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US 11,897,948 B2Granted
Treatment of chronic kidney disease and other renal dysfunction using a GDF15 modulator
AssigneeAVEO Pharmaceuticals, Inc.
InventorsJeno Gyuris, Lorena Lerner
Life of this patent
Estimating the term…
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.
Claims27
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.
25 more elements
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.
26 more elements
Dependencies are inferred from the claim text.