	US 12,043,661 B2
	Methods and compositions for increasing iduronate 2-sulfatase activity in the CNS
William M. Pardridge, Pacific Palisades, CA (US); and Ruben J. Boado, Agoura Hills, CA (US)
Assigned to ARMAGEN, INC., San Diego, CA (US)
Filed by ArmaGen, Inc., San Diego, CA (US)
Filed on Apr. 30, 2021, as Appl. No. 17/246,288.
Application 17/246,288 is a division of application No. 15/982,990, filed on May 17, 2018, granted, now 11,028,156.
Application 15/982,990 is a continuation of application No. 14/305,402, filed on Jun. 16, 2014, granted, now 10,011,651, issued on Jul. 3, 2018.
Application 14/305,402 is a continuation of application No. 12/901,481, filed on Oct. 8, 2010, granted, now 8,834,874, issued on Sep. 16, 2014.
Claims priority of provisional application 61/256,049, filed on Oct. 29, 2009.
Claims priority of provisional application 61/250,378, filed on Oct. 9, 2009.
Prior Publication US 2021/0253681 A1, Aug. 19, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/395 (2006.01); C07K 16/18 (2006.01); C07K 16/28 (2006.01); C12N 9/16 (2006.01); A61K 38/00 (2006.01); A61K 39/00 (2006.01)

CPC C07K 16/18 (2013.01) [C07K 16/2869 (2013.01); C12N 9/16 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); C07K 2317/565 (2013.01); C07K 2317/92 (2013.01); C07K 2319/30 (2013.01); C07K 2319/33 (2013.01); C12Y 301/06013 (2013.01)]

10 Claims

1. A fusion antibody comprising:

(a) an immunoglobulin or a fragment thereof that crosses a blood brain barrier (BBB), wherein the immunoglobulin or a fragment thereof comprises an immunoglobulin heavy chain or a fragment thereof; and

(b) an iduronate-2-sulfatase having the amino acid sequence identical to SEQ ID NO: 9, wherein the amino acid sequence of the iduronate-2-sulfatase is covalently linked to the amino terminus of the amino acid sequence of the immunoglobulin heavy chain or a fragment thereof, thereby forming a fusion protein;

wherein the fusion antibody crosses the blood brain barrier (BBB) via a transferrin receptor and catalyzes hydrolysis of 2-sulfate groups of the L-iduronate 2-sulfate units of dermatan sulfate, heparan sulfate or heparin and wherein the iduronate-2-sulfatase retains at least 20% of its activity compared to its activity as a separate entity.