METHODS FOR THE TREATMENT OF CANCER WITH RECOMBINANT IL-12 ALBUMIN BINDING DOMAIN FUSION PROTEINS
The present disclosure provides methods for treating a cancer such as an advanced solid tumor in a subject in need thereof by administering to the subject in need thereof an effective first dose of an IL-12 albumin binding domain (ABD) fusion protein and an effective second dose of the IL-12 ABD fusion protein every three weeks or four weeks after the first dose, wherein the second dose is greater than the first dose.
1 . A method for treating a cancer in a subject in need thereof, the method comprising: administering to the subject in need thereof an effective first dose of an IL-12 albumin binding domain (ABD) fusion protein and an effective second dose of the IL-12 ABD fusion protein every three weeks or four weeks after the first dose, wherein the second dose is greater than the first dose.
2 . The method of claim 1 , wherein the effective second and subsequent doses of the IL-12 ABD fusion protein is administered every three weeks or every four weeks after the first dose.
3 . (canceled)
4 . The method of claim 1 , wherein the first dose is about 25 ng/kg to about 750 ng/kg.
5 . (canceled)
6 . The method of claim 1 , wherein the second and subsequent doses are about 50 ng/kg to about 1.5 μg/kg.
7 - 9 . (canceled)
10 . The method of claim 1 , wherein the first dose amount and the second and subsequent dose amounts are administered intravenously or subcutaneously.
11 . (canceled)
12 . The method of claim 1 , wherein the albumin binding domain of the IL-12 ABD fusion protein comprises a variable heavy domain comprising SEQ ID NO:2 or a variant thereof, and a variable light domain comprising SEQ ID NO:6 or a variant thereof.
13 . The method of claim 12 , wherein the albumin binding domain is an scFv that comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof.
14 . The method of claim 13 , wherein the IL-12 of the IL-12 fusion protein is a single chain IL-12 comprising a p35 subunit covalently attached to a p40 subunit.
15 . The method of claim 14 , wherein the p40 subunit has the amino acid sequence of SEQ ID NO: 12 or a variant thereof, and the p35 subunit has the amino acid sequence of SEQ ID NO:13 or a variant thereof.
16 . (canceled)
17 . The method of claim 14 , wherein the single chain IL-12 has the amino acid sequence of SEQ ID NO:10.
18 . The method of claim 12 , wherein the IL-12 ABD fusion protein has the amino acid sequence of SEQ ID NO: 11.
19 - 20 . (canceled)
21 . The method of claim 1 , wherein the cancer is a solid epithelial or mesenchymal tumor.
22 . (canceled)
23 . The method of claim 1 further comprising the step of administering a checkpoint inhibitor to the subject in need thereof.
24 . (canceled)
25 . A method of achieving a clinical response or a partial clinical response of a solid tumor in a human patient, the method comprising:
administering to the human patient an effective first dose of an IL-12 albumin binding domain (ABD) fusion protein and an effective second dose of the IL-12 ABD fusion protein every two weeks, three weeks, or four weeks after the first dose, wherein the second dose is greater than the first dose.
26 . The method of claim 25 , wherein the effective second and subsequent doses of the IL-12 ABD fusion protein are administered every three weeks or four weeks after the first dose.
27 . (canceled)
28 . The method of claim 25 , wherein the first dose is about 25 ng/kg to about 750 ng/kg.
29 . (canceled)
30 . The method of claim 25 , wherein the second and subsequent doses are about 50 ng/kg to about 1.5 μg/kg.
31 - 33 . (canceled)
34 . The method of claim 25 , wherein the first dose amount and the second and subsequent dose amounts are administered intravenously or subcutaneously.
35 . (canceled)
36 . The method of claim 25 , wherein the albumin binding domain of the IL-12 ABD fusion protein comprises a variable heavy domain comprising SEQ ID NO:2 or a variant thereof, and a variable light domain comprising SEQ ID NO:6 or a variant thereof.
37 . The method of claim 36 , wherein the albumin binding domain is an scFv that comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof.
38 . The method of claim 37 , wherein the IL-12 of the IL-12 fusion protein is a single chain IL-12 comprising a p35 subunit covalently attached to a p40 subunit.
39 . The method of claim 38 , wherein the p40 subunit has the amino acid sequence of SEQ ID NO: 12 or a variant thereof, and the p35 subunit has the amino acid sequence of SEQ ID NO: 13 or a variant thereof.
40 . (canceled)
41 . The method of claim 38 , wherein the single chain IL-12 has the amino acid sequence of SEQ ID NO: 10.
42 . The method of claim 36 , wherein the IL-12 ABD fusion protein has the amino acid sequence of SEQ ID NO:11.
43 . The method of claim 25 , wherein the solid tumor is a solid epithelial or mesenchymal tumor.
44 . The method of claim 25 further comprising the step of administering a checkpoint inhibitor to the subject in need thereof.