Claims for Patent: 11,753,632

Summary for Patent: 11,753,632

Title:	Highly potent acid alpha-glucosidase with enhanced carbohydrates
Abstract:	Recombinant human alpha glucosidase (rhGAA) composition derived from CHO cells that contains a more optimized glycan composition consisting of a higher amount of rhGAA containing N-glycans carrying mannose-6-phosphate (M6P) or bis-M6P than conventional rhGAAs, along with low amount of non-phosphorylated high mannose glycans, and low amount of terminal galactose on complex oligosaccharides. Compositions containing the rhGAA, and methods of use are described.
Inventor(s):	Russell Gotschall, Hung V. Do
Assignee:	Amicus Therapeutics Inc
Application Number:	US17/249,175
Patent Claims:	1. A method for metabolizing, degrading, removing, or decreasing glycogen in tissue, muscle, muscle fiber, muscle cells, lysosomes, organelles, cellular compartments, or cytoplasm of a cell in a subject in need thereof, wherein the method comprises administering to the subject a composition comprising recombinant human acid alpha-glucosidase (rhGAA) produced from Chinese hamster ovary (CHO) cells, wherein 40%-60% of the N-glycans on the rhGAA are complex type N-glycans and the rhGAA comprises 3.0-6.0 mol mannose-6-phosphate (M6P) per mol rhGAA. 2. The method of claim 1, wherein about 45%-55% of the N-glycans on the rhGAA are complex type N-glycans. 3. The method of claim 1, wherein 50% of the N-glycans on the rhGAA are complex type N-glycans. 4. The method of claim 1, wherein the rhGAA comprises at least one mol bis-phosphorylated N-glycan per mol of rhGAA. 5. The method of claim 1, wherein the rhGAA further comprises (a) 2.0 to 8.0 mol sialic acid per mol rhGAA; or (b) at least 4 mol sialic acid per mol rhGAA. 6. The method of claim 1, wherein the method further comprises administering a pharmacological chaperone, and wherein said composition and said pharmacological chaperone are either administered as a single pharmaceutical composition or administered separately. 7. The method of claim 6, wherein the pharmacological chaperone is N-butyl-deoxynojirimycin or a pharmaceutically acceptable salt thereof. 8. The method of claim 1, wherein the method comprises degrading, decreasing, or removing glycogen from cardiac muscle, smooth muscle, or striated muscle. 9. The method of claim 8, wherein the striated muscle is selected from the group consisting of abductor digiti minimi of the foot, abductor digiti minimi of the hand, abductor halluces, abductor pollicis brevis, abductor pollicis longus, adductor brevis, adductor halluces, adductor longus, adductor magnus, adductor pollicis, anconeus, articularis cubiti, articularis genu, aryepiglotticus, aryjordanicus, auricularis, biceps brachii, biceps femoris, brachialis, brachioradialis, buccinators, bulbospongiosus, constrictor of pharynx-inferior, constrictor of pharynx-middle, constrictor of pharynxsuperior, coracobrachialis, corrugator supercilia, cremaster, cricothyroid, dartos, deep transverse perinei, deltoid, depressor anguli oris, depressor labii inferioris, diaphragm, digastric, erector spinae-spinalis, erector spinae-iliocostalis, erector spinae-longissimus, extensor carpi radialis brevis, extensor carpi radialis longus, extensor carpi ulnaris, extensor digiti minimi, extensor digitorum, extensor digitorum brevis, extensor digitorum longus, extensor hallucis longus, extensor indicis, extensor pollicis brevis, extensor pollicis longus, external oblique abdominis, flexor carpi radialis, flexor carpi ulnaris, flexor digiti minimi brevis of the foot, flexor digiti minimi brevis of the hand, flexor digitorum brevis, flexor digitorum longus, flexor digitorum profundus, flexor digitorum superficialis, flexor hallucis brevis, flexor hallucis longus, flexor pollicis brevis, flexor pollicis longus, frontalis, gastrocnemius, gemellus inferior, gemellus superior, genioglossus, geniohyoid, gluteus maximus, gluteus medius, gluteus minimus, gracilis, hyoglossus, iliacus, inferior oblique, inferior rectus, infraspinatus, intercostals external, intercostals innermost, intercostals internal, internal oblique abdominis, interossei-dorsal of hand, interosseidorsal of foot, interossei-palmar of hand, interossei-plantar of foot, interspinales, intertransversarii, intrinsic muscles of tongue, ishiocavernosus, lateral cricoarytenoid, lateral pterygoid, lateral rectus, latissimus dorsi, levator anguli oris, levator anicoccygeus, levator ani-iliococcygeus, levator ani-pubococcygeus, levator anipuborectalis, levator ani-pubovaginalis, levator labii superioris, levator labii superioris, alaeque nasi, levator palpebrae superioris, levator scapulae, levator veli palatine, levatores costarum, longus capitis, longus colli, lumbricals of foot, lumbricals of hand, masseter, medial pterygoid, medial rectus, mentalis, musculus uvulae, mylohyoid, nasalis, oblique arytenoid, obliquus capitis inferior, obliquus capitis superior, obturator externus, obturator internus, omohyoid, opponens digiti minimi, opponens pollicis, orbicularis oculi, orbicularis oris, palatoglossus, palatopharyngeus, palmaris brevis, palmaris longus, pectineus, pectoralis major, pectoralis minor, peroneus brevis, peroneus longus, peroneus tertius, piriformis, plantaris, platysma, popliteus, posterior cricoarytenoid, procerus, pronator quadratus, pronator teres, psoas major, psoas minor, pyramidalis, quadratus femoris, quadratus lumborum, quadratus plantae, rectus abdominis, rectus capitus anterior, rectus capitus lateralis, rectus capitus posterior major, rectus capitus posterior minor, rectus femoris, rhomboid major, rhomboid minor, risorius, salpingopharyngeus, sartorius, scalenus anterior, scalenus medius, scalenus minimus, scalenus posterior, semimembranosus, semitendinosus, serratus anterior, serratus posterior inferior, serratus posterior superior, soleus, sphincter ani, sphincter urethrae, splenius capitis, splenius cervicis, stapedius, sternocleidomastoid, sternohyoid, sternothyroid, styloglossus, stylohyoid, stylopharyngeus, subclavius, subcostalis, subscapularis, superficial transverse, perinei, superior oblique, superior rectus, supinator, supraspinatus, temporalis, temporoparietalis, tensor fasciae lata, tensor tympani, tensor veli palatine, teres major, teres minor, thyro-arytenoid & vocalis, thyro-epiglotticus, thyrohyoid, tibialis anterior, tibialis posterior, transverse arytenoid, transversospinalis-multifidus, transversospinalis-rotatores, transversospinalissemispinalis, transversus abdominis, transversus thoracis, trapezius, triceps, vastus intermedius, vastus lateralis, vastus medialis, zygomaticus major, zygomaticus minor, and a combination thereof. 10. The method of claim 1, wherein the rhGAA comprises the amino acid sequence that is at least 90% identical to SEQ ID NO: 4. 11. The method of claim 1, wherein the rhGAA comprises from 3.0 mol to 5.0 mol M6P residues per mol rhGAA. 12. The method of claim 11, wherein the rhGAA comprises 3.0 to 4.0 mol M6P per mol rhGAA. 13. The method of claim 11, wherein the rhGAA comprises 4.0 to 5.0 mol M6P per mol rhGAA. 14. The method of claim 1, wherein the composition further comprises at least one pharmaceutically acceptable carrier or excipient. 15. The method of claim 14, wherein the pharmaceutically acceptable carrier is water. 16. The method of claim 14, wherein the composition comprises mannitol. 17. The method of claim 14, wherein the composition comprises polysorbate 80. 18. The method of claim 1, wherein the composition further comprises a pH buffer. 19. The method of claim 1, wherein the composition is in the form of a lyophilized powder.