim 14, wherein the subject exhibits a glomerular filtration rate (GFR) below 90 ml creatinine/minute/1.73 m2 body-surface area. ### Claim 17 (depends on 14) The method of claim 14, wherein the subject exhibits albuminuria. ### Claim 18 (depends on 14) The method of claim 14, wherein the subject exhibits urinary excretion of albumin in excess of 30 mg per day, 30 mg per liter of urine, and/or 30 μg/mg of creatinine in urine. ### Claim 19 (depends on 14) The method of claim 14, wherein the subject exhibits hyperuricemia. ### Claim 20 (depends on 14) The method of claim 14, wherein the subject exhibits a serum uric acid level of at least 6.3 mg/dL. ### Claim 21 (depends on 14) The method of claim 14, wherein the subject exhibits iron deficiency. ### Claim 22 (depends on 14) The method of claim 14, wherein the subject exhibits transferrin saturation of below 25% and a low ferritin level. ### Claim 23 (depends on 14) The method of claim 14, wherein the anti-GDF15 antibody is humanized or human. ### Claim 24 (depends on 14) The method of claim 14, wherein the anti-GDF15 antibody comprises the heavy chain sequence of SEQ ID NO:47 and the light chain sequence of SEQ ID NO:30. ### Claim 25 (depends on 14) The method of claim 14, wherein the anti-GDF15 antibody comprises a heavy chain CDRH1 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO: 7, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:22. ### Claim 26 (depends on 14) The method of claim 14, wherein the anti-GDF15 antibody comprises the heavy chain sequence of SEQ ID NO:48 and the light chain sequence of SEQ ID NO:29. ### Claim 27 (depends on 14) The method of claim 14, wherein the anti-GDF15 antibody comprises a heavy chain CDRH3 sequence of SEQ ID NO:1, a heavy chain CDRH2 sequence of SEQ ID NO: 8, and a heavy chain CDRH3 sequence of SEQ ID NO:13; and a light chain CDRL1 sequence of SEQ ID NO:16, a light chain CDRL2 sequence of SEQ ID NO:18, and a light chain CDRL3 sequence of SEQ ID NO:21.