IP Library › Granted Patent US 12,686,859
Granted Patent B2
US 12,686,859 · App. 17/931,351 · Granted Jul 21, 2026

Method for selection of high M6P recombinant proteins

Inventors: Hung V. Do (New Hope, PA); Russell Gotschall (Doylestown, PA)
Assignee: Amicus Therapeutics, Inc.
C12N9/2408C12Y302/0102A61K38/00
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Quick Facts
Patent No.
US 12,686,859
App. No.
17/931,351
Filed
Sep 12, 2022
Granted
Jul 21, 2026
Kind
B2
Art Unit
1656
USPC
424/94.61
Abstract

Methods for the production, capturing and purification of recombinant human lysosomal proteins are described. Such recombinant human lysosomal proteins can have high content of mannose-6-phosphate residues. Also described are pharmaceutical compositions comprising such recombinant human lysosomal proteins, as well as methods of treatment and uses of such recombinant human lysosomal proteins.

Claims (28)

1 . A method for producing purified recombinant human acid alpha-glucosidase (rhGAA), wherein the purified rhGAA comprises an amino acid sequence that is at least 98% identical to SEQ ID NO: 2, the method comprising:

i) in a bioreactor, culturing host cells that secrete the rhGAA;

ii) removing medium from the bioreactor;

iii) filtering the medium to provide a filtrate;

iv) loading the filtrate onto a first chromatography column to capture the rhGAA, wherein the first chromatography column is an anion exchange chromatography (AEX) column, wherein the filtrate is not loaded onto a chromatography column prior to the AEX column; and

v) eluting the rhGAA from the AEX column,

wherein the purified rhGAA comprises at least 3.0% of the total N-glycans of the rhGAA are in the form of a bis-mannose-6-phosphate (bis-M6P) N-glycan and wherein at least 90% of the purified rhGAA binds to cation-independent mannose-6-phosphate receptor (CIMPR).

2 . The method of claim 1 , wherein at least 90% of the purified rhGAA comprises an N-glycan carrying mono-M6P or bis-M6P.

3 . The method of claim 1 , wherein the purified rhGAA comprises seven potential N-glycosylation sites.

4 . The method of claim 2 , wherein the rhGAA has seven potential N-glycosylation sites that are located at amino acids corresponding to N84, N177, N334, N414, N596, N826, and N869 of SEQ ID NO:2, respectively.

5 . The method of claim 3 , wherein at least 50% of the purified rhGAA comprise an N-glycan unit bearing bis-M6P at the first potential N-glycosylation site, at least 30% of the purified rhGAA comprise an N-glycan unit bearing mono-M6P at the second potential N-glycosylation site, at least 30% of the purified rhGAA comprise an N-glycan unit bearing bis-M6P at the fourth potential N-glycosylation site, or at least 20% of the purified rhGAA comprise an N-glycan unit bearing mono-M6P at the fourth potential N-glycosylation site.

6 . The method of claim 1 , further comprising:

applying the rhGAA eluted from the AEX column onto a second chromatography column; and

eluting the rhGAA from the second chromatography column.

7 . The method of claim 6 , wherein the second chromatography column is an immobilized metal affinity chromatography (IMAC) column, a cation exchange chromatography (CEX) column, or a size exclusion chromatography (SEC) column.

8 . The method of claim 1 , further comprising inactivating viruses in the rhGAA eluted from the AEX column.

9 . The method of claim 6 , further comprising inactivating viruses in the rhGAA eluted from the second chromatography column.

10 . The method of claim 1 , further comprising filtering the purified rhGAA to provide a filtered product.

11 . The method of claim 10 , further comprising filling a vial with the filtered product.

12 . The method of claim 1 , further comprising lyophilizing the purified rhGAA.

13 . The method of claim 1 , wherein the host cells comprise Chinese hamster ovary (CHO) cells.

14 . The method of claim 1 , wherein the purified rhGAA comprises 3.0-6.0 moles of M6P per mole of rhGAA.

15 . The method of claim 1 , wherein the purified rhGAA comprises 3.0-8.0 moles of sialic acid residues per mole of rhGAA.

16 . The method of claim 1 , wherein the purified rhGAA comprises 3.0-6.0 moles of M6P and 3.0-8.0 moles of sialic acid residues per mole of rhGAA.

17 . The method of claim 1 , wherein the purified rhGAA comprises on average at least 1 mol bis-M6P per mol of protein.

18 . The method of claim 1 , wherein the purified rhGAA comprises on average 1.3 mol bis-M6P per mol of protein.

19 . The method of claim 1 , wherein the purified rhGAA comprises at least 17% of the total N-glycans of the rhGAA are in the form of a bis-M6P N-glycan.

20 . The method of claim 1 , wherein the purified rhGAA comprises 4.0 moles of sialic acid residues per mole of rhGAA.

Assignments (4)
SECURITY INTEREST Recorded Apr 27, 2026
From: BIOMARIN PHARMACEUTICAL INC.; AMICUS THERAPEUTICS, INC.
To: CITIBANK, N.A., AS COLLATERAL AGENT
Reel/Frame 075493/0968 →
RELEASE OF SECURITY INTEREST Recorded Apr 27, 2026
From: WILMINGTON TRUST, NATIONAL ASSOCIATION
To: AMICUS THERAPEUTICS, INC.
Reel/Frame 075494/0030 →
SECURITY INTEREST Recorded Oct 6, 2023
From: AMICUS THERAPEUTICS, INC.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 065177/0196 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 8, 2023
From: DO, HUNG V.; GOTSCHALL, RUSSELL
To: AMICUS THERAPEUTICS, INC.
Reel/Frame 062922/0484 →
Continuity (5)
Continuation 16252519 · Jan 18, 2019
Continuation 15473994 · Mar 30, 2017
Provisional Application 62457584 · Feb 10, 2017
Provisional Application 62315400 · Mar 30, 2016
Related Publication 20230079225A1 · Mar 16, 2023
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