Claims for Patent: 11,079,379

Summary for Patent: 11,079,379

Title:	Methods of treating transthyretin (TTR) mediated amyloidosis
Abstract:	Disclosed herein are methods for reducing or arresting an increase in a Neuropathy Impairment Score (NIS) or a modified NIS (mNIS+7) in a human subject by administering an effective amount of a transthyretin (TTR)-inhibiting composition.
Inventor(s):	Bettencourt; Brian (Groton, MA)
Assignee:	ALNYLAM PHARMACEUTICALS, INC. (Minneapolis, MN)
Application Number:	16/054,854
Patent Claims:	1. A method of treating polyneuropathy in a patient with hereditary transthyretin-mediated amyloidosis (hATTR), the method comprising administering a dose of a TTR siRNA with lipid excipients to the patient, wherein the TTR siRNA consists of a sense strand consisting of SEQ ID NO:1 and an antisense strand consisting of SEQ ID NO:2; and the lipid excipients consist of DLin-MC3-DMA ((6Z, 9Z, 28Z, 31Z)-heptatriaconta-6, 9, 28, 31-tetraen-19-yl-4-(dimethylamino) butanoate), DSPC ((1,2-Distearoyl-sn-Glycero-3-Phosphocholine), cholesterol, and PEG.sub.2000-C-DMG (((R)-methoxy-PEG.sub.2000-carbamoyl-di-O-myristyl-sn-glyceride) in isotonic phosphate buffered saline; wherein the dose is 0.3 mg siRNA per kg body weight, and the TTR siRNA with lipid excipients is administered via IV infusion once every three weeks, and the patient receives a premedication before infusion to reduce the risk of infusion-related reactions. 2. The method of claim 1, wherein the patient receives the premedication on the evening before and the day of infusion. 3. The method of claim 1, wherein the premedication comprises dexamethasone, acetaminophen, diphenhydramine, and ranitidine. 4. The method of claim 1, wherein the premedication comprises dexamethasone, acetaminophen, cetirizine, and ranitidine. 5. The method of claim 1, wherein the premedication comprises dexamethasone, paracetamol (acetaminophen), an H2 blocker and an H1 blocker. 6. The method of claim 5, wherein the H2 blocker is ranitidine or famotidine. 7. The method of claim 5, wherein the H1 blocker is cetirizine, hydroxyzine or fexofenadine. 8. The method of claim 1, wherein the TTR siRNA with lipid excipients is administered via a 70 minute infusion of 1 mL/min for 15 minutes followed by 3 mL/min for 55 minutes. 9. The method of claim 1, wherein the TTR siRNA with lipid excipients is administered via a 70 minute infusion of 1 mL/min for 15 minutes followed by 3 mL/min for 55 minutes and the premedication comprises dexamethasone, paracetamol (acetaminophen), an H2 blocker and an H1 blocker. 10. The method of claim 1, wherein the patient has cardiomyopathy. 11. The method of claim 1, wherein the patient has does not have cardiomyopathy.