Granted Patent
B2
US 12,582,713 · App. 18/423,089 · Granted Mar 24, 2026
Methods of treating tumors
Inventors:
Masano Huang (Princeton, NJ); Thomas Arthur Haby (Lincroft, NJ); Mehrnaz Khossravi (West Windsor, NJ); Scott Aaron Hart (Hillsborough, NJ); Rao Venkatramana Mantri (Pennington, NJ); Heather Elizabeth Vezina (Upper Holland, PA); Amit Roy (Woodbury, CT); Bindu Purnima Murthy (Robbinsville, NJ); Urvi Ashish Aras (Kendall Park, NJ); Kinjal Sanghavi (Princeton, NJ); Xiaochen Zhao (Pennington, NJ); Akintunde Bello (Princeton Junction, NJ)
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Abstract
The disclosure provides pharmaceutical compositions comprising an anti-PD-1 antibody or an anti-PD-L1 antibody. In some aspects, the pharmaceutical compositions are formulated for subcutaneous delivery. In some aspects, the pharmaceutical compositions further comprise an endoglycosidase hydrolase enzyme. Other aspects of the present disclosure are directed to methods of subcutaneously delivering a pharmaceutical composition comprising an anti-PD-1 antibody or an anti-PD-L1 antibody.
Claims (35)
1 . A method of treating renal cell carcinoma in a human subject in need thereof, comprising subcutaneously administering to the subject a pharmaceutical composition comprising (i) nivolumab and (ii) a hyaluronidase;
(1) wherein 1200 mg of nivolumab and 20,000 units of the hyaluronidase are administered in a single unit flat dose every four weeks; or
(2) wherein 600 mg of nivolumab and 10,000 units of the hyaluronidase are administered in a single unit flat dose every two weeks.
2 . The method of claim 1 , wherein the hyaluronidase comprises the amino acid sequence as set forth in SEQ ID NO: 5.
3 . The method of claim 1 , wherein the pharmaceutical composition is administered:
(i) using a syringe, an auto-injector, or a wearable pump;
(ii) by subcutaneous infusion for less than 10 minutes; or
(iii) both (i) and (ii).
4 . The method of claim 1 , wherein the subject has a body weight from 48 kg to 133 kg.
5 . The method of claim 1 , wherein the pharmaceutical composition is subcutaneously administered by infusion in a period between 3 minutes and 5 minutes.
6 . The method of claim 1 , wherein the pharmaceutical composition has 120 mg/ml of nivolumab.
7 . The method of claim 1 , wherein 1200 mg of nivolumab and 20,000 units of the hyaluronidase are administered to the subject in a single unit flat dose every four weeks.
8 . The method of claim 7 , wherein the hyaluronidase comprises the amino acid sequence as set forth in SEQ ID NO: 5.
9 . The method of claim 7 , wherein the pharmaceutical composition is administered by subcutaneous infusion for less than 10 minutes.
10 . The method of claim 7 , wherein the pharmaceutical composition is administered by using a syringe, an auto-injector, or a wearable pump.
11 . The method of claim 7 , wherein the subject has a body weight from 48 kg to 133 kg.
12 . The method of claim 7 , wherein the pharmaceutical composition has 120 mg/mL of nivolumab.
13 . A method of treating renal cell carcinoma in a human subject in need thereof, comprising subcutaneously administering to the subject in a period between 3 minutes and 5 minutes a pharmaceutical composition comprising (i) nivolumab at 120 mg/ml and (ii) a hyaluronidase comprising the amino acid sequence as set forth in SEQ ID NO: 5; wherein 1200 mg of nivolumab and 20,000 units of the hyaluronidase are administered in a single unit flat dose once every four weeks.
14 . The method of claim 1 , wherein 600 mg of nivolumab and 10,000 units of the hyaluronidase are administered to the subject in a single unit flat dose every two weeks.
15 . The method of claim 14 , wherein the hyaluronidase comprises the amino acid sequence as set forth in SEQ ID NO: 5.
16 . The method of claim 14 , wherein the pharmaceutical composition is administered by subcutaneous infusion for less than 10 minutes.
17 . The method of claim 14 , wherein the pharmaceutical composition is administered by using, a syringe, an auto-injector, or a wearable pump.
18 . The method of claim 14 , wherein the subject has a body weight from 48 kg to 133 kg.
19 . The method of claim 14 , wherein the pharmaceutical composition has a total administered volume of 5 mL.
20 . The method of claim 14 , further comprising administering a chemotherapy.
21 . The method of claim 20 , wherein the chemotherapy comprises a platinum based chemotherapy.
22 . The method of claim 20 , wherein the chemotherapy comprises cabozantinib.
23 . The method of claim 20 , wherein the chemotherapy comprises a platinum-containing chemotherapy.
24 . A method of treating renal cell carcinoma in a human subject in need thereof, comprising subcutaneously administering to the subject in a period between 3 minutes and 5 minutes a pharmaceutical composition comprising (i) nivolumab and (ii) a hyaluronidase comprising the amino acid sequence as set forth in SEQ ID NO: 5; wherein 600 mg of nivolumab and 10,000 units of the hyaluronidase are administered in a total administered volume of 5 mL in a single unit flat dose once every two weeks.
25 . A method of treating renal cell carcinoma in a human subject in need thereof, comprising subcutaneously administering to the subject a pharmaceutical composition comprising (i) nivolumab and (ii) a hyaluronidase comprising the amino acid sequence as set forth in SEQ ID NO: 5; wherein 900 mg of nivolumab and 15,000 units of the hyaluronidase are administered in a single unit flat dose every three weeks.
26 . The method of claim 25 , further comprising administering a platinum-based therapy to the human subject.
27 . The method of claim 25 , further comprising administering a platinum-based doublet chemotherapy.
28 . The method of claim 25 , further comprising administering an anti-CTLA-4 antibody.
29 . The method of claim 28 , wherein the anti-CTLA-4 antibody comprises ipilimumab or tremelimumab.
30 . A method of treating renal cell carcinoma in a human subject in need thereof, comprising subcutaneously administering to the subject a pharmaceutical composition comprising (i) nivolumab and (ii) a hyaluronidase; (1) wherein 1200 mg of nivolumab and 20,000 units of the hyaluronidase are administered in a single unit flat dose once every four weeks; (2) wherein 900 mg of nivolumab and 15,000 units of the hyaluronidase are administered in a single unit flat dose once every three weeks; or (3) wherein 600 mg of nivolumab and 10,000 units of the hyaluronidase are administered in a single unit flat dose once every two weeks.
Continuity (5)
Provisional Application
63184082
· May 4, 2021
Provisional Application
63150420
· Feb 17, 2021
Provisional Application
63131240
· Dec 28, 2020
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