Granted Patent B2

US 12,240,894 · App. 18/313,792 · Granted Mar 4, 2025

Inventors: Gene Kinney (Boca Raton, FL); Wagner Marcelo Zago (San Carlos, CA); Carol Karp (Hillsborough, CA); Radhika Tripuraneni (Menlo Park, CA)

Assignee: Prothena Biosciences Limited

C07K16/18A61B5/0205A61B5/4839A61B5/4842A61K9/0019A61K39/3955A61K45/06A61B5/029A61B5/1124C07K2317/24C07K2317/565

Abstract

Claims (38)

1. A method of treating a patient having AL amyloidosis, comprising:

(a) selecting a patient having AL amyloidosis for treatment, if the patient has:

(i) Mayo Stage IV AL amyloidosis;

(ii) a 6 minute walk distance (6MWD)≥150 meters and an ejection fraction (EF)>50% at baseline;

(iii) Mayo Stage IV AL amyloidosis and an EF>50% at baseline; or

(iv) Mayo Stage IV AL amyloidosis, a 6MWD≥150 meters, and an EF>50% at baseline; and

(b) administering an effective dosage of an antibody to the selected patient, wherein the antibody comprises a light chain comprising the amino acid sequence set forth as SEQ ID NO: 10, and a heavy chain comprising the amino acid sequence set forth as SEQ ID NO: 12.

2. The method of claim 1 , wherein the selected patient has Mayo Stage IV AL amyloidosis.

3. The method of claim 1 , wherein the selected patient has a 6MWD≥150 meters and an EF>50% at baseline.

4. The method of claim 1 , wherein the selected patient has Mayo Stage IV AL amyloidosis, a 6MWD≥150 meters, and an EF>50% at baseline.

5. The method of claim 1 , wherein the selected patient has Mayo Stage IV AL amyloidosis and an EF>50% at baseline.

6. The method of claim 1 , wherein the selected patient is newly diagnosed and AL amyloidosis treatment naive.

7. The method of claim 1 , wherein the selected patient previously received or concomitantly receives administration of melphalan, prednisone, dexamethasone, bortezomib, cyclophosphamide, lenalidomide, doxorubicin, doxycycline, daratumumab, autologous transplant, or a combination thereof.

8. The method of claim 1 , wherein the selected patient previously received or concomitantly receives administration of Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD).

9. The method of claim 1 , wherein the effective dosage is from about 0.5 mg/kg to about 30 mg/kg and the antibody is administered intravenously or subcutaneously at a frequency of from about weekly to about quarterly.

10. The method of claim 1 , wherein the antibody is administered as a pharmaceutical composition comprising the antibody at a concentration of about 50 mg/mL.

11. The method of claim 1 , wherein the effective dosage is about 24 mg/kg and the antibody is administered intravenously every 28 days.

12. A method of reducing the risk of mortality in a patient with AL amyloidosis by at least 45%, comprising:

(a) selecting a patient having AL amyloidosis for treatment, if the patient has:

(i) Mayo Stage IV AL amyloidosis;

(ii) a six minute walk distance (6MWD) of greater than or equal to 150 meters and an ejection fraction (EF) of more than 50% at baseline, or

(iii) Mayo Stage IV AL amyloidosis and an EF of >50% at baseline; and

(b) administering an effective dosage of an antibody to the selected patient, wherein the antibody comprises a light chain comprising the amino acid sequence set forth as SEQ ID NO: 10, and a heavy chain comprising the amino acid sequence set forth as SEQ ID NO: 12.

13. The method of claim 12 , wherein the selected patient has Mayo Stage IV AL amyloidosis.

14. The method of claim 12 , wherein the selected patient has a 6MWD of greater than or equal to 150 meters and an EF of >50% at baseline.

15. The method of claim 12 , wherein the selected patient has Mayo Stage IV AL amyloidosis and an EF of >50% at baseline.

16. The method of claim 12 , wherein the risk of mortality is of all-cause mortality.

17. The method of claim 12 , wherein the risk of mortality is of cardiac mortality.

18. The method of claim 12 , wherein the effective dosage is from about 0.5 mg/kg to about 30 mg/kg and the antibody is administered intravenously or subcutaneously at a frequency of from about weekly to about quarterly.

19. The method of claim 12 , wherein the antibody is administered as a pharmaceutical composition comprising the antibody at a concentration of about 50 mg/mL.

20. The method of claim 12 , wherein the effective dosage is about 24 mg/kg and the antibody is administered intravenously every 28 days.

21. A method of improving a 6 minute walk distance (6MWD) in a patient having AL amyloidosis, comprising:

(a) selecting a patient having AL amyloidosis for treatment, if the patient has a 6MWD≥ 150 meters and an ejection fraction (EF)>50% at baseline, and

(b) administering an effective dosage of an antibody to the selected patient, wherein the antibody comprises a light chain comprising the amino acid sequence set forth as SEQ ID NO: 10, and a heavy chain comprising the amino acid sequence set forth as SEQ ID NO: 12.

22. The method of claim 21 , wherein the selected patient has Mayo Stage IV AL amyloidosis, a 6MWD≥150 meters, and an EF>50% at baseline.

23. The method of claim 21 , wherein the effective dosage is from about 0.5 mg/kg to about 30 mg/kg and the antibody is administered intravenously or subcutaneously at a frequency of from about weekly to about quarterly.

24. The method of claim 21 , wherein the antibody is administered as a pharmaceutical composition comprising the antibody at a concentration of about 50 mg/mL.

25. The method of claim 21 , wherein the effective dosage is about 24 mg/kg and the antibody is administered intravenously every 28 days.

Assignments (2)

Continuity (4)

References Cited (101)