IP Library › Granted Patent US 12,202,871
Granted Patent B2
US 12,202,871 · App. 17/586,872 · Granted Jan 21, 2025

Methods of treatment using G-CSF protein complex

Inventors: Gajanan Bhat (Irvine, CA); Shanta Chawla (Irvine, CA)
Assignee: Spectrum Pharmaceuticals, Inc.
C07K14/535A61K47/6811A61K38/00
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Quick Facts
Patent No.
US 12,202,871
App. No.
17/586,872
Granted
Jan 21, 2025
Kind
B2
Abstract

This disclosure provides a method of preventing, alleviating, or treating a condition (i.e., neutropenia) in a patient in need thereof, the condition characterized by compromised white blood cell production in the patient. The method includes administering to the patient a therapeutically effective amount of a protein complex comprising a modified human granulocyte-colony stimulating factor (hG-CSF) covalently linked to an immunoglobulin Fc region via a non-peptidyl polymer. The non-peptidyl polymer is site-specifically linked to an N-terminus of the immunoglobulin Fc region, and the modified hG-CSF comprises substitutions in at least one of Cys17 and Pro65.

Claims (20)

1. A method for treating or preventing neutropenia in a patient receiving chemotherapy, comprising administering to the patient a therapeutically effective amount of a protein complex comprising a modified human granulocyte-colony stimulating factor (hG-CSF) covalently linked to an N-terminus of an immunoglobulin Fc region via a non-peptidyl polymer, wherein the modified hG-CSF comprises the amino acid sequence of SEQ ID NO: 1.

2. The method of claim 1 , wherein the protein complex is administered to the patient within about 6 hours of completion of the chemotherapy.

3. The method of claim 1 , wherein the protein complex is administered to the patient within about 5 hours of completion of the chemotherapy.

4. The method of claim 1 , wherein the protein complex is administered to the patient within about 2 hours of completion of the chemotherapy.

5. The method of claim 1 , wherein the protein complex is administered to the patient within about 1 hour of completion of the chemotherapy.

6. The method of claim 1 , wherein the neutropenia is severe chronic neutropenia or febrile neutropenia.

7. The method of claim 1 , wherein the chemotherapy is adjuvant or neoadjuvant chemotherapy.

8. The method of claim 7 , wherein the adjuvant or neoadjuvant chemotherapy is a combination of docetaxel and cyclophosphamide.

9. The method of claim 1 , wherein the therapeutically effective amount is a unit dosage form selected from 25 μg/kg, 50 μg/kg, 100 μg/kg, and 200 μg/kg.

10. The method of claim 1 , wherein both ends of the non-peptidyl polymer are respectively linked to the modified hG-CSF and the immunoglobulin Fc region through reactive groups by a covalent bond.

11. The method of claim 1 , wherein the immunoglobulin Fc region comprises an immunoglobulin.

12. The method of claim 1 , wherein the immunoglobulin Fc region is aglycosylated.

13. The method of claim 1 , wherein the immunoglobulin Fc region comprises one or more of CH2, CH3, and CH4 domains.

14. The method of claim 1 , wherein the immunoglobulin Fc region comprises CH2 and CH3 domains.

15. The method of claim 1 , wherein the immunoglobulin Fc region further comprises a hinge region.

16. The method of claim 1 , wherein each domain of the immunoglobulin Fc fragment is a hybrid of domains, each of the domains having a different origin derived from immunoglobulins selected from IgG, IgA, IgD, IgE, and IgM.

17. The method of claim 1 , wherein the immunoglobulin Fc fragment comprises an IgG4 Fc fragment.

18. The method of claim 1 , wherein the non-peptidyl polymer is selected from polyethylene glycol, polypropylene glycol, an ethylene glycol-propylene glycol copolymer, polyoxyethylated polyol, polyvinyl alcohol, polysaccharide, dextran, polyvinyl ethyl ether, a biodegradable polymer, a lipid polymer, chitin, hyaluronic acid, and a combination thereof.

19. The method of claim 1 , wherein the non-peptidyl polymer comprises polyethylene glycol.

20. The method of claim 19 , wherein the polyethylene glycol has a molecular weight of 3.4 kDa.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 1, 2026
From: SPECTRUM PHARMACEUTICALS, INC.
To: ASSERTIO SPECIALTY PHARMACEUTICALS, LLC
Reel/Frame 074542/0184 →
TERMINATION AND RELEASE OF INTELLECTUAL PROPERTY SECURITY AGREEMENT RECORDED AT REEL 061179/FRAME 0202 Recorded Aug 1, 2023
From: SLR INVESTMENT CORP.
To: TALON THERAPEUTICS, INC.; SPECTRUM PHARMACEUTICALS, INC.; ALLOS THERAPEUTICS, INC.
Reel/Frame 064463/0709 →
SECURITY INTEREST Recorded Sep 22, 2022
From: SPECTRUM PHARMACEUTICALS, INC.; ALLOS THERAPEUTICS, INC.; TALON THERAPEUTICS, INC.
To: SLR INVESTMENT CORP., AS COLLATERAL AGENT
Reel/Frame 061179/0202 →
Continuity (2)
Division 16428351 · May 31, 2019
Related Publication 20220153799A1 · May 19, 2022
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