Recombinant Human Acid Alpha-Glucosidase and Uses Thereof

1 . A method of treating Pompe disease in a subject in need thereof, comprising administering to the subject a population of recombinant human acid α-glucosidase (rhGAA) molecules, concurrently or sequentially with a pharmacological chaperone;

wherein the rhGAA molecules comprise seven potential N-glycosylation sites;

wherein 40%-60% of the N-glycans on the rhGAA molecules are complex type N-glycans;

wherein the rhGAA molecules comprise at least 0.5 mol bis-mannose-6-phosphate (bis-M6P) per mol of rhGAA at the first potential N-glycosylation site as determined using liquid chromatography tandem mass spectrometry (LC-MS/MS); and

wherein the method improves one or more disease outcomes the subject compared to (1) baseline, or (2) a control treatment comprising administering alglucosidase alfa and a placebo for the pharmacological chaperone.

2 . The method of claim 1 , wherein the method improves the subject's motor function, as measured by a 6-minute walk test.

3 . The method of claim 2 , wherein the change from baseline in 6-minute walk distance (6MWD) is at least 20 meters.

4 . (canceled)

5 . The method of claim 2 , wherein the subject's 6MWD is increased by at least 10 compared to the control treatment.

6 . (canceled)

7 . The method of claim 1 , wherein the subject has a baseline 6MWD less than 300 meters.

8 . The method of claim 1 , wherein the subject has a baseline 6MWD greater than or equal to 300 meters.

9 . The method of claim 1 , wherein the method improves the subject's pulmonary function, as measured by a forced vital capacity (FVC) test.

10 . The method of claim 9 , wherein, after treatment, the subject's percent-predicted FVC is either increased compared to baseline, or decreased by less than 3% compared to baseline.

11 . The method of claim 10 , wherein, after treatment, the subject's percent-predicted FVC is decreased by less than 1% compared to baseline.

12 . (canceled)

13 . (canceled)

14 . The method of claim 9 , wherein, compared to the control treatment, the subject's percent-predicted FVC is improved by at least 3% after treatment.

15 . (canceled)

16 . The method of claim 1 , wherein the subject has a baseline FVC less than 55%.

17 . The method of claim 1 , wherein the subject has a baseline FVC greater than or equal to 55%.

18 . The method of claim 1 , wherein the method improves the subject's motor function, as measured by a gait, stair, gower, chair (GSGC) test.

19 . The method of claim 18 , wherein, compared to baseline, the subject's GSGC score is improved as indicated by a decrease of at least 0.5 point after treatment.

20 . (canceled)

21 . (canceled)

22 . The method of claim 2418 , wherein, compared to the control treatment, the subject's GSGC score is improved as indicated by a decrease of at least 1 point after treatment.

23 . (canceled)

24 . (canceled)

25 . The method of claim 241 , wherein the method reduces the levels of at least one marker of muscle damage comprising creatine kinase (CK), and/or the method reduces the levels of at least one marker of glycogen accumulation comprising urine hexose tetrasaccharide (Hex4).

26 . The method of claim 25 , wherein, compared to baseline, the subject's CK level is reduced by at least 20% after treatment, and/or the subject's urinary Hex4 level is reduced by at least 30% after treatment.

27 . (canceled)

28 . (canceled)

29 . The method of claim 25 , wherein, compared to the control treatment, the subject's CK level is reduced by at least 30% after treatment, and/or the subject's urinary Hex4 level is reduced by at least 40% after treatment.

30 . (canceled)

31 . The method of claim 1 , wherein the subject is an ERT-experienced patient.

32 . The method of claim 1 , wherein the subject is an ERT-naive patient.

33 - 84 . (canceled)