Methods of treating Fabry disease in patients having a mutation in the GLA gene.

Description

"METHODS OF TREATING FABRY DISEASE IN PATIENTS WITH A MUTATION IN THE GLA GENE" Split application for Invention Patent BR 11 2022 002202 6, filed on August 7, 2020. TECHNICAL AREA

[0001] The principles and embodiments of the present invention relate generally to the use of pharmacological chaperones for the treatment of Fabry disease, particularly in patients with mutations or variants in the α-galactosidase (GLA) gene. BACKGROUND

[0002] Many human diseases result from mutations that cause changes in the amino acid sequence of a protein, reducing its stability and potentially preventing it from folding properly. Proteins typically fold in a specific region of the cell known as the endoplasmic reticulum or ER. The cell has quality control mechanisms that ensure proteins are folded into their correct three-dimensional shape before they can move from the ER to their appropriate destination in the cell, a process often referred to as protein trafficking. Defectively folded proteins are frequently eliminated by quality control mechanisms after initially being retained in the ER. In some cases, defectively folded proteins may accumulate in the ER before being eliminated.The retention of misfolded proteins in the ER disrupts their proper trafficking, and the resulting reduced biological activity can lead to impaired cellular function and ultimately disease. Additionally, the accumulation of misfolded proteins in the ER can lead to various types of stress on cells, which can also contribute to cellular dysfunction and disease. Petition 870260032676, dated 08 / 04 / 2026, page 12 / 370 2 / 305

[0003] Such mutations can lead to lysosomal storage disorders (LSDs), which are characterized by lysosomal enzyme deficiencies due to mutations in the genes encoding lysosomal enzymes. The resulting disease causes the pathological accumulation of substrates for these enzymes, which include lipids, carbohydrates, and polysaccharides. Although there are many different mutant genotypes associated with each LSD, many of the mutations are missense mutations that can lead to the production of a less stable enzyme. These less stable enzymes are sometimes prematurely degraded by the ER-associated degradation pathway. This results in enzymatic deficiency in the lysosome and pathological substrate accumulation. Such mutant enzymes are sometimes referred to in the relevant art as “folding mutants” or “conformational mutants”.

[0004] Fabry disease is an LSD caused by a mutation in the GLA gene, which encodes the enzyme α-galactosidase A (α-Gal A). α-Gal A is necessary for the metabolism of glycosphingolipids. The mutation causes the substrate globotriaosylceramide (GL-3) to accumulate in various tissues and organs. Male subjects with Fabry disease are hemizygous because the disease genes are encoded on the X chromosome. Fabry disease is estimated to affect between 1 in 40,000 and 60,000 male subjects and occurs less frequently in female subjects.

[0005] Several approaches to treating Fabry disease have existed. One approved therapy for treating Fabry disease is enzyme replacement therapy (ERT), which typically involves the intravenous infusion of a purified form of the corresponding wild-type protein. Two α-Gal A products are currently available for the treatment of Fabry disease: agalsidase alfa (Replagal®, Shire Human Genetic Therapies) and agalsidase beta (Fabrazyme®; Sanofi Genzyme). Petition 870260032676, dated 08 / 04 / 2026, page 13 / 370 3 / 305 (Corporation). However, ERT has several disadvantages. One of the main complications with ERT is the rapid degradation of the infused protein, leading to the need for numerous expensive high-dose infusions. ERT has several additional caveats, such as difficulties with the generation, purification, and storage of appropriately folded proteins on a large scale; obtaining native glycosylated protein; generating an anti-protein immune response; and the protein's inability to cross the blood-brain barrier to mitigate central nervous system pathologies (i.e., low bioavailability). Additionally, the replacement enzyme cannot penetrate the heart or kidney in sufficient quantities to reduce substrate accumulation in renal podocytes or cardiac myocytes, which figure prominently in Fabry disease.

[0006] Another approach to treating some enzyme deficiencies involves the use of small molecule inhibitors to reduce the production of the natural substrate of deficient enzyme proteins, thereby improving the pathology. This “substrate reduction” approach has been specifically described for a class of approximately 40 LSDs that include glycosphingolipid storage dysfunctions. The small molecule inhibitors proposed for use as therapy are specific to inhibiting the enzymes involved in glycolipid synthesis, reducing the amount of cellular glycolipid that needs to be broken down by the deficient enzyme.

[0007] A third approach to treating Fabry disease has been treatment with what are called pharmacological chaperones (PCs). Such PCs include small molecule inhibitors of α-Gal A, which can bind to α-Gal A to increase the stability of both the mutant enzyme and the corresponding wild type. However, patients for PC therapy must have a mutation or variant. Petition 870260032676, dated 08 / 04 / 2026, p. 14 / 370 4 / 305 susceptible that results in the production of an enzyme that has the potential to be stabilized and folded into a conformation that allows trafficking out of the ER.

[0008] Thus, even when Fabry disease is diagnosed by detecting deficient α-Gal A activity in plasma or peripheral leukocytes (WBCs), it is very difficult, if not impossible, to predict whether a particular Fabry patient will respond to treatment with a PC. Therefore, the need remains to identify new GLA mutations or variants that will be responsive to a PC and make new treatment methods available for Fabry patients with these mutations or variants. SUMMARY

[0009] One aspect of the invention relates to a method of treating a patient diagnosed with Fabry disease. The method comprises administering to the patient a therapeutically effective dose of a pharmacological chaperone for α-Gal A, wherein the patient has a missense mutation of the nucleic acid sequence encoding α-Gal A.In one or more forms, the mutation is N5D, N5K, P6L, P6Q, P6R, P6S, P6T, E7D, E7K, E7V, L8I, L8P, L8Q, H9L, H9Q, H9R, H9Y, L10M, L10P, L10Q, L10R, L10V, G11C, G11D, G11R, G11S, G11V, C12G, C12R, C12S, C12Y, A13E, A13G, L14F, L14H, L14V, R17C, R17G, R17H, R17P, R17S, F18I, F18L, A20G, L21H, V22A, V22F, V22I, V22L, S23P, S23T, W24S, D25H, I26N, P27A, P27L, P27S, P27T, G28E, G28R, G28W, A29G, A29P, A29V, R30G, L32M, L32Q, L32R, L32V, D33A, D33E, D33V, L36M, L36V, A37E, A37G, A37S, R38G, R38M, R38W, T39A, T39K, T39M, T39R, T39S, T41A, T41N, T41S, G43A, L45M, L45V, H46D, H46N, H46Q, E48A, F50Y, M51R, M51T, M51V, N53H, N53I, N53S, N53T, L54H, L54R, L54V, D55A, D55E, D55H, D55Y, C56W, E58K, E59A, E59D, E59G, E59Q, E59V, P60A, P60Q, P60R, D61E, D61V, S62A, S62C, S62F, S62P, S62Y, I64L, I64V, S65C, S65G, S65R, E66D, E66V, K67E, K67M, K67N, K67Q, K67T, L68I,. Petition 870260032676, dated 08 / 04 / 2026, page 15 / 370 5 / 305 F69I, F69Y, M70I, M70K, M70L, M70R, E71A, E71D, E71G, E71Q, E71V, M72L, M72T, A73S, A73T, E74D, E74G, E74K, E74V, L75F, L75P, M76V, V77I, V77L, S78L, S78P, E79A, E79D, E79G, E79K, E79Q, E79V, G80A, G80C, G80S, W81L, K82E, K82M, K82N, K82R, K82T, D83A, D83E, D83G, D83V, A84E, A84G, A84P, A84S A84T, A84V, G85A, G85C, G85R, Y86F, E87G, Y88H, Y88N, L89V, I91F, I91L, I91M, I91S, M96L, M96T, A97D, A97S, A97T, P98H, P98L, P98R, Q99E, Q99L, Q99P, Q99R, D101A, D101E D101G, D101H, D101V, S102A, S102P, S102T, G104A, G104D, G104S, R105G, R105I, R105K, R105T, L106H, L106I, L106P, L106V, Q107E, Q107H, Q107K, A108E, A108V, D109A, D109E, D109H, D109N, D109Y, P110T, F113V, F113Y, P114L, H115D, H115N, G116R, I117M, I117T, A121V, Y123D, Y123F, Y123N, Y123S, V124I, H125D, H125N, H125R, S126C, S126I, K127E, G128A, L129V, K130M, K130N, K130Q, L131V, I133L, I133T, I133V, A135E, A135G, A135S, A135T, D136A, D136N, D136V, V137A, V137D, V137G, V137I, V137L, G138A, N139H, N139I, N139K, N139Y, K140E, K140I, K140N, K140Q, K140R, T141S, A143E, A143G, G144A, G144C, G144R, G144S , F145C , F145L, F145V, F145Y, P146A, P146H, P146L, P146T, G147A, S148C, S148G, S148T, F149C, G150E, G150V, Y151C, Y151D, Y151S, Y152F, Y152S, D153A, D153H, D153N, D153V, D153Y, A156G, Q157E, Q157K Q157L , Q157P, T158A , T158I, T158N, T158S, F159I, F159L, F159V, F159Y, A160G, A160S, A160T, A160V, D161H, D161N, D161V, D161Y, W162S, V164A, V164I, V164L, D165A, D165E, L166M, L166Q, L167I, F169C,F169L, F169V, F169Y, G171A, G171V, Y173C, Y173F, Y173H, Y173S, D175G, D175H, D175V, D175Y, S176C, S176R, L177F, L177M, L177S, L177V, L177W, E178A, E178G, E178K, E178Q, L180M, L180S, A181P, A181T, A181V, D182A, D182E, D182V, D182Y, Y184F, Y184H, Y184S, K185M, K185N, K185Q, K185T, H186D, H186L, H186N, H186Q, H186Y, M187L, S188A, S188C, S188F, S188P, S188T, S188Y, L189S, L189V, A190D, A190G, A190S, Petition 870260032676, dated 08 / 04 / 2026, page 16 / 370 6 / 305 A190T, A190V, L191M, L191V, N192D, N192H, N192K, N192S, N192T, R193G, R193M, R193T, R193W, T194N, T194P, T194S, G195C, G195R, G195S, R196I, R196K, S197C, S197G, S197I, S197N, S197T, I198M, I198S, V199E, V199L, Y200N, Y200S, S201A, S201C, S201T, E203A, E203G, E203Q, W204S, L206F, L206H, L206I, L206R, L206V, Y207F, M208K, W209C, W209G, P210H, P210T, F211C, F211L, F211S, F211V, F211Y, Q212H, Q212P, K213E, K213Q, P214A, P214H, P214R, P214T, N215H, N215K, N215T, N215Y, Y216F, Y216H, Y216N, T217A, T217I, T217K, T217P, T217R, T217S, E218A, E218D, E218G, E218K, E218Q, E218V, I219F, I219M, I219S, R220L, Q221E, Q221H, Q221K, Q221L, Q221R, Y222C, Y222D, Y222H, Y222N, Y222S, N224H, R227G, N228H, N228I, N228T, F229I, F229S, F229Y, A230D, A230G, A230P, A230V, I232L, I232M, I232V, D233A, D233E, D233G, D233V, S235A, S235T, K237I, S238C, S238I, S238T, I239L, K240E, K240M, K240R, S241C, S241I, S241T, I242L, I242M, I242S, L243M, L243S, L243V, D244A, D244E, D244G, D244V, D244Y, W245C, T246A, T246I, T246K,T246R, S247A, S247F, S247T, S247Y, F248C, F248L, F248V, F248Y, N249D, N249H, N249I, N249S N249T, N249Y, Q250E, Q250L, E251G, E251K, E251Q, E251V, R252G, I253F, I253N, I253V, V254A, V254D, V254F, V254G, D255A, D255E, D255H, D255N, D255V, D255Y, V256D, V256G, V256L, A257S, G258E, P259A, P259T, G260W, G261A, N263H, N263T, D264H, D264N, P265A, P265Q, M267L, M267V, L268F, L268I, V269L, I270L, I270S, I270V, N272D, F273Y, L275I, W277L, N278I, Q280L, Q280R, V281A, V281E, V281G, V281L, T282S, Q283E, Q283H, Q283L, M284I, M284L, A285G, A285T, A285V, L286F, L286H, L286V, A288G, A288S, A288V, I289L, I289T, I289V, A291G, A292G, A292S, L294F, L294I, L294V, F295I, F295S, F295V, F295Y, S297T, N298D, N298I, N298T, D299H, D299N, L300I, L300V, H302D, H302L, H302N, H302Y, I303S, S304I, Q306E, Q306L, Q306P, A307D, A307G, A307P, A307S, A307V, K308I, K308Q, K308R, A309D, A309T Petition 870260032676, dated 08 / 04 / 2026, page 17 / 370 7 / 305 L310I, L311I, Q312E, Q312K, Q312L, D313E, D313V, K314E, K314M, K314N, K314T, D315A, D315G, D315H, D315N, D315V, D315Y, V316A, V316L, I317L, I317M, I317V, A318D, A318P, A318T, A318V, I319M, N320S, N320T, Q321K, D322A, D322V, L324V, L324W, G325A, G325C, G325V, K326E, K326M, K326Q, K326R, K326T, Q327H, Q327P, Y329C, Y329D, Y329F, Y329H, Y329N, Q330E, Q330H, Q330K, L331H, L331P, L331R, L331V, R332G, R332I, R332S, R332T, Q333E, Q333L, Q333P, G334R, G334V, D335A, D335E, D335G, D335V, D335Y, N336D, N336I, N336S, N336T, N336Y, F337C, F337L, F337V, F337Y, E338A, E338D, E338G, V339M, E341A, E341Q, P343A, P343S, L344F, L344R, L344V, G346A, G346C, G346D, G346V, L347I, A348D, W349C, W349L, A350G, A350S, A350T, A350V, V351A, V351E, A352S, A352T, M353K, M353L, M353T, I354R, N355D, N355H, N355S, N355Y, R356L, Q357E, I359F, I359L, I359N, I359S, I359V, P362A, P362H, P362R, P362S, R363G, R363L, R363S, S364C, S364P, Y365D, Y365F, Y365N, Y365S, T366I, T366N, T366P, T366S, I367F, I367L, I367M A368G, A368P, V369A, V369F, V369G, V369I, V369L, A370D, A370G, A370P, A370T, A370V, S371C, S371T, G373A, G373C, K374E, K374I, K374R, K374T, G375R, V376E, V376G, V376L, V376M, A377G, A377P, A377S, A377T, N379D, N379I, N379K, N379T, P380A, P380H, P380R, P380T, A381D, F383C, F383I, F383Y I384F, I384M, I384T, T385I, Q386H, Q386K, Q386L, L387F, L387H, L387I, L387R, L388F, L388H, L388I, L388R, L388V, K391I, K391N, K391Q, K391R, R392G, R392K, R392M, R392W, K393E, K393N, K393Q, K393T, L394I, L394Q, L394R, G395R, F396C, F396I, F396L, F396V, Y397C, Y397F, Y397H, Y397N, Y397S E398G, E398Q, W399G, W399R, T400A, T400I, T400N, T400P, T400S, S401A, S401L, S401T, R402G, R402M, R402S, R402T, R402W, L403F, L403V, R404G,R404I, R404K, R404S, R404T, S405G, H406D, H406L, H406Q, I407L, I407M, I407T, N408D, N408H, N408T, P409L, T410S, G411A, G411C, G411V, T412A, T412I, T412S, V413F, Petition 870260032676, dated 08 / 04 / 2026, p. 18 / 370 8 / 305 V413G, V413I, L414F, L414V, L415H, L415I, Q416E, Q416H, Q416L, L417I, E418A, E418D, E418K, E418Q, N419I, N419S, N419T, N419Y, T420K, T420P, T420R, T420S, M421I, M421K, M421L, M421R, M421T, Q422P, M423I, M423K, M423L, M423T, S424L, L425F, D427N or L429R. In several embodiments, these mutations are relative to SEQ ID NO: 2. A further aspect of the invention relates to a medicament for treating a patient diagnosed with Fabry disease who has a missense mutation of the nucleic acid sequence encoding α-Gal A. In one or more embodiments, the mutation is provided above. In several embodiments, these mutations are relative to SEQ ID NO: 2.

[0010] In some embodiments, the pharmacological chaperone or medicament comprises migalastat or its salt. In one or more embodiments, the dose of migalastat or its salt is about 100 mg to about 150 mg of free base equivalent (FBE). In some embodiments, the salt of migalastat is migalastat hydrochloride. In one or more embodiments, the dose is about 150 mg on alternate days of migalastat hydrochloride or an equivalent dose of migalastat or a salt other than the hydrochloride salt. In some embodiments, migalastat or its salt is administered orally or by injection.These embodiments can be combined with each other or with other embodiments of the invention, for example embodiments relating to a method of enhancing α-Gal A in a patient diagnosed with or suspected of having Fabry disease, use of a pharmacological chaperone for α-Gal A for the manufacture of a medicament to treat a patient diagnosed with Fabry disease or with a pharmacological chaperone for α-Gal A for use in treating a patient diagnosed with Fabry disease, as well as embodiments relating to susceptible mutations, suitable PCs and their dosages, formulations and routes of administration. Petition 870260032676, dated 08 / 04 / 2026, page 19 / 370 9 / 305

[0011] Another aspect of the invention relates to a method of enhancing α-Gal A in a patient diagnosed with or suspected of having Fabry disease. The method comprises administering to a patient a therapeutically effective dose of a pharmacological chaperone for α-Gal A, wherein the patient has a missense mutation in the nucleic acid sequence encoding α-Gal A. Accordingly, a further aspect of the invention relates to a medicament for enhancing α-Gal A in a patient diagnosed with or suspected of having Fabry disease who has a missense mutation of the nucleic acid sequence encoding α-Gal A. In one or more embodiments, the mutation is provided below.

[0012] In one or more forms, the mutation is N5D, N5K, P6L, P6Q, P6R, P6S, P6T, E7D, E7K, E7V, L8I, L8P, L8Q, H9L, H9Q, H9R, H9Y, L10M, L10P, L10Q, L10R, L10V, G11C, G11D, G11R, G11S, G11V, C12G, C12R, C12S, C12Y, A13E, A13G, L14F, L14H, L14V, R17C, R17G, R17H, R17P, R17S, F18I, F18L, A20G, L21H, V22A, V22F, V22I, V22L, S23P, S23T, W24S, D25H, I26N, P27A, P27L, P27S, P27T, G28E, G28R, G28W, A29G, A29P, A29V, R30G, L32M, L32Q, L32R, L32V, D33A, D33E, D33V, L36M, L36V, A37E, A37G, A37S, R38G, R38M, R38W, T39A, T39K, T39M, T39R, T39S, T41A, T41N, T41S, G43A, L45M, L45V, H46D, H46N, H46Q, E48A, F50Y, M51R, M51T, M51V, N53H, N53I, N53S, N53T, L54H, L54R, L54V, D55A, D55E, D55H, D55Y, C56W, E58K, E59A, E59D, E59G, E59Q, E59V, P60A, P60Q, P60R, D61E, D61V, S62A, S62C, S62F, S62P, S62Y, I64L, I64V, S65C, S65G, S65R, E66D, E66V, K67E, K67M, K67N, K67Q, K67T, L68I, F69I, F69Y, M70I, M70K, M70L, M70R, E71A, E71D, E71G, E71Q, E71V, M72L, M72T, A73S, A73T, E74D, E74G, E74K, E74V, L75F, L75P, M76V,V77I, V77L, S78L, S78P, E79A, E79D, E79G, E79K, E79Q, E79V, G80A, G80C, G80S, W81L, K82E, K82M, K82N, K82R, K82T, D83A, D83E, D83G, D83V, A84E, A84G, A84P, A84S, A84T, A84V, G85A, G85C, G85R, Y86F, E87G, Y88H, Y88N, L89V, I91F, I91L, I91M, I91S, Petition 870260032676, dated 08 / 04 / 2026, page 20 / 370 10 / 305 M96L, M96T, A97D, A97S, A97T, P98H, P98L, P98R, Q99E, Q99L, Q99P, Q99R, D101A, D101E, D101G, D101H, D101V, S102A, S102P, S102T, G104A, G104D, G104S, R105G, R105I, R105K, R105T, L106H, L106I, L106P, L106V, Q107E, Q107H, Q107K, A108E, A108V, D109A, D109E, D109H, D109N, D109Y, P110T, F113V, F113Y, P114L, H115D, H115N, G116R, I117M, I117T, A121V, Y123D, Y123F, Y123N, Y123S, V124I, H125D, H125N, H125R, S126C, S126I, K127E, G128A, L129V, K130M, K130N, K130Q, L131V, I133L, I133T, I133V, A135E, A135G, A135S, A135T, D136A, D136N, D136V, V137A, V137D, V137G, V137I, V137L, G138A, N139H, N139I, N139K, N139Y, K140E, K140I, K140N, K140Q, K140R, T141S, A143E, A143G, G144A, G144C, G144R, G144S, F145C, F145L, F145V, F145Y, P146A, P146H, P146L, P146T, G147A, S148C, S148G, S148T, F149C, G150E, G150V, Y151C, Y151D, Y151S, Y152F, Y152S, D153A, D153H, D153N, D153V, D153Y, A156G, Q157E, Q157K, Q157L, Q157P, T158A, T158I, T158N, T158S, F159I, F159L, F159V, F159Y, A160G, A160S, A160T, A160V, D161H, D161N, D161V, D161Y, W162S, V164A, V164I, V164L, D165A, D165E, L166M, L166Q, L167I, F169C, F169L, F169V, F169Y, G171A, G171V, Y173C, Y173F, Y173H, Y173S, D175G, D175H, D175V, D175Y, S176C, S176R, L177F, L177M, L177S, L177V, L177W, E178A, E178G, E178K, E178Q, L180M, L180S, A181P, A181T, A181V, D182A, D182E, D182V, D182Y, Y184F, Y184H, Y184S, K185M, K185N, K185Q, K185T, H186D, H186L, H186N, H186Q, H186Y, M187L, S188A, S188C, S188F, S188P, S188T, S188Y, L189S, L189V, A190D, A190G, A190S, A190T, A190V, L191M, L191V, N192D, N192H, N192K, N192S, N192T, R193G, R193M, R193T, R193W, T194N, T194P, T194S, G195C, G195R, G195S, R196I, R196K, S197C, S197G, S197I, S197N, S197T, I198M, I198S, V199E, V199L, Y200N, Y200S, S201A, S201C, S201T, E203A, E203G, E203Q, W204S, L206F, L206H, L206I, L206R, L206V, Y207F, M208K, W209C, W209G, P210H, P210T, F211C, F211L, F211S, Petition 870260032676, dated 08 / 04 / 2026, page 21 / 370 11 / 305 F211V, F211Y, Q212H, Q212P, K213E, K213Q, P214A, P214H, P214R, P214T, N215H, N215K, N215T, N215Y, Y216F, Y216H, Y216N, T217A, T217I, T217K, T217P, T217R, T217S, E218A, E218D, E218G, E218K, E218Q, E218V, I219F, I219M, I219S, R220L, Q221E, Q221H, Q221K, Q221L, Q221R, Y222C, Y222D, Y222H, Y222N, Y222S, N224H, R227G, N228H, N228I, N228T, F229I, F229S, F229Y, A230D, A230G, A230P, A230V, I232L, I232M, I232V, D233A, D233E, D233G, D233V, S235A, S235T, K237I, S238C, S238I, S238T, I239L, K240E, K240M, K240R, S241C, S241I, S241T, I242L, I242M, I242S, L243M, L243S, L243V, D244A, D244E, D244G, D244V, D244Y, W245C, T246A, T246I, T246K, T246R, S247A, S247F, S247T, S247Y, F248C, F248L, F248V, F248Y, N249D, N249H, N249I, N249S, N249T, N249Y, Q250E, Q250L, E251G, E251K, E251Q, E251V, R252G, I253F, I253N, I253V, V254A, V254D, V254F, V254G, D255A, D255E, D255H, D255N, D255V, D255Y, V256D, V256G, V256L, A257S, G258E, P259A, P259T, G260W, G261A, N263H, N263T, D264H, D264N, P265A, P265Q, M267L, M267V, L268F, L268I, V269L, I270L, I270S, I270V, N272D, F273Y, L275I, W277L, N278I, Q280L, Q280R, V281A, V281E, V281G, V281L, T282S, Q283E, Q283H, Q283L, M284I, M284L, A285G, A285T, A285V, L286F, L286H, L286V, A288G, A288S, A288V, I289L, I289T, I289V, A291G, A292G, A292S, L294F, L294I, L294V, F295I, F295S, F295V, F295Y, S297T, N298D, N298I, N298T, D299H, D299N, L300I, L300V, H302D, H302L, H302N, H302Y, I303S, S304I, Q306E, Q306L, Q306P, A307D, A307G, A307P, A307S, A307V, K308I, K308Q, K308R, A309D, A309T, L310I, L311I, Q312E, Q312K, Q312L, D313E, D313V, K314E, K314M, K314N, K314T, D315A, D315G, D315H, D315N, D315V, D315Y, V316A, V316L, I317L, I317M, I317V, A318D, A318P, A318T, A318V, I319M, N320S, N320T, Q321K, D322A, D322V, L324V, L324W, G325A, G325C, G325V, K326E, K326M, K326Q, K326R, K326T, Q327H, Q327P, Y329C, Y329D, Y329F, Y329H, Y329N, Q330E, Q330H, Q330K, L331H, Petition 870260032676, dated 08 / 04 / 2026, page 22 / 370 12 / 305 L331P, L331R, L331V, R332G, R332I, R332S, R332T, Q333E, Q333L, Q333P, G334R, G334V, D335A, D335E, D335G, D335V, D335Y, N336D, N336I, N336S, N336T, N336Y, F337C, F337L, F337V, F337Y, E338A, E338D, E338G, V339M, E341A, E341Q, P343A, P343S, L344F, L344R, L344V, G346A, G346C, G346D, G346V L347I, A348D, W349C, W349L, A350G, A350S, A350T, A350V, V351A, V351E, A352S, A352T, M353K, M353L, M353T, I354R, N355D, N355H, N355S, N355Y, R356L, Q357E, I359F, I359L, I359N, I359S, I359V, P362A, P362H, P362R, P362S, R363G, R363L, R363S, S364C, S364P, Y365D, Y365F, Y365N, Y365S, T366I T366N, T366P, T366S, I367F, I367L, I367M, A368G, A368P, V369A, V369F, V369G, V369I, V369L, A370D, A370G, A370P, A370T, A370V, S371C, S371T, G373A, G373C, K374E, K374I, K374R, K374T, G375R, V376E, V376G, V376L, V376M, A377G, A377P, A377S, A377T, N379D, N379I, N379K, N379T, P380A, P380H P380R, P380T, A381D, F383C, F383I, F383Y, I384F, I384M, I384T, T385I, Q386H, Q386K, Q386L, L387F, L387H, L387I, L387R, L388F, L388H, L388IL388R, L388V, K391I, K391N, K391Q, K391R, R392G, R392K, R392M, R392W, K393E, K393N, K393Q, K393T, L394I, L394Q, L394R, G395R, F396C, F396I, F396L, F396V, Y397C, Y397F, Y397H, Y397N, Y397S, E398G, E398Q, W399G, W399R, T400A , T400I, T400N, T400P, T400S, S401A, S401L, S401T, R402G, R402M, R402S, R402T, R402W, L403F, L403V, ​​R404G, R404I, R404K, R404S, R404T, S405G, H406D, H406L, H406Q, I407L, I407M, I407T, N408D, N408H, N408T, P409L, T410S, G411A, G411C, G411V, T412A, T412I, T412S, V413F, V413G, V413I, L414F, L414V, L415H, L415I, Q416E, Q416H, Q416L, L417I, E418A, E418D, E418K, E418Q, N419I, N419S, N419T, N419Y, T420K, T420P, T420R, T420S, M421I, M421K, M421L, M421R, M421T, Q422P, M423I, M423K, M423L, M423T, S424L, L425F, D427N or L429R. In several modalities, these mutations are related to SEQ ID NO: 2. Petition 870260032676, dated 08 / 04 / 2026, page 23 / 370 13 / 305

[0013] In some embodiments, the pharmacological chaperone comprises migalastat or its salt. In one or more embodiments, the dose of migalastat or its salt is about 100 mg to about 150 mg of FBE. In some embodiments, the salt of migalastat is migalastat hydrochloride. In one or more embodiments, the dose is about 150 mg on alternate days of migalastat hydrochloride or an equivalent dose of migalastat or a salt other than the hydrochloride salt. In some embodiments, migalastat or its salt is administered orally or by injection.These embodiments can be combined with each other or with other embodiments of the invention, for example embodiments relating to a method of treating a patient with Fabry disease, use of a pharmacological chaperone for α-Gal A for the manufacture of a medicament to treat a patient diagnosed with Fabry disease or with a pharmacological chaperone for α-Gal A for use in treating a patient diagnosed with Fabry disease, as well as embodiments relating to susceptible mutations, suitable PCs and their dosages, formulations and routes of administration.

[0014] Another aspect of the invention relates to the use of a pharmacological chaperone for α-Gal A for the manufacture of a medicament to treat a patient diagnosed with Fabry disease, wherein the patient has a missense mutation in the nucleic acid sequence encoding α-Gal A. In one or more embodiments, the mutation is N5D, N5K, P6L, P6Q, P6R, P6S, P6T, E7D, E7K, E7V, L8I, L8P, L8Q, H9L, H9Q, H9R, H9Y, L10M, L10P, L10Q, L10R, L10V, G11C, G11D, G11R, G11S, G11V, C12G, C12R, C12S, C12Y, A13E, A13G, L14F, L14H, L14V, R17C, R17G, R17H, R17P, R17S, F18I, F18L, A20G, L21H, V22A, V22F, V22I, V22L, S23P, S23T, W24S, D25H, I26N, P27A, P27L, P27S, P27T, G28E, G28R, G28W, A29G, A29P, A29V, R30G, L32M, L32Q, L32R, L32V, D33A, D33E, D33V, L36M, L36V, A37E, A37G, A37S, R38G, R38M, Petition 870260032676, dated 08 / 04 / 2026, p. 24 / 370 14 / 305 R38W, T39A, T39K, T39M, T39R, T39S, T41A, T41N, T41S, G43A, L45M, L45V, H46D, H46N, H46Q, E48A, F50Y, M51R, M51T, M51V, N53H, N53I, N53S, N53T, L54H, L54R, L54V, D55A, D55E, D55H, D55Y, C56W, E58K, E59A, E59D, E59G, E59Q, E59V, P60A, P60Q, P60R, D61E, D61V, S62A, S62C, S62F, S62P, S62Y, I64L, I64V, S65C, S65G, S65R, E66D, E66V, K67E, K67M, K67N, K67Q, K67T, L68I, F69I, F69Y, M70I, M70K, M70L, M70R, E71A, E71D, E71G, E71Q, E71V, M72L, M72T, A73S, A73T, E74D, E74G, E74K, E74V, L75F, L75P, M76V, V77I, V77L, S78L, S78P, E79A, E79D, E79G, E79K, E79Q, E79V, G80A, G80C, G80S, W81L, K82E, K82M, K82N, K82R, K82T, D83A, D83E, D83G, D83V, A84E, A84G, A84P, A84S, A84T, A84V, G85A, G85C, G85R, Y86F, E87G, Y88H, Y88N, L89V, I91F, I91L, I91M, I91S, M96L, M96T, A97D, A97S, A97T, P98H, P98L, P98R, Q99E, Q99L, Q99P, Q99R, D101A, D101E, D101G, D101H, D101V, S102A, S102P, S102T, G104A, G104D, G104S, R105G, R105I, R105K, R105T, L106H, L106I, L106P, L106V, Q107E, Q107H, Q107K, A108E, A108V, D109A, D109E,D109H, D109N, D109Y, P110T, F113V, F113Y, P114L, H115D, H115N, G116R, I117M, I117T, A121V, Y123D, Y123F, Y123N, Y123S, V124I, H125D, H125N, H125R, S126C, S126I, K127E, G128A, L129V, K130M, K130N, K130Q, L131V, I133L, I133T, I133V, A135E, A135G, A135S, A135T, D136A, D136N, D136V, V137A, V137D, V137G, V137I, V137L, G138A, N139H, N139I, N139K, N139Y, K140E, K140I, K140N, K140Q, K140R, T141S, A143E, A143G, G144A, G144C, G144R, G144S, F145C, F145L, F145V, F145Y, P146A, P146H, P146L, P146T, G147A, S148C, S148G, S148T, F149C, G150E, G150V, Y151C, Y151D, Y151S, Y152F, Y152S, D153A, D153H, D153N, D153V, D153Y, A156G, Q157E, Q157K, Q157L, Q157P, T158A, T158I, T158N, T158S, F159I, F159L, F159V, F159Y, A160G, A160S, A160T, A160V, D161H, D161N, D161V, D161Y, W162S, V164A, V164I, V164L, D165A, D165E, L166M, L166Q, L167I, F169C, F169L, F169V, F169Y, G171A, G171V, Y173C, Y173F, Y173H, Petition 870260032676, dated 08 / 04 / 2026, p. 25 / 370 15 / 305 Y173S, D175G, D175H, D175V, D175Y, S176C, S176R, L177F, L177M, L177S, L177V, L177W, E178A, E178G, E178K, E178Q, L180M, L180S, A181P, A181T, A181V, D182A, D182E, D182V, D182Y, Y184F, Y184H, Y184S, K185M, K185N, K185Q, K185T, H186D, H186L, H186N, H186Q, H186Y, M187L, S188A, S188C, S188F, S188P, S188T, S188Y, L189S, L189V, A190D, A190G, A190S, A190T, A190V, L191M, L191V, N192D, N192H, N192K, N192S, N192T, R193G, R193M, R193T, R193W, T194N, T194P, T194S, G195C, G195R, G195S, R196I, R196K, S197C, S197G, S197I, S197N, S197T, I198M, I198S, V199E, V199L, Y200N, Y200S, S201A, S201C, S201T, E203A, E203G, E203Q, W204S, L206F , L206H, L206I, L206R, L206V, Y207F, M208K, W209C, W209G, P210H, P210T, F211C, F211L, F211S, F211V, F211Y, Q212H, Q212P, K213E, K213Q, P214A, P214H, P214R, P214T, N215H, N215K, N215T, N215Y, Y216F, Y216H, Y216N, T217A, T217I, T217K, T217P, T217R, T217S, E218A, E218D, E218G, E218K, E218Q, E218V, I219F, I219M, I219S, R220L, Q221E, Q221H, Q221K, Q221L, Q221R, Y222C, Y222D, Y222H,Y222N, Y222S, N224H, R227G, N228H, N228I, N228T, F229I, F229S, F229Y, A230D, A230G, A230P, A230V, I232L, I232M, I232V, D233A, D233E, D233G, D233V, S235A, S235T, K237I, S238C, S238I, S238T, I239L, K240E, K240M, K240R, S241C, S241I, S241T, I242L, I242M, I242S, L243M, L243S, L243V, D244A, D244E, D244G, D244V, D244Y, W245C, T246A, T246I, T246K, T246R, S247A, S247F, S247T, S247Y, F248C, F248L, F248V, F248Y, N249D, N249H, N249I, N249S, N249T, N249Y, Q250E, Q250L, E251G, E251K, E251Q, E251V, R252G, I253F, I253N, I253V, V254A, V254D, V254F, V254G, D255A, D255E, D255H, D255N, D255V, D255Y, V256D, V256G, V256L, A257S, G258E, P259A, P259T, G260W, G261A, N263H, N263T, D264H, D264N, P265A, P265Q, M267L, M267V, L268F, L268I, V269L, I270L, I270S, I270V, N272D, F273Y, L275I, W277L, N278I, Q280L, Q280R, V281A, V281E, V281G, V281L, T282S, Q283E, Q283H, Q283L, M284I, Petition 870260032676, dated 08 / 04 / 2026, page 26 / 370 16 / 305 M284L, A285G, A285T, A285V, L286F, L286H, L286V, A288G, A288S, A288V, I289L, I289T, I289V, A291G, A292G, A292S, L294F, L294I, L294V, F295I, F295S, F295V, F295Y, S297T, N298D, N298I, N298T, D299H, D299N, L300I, L300V, H302D, H302L, H302N, H302Y, I303S, S304I, Q306E, Q306L, Q306P, A307D, A307G, A307P, A307S, A307V, K308I, K308Q, K308R, A309D, A309T, L310I, L311I, Q312E, Q312K, Q312L, D313E, D313V, K314E, K314M, K314N, K314T, D315A, D315G, D315H, D315N D315V, D315Y, V316A, V316L, I317L, I317M, I317V, A318D, A318P, A318T A318V, I319M, N320S, N320T, Q321K, D322A, D322V, L324V, L324W, G325A, G325C, G325V, K326E, K326M, K326Q, K326R, K326T, Q327H, Q327P, Y329C, Y329D, Y329F, Y329H, Y329N, Q330E, Q330H, Q330K, L331H, L331P, L331R, L331V, R332G, R332I, R332S, R332T, Q333E, Q333L, Q333P, G334R, G334V, D335A D335E, D335G, D335V, D335Y, N336D, N336I, N336S, N336T, N336Y, F337C, F337L, F337V, F337Y, E338A, E338D, E338G, V339M, E341A, E341Q, P343A, P343S, L344F, L344R, L344V, G346A, G346C, G346D, G346V, L347I, A348D, W349C, W349L, A350G, A350S, A350T, A350V, V351A, V351E, A352S, A352T, M353K M353L, M353T, I354R, N355D, N355H, N355S, N355Y, R356L, Q357E, I359F, I359L, I359N, I359S, I359V, P362A, P362H, P362R, P362S, R363G, R363L, R363S, S364C, S364P, Y365D, Y365F, Y365N, Y365S, T366I, T366N, T366P, T366S, I367F, I367L, I367M, A368G, A368P, V369A, V369F, V369G, V369I, V369L A370D, A370G, A370P, A370T, A370V, S371C, S371T, G373A, G373C, K374E, K374I, K374R, K374T, G375R, V376E, V376G, V376L, V376M, A377G, A377PA377S, A377T, N379D, N379I, N379K, N379T, P380A, P380H, P380R, P380T, A381D, F383C F383I, F383Y, I384F, I384M, I384T, T385I, Q386H, Q386K, Q386L, L387F L387H, L387I, L387R, L388F, L388H, L388I, L388R, L388V, K391I, K391N K391Q, K391R, R392G, R392K, R392M, R392W, K393E, K393N, K393Q K393T, L394I, L394Q, L394R, G395R, F396C, F396I, F396L, F396V, Y397C Petition: 870260032676, on 04 / 08 / 2026, page. 27 / 370 17 / 305 Y397F, Y397H, Y397N, Y397S, E398G, E398Q, W399G, W399R, T400A, T400I, T400N, T400P, T400S, S401A, S401L, S401T, R402G, R402M, R402S, R402T, R402W, L403F, L403V, ​​R404G, R404I, R404K, R404S, R404T, S405G, H406D, H406L, H406Q, I407L, I407M, I407T, N408D, N408H, N408T, P409L, T410S, G411A, G411C, G411V, T412A, T412I, T412S, V413F, V413G, V413I, L414F, L414V, L415H, L415I, Q416E, Q416H, Q416L, L417I, E418A, E418D, E418K, E418Q, N419I, N419S, N419T, N419Y, T420K, T420P, T420R, T420S, M421I, M421K, M421L, M421R, M421T, Q422P, M423I, M423K, M423L, M423T, S424L, L425F, D427N or L429R. In several modalities, these mutations are related to SEQ ID NO: 2.

[0015] In some embodiments, the pharmacological chaperone comprises migalastat or its salt. In one or more embodiments, the dose of migalastat or its salt is about 100 mg to about 150 mg of FBE. In some embodiments, the salt of migalastat is migalastat hydrochloride. In one or more embodiments, the dose is about 150 mg on alternate days of migalastat hydrochloride or an equivalent dose of migalastat or a salt other than the hydrochloride salt. In some embodiments, migalastat or its salt is administered orally or by injection.These embodiments can be combined with each other or with other embodiments of the invention, for example embodiments relating to a method of treating a patient with Fabry disease, a method of enhancing α-Gal A in a patient diagnosed with or suspected of having Fabry disease, or with a pharmacological chaperone for α-Gal A for use in treating a patient diagnosed with Fabry disease, as well as embodiments relating to susceptible mutations, suitable PCs and their dosages, formulations and routes of administration.

[0016] Another aspect of the invention relates to a pharmacological chaperone for α-Gal A for use in treating a patient Petition 870260032676, dated 08 / 04 / 2026, page 28 / 370 18 / 305 diagnosed with Fabry disease, in which the patient has a missense mutation in the nucleic acid sequence encoding α-Gal A. In one or more forms, the mutation is N5D, N5K, P6L, P6Q, P6R, P6S, P6T, E7D, E7K, E7V, L8I, L8P, L8Q, H9L, H9Q, H9R, H9Y, L10M, L10P, L10Q, L10R, L10V, G11C, G11D, G11R, G11S, G11V, C12G, C12R, C12S, C12Y, A13E, A13G, L14F, L14H, L14V, R17C, R17G, R17H, R17P, R17S, F18I, F18L, A20G, L21H, V22A, V22F, V22I, V22L, S23P, S23T, W24S, D25H, I26N, P27A, P27L, P27S, P27T, G28E, G28R, G28W, A29G, A29P, A29V, R30G, L32M, L32Q, L32R, L32V, D33A, D33E, D33V, L36M, L36V, A37E, A37G, A37S, R38G, R38M, R38W, T39A, T39K, T39M, T39R, T39S, T41A, T41N, T41S, G43A, L45M, L45V, H46D, H46N, H46Q, E48A, F50Y, M51R, M51T, M51V, N53H, N53I, N53S, N53T, L54H, L54R, L54V, D55A, D55E, D55H, D55Y, C56W, E58K, E59A, E59D, E59G, E59Q, E59V, P60A, P60Q, P60R, D61E, D61V, S62A, S62C, S62F, S62P, S62Y, I64L, I64V, S65C, S65G, S65R, E66D, E66V, K67E, K67M, K67N, K67Q,K67T, L68I, F69I, F69Y, M70I, M70K, M70L, M70R, E71A, E71D, E71G, E71Q, E71V, M72L, M72T, A73S, A73T, E74D, E74G, E74K, E74V, L75F, L75P, M76V, V77I, V77L, S78L, S78P, E79A, E79D, E79G, E79K, E79Q, E79V, G80A, G80C, G80S, W81L, K82E, K82M, K82N, K82R, K82T, D83A, D83E, D83G, D83V, A84E, A84G, A84P, A84S, A84T, A84V, G85A, G85C, G85R, Y86F, E87G, Y88H, Y88N, L89V, I91F, I91L, I91M, I91S, M96L, M96T, A97D, A97S, A97T, P98H, P98L, P98R, Q99E, Q99L, Q99P, Q99R, D101A, D101E, D101G, D101H, D101V, S102A, S102P, S102T, G104A, G104D, G104S, R105G, R105I, R105K, R105T, L106H, L106I, L106P, L106V, Q107E, Q107H, Q107K, A108E, A108V, D109A, D109E, D109H, D109N, D109Y, P110T, F113V, F113Y, P114L, H115D, H115N, G116R, I117M, I117T, A121V, Y123D, Y123F, Y123N, Y123S, V124I, H125D, H125N, H125R, S126C, S126I, K127E, G128A, L129V, K130M, K130N, K130Q, L131V, I133L, I133T, I133V, A135E, A135G, A135S, A135T, D136A, D136N, D136V, Petition 870260032676, dated 08 / 04 / 2026, p. 29 / 370 19 / 305 V137A, V137D, V137G, V137I, V137L, G138A, N139H, N139I, N139K, N139Y, K140E, K140I, K140N, K140Q, K140R, T141S, A143E, A143G, G144A, G144C, G144R, G144S, F145C, , F145L, F145V, F145Y, P146A, P146H, P146L, P146T, G147A, S148C, S148G, S148T, F149C, G150E, G150V, Y151C, Y151D, Y151S, Y152F, Y152S, D153A, D153H, D153N, D153V, D153Y, A156G, Q157E, Q157K, , Q157L, , Q157P, T158A , T158I, T158N, T158S, F159I, F159L, F159V, F159Y, A160G, A160S, A160T, A160V, D161H, D161N, D161V, D161Y, W162S, V164A , V164I, V164L, D165A, D165E, L166M, L166Q, L167I, F169C, F169L, F169V, F169Y, G171A, G171V, Y173C, Y173F, Y173H, Y173S, D175G, D175H, D175V, D175Y, S176C, S176R, L177F, L177M, L177S, L177V, L177W, E178A, E178G, E178K, E178Q, L180M, L180S, A181P, A181T, A181V, D182A, D182E, D182V, D182Y, Y184F, Y184H, Y184S, K185M, K185N, K185Q, K185T, H186D, H186L, H186N, H186Q, H186Y, M187L, S188A, S188C, S188F, S188P, S188T, S188Y, L189S, L189V, A190D, A190G, A190S, A190T, A190V, L191M, L191V, N192D, N192H, N192K,N192S, N192T, R193G, R193M, R193T, R193W, T194N, T194P, T194S, G195C, G195R, G195S, R196I, R196K, S197C, S197G, S197I, S197T, S197T I198M, I198S, V199E, V199L, Y200N, Y200S, S201A, S201C, S201T, E203A, E203G, E203Q, W204S, L206F, L206H, L206I, L206R, L206F, L206V, Y M208K, W209C, W209G, P210H, P210T, F211C , F211L, F211S, F211V, F211Y, Q212H, Q212P, K213E, K213Q, P214A, P214H, P214T, P214H, N, N N215K, N215T, N215Y, Y216F, Y216H, Y216N, T217A, T217I, T217K, T217P, T217R, T217S, E218A, E218D, E218G, E218K, E218Q, E218Q, E218V, E219V I219M, I219S, R220L, Q221E, Q221H, ι Q221K, Q221L, Q221R, Y222C, Y222D, Y222H, Y222N, Y222S, N224H, R227G, N228H, N228I, N N228T, F229I, F229S, F229Y, A230D, A230G, A230P, A230V, I232L, I232M, I232V, D233A, D233E, D233G, D233V, S235A, S235T, S235C, S238C, K38C S238I, S238T, I239L, K240E, K240M, K240R, S241C, S241I, S241T, I242L, Petition 870260032676, of 08 / 04 / 2026, p. 30 / 370 20 / 305 I242M, I242S, L243M, L243S, L243V, D244A, D244E, D244G, D244V, D244Y, W245C, T246A, T246I, T246K, T246R, S247A, S247F, S247T, S247Y, F248C, F248L, F248V, F248Y, N249D, N249H, N249I, N249S, N249T, N249Y, Q250E, Q250L, E251G, E251K, E251Q, E251V, R252G, I253F, I253N, I253V, V254A, V254D, V254F, V254G, D255A, D255E, D255H, D255N, D255V, D255Y, V256D, V256G, V256L, A257S, G258E, P259A, P259T, G260W, G261A, N263H, N263T, D264H, D264N, P265A, P265Q, M267L, M267V, L268F, L268I, V269L, I270L, I270S, I270V, N272D, F273Y, L275I, W277L, N278I, Q280L, Q280R, V281A, V281E, V281G, V281L, T282S, Q283E, Q283H, Q283L, M284I, M284L, A285G, A285T, A285V, L286F, L286H, L286V, A288G, A288S, A288V, I289L, I289T, I289V, A291G, A292G, A292S, L294F, L294I, L294V, F295I, F295S, F295V, F295Y, S297T, N298D, N298I, N298T, D299H, D299N, L300I, L300V, H302D, H302L, H302N, H302Y, I303S, S304I, Q306E, Q306L, Q306P, A307D, A307G, A307P, A307S, A307V, K308I, K308Q, K308R, A309D, A309T, L310I, L311I, Q312E, Q312K, Q312L, D313E, D313V, K314E, K314M K314N, K314T, D315A, D315G, D315H, D315N, D315V, D315Y, V316A, V316L, I317L, I317M, I317V, A318D, A318P, A318T, A318V, I319M, N320S, N320T, Q321K, D322A, D322V, L324V, L324W, G325A, G325C, G325V K326E, K326M, K326Q, K326R, K326T, Q327H, Q327P, Y329C, Y329D Y329F, Y329H, Y329N, Q330E, Q330H, Q330K, L331H, L331P, L331R L331V, R332G, R332I, R332S, R332T, Q333E, Q333L, Q333P, G334R G334V, D335A, D335E, D335G, D335V, D335Y, N336D, N336I, N336S N336T, N336Y, F337C, F337L, F337V, F337Y, E338A, E338D, E338G V339M, E341A, E341Q, P343A, P343S, L344F, L344R, L344V, G346A, G346C, G346D, G346V, L347I, A348D, W349C, W349L, A350G, A350S A350T, A350V, V351A, V351E, A352S, A352T, M353K, M353L, M353T, I354R, N355D, N355H, N355S, N355Y, R356L, Q357E, I359F, I359L, I359N, I359S, I359V, P362A, P362H, P362R, P362S, R363G, R363L, R363S Petition: 870260032676, on 04 / 08 / 2026, page. 31 / 370 21 / 305 S364C, S364P, Y365D, Y365F, Y365N, Y365S, T366I, T366N, T366P, T366S, I367F, I367L, I367M, A368G, A368P, V369A, V369F, V369G, V369I, V369L, A370D, A370G, A370P, A370T, A370V, S371C, S371T, G373A, G373C, K374E, K374I, K374R, K374T, G375R, V376E, V376G, V376L, V376M, A377G, A377P, A377S, A377T, N379D, N379I, N379K, N379T, P380A, P380H, P380R, P380T, A381D, F383C, F383I, F383Y, I384F, I384M, I384T, T385I, Q386H, Q386K, Q386L, L387F, L387H, L387I, L387R, L388F, L388H, L388I, L388R, L388V, K391I, K391N, K391Q, K391R, R392G, R392K, R392M, R392W, K393E, K393N, K393Q, K393T L394I, L394Q, L394R, G395R, F396C, F396I, F396L, F396V, Y397C, Y397F, Y397H, Y397N, Y397S, E398G, E398Q, W399G, W399R, T400A, T400I, T400N, T400P, T400S, S401A, S401L, S401T, R402G, R402M, R402S, R402T, R402W, L403F, L403V, ​​R404G, R404I, R404K, R404S, R404T, S405G, H406D, H406L, H406Q, I407L, I407M, I407T, N408D, N408H, N408T, P409L, T410S, G411A, G411C, G411V, T412A, T412I, T412S, V413F, V413G, V413I, L414F, L414V, L415H,L415I, Q416E, Q416H, Q416L, L417I, E418A, E418D, E418K, E418Q, N419I, N419S, N419T, N419Y, T420K, T420P, T420R, T420S, M421I, M421K, M421L, M421R, M421T, Q422P, M423I, M423K, M423L, M423T, S424L, L425F, D427N or L429R. In several modalities, these mutations are related to SEQ ID NO: 2.

[0017] In some embodiments, the pharmacological chaperone comprises migalastat or its salt. In one or more embodiments, the dose of migalastat or its salt is about 100 mg to about 150 mg of FBE. In some embodiments, the salt of migalastat is migalastat hydrochloride. In one or more embodiments, the dose is about 150 mg on alternate days of migalastat hydrochloride or an equivalent dose of migalastat or a salt other than the hydrochloride salt. In some embodiments, migalastat or its salt is administered orally or by injection. These embodiments may be combined with each other or with other Petition 870260032676, dated 08 / 04 / 2026, p. 32 / 370 22 / 305 embodiments of the invention, for example embodiments relating to a method of treating a patient with Fabry disease, a method of enhancing α-Gal A in a patient diagnosed with or suspected of having Fabry disease, or the use of a pharmacological chaperone for α-Gal A for the manufacture of a medicament to treat a patient diagnosed with Fabry disease, as well as embodiments relating to susceptible mutations, suitable PCs and their dosages, formulations and routes of administration.

[0018] Another aspect of the invention relates to migalastate or a salt thereof for use in a method for treating Fabry disease in a human patient, wherein the patient has an α-galactosidase A mutation selected from the group consisting of those mutations provided in Table 2.

[0019] Another aspect of the invention relates to a method of treating a patient diagnosed with Fabry disease, wherein the patient has a mutation susceptible to the HEK assay in α-galactosidase A disclosed in a pharmacological reference table as disclosed herein. This aspect may have any of the features described in the other aspects as disclosed herein.

[0020] Another aspect of the invention relates to a method of enhancing α-galactosidase A in a patient diagnosed with or suspected of having Fabry disease, wherein the patient has a mutation susceptible to the HEK assay in α-galactosidase A disclosed in a pharmacological reference table as disclosed herein. This aspect may have any of the features described in the other aspects as disclosed herein.

[0021] Some modalities relate to a method of treating Fabry disease in a subject. The mutation information corresponding to the subject is accessed. The mutation information identifies Petition 870260032676, dated 08 / 04 / 2026, page 33 / 370 23 / 305 one or more α-galactosidase A mutations. Based on the mutation information, it is determined that the subject has at least one mutation as identified in Table 2 and / or at least one mutation of: N5D, N5K, P6L, P6Q, P6R, P6S, P6T, E7D, E7K, E7V, L8I, L8P, L8Q, H9L, H9Q, H9R, H9Y, L10M, L10P, L10Q, L10R, L10V, G11C, G11D, G11R, G11S, G11V, C12G, C12R, C12S, C12Y, A13E, A13G, L14F, L14H, L14V, R17C, R17G, R17H, R17P, R17S, F18I, F18L, A20G, L21H, V22A, V22F, V22I, V22L, S23P, S23T, W24S, D25H, I26N, P27A, P27L, P27S, P27T, G28E, G28R, G28W, A29G, A29P, A29V, R30G, L32M, L32Q, L32R, L32V, D33A, D33E, D33V, L36M, L36V, A37E, A37G, A37S, R38G, R38M, R38W, T39A, T39K, T39M, T39R, T39S, T41A, T41N, T41S, G43A, L45M, L45V, H46D, H46N, H46Q, E48A, F50Y, M51R, M51T, M51V, N53H, N53I, N53S, N53T, L54H, L54R, L54V, D55A, D55E, D55H, D55Y, C56W, E58K, E59A, E59D, E59G, E59Q, E59V, P60A, P60Q, P60R, D61E, D61V, S62A, S62C, S62F, S62P, S62Y, I64L, I64V, S65C, S65G, S65R, E66D, E66V, K67E, K67M,K67N, K67Q, K67T, L68I, F69I, F69Y, M70I, M70K, M70L, M70R, E71A, E71D, E71G, E71Q, E71V, M72L, M72T, A73S, A73T, E74D, E74G, E74K, E74V, L75F, L75P, M76V, V77I, V77L, S78L, S78P, E79A, E79D, E79G, E79K, E79Q, E79V, G80A, G80C, G80S, W81L, K82E, K82M, K82N, K82R, K82T, D83A, D83E, D83G, D83V, A84E, A84G, A84P, A84S, A84T, A84V, G85A, G85C, G85R, Y86F, E87G, Y88H, Y88N, L89V, I91F, I91L, I91M, I91S, M96L, M96T, A97D, A97S, A97T, P98H, P98L, P98R, Q99E, Q99L, Q99P, Q99R, D101A, D101E, D101G, D101H, D101V, S102A, S102P, S102T, G104A, G104D, G104S, R105G, R105I, R105K, R105T, L106H, L106I, L106P, L106V, Q107E, Q107H, Q107K, A108E, A108V, D109A, D109E, D109H, D109N, D109Y, P110T, F113V, F113Y, P114L, H115D, H115N, G116R, I117M, I117T, A121V, Y123D, Y123F, Y123N, Y123S, V124I, H125D, H125N, H125R, S126C, S126I, K127E, G128A, L129V, K130M, K130N, K130Q, L131V, I133L, I133T, I133V, A135E, A135G, A135S, A135T, D136A, Petition 870260032676, dated 08 / 04 / 2026, p. 34 / 370 24 / 305 D136N, D136V, V137A, V137D, V137G, V137I, V137L, G138A, N139H, N139I, N139K, N139Y, K140E, K140I, K140N, K140Q, K140R, T141S, A143E, A143G, G144A, G144C, G144R, G144S, F145C, F145L, F145V, F145Y, P146A, P146H, P146L, P146T, G147A, S148C, S148G, S148T, F149C, G150E, G150V, Y151C, Y151D, Y151S, Y152F, Y152S, D153A, D153H, D153N, D153V, D153Y, A156G, Q157E, Q157K, Q157L, Q157P, T158A, T158I, T158N, T158S, F159I, F159L, F159V, F159Y, A160G, A160S, A160T, A160V, D161H, D161N, D161V, D161Y, W162S, V164A , V164I, V164L, D165A, D165E, L166M, L166Q, L167I, F169C, F169L, F169V, F169Y, G171A, G171V, Y173C, Y173F, Y173H, Y173S, D175G, D175H, D175V, D175Y, S176C, S176R, L177F, L177M, L177S, L177V, L177W, E178A, E178G, E178K, E178Q, L180M, L180S, A181P, A181T, A181V, D182A, D182E, D182V, D182Y, Y184F, Y184H, Y184S, K185M, K185N, K185Q, K185T, H186D, H186L, H186N, H186Q, H186Y, M187L, S188A, S188C, S188F, S188P, S188T, S188Y, L189S, L189V, A190D, A190G, A190S, A190T, A190V, L191M, L191V, N192D, N192H,N192K, N192S, N192T, R193G, R193M, R193T, R193W, T194N, T194P, T194S, G195C, G195R, G195S, R196I, R196K, S197C, S197G, S197I, S197N, S197T, I198M, I198S, 'V199E, V199L, Y200N, Y200S, S201A, S201C, S201T, E203A, E203G, E203Q, W204S, L206F, L206H, L206I, L206R, L206V, Y207F, M208K, W209C, W209G, P210H, P210T, F211C, F211L, F211S, F211V, F211Y, Q212H, Q212P, K213E, K213Q, P214A, P214H, P214R, P214T, N215H, N215K, N215T, N215Y, Y216F, Y216H, Y216N, T217A, T217I, T217K, T217P, T217R, T217S, E218A, E218D, E218G, E218K, E218Q, E218V, I219F, I219M, I219S, R220L, Q221E, Q221H, Q221K, Q221L, Q221R, Y222C, Y222D, Y222H, Y222N, Y222S, N224H, R227G, N228H, N228I, N228T, F229I, F229S, F229Y, A230D, A230G, A230P, A230V, I232L, I232M, I232V, D233A, D233E, D233G, D233V, S235A, S235T, K237I, S238C, S238I, S238T, I239L, K240E, K240M, K240R, S241C, Petition 870260032676, dated 08 / 04 / 2026, page 35 / 370 25 / 305 S241I, S241T, I242L, I242M, I242S, L243M, L243S, L243V, D244A, D244E, D244G, D244V, D244Y, W245C, T246A, T246I, T246K, T246R, S247A, S247F, S247T, S247Y, F248C, F248L, F248V, F248Y, N249D, N249H, N249I, N249S, N249T, N249Y, Q250E, Q250L, E251G, E251K, E251Q, E251V, R252G, I253F, I253N, I253V, V254A, V254D, V254F, V254G, D255A, D255E, D255H, D255N, D255V, D255Y, V256D, V256G, V256L, A257S, G258E, P259A, P259T, G260W, G261A, N263H, N263T, D264H, D264N, P265A, P265Q, M267L, M267V, L268F, L268I, V269L, I270L, I270S, I270V, N272D, F273Y, L275I, W277L, N278I, Q280L, Q280R, V281A, V281E, V281G, V281L, T282S, Q283E, Q283H, Q283L, M284I, M284L, A285G, A285T, A285V, L286F, L286H, L286V, A288G, A288S, A288V, I289L, I289T, I289V, A291G, A292G, A292S, L294F, L294I, L294V, F295I, F295S, F295V, F295Y, S297T, N298D, N298I, N298T, D299H, D299N, L300I, L300V, H302D, H302L, H302N, H302Y, I303S, S304I, Q306E, Q306L, Q306P, A307D, A307G, A307P, A307S, A307V, K308I, K308Q, K308R, A309D, A309T, L310I, L311I, Q312E, Q312K, Q312L D313E, D313V, K314E, K314M, K314N, K314T, D315A, D315G, D315H, D315N, D315V D315Y, V316A, V316L, I317L, I317M, I317V, A318D, A318P, A318T, A318V I319M, N320S, N320T, Q321K, D322A, D322V, L324V, L324W, G325A, G325C, G325V, K326E, K326M, K326Q, K326R, K326T, Q327H, Q327P, Y329C, Y329D, Y329F, Y329H, Y329N, Q330E, Q330H, Q330K, L331H, L331P, L331R, L331V, R332G, R332I, R332S, R332T, Q333E, Q333L, Q333P, G334R, G334V, D335A, D335E D335G, D335V, D335Y, N336D, N336I, N336S, N336T, N336Y, F337C, F337L, F337V, F337Y, E338A, E338D, E338G, V339M, E341A, E341Q, P343A, P343S, L344F, L344R, L344V, G346A, G346C, G346D, G346V, L347I, A348D, W349C, W349L, A350G, A350S, A350T, A350V, V351A, V351E, A352S, A352T, M353K, M353L M353T, I354R, N355D, N355H, N355S, N355Y, R356L, Q357E, I359F, I359L, I359N, I359S, I359V, P362A, P362H, P362R, P362S, R363G Petition: 870260032676, on 04 / 08 / 2026, page. 36 / 370 26 / 305 R363L, R363S, S364C, S364P, Y365D, Y365F, Y365N, Y365S, T366I, T366N, T366P, T366S, I367F, I367L, I367M, A368G, A368P, V369A, V369F, V369G, V369I, V369L, A370D, A370G, A370P, A370T, A370V, S371C, S371T, G373A, G373C, K374E, K374I, K374R, K374T, G375R, V376E, V376G, V376L, V376M, A377G, A377P, A377S, A377T, N379D, N379I, N379K, N379T, P380A, P380H, P380R, P380T, A381D, F383C, F383I, F383Y, I384F, I384M, I384T, T385I, Q386H, Q386K, Q386L, L387F, L387H, L387I, L387R, L388F, L388H, L388I, L388R, L388V, K391I, K391N, K391Q, K391R, R392G, R392K, R392M, R392W, K393E, K393N K393Q, K393T, L394I, L394Q, L394R, G395R, F396C, F396I, F396L, F396V, Y397C, Y397F, Y397H, Y397N, Y397S, E398G, E398Q, W399G, W399R, T400A, T400I, T400N, T400P, T400S, S401A, S401L, S401T, R402G, R402M, R402S, R402T, R402W, L403F, L403V, ​​R404G, R404I, R404K, R404S, R404T, S405G, H406D, H406L, H406Q, I407L, I407M, I407T, N408D, N408H, N408T, P409L, T410S, G411A, G411C, G411V, T412A, T412I, T412S, V413F, V413G, V413I, L414F,L414V, L415H, L415I, Q416E, Q416H, Q416L, L417I, E418A, E418D, E418K, E418Q, N419I, N419S, N419T, N419Y, T420K, T420P, T420R, T420S, M421I, M421K, M421L, M421R, M421T, Q422P, M423I, M423K, M423L, M423T, S424L, L425F, D427N or L429R. In response to the determination, migalastat or a salt thereof is administered to the subject.

[0022] At least one mutation may include one or more α-galactosidase A mutations at amino acid residues 5-14, 17-18, 20-30, 32-33, 36-39, 41, 43, 45-46, 48, 50-51, 53-56, 58-62, 64-89, 91, 96-99, 101-102, 104-110, 113-117, 121, 123-131, 133, 135-141, 143-153, 156-162, 164-167, 169, 171, 173, 175-178, 180-182, 184-201, 203, 204, 206-222, 224, 227-230, 232-233, 235, 237-261, 263-265, 267-270, 272-273, 275, 277-278, 280-286, 288-289, 291-292, 294-295, 297-300, 302-304, 306-322, 324-327, 329-339, 341, 343-344, 346-357, 359, 362-371, 373-377, 379-381, 383 Petition 870260032676, dated 08 / 04 / 2026, p. 37 / 370 27 / 305 388, 391-425, 427 or 429, or any combination thereof, wherein the residues are numbered in relation to SEQ ID NO:2.

[0023] Determining that a subject has at least one mutation as identified in Table 2 may involve initiating a query of a data store that identifies two or more mutations from a set of mutations identified in Table 2 and receiving a query result that identifies that at least one mutation is represented in the mutation information and also in Table 2. The data store may additionally identify two or more mutations from another set of mutations (e.g., identified in Table 2). The data store may identify at least 10%, 25%, 50%, 75%, 90%, or 95% of the mutations included in Table 1 and / or at least 10%, 25%, 50%, 75%, 90%, or 95% of the mutations as included in Table 2. The query may be initiated by accessing a particular webpage hosted by a web server that controls a data store identifying at least some of the mutations in Table 2.The query can be initiated by accessing a particular webpage on a website; providing input on the particular webpage that identifies at least part of the mutation information; and selecting an option on the webpage to submit an electronic request to a web server to perform the query, the electronic request including a representation of the input. The result of the query can be received from the web server in response to the query and can be displayed on the particular webpage or another webpage on the website.

[0024] Migalastat or its salt may be administered to the subject on alternate days. Administering migalastat or its salt may include administering migalastat or its salt at a dose of approximately 100 to approximately 150 mg of free base equivalent of migalastat or its salt; or administering approximately 123 mg of free base equivalent of migalastat or its salt. Migalastat or its salt may enhance α-galactosidase A activity in Petition 870260032676, dated 08 / 04 / 2026, pp. 38 / 370 28 / 305 subject. At least one mutation may include a mutation susceptible to the HEK assay in α-galactosidase A. Migalastat or its salt can be administered orally or by injection.

[0025] In some embodiments, a computer-implemented method is provided. An electronic communication is received. The electronic communication corresponds to an identification of a particular mutation. A data store is queried using the identification of the particular mutation. The data store includes an identification of each of a set of susceptible mutations. Each of the susceptible mutations corresponds to a mutation listed in Table 2. A query result is detected, the result indicating whether the particular mutation is represented in the set of susceptible mutations. Based on the response, an output is generated that is indicative of the suitability of treating a patient with the particular mutation with migalastat or a migalastat salt. The output is transmitted.

[0026] Electronic communication may include identifying the particular mutation in a first format, and the method may further include determining that the first format differs from a second format used by the data store; extracting one or more components from the identification; generating a second identification based on the components, the second identification being in the second format; transmitting the second identification; and receiving a second electronic communication indicating that the second identification matches the first identification. The data store may be consulted in response to receiving the second electronic communication. The data store may further include identifying another set of susceptible mutations. Each of the second set of susceptible mutations corresponds to a mutation listed in Table 1, and the result may further be indicative of whether the particular mutation is Petition 870260032676, dated 08 / 04 / 2026, page 39 / 370 29 / 305 represented in the second set of susceptible mutations. The result may include a binary indication as to whether migalastat or migalastat salt is an appropriate treatment for a condition attributed to the particular mutation. The identification of the particular mutation may correspond to the entry detected on a webpage (generated at least in part based on webpage data transmitted to a user device from which the electronic device is received). The data store may identify at least 10%, at least 25%, at least 50%, at least 75%, or at least 90% of the mutations listed in Table 2.

[0027] In some embodiments, a computer-implemented method is provided. A dataset unit is accessed by storing a dataset that identifies, for each mutation in a set of mutations, the degree to which αGal A activity responds to migalastate or a migalastate salt when the mutation is present. The set of mutations includes one or more mutations listed in Table 2. A communication is received that identifies one or more particular mutations. The dataset unit is queried using a representation of the one or more particular mutations. A query result is detected. The result indicates, for each particular mutation in the one or more particular mutations, the degree to which α-Gal A activity responds to migalastate or a migalastate salt when the particular mutation is present.A metric is determined that corresponds to the predicted effectiveness of treating a patient having one or more particular mutations with migalastat or a migalastat salt. The metric is then issued.

[0028] One or more particular mutations may include a plurality of particular mutations, and determining the metric involves identifying a minimum or maximum of the degrees to which α-Gal A activity is responsive to migalastate or a migalastate salt across the plurality of particular mutations. The metric may be a binary indication of whether Petition 870260032676, dated 08 / 04 / 2026, p. 40 / 370 30 / 305 a condition associated with one or more particular mutations is amenable to treatment with migalastat or a migalastat salt. The metric may include a number, category, or descriptor indicating a predicted extent to which a condition associated with one or more particular mutations is amenable to treatment with migalastat or a migalastat salt. The query result may indicate, for a particular mutation of one or more particular mutations and as a result of the particular mutation not being detected within the dataset, that the α-Gal A activity corresponding to the particular mutation is not responsive to migalastat or a migalastat salt. The set of mutations may additionally include one or more mutations listed in Table 1.One or more particular mutations may include a plurality of particular mutations, and determining the metric may include identifying a minimum or maximum of the degrees to which α-Gal A activity is responsive to migalastate or a migalastate salt across the plurality of particular mutations.

[0029] In some cases, a method of treating Fabry disease in a subject is provided. Mutation information corresponding to the subject is accessed. The mutation information identifies one or more α-galactosidase A mutations. It is determined, based on the mutation information, that the subject has a mutation for which the α-Gal A activity in lysates prepared from HEK-293 cells transiently transfected with a mutant form of α-Gal A and incubated for 5 days in the presence of 10 μM migalastat is greater than a reference α-Gal A activity in other lysates prepared from other HEK293 cells transiently transfected with the mutant form of α-Gal A and incubated for 5 days in the absence of 10 μM migalastat, the mutant form of α-Gal A corresponding to the mutation. In response to the determination, migalastate or one of its salts is administered to the subject. Petition 870260032676, dated 08 / 04 / 2026, page 41 / 370 31 / 305

[0030] α-Gal A activity can be defined as the nmoles of free 4-MU released per milligram of protein per hour. The determination may include determining that the subject has a mutation for which the α-Gal A activity is at least 1%, at least 5%, at least 10%, at least 25%, at least 50%, or at least 100% higher than the reference α-Gal A activity. The determination may include querying a data store with an identifier of one or more α-galactosidase A mutations and receiving a query result. The result may indicate that the mutation representation is included in the data store. The result may include one or more values ​​associated with a mutation representation in the data store, and the method may additionally include comparing the one or more values ​​or a processed version thereof with a predefined threshold.

[0031] In some cases, a method is provided. Mutation information corresponding to a subject is accessed. The mutation information identifies one or more α-galactosidase A mutations. It is determined, based on the mutation information, that the subject has a mutation for which the α-Gal A activity in lysates prepared from HEK-293 cells transiently transfected with a mutant form of α-Gal A and incubated for 5 days in the presence of 10 μM migalastat is greater than a reference α-Gal A activity in other lysates prepared from other HEK-293 cells transiently transfected with the mutant form of α-Gal A and incubated for 5 days in the absence of 10 μM migalastat, the mutant form of α-Gal A corresponding to the mutation. In response to the determination, an indication is issued that the mutation is susceptible to treatment with migalastat or one of its salts.

[0032] α-Gal A activity can be defined as the nmoles of free 4-MU released per milligram of protein per hour. The determination Petition 870260032676, dated 08 / 04 / 2026, page 42 / 370 32 / 305 may include determining that the subject has a mutation for which the α-Gal A activity is at least 1%, at least 5%, at least 10%, at least 25%, at least 50%, or at least 100% greater than the reference α-Gal A activity. The determination may include querying a data store with an identifier of one or more α-galactosidase A mutations and receiving a query result. The result may indicate that the mutation representation is included in the data store. The result may include one or more values ​​associated with a mutation representation in the data store, and the method may additionally include comparing the one or more values ​​or a processed version thereof with a predefined threshold.The method may involve receiving, from a user device, an initial communication that includes the mutation information, and issuing the indication may include transmitting a second communication to the user device, the second communication including the indication.

[0033] In some cases, a system is provided. The system includes one or more data processors and a non-transient, machine-readable storage medium containing instructions that, when executed on the one or more data processors, cause the one or more data processors to perform part or all of one or more methods disclosed herein. In some cases, a computer program product is provided that is tangibly embodied in a non-transient, machine-readable storage medium. The computer program product may include instructions configured to cause one or more data processors to perform part or all of one or more methods disclosed herein.

[0034] Another aspect of the invention relates to a method for diagnosing Fabry disease in a subject that is amenable to treatment with migalastate or a salt thereof, the method comprising Petition 870260032676, dated 08 / 04 / 2026, page 43 / 370 33 / 305 determine whether α-Gal A in a sample from the subject has an amino acid sequence comprising at least one mutation as identified in Table 2; wherein, if the α-Gal A in the subject's sample has an amino acid sequence comprising such a mutation, the subject has, or is at risk of developing, Fabry disease that is amenable to treatment with migalastat or a salt thereof. In one or more embodiments, the subject has one or more symptoms of Fabry disease. In other embodiments, the subject has no symptoms of Fabry disease. In one or more embodiments, the subject is a child. In one or more embodiments, the subject is a male subject. In one or more embodiments, the subject is a female subject. In one or more embodiments, the subject has a family history of Fabry disease. In one or more embodiments, the subject is the daughter of a classically affected male Fabry patient.

[0035] Another aspect of the invention relates to a method for identifying a subject with Fabry disease who is amenable to treatment with migalastat or a salt thereof, the method comprising determining whether α-Gal A in a sample from the subject has an amino acid sequence comprising at least one mutation as identified in Table 2; wherein, if the α-Gal A in the sample from the subject has an amino acid sequence comprising such a mutation, the subject has, or is at risk of developing, Fabry disease who is amenable to treatment with migalastat or a salt thereof. In one or more embodiments, the subject has one or more symptoms of Fabry disease. In other embodiments, the subject has no symptoms of Fabry disease. In one or more embodiments, the subject is a child. In one or more embodiments, the subject is a male subject. In one or more embodiments, the subject is a female subject.In one or more forms, the subject has a family history of Fabry disease. In one... Petition 870260032676, dated 08 / 04 / 2026, page 44 / 370 34 / 305 or more modalities, the subject is the daughter of a classically affected male Fabry patient.

[0036] Another aspect of the invention relates to a method for diagnosing Fabry disease in a subject that is amenable to treatment with migalastat or a salt thereof, the method comprising determining whether the GLA gene in a sample from a subject comprises a point mutation compared with the nucleic acid sequence of SEQ ID NO: 1; if the GLA gene in the sample comprises such a point mutation, determining whether the point mutation results in an amino acid mutation of α-Gal A as identified in Table 2; wherein the point mutation results in an amino acid mutation of α-Gal A as identified in Table 2, the subject has, or is at risk of developing, Fabry disease that is amenable to treatment with migalastat or a salt thereof. In other embodiments, the subject has no symptoms of Fabry disease. In one or more embodiments, the subject is an embryo. In one or more embodiments, the subject is a child.In one or more modalities, the subject is a male subject. In one or more modalities, the subject is a female subject. In one or more modalities, the subject has a family history of Fabry disease. In one or more modalities, the subject is the daughter of a classically affected male Fabry patient.

[0037] Another aspect of the invention relates to a method for identifying a subject with Fabry disease who is amenable to treatment with migalastate or a salt thereof, the method comprising determining whether the GLA gene in a sample from a subject comprises a point mutation by comparison with the nucleic acid sequence of SEQ ID NO: 1; if the GLA gene in the sample comprises such a point mutation, determining whether the point mutation results in an amino acid mutation of α-Gal A as identified in Table 2; wherein the mutation Petition 870260032676, dated 08 / 04 / 2026, page 45 / 370 35 / 305 point mutation results in an amino acid mutation of α-Gal A as identified in Table 2; the subject has, or is at risk of developing, Fabry disease and is amenable to treatment with migalastat or one of its salts. In other embodiments, the subject has no symptoms of Fabry disease. In one or more embodiments, the subject is an embryo. In one or more embodiments, the subject is a child. In one or more embodiments, the subject is a male subject. In one or more embodiments, the subject is a female subject. In one or more embodiments, the subject has a family history of Fabry disease. In one or more embodiments, the subject is the daughter of a classically affected male Fabry patient.

[0038] Several embodiments are listed below. It will be understood that the embodiments listed below can be combined not only as listed below, but in other suitable combinations according to the scope of the invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] FIGs. 1A-E show the complete DNA sequence of the wild-type human GLA gene (SEQ ID NO: 1);

[0040] FIG. 2 shows the wild-type α-Gal A protein (SEQ ID NO: 2); and

[0041] FIG. 3 shows the nucleic acid sequence encoding the wild-type α-Gal A protein (SEQ ID NO: 3).

[0042] FIG. 4A shows an exemplary interaction system for generating treatment classifications based on mutation data.

[0043] FIG. 4B shows a schematic view of an exemplary mutation classifier system.

[0044] FIG. 5 illustrates an exemplary process for using mutation data to generate predictive metrics. Petition 870260032676, dated 08 / 04 / 2026, page 46 / 370 36 / 305

[0045] FIG. 6 illustrates an exemplary process for using mutation data to generate predictive outputs.

[0046] FIG. 7 illustrates exemplary mutation representations being used to facilitate mutation-based effects assessments.

[0047] FIG. 8 illustrates an exemplary interface to facilitate mutation-based treatment classifications. DETAILED DESCRIPTION

[0048] Before describing various exemplary embodiments of the invention, it should be understood that the invention is not limited to the details of construction steps or processes set forth in the following description. The invention is capable of other embodiments and of being practiced or carried out in various ways.

[0049] As described above, it is very difficult, if not impossible, to predict whether a particular Fabry patient will respond to treatment with a PC. Currently, when a patient is evaluated, it is first necessary to determine the particular mutation in α-Gal A, then test the patient's specific mutated form of α-Gal A in an assay to determine whether or not the mutation is susceptible to treatment with migalastat. The migalastat susceptibility test is typically performed by someone other than the physician evaluating the patient for treatment. This test is time-consuming and delays the start of treatment.

[0050] Accordingly, several aspects of the invention relate to the identification of novel GLA mutations in Fabry patients that will respond to treatment with pharmacological chaperones. Other aspects of the invention also relate to the treatment of these Fabry patients. For example, it was unexpectedly discovered that the low α-Gal A activity resulting from the missense mutations in α-Gal A shown in Table 2 can be increased when exposed to chaperones. Petition 870260032676, dated 08 / 04 / 2026, page 47 / 370 37 / 305 pharmacological, even though no patients have been previously identified with these particular mutations. By extension, patients with these mutations are expected to respond to treatment with pharmacological chaperones.

[0051] The use of the information in Table 2 prevents delays in starting treatment, as it is no longer necessary to additionally test the patient's α-Gal A PC susceptibility. In fact, after determining the patient's particular mutation, the physician can consult a list of α-Gal A mutations (e.g., including one or more mutations listed in Table 2) and, if the patient's mutation is on the list, can start treatment immediately.

[0052] The identification of these new mutations can also be used to determine if a subject, including an embryo or a newborn, is at risk of developing Fabry disease before the onset of symptoms. In one or more ways, the subject may be at risk of developing Fabry disease, such as having a family history of Fabry disease. Definitions

[0053] The terms used in this descriptive report generally have their usual meanings in the art, within the context of this invention and in the specific context where each term is used. Certain terms are discussed below, or elsewhere in the descriptive report, to provide additional guidance to the physician in describing the compositions and methods of the invention and on how to prepare and use them.

[0054] The term “Fabry disease” refers to a congenital X-linked error of glycosphingolipid catabolism due to deficient lysosomal α-Gal A activity. This defect causes accumulation of the substrate globotriaosylceramide (“GL-3”, also known as Gb3 or ceramide trihexoside) and related glycosphingolipids in endothelial lysosomes. Petition 870260032676, dated 08 / 04 / 2026, p. 48 / 370 38 / 305 vascular tissues of the heart, kidneys, skin, and other tissues. Another substrate of the enzyme is plasma globotriaosylsphingosine ("plasma lyso-Gb3").

[0055] A “carrier” is a female subject who has one X chromosome with a defective α-Gal A gene and one X chromosome with a normal gene, and on whose X chromosome the inactivation of the normal allele is present in one or more cell types. A carrier is frequently diagnosed with Fabry disease.

[0056] A “patient” refers to a subject who has been diagnosed with or is suspected of having a particular disease. The patient can be human or an animal.

[0057] A “Fabry patient” refers to an individual who has been diagnosed with or is suspected of having Fabry disease and has a mutated αGal A as further defined below. Characteristic markers of Fabry disease can occur in male hemizygotes and female carriers with the same prevalence, although female subjects are typically less severely affected.

[0058] Human α-galactosidase A (α-Gal A) refers to an enzyme encoded by the human GLA gene. The complete DNA sequence of αGal A, including introns and exons, is available in GenBank Accession No. X14448.1 and is shown in FIGS. 1A-E (SEQ ID NO: 1). The human α-Gal A enzyme consists of 429 amino acids and is available in GenBank Accession Nos. X14448.1 and U78027 and is shown in FIG. 2 (SEQ ID NO: 2). The nucleic acid sequence that includes only the coding regions (i.e., exons) of SEQ ID NO: 1 is shown in FIG. 3 (SEQ ID NO: 3).

[0059] The term “mutant protein” includes a protein that has a mutation in the gene encoding the protein that results in the protein's inability to achieve a stable conformation under the conditions normally present in the ER. The inability to achieve a stable conformation results in a substantial amount of the enzyme being degraded instead Petition 870260032676, dated 08 / 04 / 2026, p. 49 / 370 39 / 305 of being transported to the lysosome. Such a mutation is sometimes called a “conformational mutant”. Such mutations include, but are not limited to, missense mutations and small lattice deletions and insertions.

[0060] As used herein in one embodiment, the term “α-Gal A mutant” includes an α-Gal A that has a mutation in the gene encoding αGal A that results in the enzyme being unable to achieve a stable conformation under the conditions normally present in the ER. The inability to achieve a stable conformation results in a substantial amount of the enzyme being degraded instead of being transported to the lysosome.

[0061] As used herein, the term “specific pharmacological chaperone” (“SPC”) or “pharmacological chaperone” (“PC”) refers to any molecule including a small molecule, protein, peptide, nucleic acid, carbohydrate, etc., that specifically binds to a protein and has one or more of the following effects: (i) enhances the formation of a stable molecular conformation of the protein; (ii) induces trafficking of the protein from the ER to another cellular location, preferably a native cellular location, i.e., prevents degradation of the ER-associated protein; (iii) prevents the aggregation of defective folding proteins; and / or (iv) restores or enhances at least partial wild-type function and / or activity of the protein. A compound that specifically binds, e.g., to α-Gal A, means that it binds to and exerts a chaperone effect on the enzyme and not a generic group of related or unrelated enzymes.More specifically, this term does not refer to endogenous chaperones, such as BiP, or to non-specific agents that have demonstrated non-specific chaperone activity against various proteins, such as glycerol, DMSO, or deuterated water, i.e., chemical chaperones. In one or more embodiments of the present invention, PC may be a reversible competitive inhibitor. Petition 870260032676, dated 08 / 04 / 2026, p. 50 / 370 40 / 305 In one embodiment, PC is migalastat or its salt. In another embodiment, PC is the free base of migalastat (e.g., 123 mg of migalastat free base). In yet another embodiment, PC is a salt of migalastat (e.g., 150 mg of migalastat HCl).

[0062] A “competitive inhibitor” of an enzyme can refer to a compound that structurally resembles the chemical structure and molecular geometry of the enzyme substrate in order to bind to the enzyme at approximately the same location as the substrate. Thus, the inhibitor competes for the same active site as the substrate molecule, thereby increasing Km. Competitive inhibition is usually reversible if sufficient substrate molecules are available to displace the inhibitor, i.e., competitive inhibitors can bind reversibly. Therefore, the amount of enzyme inhibition depends on the concentration of the inhibitor, the concentration of the substrate, and the relative affinities of the inhibitor and substrate for the active site.

[0063] As used herein, the term “specifically binds” refers to the interaction of a pharmacological chaperone with a protein such as α-Gal A, specifically, an interaction with amino acid residues of the protein that directly participate in the contact with the pharmacological chaperone. A pharmacological chaperone specifically binds to a target protein, e.g., α-Gal A, to exert a chaperone effect on the protein and not a generic group of related or unrelated proteins. The amino acid residues of a protein that interact with any given pharmacological chaperone may or may not be within the protein's “active site.” Specific binding can be assessed through routine binding assays or through structural studies, e.g., cocrystallization, NMR, and the like. The active site for α-Gal A is the substrate binding site. Petition 870260032676, dated 08 / 04 / 2026, p. 51 / 370 41 / 305

[0064] “Deficient α-Gal A activity” refers to α-Gal A activity in a patient’s cells that is below the normal range when compared (using the same methods) with activity in normal individuals who do not have or are suspected of having Fabry or any other disease (especially a blood disease).

[0065] As used herein, the terms “intensify α-Gal A activity” or “increase α-Gal A activity” refer to increasing the amount of α-Gal A that adopts a stable conformation in a cell contacted with a specific α-Gal A drug chaperone, relative to the amount in a cell (preferably of the same cell type or in the same cell, e.g., at an earlier time) not contacted with the specific α-Gal A drug chaperone. This term also refers to increasing the trafficking of α-Gal A to the lysosome in a cell contacted with a specific α-Gal A drug chaperone, relative to the trafficking of α-Gal A not contacted with the specific drug chaperone for the protein. These terms refer to both wild-type and mutant α-Gal A. In one embodiment, the increase in the amount of α-Gal A in the cell is measured by measuring the hydrolysis of an artificial substrate in lysates of cells that have been treated with PC.An increase in hydrolysis is indicative of increased α-Gal A activity.

[0066] The term “α-Gal A activity” refers to the normal physiological function of a wild-type α-Gal A in a cell. For example, α-Gal A activity includes the hydrolysis of GL-3.

[0067] A “responder” is an individual diagnosed with or suspected of having a lysosomal storage disorder, such as, for example, Fabry disease, whose cells exhibit sufficiently increased α-Gal A activity, respectively, and / or improvement in symptoms or enhancement in surrogate markers, in response to contact with a PC. Non-limiting examples of enhancements in surrogate markers Petition 870260032676, dated 08 / 04 / 2026, p. 52 / 370 42 / 305 for Fabry are smooth-Gb3 and those disclosed in U.S. Patent Application Publication No. US 2010-0113517, which is hereby incorporated by reference in its entirety.

[0068] Non-limiting examples of improvements in surrogate markers for Fabry disease disclosed in US 2010 / 0113517 include increases in α-Gal A levels or activity in cells (e.g., fibroblasts) and tissue; reductions in GL-3 accumulation; decreased plasma concentrations of homocysteine ​​and vascular cell adhesion molecule-1 (VCAM-1); reduced accumulation of GL-3 within myocardial cells and valvular fibrocytes; reduction in plasma lyso-Gb3; reduction in cardiac hypertrophy (especially of the left ventricle), improvement in valvular insufficiency and arrhythmias; improvement in proteinuria; reduced urinary concentrations of lipids such as CTH, lactosylceramide, ceramide and increased urinary concentrations of glycosylceramide and sphingomyelin; the absence of laminated inclusion bodies (Zebra bodies) in glomerular epithelial cells; improvements in renal function; mitigation of hypohidrosis; the absence of angiokeratomas; and improvements in auditory abnormalities such as high-frequency sensorineural hearing loss, progressive hearing loss, sudden deafness or tinnitus.Improvements in neurological symptoms include prevention of transient ischemic attack (TIA) or stroke; and improvement in neuropathic pain manifesting as acroparesthesia (burning or tingling in the extremities). Another type of clinical marker that can be assessed for Fabry disease is the prevalence of detrimental cardiovascular manifestations. Common heart-related signs and symptoms of Fabry disease include left ventricular hypertrophy, valvular disease (especially mitral valve prolapse and / or regurgitation), premature coronary artery disease, angina, myocardial infarction, conduction abnormalities, arrhythmias, and congestive heart failure. Petition 870260032676, dated 08 / 04 / 2026, p. 53 / 370 43 / 305

[0069] A dose that achieves one or more of the aforementioned responses is a “therapeutically effective dose”.

[0070] The phrase “pharmaceutically acceptable” refers to molecular entities and compositions that are physiologically tolerable and typically do not produce undesirable reactions when administered to a human. In some embodiments, as used herein, the term “pharmaceutically acceptable” means approved by a federal or state government regulatory agency or listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals and, more particularly, in humans. The term “carrier” in reference to a pharmaceutical carrier refers to a diluent, adjuvant, excipient, or vehicle with which the compound is administered. Such pharmaceutical carriers may be sterile liquids, such as water and oils. Water or aqueous solution, saline solutions, and aqueous solutions of dextrose and glycerol are preferably employed as carriers, particularly for injectable solutions.Suitable pharmaceutical carriers are described in "Remington's Pharmaceutical Sciences" by E.W. Martin, 18th Edition or other editions.

[0071] As used herein, the term “isolate” means that the referenced material is removed from the environment in which it is normally found. Thus, an isolated biological material may be free of cellular components, i.e., components of the cells in which the material is found or produced. In the case of nucleic acid molecules, an isolated nucleic acid includes a PCR product, an mRNA band on a gel, a cDNA, or a restriction fragment. In another embodiment, an isolated nucleic acid is preferably excised from the chromosome on which it may be found and, more preferably, is no longer associated with non-regulatory genes, non-coding regions, or other genes located upstream or downstream of the gene contained by the Petition 870260032676, dated 08 / 04 / 2026, p. 54 / 370 44 / 305 Isolated nucleic acid molecule when found on a chromosome. In yet another embodiment, the isolated nucleic acid lacks one or more introns. Isolated nucleic acids include sequences inserted into plasmids, cosmids, artificial chromosomes, and the like. Thus, in a specific embodiment, a recombinant nucleic acid is an isolated nucleic acid. An isolated protein may be associated with other proteins or nucleic acids, or both, to which it associates in the cell, or with cell membranes if it is a membrane-associated protein. An isolated organelle, cell, or tissue is removed from the anatomical location where it is found in an organism. Isolated material may be, but does not need to be, purified.

[0072] The terms “about” and “approximately” should generally mean an acceptable degree of error for the measured quantity given the nature or precision of the measurements. Exemplary and typical degrees of error are within 20 percent (%), preferably within 10 percent and, more preferably, within 5 percent of a given value or range of values. Alternatively, and particularly in biological systems, the terms “about” and “approximately” may mean values ​​that are within an order of magnitude, preferably within 10 or 5 times and, more preferably, within 2 times of a given value. The numerical quantities given here are approximate unless otherwise stated, meaning that the term “about” or “approximately” may be inferred when not expressly stated.

[0073] The term “enzyme replacement therapy” or “ERT” refers to the introduction of a purified, non-native enzyme into an individual having a deficiency in that enzyme. The administered protein may be obtained from natural sources or by recombinant expression (as described in more detail below). The term also refers to the introduction of a purified enzyme into an individual requiring or benefiting from Petition 870260032676, dated 08 / 04 / 2026, p. 55 / 370 45 / 305 another method of administering a purified enzyme, e.g., in patients suffering from enzyme deficiency. The enzyme introduced may be a recombinant enzyme, purified enzyme produced in vitro, or purified protein from isolated tissue or fluid, such as, for example, placenta or animal milk, or from plants.

[0074] As used herein, the term “free base equivalent” or “FBE” refers to the amount of migalastate present in migalastate or its salt. In other words, the term “FBE” means both a free base amount of migalastate and the free base equivalent amount of migalastate that is provided by a migalastate salt. For example, due to the weight of the hydrochloride salt, 150 mg of migalastate hydrochloride provides only as much migalastate as 123 mg of the free base form of migalastate. Other salts are expected to have different conversion factors depending on the molecular weight of the salt.

[0075] The term “migalastate” includes migalastate free base or a pharmaceutically acceptable salt thereof (e.g., migalastate HCl), unless specifically indicated otherwise.

[0076] The terms “mutation” and “variant” (e.g., as in “susceptible mutation or variant”) refer to a change in the nucleotide sequence of a gene or chromosome. The two terms referred to here are typically used together—e.g., as in “mutation or variant”—referring to the nucleotide sequence change stated in the preceding sentence. If only one of the two terms is recited for some reason, the missing term should be included and understood as such. Furthermore, the terms “susceptible mutation” and “susceptible variant” refer to a mutation or variant that is susceptible to PC therapy, e.g., a mutation that is susceptible to migalastat therapy. A particular type of susceptible mutation or variant is a “HEK assay susceptible mutation or variant,” which is a mutation or variant that is determined to be Petition 870260032676, dated 08 / 04 / 2026, p. 56 / 370 46 / 305 susceptible to migalastat therapy according to the criteria in the HEK in vitro trial described here. Fabry disease

[0077] Fabry disease is a rare, progressive, and devastating X-linked lysosomal storage disorder. Mutations in the GLA gene result in a deficiency of the lysosomal enzyme, α-Gal A, which is required for the metabolism of glycosphingolipids. Beginning early in life, the reduction in α-Gal A activity results in an accumulation of plasma glycosphingolipids, including GL-3 and lyso-Gb3, and leads to the life-limiting symptoms and sequelae of Fabry disease, including pain, gastrointestinal symptoms, renal failure, cardiomyopathy, cerebrovascular events, and premature mortality. Early initiation of therapy and lifelong treatment provide an opportunity to slow disease progression and prolong life expectancy.

[0078] Fabry disease encompasses a spectrum of disease severity and age of onset, although it has traditionally been divided into 2 main phenotypes, “classic” and “late-onset”. The classic phenotype has been primarily attributed to male subjects with undetectable to low α-Gal A activity and earlier onset of renal, cardiac, and / or cerebrovascular manifestations. The late-onset phenotype has been primarily attributed to male subjects with higher residual α-Gal A activity and later onset of these pathological manifestations. Heterozygous female carriers typically express the late-onset phenotype but, depending on the X chromosome inactivation pattern, may also exhibit the classic phenotype.

[0079] More than 1,000 GLA mutations causing Fabry disease have been identified. Approximately 60% are missense mutations, resulting in single amino acid substitutions in the α-Gal A enzyme. Missense GLA mutations result Petition 870260032676, dated 08 / 04 / 2026, page 57 / 370 47 / 305 frequently produce abnormally folded and unstable forms of α-Gal A, and most are associated with the classic phenotype. Normal cellular quality control mechanisms in the endoplasmic reticulum block the transit of these abnormal proteins to lysosomes and target them for premature degradation and elimination. Many missense mutant forms are targets for migalastat, a pharmacological chaperone specific for α-Gal A.

[0080] The clinical manifestations of Fabry disease encompass a wide spectrum of severity and correlate roughly with a patient's residual α-GAL levels. Most currently treated patients are referred to as patients with classic Fabry disease, the majority of whom are male subjects. These patients experience multi-organ disease, including the kidneys, heart, and brain, with disease symptoms first appearing in adolescence and typically progressing in severity until death in the fourth or fifth decade of life. A number of recent studies suggest that there is a large number of undiagnosed male and female subjects who have a range of Fabry disease symptoms, such as impaired cardiac or renal function and strokes, which usually first appear in adulthood.Individuals with this type of Fabry disease, referred to as late-onset Fabry disease, tend to have higher residual α-GAL levels than patients with classic Fabry disease. Individuals with late-onset Fabry disease typically first experience symptoms of the disease in adulthood and often have symptoms focused on a single organ, such as left ventricular dilation or progressive renal failure. Additionally, late-onset Fabry disease can also manifest as strokes of unknown cause. Petition 870260032676, dated 08 / 04 / 2026, p. 58 / 370 48 / 305

[0081] Fabry patients have progressive renal failure, and untreated patients exhibit end-stage renal failure in the fifth decade of life. Deficiency in α-Gal A activity leads to the accumulation of GL-3 and related glycosphingolipids in many cell types, including cells in the kidneys. GL-3 accumulates in podocytes, epithelial cells, and tubular cells of the distal tubule and loop of Henle. Impaired renal function may manifest as proteinuria and reduced glomerular filtration rate.

[0082] Because Fabry disease is rare, involves multiple organs, has a wide age range of onset, and is heterogeneous, appropriate diagnosis is challenging. Knowledge is limited among healthcare professionals, and diagnostic errors are frequent. The diagnosis of Fabry disease is most often confirmed based on decreased α-Gal A activity in plasma or peripheral leukocytes (WBCs) as soon as the patient becomes symptomatic, coupled with mutational analysis. In female subjects, diagnosis is even more challenging since enzymatic identification of female carriers is less reliable due to random X chromosome inactivation in some carrier cells. For example, some obligate carriers (daughters of classically affected male subjects) have α-Gal A enzyme activities ranging from normal to very low.Since carriers may have normal α-Gal A enzyme activity in leukocytes, only the identification of an α-Gal A mutation by genetic testing provides accurate identification and / or diagnosis of the carrier.

[0083] Similarly, as described above, the age of onset, progression, and severity of Fabry disease is at least partially dependent on the rate of substrate accumulation, which correlates with enzymatic activity in lysosomes. Thus, a complete absence of Petition 870260032676, dated 08 / 04 / 2026, page 59 / 370 49 / 305 residual activity may correspond to rapid substrate accumulation and therefore to a more severe form of the disease (having early onset and rapid progression). However, even small amounts of residual activity may be sufficient to degrade a large amount of substrate. This in turn would lead to milder disease with late onset and slower progression due to the decelerated substrate accumulation. Considering these factors, it is thought that even modest increases in enzymatic activity may reduce the effect of a severe clinical phenotype. Data suggest that, for most LSDs, only 1% to 6% of normal activity was estimated as sufficient to delay or prevent disease onset or result in a milder form of the disease. That is, only small increases in activity could have a significant impact on substrate levels and, consequently, on disease severity and disease progression rate.Conversely, it is expected that a mutant lysosomal enzyme that does not show a response in vitro will also not respond in vivo.

[0084] In one or more embodiments, mutant or variant forms of α-Gal A considered to be susceptible to migalastat are defined as showing a relative increase (+migalastat at 10 μM) of >1.20 times and an absolute increase (+migalastat at 10 μM) of >3.0% from wild type when the mutant form of α-Gal A is expressed in HEK-293 cells (referred to as the “HEK assay”) according to the Good Laboratory Practice (GLP) validated in vitro assay (HEK GLP Assay or Migalastat Susceptible). Such mutations or variants are also referred to herein as “HEK assay susceptible” mutations or variants.

[0085] Previous screening methods have been provided that assess enzyme enhancement before the start of treatment. For example, an assay using HEK-293 cells has been used in clinical trials to predict whether a given mutation will be responsive to treatment with Petition 870260032676, dated 08 / 04 / 2026, page 60 / 370 50 / 305 pharmacological chaperones (e.g., migalastat). In this assay, cDNA constructs are created. The corresponding mutant forms of α-Gal A are transiently expressed in HEK-293 cells. The cells are then incubated with ± migalastat (17 nM to 1 mM) for 4 to 5 days. Then, α-Gal A levels are measured in cell lysates using a synthetic fluorogenic substrate (4-MU-α-Gal) or by Western blotting. This was done for known disease-causing missense mutations or small grid insertion / deletion mutations. Mutations that have been previously identified as responsive to a PC (e.g., migalastat) using these methods are listed in U.S. Patent No. 8,592,362, which is hereby incorporated by reference in its entirety.

[0086] Mutations susceptible to the HEK assay include at least those mutations listed in a pharmacological reference table (e.g., those recited on the U.S. or International Product labels for a migalastat product such as GALAFOLD®). As used herein, “pharmacological reference table” refers to any publicly accessible written or electronic record, included on the product label inside the packaging of a migalastat product (e.g., GALAFOLD®) or on a website accessible by healthcare providers, that conveys whether a particular mutation or variant is responsive to PC therapy with migalastat (e.g., GALAFOLD®) and is not necessarily limited to written records presented in tabular form. In one embodiment of the present invention, a “pharmacological reference table” thus refers to any repository of information that includes one or more susceptible mutations or variants.In another embodiment, a “pharmacological reference table” refers to an up-to-date repository of susceptible mutations or variants that includes the new mutations or variants disclosed herein (i.e., mutations presented in Table 2). An exemplary pharmacological reference table for... Petition 870260032676, dated 08 / 04 / 2026, p. 61 / 370 51 / 305 mutations susceptible to the HEK assay can be found in the summary of product characteristics and / or prescribing information for GALAFOLD® in various countries where GALAFOLD® is approved for use or on a website such as www.galafoldamenabilitytable.com or www.fabrygenevariantsearch.com, each of which is hereby incorporated by reference in its entirety.

[0087] An illustrative pharmacological reference table for mutations susceptible to the HEK assay is provided in Table 1 below. In one or more embodiments, if a double mutation is present on the same chromosome (male and female subjects), that patient is considered susceptible to the HEK assay if the double mutation is present in an entry in Table 1 (e.g., D55V / Q57L). In some embodiments, if a double mutation is present on different chromosomes (female subjects only), that patient is considered susceptible to the HEK assay if either of the individual mutations is present in Table 1. Table 1 Nucleotide change Nucleotide change Protein sequence change c.7C>G c.C7G L3V c.8T>C c.T8C L3P c.[11G>T; 620A>C] c.G11T / A620C R4M / Y207S c.37G>A c.G37A A13T c.37G>C c.G37C A13P c.43G>A c.G43A A15T c.44C>G c.C44G A15G c.53T>G c.T53G F18C c.58G>C c.G58C A20P Petition 870260032676, dated 08 / 04 / 2026, p. 62 / 370 52 / 305 Table 1 Nucleotide change Nucleotide change Protein sequence change c.59C>A c.C59A A20D c.65T>G c.T65G V22G c.70T>C or c.70T>A c.T70C or c.T70A W24R c.70T>G c.T70G W24G c.72G>C or c.72G>T c.G72C or c.G72T W24C c.95T>C c.T95C L32P c.97G>C c.G97C D33H c.97G>T c.G97T D33Y c.98A>G c.A98G D33G c.100A>G c.A100G N34D c.100A>C c.A100C N34H c.101A>C c.A101C N34T c.101A>G c.A101G N34S c.102T>G or c.102T>A c.T102G or c.T102A N34K c.103G>C or c.103G>A c.G103C or c.G103A G35R c.104G>A c.G104A G35E c.104G>C c.G104C G35A c.104G>T c.G104T G35V c.107T>C c.T107C L36S c.107T>G c.T107G L36W c.108G>C or c.108G>T c.G108C or c.G108T L36F c.109G>A c.G109A A37T c.110C>T c.C110T A37V c.122C>T c.C122T T41I Petition 870260032676, dated 08 / 04 / 2026, p. 63 / 370 53 / 305 Table 1 Nucleotide change Nucleotide change Protein sequence change c.124A>C or c.124A>T c.A124C or c.A124T M42L c.124A>G c.A124G M42V c.125T>A c.T125A M42K c.125T>C c.T125C M42T c.125T>G c.T125G M42R c.126G>A or c.126G>C or c.126G>T c.G126A or c.G126C or c.G126T M42I c.137A>C c.A137C H46P c.142G>C c.G142C E48Q c.152T>A c.T152A M51K c.153G>A or c.153G>T or c.153G>C c.G153A or c.G153T or c.G153C M51I c.159C>G or c.159C>A c.C159G or c.C159A N53K c.157A>G c.A157G N53D c.[157A>C; 158A>T] c.A157C / A158T N53L c.160C>T c.C160T L54F c.161T>C c.T161C L54P c.164A>G c.A164G D55G c.164A>T c.A164T D55V c.[164A>T; 170A>T] c.A164T / A170T D55V / Q57L c.167G>T c.G167T C56F c.167G>A c.G167A C56Y c.170A>G c.A170G Q57R c.170A>T c.A170T Q57L Petition 870260032676, dated 08 / 04 / 2026, p. 64 / 370 54 / 305 Table 1 Nucleotide change Nucleotide change Protein sequence change c.175G>A c.G175A E59K c.178C>A c.C178A P60T c.178C>T c.C178T P60S c.179C>T c.C179T P60L c.184_185insTAG c.184_185insTAG S62delinsLA c.196G>A c.G196A E66K c.197A>G c.A197G E66G c.207C>A or c.207C>G c.C207A or c.C207G F69L c.214A>G c.A214G M72V c.216G>A or c.216G>T or c.216G>C c.G216A or c.G216T or c.G216C M72I c.218C>T c.C218T A73V c.227T>C c.T227C M76T c.239G>A c.G239A G80D c.239G>T c.G239T G80V c.247G>A c.G247A D83N c.253G>A c.G253A G85S c.254G>A c.G254A G85D c.[253G>A; 254G>A] c.G253A / G254A G85N c.[253G>A; 254G>T; 255T>G] c.G253A / G254T / T255G G85M c.261G>C or c.261G>T c.G261C or c.G261T E87D c.263A>C c.A263C Y88S c.265C>T c.C265T L89F Petition 870260032676, dated 08 / 04 / 2026, p. 65 / 370 55 / 305 Table 1 Mudança de nucleotídeos Mudança de nucleotídeos Mudança da sequência de proteína c.272T>C c.T272C I91T c.288G>A ou c.288G>T ou c.288G>C c.G288A ou c.G288T ou c.G288C M96I c.286A>G c.A286G M96V c.289G>C c.G289C A97P c.290C>T c.C290T A97V c.305C>T c.C305T S102L c.311G>T c.G311T G104V c.316C>T c.C316T L106F c.320A>G c.A320G Q107R c.322G>A c.G322A A108T c.326A>G c.A326G D109G c.334C>G c.C334G R112G c.335G>A c.G335A R112H c.335G>T c.G335T R112L c.337T>A c.T337A F113I c.337T>C ou c.339T>A ou c.339T>G c.T337C ou c.T339A ou c.T339G F113L c.352C>T c.C352T R118C c.361G>A c.G361A A121T c.368A>G c.A368G Y123C c.373C>T c.C373T H125Y c.374A>T c.A374T H125L c.376A>G c.A376G S126G Petição 870260032676, de 08 / 04 / 2026, pág. 66 / 370 56 / 305 Tabela 1 Nucleotide change Nucleotide change Protein sequence change c.383G>A c.G383A G128E c.399T>G c.T399G I133M c.404C>T c.C404T A135V c.408T c.404C>T c.C404T A135V c.408T c.408T or c. c.T408G D136E c.416A>G c.A416G N139S c.419A>C c.A419C K140T c.427G>A c.G427A A143T c.431G>A c.G431A G144D c.431G>T c.G431G141VT c.434T>C c.T434C F145S c.436C>T c.C436T P146S c.437C>G c.C437G P146R c.454T>G c.T454G Y152D c.454T>C c.T454C Y152A>H. Y152C c.465T>A or c.465T>G c.T465A or c.T465G D155E c.466G>T c.G466T A156S c.466G>A c.G466A A156T c.467C>T c.C467VT c.467G>C or c. c.471G>T c.G471C or c.G471T Q157H c.484T>G c.T484G W162G c.493G>C c.G493C D165H c.494A>G c.A494G D165G c.[496C>G; 497T>G] c.C496G / T497G L166G Petition 870260032676, of 08 / 04 / 2026, p. 67 / 370 57 / 305 Table 1 Nucleotide change Nucleotide change Protein sequence change c.496C>G c.C496G L166V c.496_497delinsTC c.496_497delinsTC L166S c.499C>G c.C499G L167V c.506T>C c.T506C F169S c.511G>A c.G511A G171S c.520T>C c.T520C C174R c.520T>G c.T520G C174G c.525C>G or c.525C>A c.C525G or c.C525A D175E c.539T>G c.T539G L180W c.540G>C c.G540C L180F c.548G>C c.G548C G183A c.548G>A c.G548A G183D c.550T>A c.T550A Y184N c.551A>G c.A551G Y184C c.553A>G c.A553G K185E c.559A>G c.A559G M187V c.559_564dup c.559_564dup p.M187_S188dup c.560T>C c.T560C M187T c.561G>T or c.561G>A or c.561G>C c.G561T or c.G561A or c.G561C M187I c.567G>C or c.567G>T c.G567C or c.G567T L189F c.572T>A c.T572A L191Q c.580A>G c.A580G T194A c.581C>T c.C581T T194I Petition 870260032676, dated 08 / 04 / 2026, p. 68 / 370 58 / 305 Table 1 Mudança de nucleotídeos Mudança de nucleotídeos Mudança da sequência de proteína c.584G>T c.G584T G195V c.586A>G c.A586G R196G c.593T>C c.T593C I198T c.595G>A c.G595A V199M c.596T>C c.T596C V199A c.596T>G c.T596G V199G c.599A>G c.A599G Y200C c.602C>T c.C602T S201F c.602C>A c.C602A S201Y c.608A>T c.A608T E203V c.609G>C ou c.609G>T c.G609C ou c.G609T E203D c.610T>G c.T610G W204G c.611G>T c.G611T W204L c.613C>A c.C613A P205T c.613C>T c.C613T P205S c.614C>T c.C614T P205L c.619T>C c.T619C Y207H c.620A>C c.A620C Y207S c.623T>G c.T623G M208R c.628C>T c.C628T P210S c.629C>T c.C629T P210L c.638A>G c.A638G K213R c.638A>T c.A638T K213M c.640C>T c.C640T P214S Petição 870260032676, de 08 / 04 / 2026, pág. 69 / 370 59 / 305 Tabela 1 Nucleotide change Nucleotide change Protein sequence change c.641C>T c.C641T P214L c.643A>G c.A643G N215D c.644A>G c.A644G N215S c.644A>T c.A644G N215S c.644A>T c. c.[644A>G; 937G>T] c.A644G / G937T N215S / D313Y c.646T>G c.T646G Y216D c.647A>C c.A647C Y216S c.647A>G c.A647G Y216C c.655A>C c.A647G Y216C c.655A>C c.A647C I215C c.656T>A c.T656A I219N c.656T>C c.T656C I219T c.659G>A c.G659A R220Q c.659G>C c.G659C R220P c.662A>C c.A662C Q221P>C c.662A>C. N224T c.671A>G c.A671G N224S c.673C>G c.C673G H225D c.682A>G c.A682G N228D c.683A>G c.A683G N228S c.687T>A or c.68T>A c.678G. F229L c.695T>C c.T695C I232T c.712A>G c.A712G S238G c.713G>A c.G713A S238N c.716T>C c.T716C I239T Petition 870260032676, of 08 / 04 / 2026, p. 70 / 370 60 / 305 Table 1 Nucleotide change Nucleotide change Protein sequence change c.717A>G c.A717G I239M c.720G>C or c.720G>T c.G720C or c.G720T K240N c.724A>G c.A724G I242V c.724A>T c.A724T I242F c.725T>A c.T725A I242N c.725T>C c.T725C I242T c.728T>G c.T728G L243W c.729G>C or c.729G>T c.G729C or c.G729T L243F c.730G>A c.G730A D244N c.730G>C c.G730C D244H c.733T>G c.T733G W245G c.740C>G c.C740G S247C c.747C>G or c.747C>A c.C747G or c.C747A N249K c.748C>A c.C748A Q250K c.749A>C c.A749C Q250P c.749A>G c.A749G Q250R c.750G>C c.G750C Q250H c.758T>C c.T758C I253T c.758T>G c.T758G I253S c.760-762delGTT c.760_762delGTT p.V254del c.769G>C c.G769C A257P c.770C>T c.C770T A257V c.770C>G c.C770G A257G c.772G>C or c.772G>A c.G772C or c.G772A G258R Petition 870260032676, dated 08 / 04 / 2026, p. 71 / 370 61 / 305 Table 1 Nucleotide change Nucleotide change Protein sequence change c.773G>T c.G773T G258V c.776C>A c.C776A P259Q c.776C>G c.C776G P259R c.776C>T c.C776T P259L c.779G>A c.G779A G260E c.779G>C c.G779C G260A c.781G>A c.G781A G261S c.781G>C c.G781C G261R c.781G>T c.G781T G261C c.788A>G c.A788G N263S c.790G>T c.G790T D264Y c.794C>T c.C794T P265L c.800T>C c.T800C M267T c.805G>A c.G805A V269M c.806T>C c.T806C V269A c.809T>C c.T809C I270T c.810T>G c.T810G I270M c.811G>A c.G811A G271S c.[811G>A; 937G>T] c.G811A / G937T G271S / D313Y c.812G>A c.G812A G271D c.823C>G c.C823G L275V c.827G>A c.G827A S276N c.829T>G c.T829G W277G c.831G>T or c.831G>C c.G831T or c.G831C W277C Petition 870260032676, dated 08 / 04 / 2026, p. 72 / 370 62 / 305 Table 1 Nucleotide change Nucleotide change Protein sequence change c.832A>T c.A832T N278Y c.835C>G c.C835G Q279E c.838C>A c.C838A Q280K c.840A>T or c.840A>C c.A840T or c.A840C Q280H c.844A>G c.A844G T282A c.845C>T c.C845T T282I c.850A>G c.A850G M284V c.851T>C c.T851C M284T c.860G>T c.G860T W287L c.862G>C c.G862C A288P c.866T>G c.T866G I289S c.868A>C or c.868A>T c.A868C or c.A868T M290L c.869T>C c.T869C M290T c.870G>A or c.870G>C or c.870G>T c.G870A or c.G870C or c.G870T M290I c.871G>A c.G871A A291T c.877C>A c.C877A P293T c.881T>C c.T881C L294S c.884T>G c.T884G F295C c.886A>G c.A886G M296V c.886A>T or c.886A>C c.A886T or c.A886C M296L c.887T>C c.T887C M296T c.888G>A or c.888G>T or c.888G>C c.G888A or c.G888T or c.G888C M296I Petition 870260032676, dated 08 / 04 / 2026, p. 73 / 370 63 / 305 Table 1 Mudança de nucleotídeos Mudança de nucleotídeos Mudança da sequência de proteína c.893A>G c.A893G N298S c.897C>G ou c.897C>A c.C897G ou c.C897A D299E c.898C>T c.C898T L300F c.899T>C c.T899C L300P c.901C>G c.C901G R301G c.902G>C c.G902C R301P c.902G>A c.G902A R301Q c.902G>T c.G902T R301L c.907A>T c.A907T I303F c.908T>A c.T908A I303N c.911G>A c.G911A S304N c.911G>C c.G911C S304T c.919G>A c.G919A A307T c.922A>G c.A922G K308E c.924A>T ou c.924A>C c.A924T ou c.A924C K308N c.925G>C c.G925C A309P c.926C>T c.C926T A309V c.928C>T c.C928T L310F c.931C>G c.C931G L311V c.935A>G c.A935G Q312R c.936G>T ou c.936G>C c.G936T ou c.G936C Q312H c.937G>T c.G937T D313Y c.[937G>T; 1232G>A] c.G937T / G1232A D313Y / G411D c.938A>G c.A938G D313G Petição 870260032676, de 08 / 04 / 2026, pág. 74 / 370 64 / 305 Tabela 1 Mudança de nucleotídeos Mudança de nucleotídeos Mudança da sequência de proteína c.946G>A c.G946A V316I c.947T>G c.T947G V316G c.950T>C c.T950C I317T c.955A>T c.A955T I319F c.956T>C c.T956C I319T c.958A>C c.A958C N320H c.959A>T c.A959T N320I c.962A>G c.A962G Q321R c.962A>T c.A962T Q321L c.963G>C ou c.963G>T c.G963C ou c.G963T Q321H c.964G>A c.G964A D322N c.964G>C c.G964C D322H c.966C>A ou c.966C>G c.C966A ou c.C966G D322E c.967C>A c.C967A P323T c.968C>G c.C968G P323R c.973G>A c.G973A G325S c.973G>C c.G973C G325R c.978G>C ou c.978G>T c.G978C ou c.G978T K326N c.979C>G c.C979G Q327E c.980A>T c.A980T Q327L c.983G>C c.G983C G328A c.989A>C c.A989C Q330P c.989A>G c.A989G Q330R c.1001G>A c.G1001A G334E Petição 870260032676, de 08 / 04 / 2026, pág. 75 / 370 65 / 305 Tabela 1 Nucleotide change Nucleotide change Protein sequence change c.1010T>C c.T1010C F337S c.1012G>A c.G1012A E338K c.1013A>T c.A1013T E338V c.1016T>C c.T1016C V339A c.1016T>A c.T1016A V339E c.1027C>A c.C1027A P343T c.1028C>T c.C1028T P343L c.1033T>C c.T1033C S345P c.1046G>C c.G1046C W349S c.1055C>G c.C1055G A352G c.1055C>T c.C1055T A352V c.1061T>A c.T1061A I354K c.1066C>G c.C1066G R356G c.1066C>T c.C1066T R356W c.1067G>A c.G1067A R356Q c.1067G>C c.G1067C R356P c.1072G>C c.G1072C E358Q c.1073A>C c.A1073C E358A c.1073A>G c.A1073G E358G c.1074G>T or c.1074G>C c.G1074T or c.G1074C E358D c.1076T>C c.T1076C I359T c.1078G>A c.G1078A G360S c.1078G>T c.G1078T G360C Petition 870260032676, dated 08 / 04 / 2026, p. 76 / 370 66 / 305 Table 1 Nucleotide change Nucleotide change Protein sequence change c.1079G>A c.G1079A G360D c.1082G>A c.G1082A G361E c.1082G>C c.G1082C G361A c. P362T c.1085C>T c.C1085T P362L c.1087C>T c.C1087T R363C c.1088G>A c.G1088A R363H c.1102G>A c.G1102A A368T c.1117A c.G17G>G317G. c.1124G>A c.G1124A G375E c.1139C>T c.C1139T P380L c.1153A>G c.A1153G T385A c.1168G>A c.G1168A V390M c.1171A>G c.A11171EG K.385A c.1172A>C c.A1172C K391T c.1175G>C c.G1175C R392T c.1184G>A c.G1184A G395E c.1184G>C c.G1184C G395A c.1192G>A c.G1192K c.1202_1203insGACTT C c.1202_1203insGACTT C p.T400_S401dup c.1208T>C c.T1208C L403S c.1222A>T c.A1222T N408Y c.1225C>G c1222G P4095 Petition 870260032676, of 08 / 04 / 2026, p. 77 / 370 67 / 305 Table 1 Nucleotide change Nucleotide change Protein sequence change c.1225C>T c.C1225T P409S c.1225C>A c.C1225A P409T c.1228A>G c.A1228G T410A c.1229C>T c.C1229T T410I c.1232G>A c.G1232A G411D c.1234A>C c.A1234C T412P c.1235C>A c.C1235A T412N c.1253A>G c.A1253G E418G c.1261A>G c.A1261G M421V

[0088] However, since only certain mutations are susceptible to treatment with migalastat, there is a need to identify new mutations and determine whether such mutations are susceptible to migalastat therapy. As described in the Example below, several new mutations have been identified and determined to be mutations that are susceptible to migalastat therapy.

[0089] As described above, α-Gal A refers to an enzyme encoded by the human GLA gene. The coding sequence of the GLA gene consists of 1287 nucleotides. The human α-Gal A enzyme consists of 429 amino acid residues. To create a list of all possible non-synonymous missense mutations for GLA, each nucleotide in the coding sequence was individually substituted in the coding sequence by the other 3 nucleotides, and the effect of each substitution on the protein sequence was examined.

[0090] If the codon change has led to a change in the protein sequence by a single amino acid residue substitution Petition 870260032676, dated 08 / 04 / 2026, page 78 / 370 If, in sequence 68 / 305, this amino acid substitution had not been previously identified, the mutation was recorded and tested with an HEK assay. Those mutations found to be susceptible to the HEK assay were labeled as susceptible prognostic mutations. When multiple different nucleotide changes within a single codon led to the same amino acid residue substitution at that position, the protein sequence change was listed as a single entry with alternative nucleotide changes.

[0091] The susceptible prophetic mutations identified include N5D, N5K, P6L, P6Q, P6R, P6S, P6T, E7D, E7K, E7V, L8I, L8P, L8Q, H9L, H9Q, H9R, H9Y, L10M, L10P, L10Q, L10R, L10V, G11C, G11D, G11R, G11S, G11V, C12G, C12R, C12S, C12Y, A13E, A13G, L14F, L14H, L14V, R17C, R17G, R17H, R17P, R17S, F18I, F18L, A20G, L21H, V22A, V22F, V22I, V22L, S23P, S23T, W24S, D25H, I26N, P27A, P27L, P27S, P27T, G28E, G28R, G28W, A29G, A29P, A29V, R30G, L32M, L32Q, L32R, L32V, D33A, D33E, D33V, L36M, L36V, A37E, A37G, A37S, R38G, R38M, R38W, T39A, T39K, T39M, T39R, T39S, T41A, T41N, T41S, G43A, L45M, L45V, H46D, H46N, H46Q, E48A, F50Y, M51R, M51T, M51V, N53H, N53I, N53S, N53T, L54H, L54R, L54V, D55A, D55E, D55H, D55Y, C56W, E58K, E59A, E59D, E59G, E59Q, E59V, P60A, P60Q, P60R, D61E, D61V, S62A, S62C, S62F, S62P, S62Y, I64L, I64V, S65C, S65G, S65R, E66D, E66V, K67E, K67M, K67N, K67Q, K67T, L68I, F69I, F69Y, M70I, M70K, M70L, M70R, E71A, E71D, E71G, E71Q, E71V, M72L, M72T, A73S, A73T, E74D, E74G, E74K, E74V,L75F, L75P, M76V, V77I, V77L, S78L, S78P, E79A, E79D, E79G, E79K, E79Q, E79V, G80A, G80C, G80S, W81L, K82E, K82M, K82N, K82R, K82T, D83A, D83E, D83G, D83V, A84E, A84G, A84P, A84S, A84T, A84V, G85A, G85C, G85R, Y86F, E87G, Y88H, Y88N, L89V, I91F, I91L, I91M, I91S, M96L, M96T, A97D, A97S, A97T, P98H, P98L, P98R, Q99E, Q99L, Q99P, Q99R, D101A, D101E, D101G, D101H, D101V, S102A, S102P, Petition 870260032676, dated 08 / 04 / 2026, page 79 / 370 69 / 305 S102T, G104A, G104D, G104S, R105G, R105I, R105K, R105T, L106H, L106I, L106P, L106V, Q107E, Q107H, Q107K, A108E, A108V, D109A, D109E, D109H, D109N, D109Y, P110T, F113V, F113Y, P114L, H115D, H115N, G116R, I117M, I117T, A121V, Y123D, Y123F, Y123N, Y123S, V124I, H125D, H125N, H125R, S126C, S126I, K127E, G128A, L129V, K130M, K130N, K130Q, L131V, I133L, I133T, I133V, A135E, A135G, A135S, A135T, D136A, D136N, D136V, V137A, V137D, V137G, V137I, V137L, G138A, N139H, N139I, N139K, N139Y, K140E, K140I, K140N, K140Q, K140R, T141S, A143E, A143G, G144A, G144C, G144R, G144S, F145C, F145L, F145V, F145Y, P146A, P146H, P146L, P146T, G147A, S148C, S148G, S148T, F149C, G150E, G150V, Y151C, Y151D, Y151S, Y152F, Y152S, D153A, D153H, D153N, D153V, D153Y, A156G, Q157E, Q157K, Q157L, Q157P, T158A, T158I, T158N, T158S, F159I, F159L, F159V, F159Y, A160G, A160S, A160T, A160V, D161H, D161N, D161V, D161Y, W162S, V164A, V164I, V164L, D165A, D165E, L166M, L166Q, L167I, F169C, F169L, F169V, F169Y, G171A, G171V, Y173C,Y173F, Y173H, Y173S, D175G, D175H, D175V, D175Y, S176C, S176R, L177F, L177M, L177S, L177V, L177W, E178A, E178G, E178K, E178Q, L180M, L180S, A181P, A181T, A181V, D182A, D182E, D182V, D182Y, Y184F, Y184H, Y184S, K185M, K185N, K185Q, K185T, H186D, H186L, H186N, H186Q, H186Y, M187L, S188A, S188C, S188F, S188P, S188T, S188Y, L189S, L189V, A190D, A190G, A190S, A190T, A190V, L191M, L191V, N192D, N192H, N192K, N192S, N192T, R193G, R193M, R193T, R193W, T194N, T194P, T194S, G195C, G195R, G195S, R196I, R196K, S197C, S197G, S197I, S197N, S197T, I198M, I198S, V199E, V199L, Y200N, Y200S, S201A, S201C, S201T, E203A, E203G, E203Q, W204S, L206F, L206H, L206I, L206R, L206V, Y207F, M208K, W209C, W209G, P210H, P210T, F211C, F211L, F211S, F211V, F211Y, Q212H, Q212P, K213E, K213Q, P214A, P214H, P214R, P214T, N215H, N215K, N215T, N215Y, Y216F, Y216H, Y216N, Petition 870260032676, dated 08 / 04 / 2026, page 80 / 370 70 / 305 T217A, T217I, T217K, T217P, T217R, T217S, E218A, E218D, E218G, E218K, E218Q, E218V, I219F, I219M, I219S, R220L, Q221E, Q221H, Q221K, Q221L, Q221R, Y222C, Y222D, Y222H, Y222N, Y222S, N224H, R227G, N228H, N228I, N228T, F229I, F229S, F229Y, A230D, A230G, A230P, A230V, I232L, I232M, I232V, D233A, D233E, D233G, D233V, S235A, S235T, K237I, S238C, S238I, S238T, I239L, K240E, K240M, K240R, S241C, S241I, S241T, I242L, I242M, I242S, L243M, L243S, L243V, D244A, D244E, D244G, D244V, D244Y, W245C, T246A, T246I, T246K, T246R, S247A, S247F, S247T, S247Y, F248C, F248L, F248V, F248Y, N249D, N249H, N249I, N249S, N249T, N249Y, Q250E, Q250L, E251G, E251K, E251Q, E251V, R252G, I253F, I253N, I253V, V254A, V254D, V254F, V254G, D255A, D255E, D255H, D255N, D255V, D255Y, V256D, V256G, V256L, A257S, G258E, P259A, P259T, G260W, G261A, N263H, N263T, D264H, D264N, P265A, P265Q, M267L, M267V, L268F, L268I, V269L, I270L, I270S, I270V, N272D, F273Y, L275I, W277L, N278I, Q280L, Q280R, V281A, V281E, V281G, V281L, T282S, Q283E, Q283H, Q283L, M284I, M284L, A285G, A285T, A285V, L286F, L286H, L286V, A288G, A288S, A288V, I289L, I289T, I289V, A291G, A292G, A292S, L294F, L294I, L294V, F295I, F295S, F295V, F295Y, S297T, N298D, N298I, N298T, D299H, D299N, L300I, L300V, H302D, H302L, H302N, H302Y, I303S, S304I, Q306E, Q306L, Q306P, A307D, A307G, A307P, A307S, A307V, K308I, K308Q, K308R, A309D, A309T, L310I, L311I, Q312E, Q312K Q312L, D313E, D313V, K314E, K314M, K314N, K314T, D315A, D315G, D315H, D315N, D315V, D315Y, V316A, V316L, I317L, I317M, I317V, A318D, A318P, A318T, A318V, I319M, N320S, N320T, Q321K, D322A, D322V, L324V, L324W, G325A, G325C, G325V, K326E, K326M, K326Q, K326R, K326T, Q327H, Q327P, Y329C Y329D, Y329F, Y329H, Y329N, Q330E, Q330H, Q330K, L331H, L331P, L331R, L331V, R332G, R332I, R332S, R332T, Q333E, Q333L, Q333P, G334R, G334VD335A, D335E, D335G, D335V, D335Y Petition: 870260032676, on 04 / 08 / 2026, page. 81 / 370 71 / 305 N336D, N336I, N336S, N336T, N336Y, F337C, F337L, F337V, F337Y E338A, E338D, E338G, V339M, E341A, E341Q, P343A, P343S, L344F L344R, L344V, G346A, G346C, G346D, G346V, L347I, A348D, W349C, W349L, A350G, A350S, A350T, A350V, V351A, V351E, A352S, A352T M353K, M353L, M353T, I354R, N355D, N355H, N355S, N355Y, R356L Q357E, I359F, I359L, I359N, I359S, I359V, P362A, P362H, P362R, P362S, R363G, R363L, R363S, S364C, S364P, Y365D, Y365F, Y365N, Y365S, T366I, T366N, T366P, T366S, I367F, I367L, I367M, A368G, A368P, V369A, V369F, V369G, V369I, V369L, A370D, A370G, A370P, A370T, A370V, S371C, S371T, G373A G373C, K374E, K374I, K374R, K374T, G375R, V376E, V376G, V376L, V376M, A377G, A377P, A377S, A377T, N379D, N379I, N379K, N379T, P380A, P380H, P380R, P380T, A381D, F383C, F383I, F383Y, I384F, I384M, I384T, T385I, Q386H, Q386K, Q386L, L387F, L387H, L387I, L387R, L388F, L388H, L388I, L388R L388V, K391I, K391N, K391Q, K391R, R392G, R392K, R392M, R392W, K393E, K393N, K393Q, K393T, L394I, L394Q, L394R, G395R, F396C, F396I, F396L, F396V, Y397C, Y397F, Y397H, Y397N, Y397S, E398G, E398Q, W399G, W399R, T400A, T400I, T400N, T400P, T400S, S401A, S401L, S401T, R402G, R402M, R402S R402T, R402W, L403F, L403V, ​​R404G, R404I, R404K, R404S, R404T, S405G, H406D, H406L, H406Q, I407L, I407M, I407T, N408D, N408H, N408T, P409L,T410S, G411A, G411C, G411V, T412A, T412I, T412S, V413F, V413G, V413I, L414F, L414V, L415H, L415I, Q416E, Q416H, Q416L, L417I, E418A, E418D, E418K, E418Q, N419I, N419S, N419T, N419Y, T420K, T420P, T420R, T420S, M421I, M421K, M421L, M421R, M421T, Q422P, M423I, M423K, M423L, M423T, S424L, L425F, D427N and L429R. These mutations are also shown in Table 2 with their corresponding nucleotide changes.

[0092] Accordingly, in one or more forms, migalastate is used to treat Fabry disease and / or enhance the Petition 870260032676, dated 08 / 04 / 2026, p. 82 / 370 72 / 305 α-Gal A activity in a patient having an α-Gal A mutation selected from the group consisting of the mutations presented in Table 2. In several modalities, these α-Gal A mutations are relative to the amino acid sequence shown in SEQ ID NO: 2.

[0093] Exemplary nucleotide changes associated with these new mutations are shown in Table 2 below: Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) c.13A>G c.A13G N5D p.(Asn5Asp) c.15C>G c.C15G N5K p.(Asn5Lys) c.17C>T c.C17T P6L p.(Pro6Leu) c.17C>A c.C17A P6Q p.(Pro6Gln) c.17C>G c.C17G P6R p.(Pro6Arg) c.16C>T c.C16T P6S p.(Pro6Ser) c.16C>A c.C16A P6T p.(Pro6Thr) c.21A>T c.A21T E7D p.(Glu7Asp) c.19G>A c.G19A E7K p.(Glu7Lys) c.20A>T c.A20T E7V p.(Glu7Val) c.22C>A c.C22A L8I p.(Leu8Ile) c.23T>C c.T23C L8P p.(Leu8Pro) c.23T>A c.T23A L8Q p.(Leu8Gln) c.26A>T c.A26T H9L p.(His9Leu) c.27T>A c.T27A H9Q p.(His9Gln) c.26A>G c.A26G H9R p.(His9Arg) c.25C>T c.C25T H9Y p.(His9Tyr) c.28C>A c.C28A L10M p.(Leu10Met) Petition 870260032676, dated 08 / 04 / 2026, p. 83 / 370 73 / 305 Table 2 Nucleotide change Nucleotide change Protein change (1 Letter) Protein change (3 Letters) c.29T>C c.T29C L10P p.(Leu10Pro) c.29T>A c.T29A L10Q p.(Leu10Gln) c. p.(Leu10Arg) c.28C>G c.C28G L10V p.(Leu10Val) c.31G>T c.G31T G11C p.(Gly11Cys) c.32G>A c.G32A G11D p.(Gly11Asp) c.31G>C c.C. c.31G>A c.G31A G11S p.(Gly11Ser) c.32G>T c.G32T G11V p.(Gly11Val) c.34T>G c.T34G C12G p.(Cys12Gly) c.34T>C c.T34C C12R p.Cys>Ag. c.T34A C12S p.(Cys12Ser) c.35G>A c.G35A C12Y p.(Cys12Tyr) c.38C>A c.C38A A13E p.(Ala13Glu) c.38C>G c.C38G A13G p.(Ala13Gly) c. p.(Leu14Phe) c.41T>A c.T41A L14H p.(Leu14His) c.40C>G c.C40G L14V p.(Leu14Val) c.49C>T c.C49T R17C p.(Arg17Cys) c.49C>Gly p. c.50G>A c.G50A R17H p.(Arg17His) c.50G>C c.G50C R17P p.(Arg17Pro) c.49C>A c.C49A R17S p.(Arg17Ser) c.52T>A c.T52A F18I p.(Arg18I) Petition 870260032676, of 08 / 04 / 2026, p. 84 / 370 74 / 305 Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) c.54C>G c.C54G F18L p.(Phe18Leu) c.59C>G c.C59G A20G p.(Ala20Gly) p.(Leu21His) c.65T>C c.T65C V22A p.(Val22Ala) c.64G>T c.G64T V22F p.(Val22Phe) c.64G>A c.G64A V22I p.(Val22Ile) c.64G>C c. c.67T>C c.T67C S23P p.(Ser23Pro) c.67T>A c.T67A S23T p.(Ser23Thr) c.71G>C c.G71C W24S p.(Trp24Ser) c.73G>C c.G73C D25H. C.T77A I26N p.(Ile26Asn) c.79C>G c.C79G P27A p.(Pro27Ala) c.80C>T c.C80T P27L p.(Pro27Leu) c.79C>T c.C79T P27S p.(Pro27Ser) c.A P27C>A p.(Pro27Thr) c.83G>A c.G83A G28E p.(Gly28Glu) c.82G>C c.G82C G28R p.(Gly28Arg) c.82G>T c.G82T G28W p.(Gly28Trp) c.86C>G c.G A.29G6 p.(Ala29Gly) c.85G>C c.G85C A29P p.(Ala29Pro) c.86C>T c.C86T A29V p.(Ala29Val) c.88A>G c.A88G R30G p.(Arg30Gly) c.94C>A c.C30G p.(Arg30Gly) Petition 870260032676, of 08 / 04 / 2026, p. 85 / 370 75 / 305 Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) L32V p.(Leu32Val) c.98A>C c.A98C D33A p.(Asp33Ala) c.99C>G c.C99G D33E p.(Asp33Glu) c.98A>T C.A98T D33V p.(Asp33Val) c. p.(Leu36Met) c.106T>G C.T106G L36V p.(Leu36Val) c.110C>A C.C110A A37E p.(Ala37Glu) c.110C>G C.C110G A37G p.(Ala37Gly) c. p.(Ala37Ser) c.112A>G C.A112G R38G p.(Arg38Gly) c.113G>T C.G113T R38M p.(Arg38Met) c.112A>T C.A112T R38W p.(Arg38Trp)c. p.(Thr39Ala) c.116C>A C.C116A T39K p.(Thr39Lys) c.116C>T C.C116T T39M p.(Thr39Met) c.116C>G C.C116G T39R p.(Thr3 c.Ag1515)T. T39S p.(Thr39Ser) c.121A>G C.A121G T41A p.(Thr41Ala) c.122C>A C.C122A T41N p.(Thr41Asn) c.121A>T C.A121T T41S c. C.G128C G43A p.(Gly43Ala) c.133C>A C.C133A L45M p.(Leu45Met) Petition 870260032676, dated 08 / 04 / 2026, page 86 / 370 76 / 305 Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) c.133C>G C.C133G L45V p.(Leu45Val) c.136C>G C.C136G H46D p.(His>A46A) C.C136A H46N p.(His46Asn) c.138C>G C.C138G H46Q p.(His46Gln) c.143A>C C.A143C E48A p.(Glu48Ala) c.149T>A C.T149A p.YT149A c. C.T152G M51R p.(Met51Arg) c.152T>C c.T152C M51T p.(Met51Thr) c.151A>G C.A151G M51V p.(Met51Val) c.157A>C C.A157C N53H p.His>His. C.A158T N53I p.(Asn53Ile) c.158A>G C.A158G N53S p.(Asn53Ser) c.158A>C C.A158C N53T p.(Asn53Thr) c.161T>A C.T161A p.(Asn53H) c.161T>G C.T161G L54R p.(Leu54Arg) c.160C>G C.C160G L54V p.(Leu54Val) c.164A>C C.A164C D55A p.(Asp55Ala) c.165C>G C.C165E p.Asp55Glu. c.163G>C C.G163C D55H p.(Asp55His) c.163G>T C.G163T D55Y p.(Asp55Tyr) c.168C>G C.C168G C56W p.(Cys56Trp) c.172G>A C.G72A p.Glu. c.176A>C C.A176C E59A p.(Glu59Ala) c.177G>C C.G177C E59D p.(Glu59Asp) Petition 870260032676, dated 08 / 04 / 2026, page 87 / 370 77 / 305 Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) c.176A>G C.A176G E59G p.(Glu59Gly) c.175G>C C.G175C E59Q p.(Glu59G) c. C.A176T E59V p.(Glu59Val) c.178C>G C.C178G P60A p.(Pro60Ala) c.179C>A C.C179A P60Q p.(Pro60Gln) c.179C>G C.C179G P60R p60R83Ag. C.T183A D61E p.(Asp61Glu) c.182A>T C.A182T D61V p.(Asp61Val) c.184T>G C.T184G S62A p.(Ser62Ala) c.185C>G C.C185G S62C p.C. C.C185T S62F p.(Ser62Phe) c.184T>C C.T184C S62P p.(Ser62Pro) c.185C>A C.C185A S62Y p.(Ser62Tyr) c.190A>C C.A190C I64L p.(Ser62Phe) c. C.A190G I64V p.(Ile64Val) c.193A>T C.A193T S65C p.(Ser65Cys) c.193A>G C.A193G S65G p.(Ser65Gly) c.195T>A C.T195A S65R p.(Ser65Cy>Cerg>Cerg. C.G198C E66D p.(Glu66Asp) c.197A>T C.A197T E66V p.(Glu66Val) c.199A>G C.A199G K67E p.(Lys67Glu) c.200A>T C.A200T K67M p.(Glu66Asp) c.C. C.G201C K67N p.(Lys67Asn) c.199A>C C.A199C K67Q p.(Lys67Gln) Petition 870260032676, dated 08 / 04 / 2026, page 88 / 370 78 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.200A>C C.A200C K67T p.(Lys67Thr) c.202C>A C.C202A L68I p.(Leu68Ile) c.205T>A C.T205A F69I p.(Phe69Ile) c.206T>A C.T206A F69Y p.(Phe69Tyr) c.210G>C C.G210C M70I p.(Met70Ile) c.209T>A C.T209A M70K p.(Met70Lys) c.208A>T C.A208T M70L p.(Met70Leu) c.209T>G C.T209G M70R p.(Met70Arg) c.212A>C C.A212C E71A p.(Glu71Ala) c.213G>C C.G213C E71D p.(Glu71Asp) c.212A>G C.A212G E71G p.(Glu71Gly) c.211G>C C.G211C E71Q p.(Glu71Gln) c.212A>T C.A212T E71V p.(Glu71Val) c.214A>T C.A214T M72L p.(Met72Leu) c.215T>C C.T215C M72T p.(Met72Thr) c.217G>T C.G217T A73S p.(Ala73Ser) c.217G>A C.G217A A73T p.(Ala73Thr) c.222G>C C.G222C E74D p.(Glu74Asp) c.221A>G C.A221G E74G p.(Glu74Gly) c.220G>A C.G220A E74K p.(Glu74Lys) c.221A>T C.A221T E74V p.(Glu74Val) c.223C>T C.C223T L75F p.(Leu75Phe) c.224T>C C.T224C L75P p.(Leu75Pro) c.226A>G C.A226G M76V p.(Met76Val) Petition 870260032676, dated 08 / 04 / 2026, page 89 / 370 79 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.229G>A C.G229A V77I p.(Val77Ile) c.229G>C C.G229C V77L p.(Val77Leu) c.233C>T C.C233T S78L p.(Ser78Leu) c.232T>C C.T232C S78P p.(Ser78Pro) c.236A>C C.A236C E79A p.(Glu79Ala) c.237A>T C.A237T E79D p.(Glu79Asp) c.236A>G C.A236G E79G p.(Glu79Gly) c.235G>A C.G235A E79K p.(Glu79Lys) c.235G>C C.G235C E79Q p.(Glu79Gln) c.236A>T C.A236T E79V p.(Glu79Val) c.239G>C C.G239C G80A p.(Gly80Ala) c.238G>T C.G238T G80C p.(Gly80Cys) c.238G>A C.G238A G80S p.(Gly80Ser) c.242G>T C.G242T W81L p.(Trp81Leu) c.244A>G C.A244G K82E p.(Lys82Glu) c.245A>T C.A245T K82M p.(Lys82Met) c.246G>C C.G246C K82N p.(Lys82Asn) c.245A>G C.A245G K82R p.(Lys82Arg) c.245A>C C.A245C K82T p.(Lys82Thr) c.248A>C C.A248C D83A p.(Asp83Ala) c.249T>A C.T249A D83E p.(Asp83Glu) c.248A>G C.A248G D83G p.(Asp83Gly) c.248A>T C.A248T D83V p.(Asp83Val) c.251C>A C.C251A A84E p.(Ala84Glu) Petition 870260032676, dated 08 / 04 / 2026, page 90 / 370 80 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.251C>G C.C251G A84G p.(Ala84Gly) c.250G>C C.G250C A84P p.(Ala84Pro) c.250G>T C.G250T A84S p.(Ala84Ser) c.250G>A C.G250A A84T p.(Ala84Thr) c.251C>T C.C251T A84V p.(Ala84Val) c.254G>C C.G254C G85A p.(Gly85Ala) c.253G>T C.G253T G85C p.(Gly85Cys) c.253G>C C.G253C G85R p.(Gly85Arg) c.257A>T C.A257T Y86F p.(Tyr86Phe) c.260A>G C.A260G E87G p.(Glu87Gly) c.262T>C C.T262C Y88H p.(Tyr88His) c.262T>A C.T262A Y88N p.(Tyr88Asn) c.265C>G C.C265G L89V p.(Leu89Val) c.271A>T C.A271T I91F p.(Ile91Phe) c.271A>C C.A271C I91L p.(Ile91Leu) c.273T>G C.T273G I91M p.(Ile91Met) c.272T>G C.T272G I91S p.(Ile91Ser) c.286A>T C.A286T M96L p.(Met96Leu) c.287T>C C.T287C M96T p.(Met96Thr) c.290C>A C.C290A A97D p.(Ala97Asp) c.289G>T C.G289T A97S p.(Ala97Ser) c.289G>A C.G289A A97T p.(Ala97Thr) c.293C>A C.C293A P98H p.(Pro98His) c.293C>T C.C293T P98L p.(Pro98Leu) Petition 870260032676, dated 08 / 04 / 2026, page 91 / 370 81 / 305 Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) c.293C>G C.C293G P98R p.(Pro98Arg) c.295C>G C.C295G Q99E p.(Gl>n>T. C.A296T Q99L p.(Gln99Leu) c.296A>C C.A296C Q99P p.(Gln99Pro) c.296A>G C.A296G Q99R p.(Gln99Arg) c.302A>C C.A302C p.Alasp1011 c.303T>A C.T303A D101E p.(Asp101Glu) c.302A>G C.A302G D101G p.(Asp101Gly) c.301G>C C.G301C D101H p.(Asp101His) c.302A>T C.A302T D. p.(Asp101Val) c.304T>G C.T304G S102A p.(Ser102Ala) c.304T>C C.T304C S102P p.(Ser102Pro) c.304T>A C.T304A S102T p.(Ser1020) c.31G>C. C.G311C G104A p.(Gly104Ala) c.311G>A C.G311A G104D p.(Gly104Asp) c.310G>A C.G310A G104S p.(Gly104Ser). c.314G>T C.G314T R105I p.(Arg105Ile) c.314G>A C.G314A R105K p.(Arg105Lys) c.314G>C C.G314C R105T p.(Arg105Thr) c.3T>A L p.(Leu106His) c.316C>A C.C316A L106I p.(Leu106Ile) c.317T>C C.T317C L106P p.(Leu106Pro) c.316C>G C.C316G L106V p.(Leu106V) Petition 870260032676, dated 08 / 04 / 2026, page 92 / 370 82 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.319C>G C.C319G Q107E p.(Gln107Glu) c.321G>C C.G321C Q107H p.(Gln107His) c.319C>A C.C319A Q107K p.(Gln107Lys) c.323C>A C.C323A A108E p.(Ala108Glu) c.323C>T c.C323T A108V p.(Ala108Val) c.326A>C C.A326C D109A p.(Asp109Ala) c.327C>G c.C327G D109E p.(Asp109Glu) c.325G>C c.G325C D109H p.(Asp109His) c.325G>A C.G325A D109N p.(Asp109Asn) c.325G>T C.G325T D109Y p.(Asp109Tyr) c.328C>A C.C328A P110T p.(Pro110Thr) c.337T>G C.T337G F113V p.(Phe113Val) c.338T>A C.T338A F113Y p.(Phe113Tyr) c.341C>T C.C341T P114L p.(Pro114Leu) c.343C>G C.C343G H115D p.(His115Asp) c.343C>A C.C343A H115N p.(His115Asn) c.346G>C C.G346C G116R p.(Gly116Arg) c.351T>G C.T351G I117M p.(Ile117Met) c.350T>C C.T350C I117T p.(Ile117Thr) c.362C>T C.C362T A121V p.(Ala121Val) c.367T>G C.T367G Y123D p.(Tyr123Asp) c.368A>T C.A368T Y123F p.(Tyr123Phe) c.367T>A C.T367A Y123N p.(Tyr123Asn) c.368A>C C.A368C Y123S p.(Tyr123Ser) Petition 870260032676, dated 08 / 04 / 2026, page 93 / 370 83 / 305 Table 2 Nucleotide change Nucleotide change Protein change (1 Letter) Protein Change (3 Letters) c.370G>A C.G370A V124I p.(Val124Ile) c.373C>G C.C373G H125D p. C.C373A H125N p.(His125Asn) c.374A>G C.A374G H125R p.(His125Arg) c.376A>T C.A376T S126C p.(Ser126Cys) c.377G>T C.G377S p.(His125Asn) c.379A>G C.A379G K127E p.(Lys127Glu) c.383G>C C.G383C G128A p.(Gly128Ala) c.385C>G C.C385G L129V p.(Leu129Val) c.389A>T C.389M K. p.(Lys130Met) c.390G>C C.G390C K130N p.(Lys130Asn) c.388A>C C.A388C K130Q p.(Lys130Gln) c.391C>G C.C391G L131V p.(Leu1313A>C. C.A397C I133L p.(Ile133Leu) c.398T>C C.T398C I133T p.(Ile133Thr) c.397A>G C.A397G I133V p.(Ile133Val) c.404C>A C.C404A p.Glu. c.404C>G C.C404G A135G p.(Ala135Gly) c.403G>T C.G403T A135S p.(Ala135Ser) c.403G>A C.G403A A135T p.(Ala135Thr) c.4 C0A>A136D. p.(Asp136Ala) c.406G>A C.G406A D136N p.(Asp136Asn) c.407A>T C.A407T D136B p.(Asp136Val) c.410T>C C.T410C V137A p.(Asp136Ala) Petition 870260032676, dated 08 / 04 / 2026, page 94 / 370 84 / 305 Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) c.410T>A C.T410A V137D p.(Val137Asp) c.410T>G C.T410G V137G p. C.G409A V137I p.(Val137Ile) c.409G>C C.G409C V137L p.(Val137Leu) c.413G>C C.G413C G138A p.(Gly138Ala) c.415A>C C.A415C N c.416A>T C.A416T N139I p.(Asn139Ile) c.417T>A C.T417A N139K p.(Asn139Lys) c.415A>T C.A415T N139Y p.(Asn139Tyr) c. p.(Lys140Glu) c.419A>T C.A419T K140I p.(Lys140Ile) c.420A>T C.A420T K140N p.(Lys140Asn) c.418A>C C.A418C K140Q p.(Lys140Gn)c. C.A419G K140R p.(Lys140Arg) c.421A>T C.A421T T141S p.(Thr141Ser) c.428C>A C.C428A A143E p.(Ala143Glu) c.428C>G C.C. c.431G>C C.G431C G144A p.(Gly144Ala) c.430G>T C.G430T G144C p.(Gly144Cys) c.430G>C C.G430C G144R p.(Gly144Arg) c.430G>A G144A G144A p.(Gly144Ser) c.434T>G C.T434G F145C p.(Phe145Cys) c.435C>G C.C435G F145L p.(Phe145Leu) c.433T>G C.T433G F145V p.(Val) Petition 870260032676, dated 08 / 04 / 2026, page 95 / 370 85 / 305 Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) c.434T>A C.T434A F145Y p.(Phe145Tyr) c.436C>G C.C436G P146A p146A p. C.C437A P146H p.(Pro146His) c.437C>T C.C437T P146L p.(Pro146Leu) c.436C>A C.C436A P146T p.(Pro146Thr). c.442A>T C.A442T S148C p.(Ser148Cys) c.442A>G C.A442G S148G p.(Ser148Gly) c.443G>C C.G443C S148T p.(Ser148Thr) c.4 C46T>G FT146G. p.(Phe149Cys) c.449G>A C.G449A G150E p.(Gly150Glu) c.449G>T C.G449T G150V p.(Gly150Val) c.452A>G C.A452G Y151C p.(Tyr151G>151G. C.T451G Y151D p.(Tyr151Asp) c.452A>C C.A452C Y151S p.(Tyr151Ser) c.455A>T C.A455T Y152F p.(Tyr152Phe) c.455A>C C.A455C p.(Tyr151Ser) c.458A>C C.A458C D153A p.(Asp153Ala) c.457G>C C.G457C D153H p.(Asp153His) c.457G>A C.G457A D153N p.(Asp153Asn) c.4 T C5A>T D1538 D. p.(Asp153Val) c.457G>T C.G457T D153Y p.(Asp153Tyr) c.467C>G C.C467G A156G p.(Ala156Gly) c.469C>G C.C469G Q157E p.(Glun15) Petition 870260032676, dated 08 / 04 / 2026, page 96 / 370 86 / 305 Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) c.469C>A C.C469A Q157K p.(Gln157Lys) c.470A>T C.A470T Q157L p. c.470A>C C.A470C Q157P p.(Gln157Pro) c.472A>G C.A472G T158A p.(Thr158Ala) c.473C>T C.C473T T158I p.(Thr158Ile) c. p.(Thr158Asn) c.472A>T C.A472T T158S p.(Thr158Ser) c.475T>A C.T475A F159I p.(Phe159Ile) c.477T>A C.T477A F159L p. C.T475G F159V p.(Phe159Val) c.476T>A C.T476A F159Y p.(Phe159Tyr) c.479C>G C.C479G A160G p.(Ala160Gly) c.478G>T C.G478T p.AS. c.478G>A C.G478A A160T p.(Ala160Thr) c.479C>T C.C479T A160V p.(Ala160Val) c.481G>C C.G481C D161H p.(Asp161His) c. p.(Asp161Asn) c.482A>T C.A482T D161V p.(Asp161Val) c.481G>T C.G481T D161Y p.(Asp161Tyr) c.485G>C C.G485C W162S p.(Trp>14T)c. C.T491C V164A p.(Val164Ala) c.490G>A C.G490A V164I p.(Val164Ile) c.490G>C C.G490C V164L p.(Val164Leu) c.494A>C C.A494A p.A. Petition 870260032676, dated 08 / 04 / 2026, page 97 / 370 87 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.495T>A c.T495A D165E p.(Asp165Glu) c.496C>A c.C496A L166M p.(Leu166Met) c.497T>A c.T497A L166Q p.(Leu166Gln) c.499C>A c.C499A L167I p.(Leu167Ile) c.506T>G c.T506G F169C p.(Phe169Cys) c.507T>A c.T507A F169L p.(Phe169Leu) c.505T>G c.T505G F169V p.(Phe169Val) c.506T>A c.T506A F169Y p.(Phe169Tyr) c.512G>C c.G512C G171A p.(Gly171Ala) c.512G>T c.G512T G171V p.(Gly171Val) c.518A>G c.A518G Y173C p.(Tyr173Cys) c.518A>T c.A518T Y173F p.(Tyr173Phe) c.517T>C c.T517C Y173H p.(Tyr173His) c.518A>C c.A518C Y173S p.(Tyr173Ser) c.524A>G c.A524G D175G p.(Asp175Gly) c.523G>C c.G523C D175H p.(Asp175His) c.524A>T c.A524T D175V p.(Asp175Val) c.523G>T c.G523T D175Y p.(Asp175Tyr) c.526A>T c.A526T S176C p.(Ser176Cys) c.528T>A ou c.528T>G c.T528A ou c.T528G S176R p.(Ser176Arg) c.531G>C c.G531C L177F p.(Leu177Phe) c.529T>A c.T529A L177M p.(Leu177Met) c.530T>C c.T530C L177S p.(Leu177Ser) Petition 870260032676, dated 08 / 04 / 2026, page 98 / 370 88 / 305 Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) c.529T>G C.T529G L177V p.(Leu177Val) c.530T>G C.T530G L177W p. C.A533C E178A p.(Glu178Ala) c.533A>G C.A533G E178G p.(Glu178Gly) c.532G>A C.G532A E178K p.(Glu178Lys) c.532G>C C.G532C p.Glu178Gl. c.538T>A C.T538A L180M p.(Leu180Met) c.539T>C C.T539C L180S p.(Leu180Ser) c.541G>C C.G541C A181P p.(Ala181Pro) c.541G>A C.G51A p.(Ala181Thr) c.542C>T C.C542T A181V p.(Ala181Val) c.545A>C C.A545C D182A p.(Asp182Ala) c.546T>A C.T546A D182E p.(Asp2A>15A) c. C.A545T D182V p.(Asp182Val) c.544G>T C.G544T D182Y p.(Asp182Tyr) c.551A>T C.A551T Y184F p.(Tyr184Phe) c.550T>C C.T550T182Y p.His. c.551A>C C.A551C Y184S p.(Tyr184Ser) c.554A>T C.A554T K185M p.(Lys185Met) c.555G>C C.G555C K185N p.(Lys185Asn) c.5A>C5A>C185QK. p.(Lys185Gln) c.554A>C C.A554C K185T p.(Lys185Thr) c.556C>G C.C556G H186D p.(His186Asp) c.557A>T C.A557T H186L p.66(Leu) Petition 870260032676, dated 08 / 04 / 2026, page 99 / 370 89 / 305 Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) c.556C>A C.C556A H186N p.(His186Asn) c.558C>G C.C558G H186Q p.(His186Gln) c.556C>T C.C556T H186Y p.(His186Tyr) c.559A>T C.A559T M187L p.(Met187Leu) c.562T>G C.T562G S188A p.(Ser188Ala) c.563C>G C.C563G S188C p.(Ser188Cys) c.563C>T C.C563T S188F p.(Ser188Phe) c.562T>C C.T562C S188P p.(Ser188Pro) c.562T>A C.T562A S188T p.(Ser188Thr) c.563C>A C.C563A S188Y p.(Ser188Tyr) c.566T>C C.T566C L189S p.(Leu189Ser) c.565T>G C.T565G L189V p.(Leu189Val) c.569C>A C.C569A A190D p.(Ala190Asp) c.569C>G C.C569G A190G p.(Ala190Gly) c.568G>T C.G568T A190S p.(Ala190Ser) c.568G>A C.G568A A190T p.(Ala190Thr) c.569C>T C.C569T A190V p.(Ala190Val) c.571C>A C.C571A L191M p.(Leu191Met) c.571C>G C.C571G L191V p.(Leu191Val) c.574A>G C.A574G N192D p.(Asn192Asp) c.574A>C C.A574C N192H p.(Asn192His) c.576T>A C.T576A N192K p.(Asn192Lys) c.575A>G C.A575G N192S p.(Asn192Ser) c.575A>C C.A575C N192T p.(Asn192Thr) Petition 870260032676, dated 08 / 04 / 2026, page 100 / 370 90 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.577A>G C.A577G R193G p.(Arg193Gly) c.578G>T C.G578T R193M p.(Arg193Met) c.578G>C C.G578C R193T p.(Arg193Thr) c.577A>T C.A577T R193W p.(Arg193Trp) c.581C>A C.C581A T194N p.(Thr194Asn) c.580A>C C.A580C T194P p.(Thr194Pro) c.580A>T C.A580T T194S p.(Thr194Ser) c.583G>T C.G583T G195C p.(Gly195Cys) c.583G>C C.G583C G195R p.(Gly195Arg) c.583G>A C.G583A G195S p.(Gly195Ser) c.587G>T C.G587T R196I p.(Arg196Ile) c.587G>A C.G587A R196K p.(Arg196Lys) c.589A>T C.A589T S197C p.(Ser197Cys) c.589A>G C.A589G S197G p.(Ser197Gly) c.590G>T C.G590T S197I p.(Ser197Ile) c.590G>A C.G590A S197N p.(Ser197Asn) c.590G>C C.G590C S197T p.(Ser197Thr) c.594T>G C.T594G I198M p.(Ile198Met) c.593T>G C.T593G I198S p.(Ile198Ser) c.596T>A C.T596A V199E p.(Val199Glu) c.595G>C C.G595C V199L p.(Val199Leu) c.598T>A C.T598A Y200N p.(Tyr200Asn) c.599A>C C.A599C Y200S p.(Tyr200Ser) c.601T>G C.T601G S201A p.(Ser201Ala) Petition 870260032676, dated 08 / 04 / 2026, page 101 / 370 91 / 305 Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) c.602C>G C.C602G S201C p.(Ser201Cys) c.601T>A C.T601A S201T p. C.A608C E203A p.(Glu203Ala) c.608A>G C.A608G E203G p.(Glu203Gly) c.607G>C C.G607C E203Q p.(Glu203Gln) c.611G>C C.G61C. c.616C>T C.C616T L206F p.(Leu206Phe) c.617T>A C.T617A L206H p.(Leu206His) c.616C>A C.C616A L206G p.(Leu206Ile) c.6 C17T>R206G L2067G p.(Leu206Arg) c.616C>G C.C616G L206V p.(Leu206Val) c.620A>T C.A620T Y207F p.(Tyr207Phe) c.623T>G C.T623G M208K p.(Met)2027G>C. C.G627C W209C p.(Trp209Cys) c.625T>G C.T625G W209G p.(Trp209Gly) c.629C>A C.C629A P210H p.(Pro210His) c.628C>A C.C628A p.Pro210T(Trp209Gly) p. c.632T>G C.T632G F211C p.(Phe211Cys) c.633T>A C.T633A F211L p.(Phe211Leu) c.632T>C C.T632C F211S p.(Phe211Ser) c.631T>G F211VG F211V p.(Phe211Val) c.632T>A C.T632A F211Y p.(Phe211Tyr) c.636A>T C.A636T Q212H p.(Gln212His) c.635A>C C.A635C Q212P p.(2Gln211) Petition 870260032676, dated 08 / 04 / 2026, page 102 / 370 92 / 305 Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) c.637A>G C.A637G K213E p.(Lys213Glu) c.637A>C C.A637C K213Q p. C.C640G P214A p.(Pro214Ala) c.641C>A C.C641A P214H p.(Pro214His) c.641C>G C.C641G P214R p.(Pro214Arg) c.640C>A C.C640A P214T p214T. c.643A>C C.A643C N215H p.(Asn215His) c.645T>A C.T645A N215K p.(Asn215Lys) c.644A>C C.A644C N215T p.(Asn215Thr) c. p.(Asn215Tyr) c.647A>T C.A647T Y216F p.(Tyr216Phe) c.646T>C C.T646C Y216H p.(Tyr216His) c.646T>A C.T646A Y216N p.(Asn216G)c. C.A649G T217A p.(Thr217Ala) c.650C>T C.C650T T217I p.(Thr217Ile) c.650C>A C.C650A T217K p.(Thr217Lys) c.649A>C C.A69PC T217 p.(Thr217Pro) c.650C>G C.C650G T217R p.(Thr217Arg) c.649A>T C.A649T T217S p.(Thr217Ser) c.653A>C C.A653C E218A c. C.A654T E218D p.(Glu218Asp) c.653A>G C.A653G E218G p.(Glu218Gly) c.652G>A C.G652A E218K p.(Glu218Lys) c.652G>C C.G652C E218Gl. Petition 870260032676, dated 08 / 04 / 2026, page 103 / 370 93 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.653A>T C.A653T E218V p.(Glu218Val) c.655A>T C.A655T I219F p.(Ile219Phe) c.657C>G C.C657G I219M p.(Ile219Met) c.656T>G C.T656G I219S p.(Ile219Ser) c.659G>T C.G659T R220L p.(Arg220Leu) c.661C>G C.C661G Q221E p.(Gln221Glu) c.663G>C C.G663C Q221H p.(Gln221His) c.661C>A C.C661A Q221K p.(Gln221Lys) c.662A>T C.A662T Q221L p.(Gln221Leu) c.662A>G C.A662G Q221R p.(Gln221Arg) c.665A>G C.A665G Y222C p.(Tyr222Cys) c.664T>G C.T664G Y222D p.(Tyr222Asp) c.664T>C C.T664C Y222H p.(Tyr222His) c.664T>A C.T664A Y222N p.(Tyr222Asn) c.665A>C C.A665C Y222S p.(Tyr222Ser) c.670A>C C.A670C N224H p.(Asn224His) c.679C>G C.C679G R227G p.(Arg227Gly) c.682A>C C.A682C N228H p.(Asn228His) c.683A>T C.A683T N228I p.(Asn228Ile) c.683A>C C.A683C N228T p.(Asn228Thr) c.685T>A C.T685A F229I p.(Phe229Ile) c.686T>C C.T686C F229S p.(Phe229Ser) c.686T>A C.T686A F229Y p.(Phe229Tyr) c.689C>A C.C689A A230D p.(Ala230Asp) Petition 870260032676, dated 08 / 04 / 2026, page 104 / 370 94 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.689C>G C.C689G A230G p.(Ala230Gly) c.688G>C C.G688C A230P p.(Ala230Pro) c.689C>T C.C689T A230V p.(Ala230Val) c.694A>C C.A694C I232L p.(Ile232Leu) c.696T>G C.T696G I232M p.(Ile232Met) c.694A>G C.A694G I232V p.(Ile232Val) c.698A>C C.A698C D233A p.(Asp233Ala) c.699T>A C.T699A D233E p.(Asp233Glu) c.698A>G C.A698G D233G p.(Asp233Gly) c.698A>T C.A698T D233V p.(Asp233Val) c.703T>G C.T703G S235A p.(Ser235Ala) c.703T>A C.T703A S235T p.(Ser235Thr) c.710A>T C.A710T K237I p.(Lys237Ile) c.712A>T C.A712T S238C p.(Ser238Cys) c.713G>T C.G713T S238I p.(Ser238Ile) c.713G>C C.G713C S238T p.(Ser238Thr) c.715A>T C.A715T I239L p.(Ile239Leu) c.718A>G C.A718G K240E p.(Lys240Glu) c.719A>T C.A719T K240M p.(Lys240Met) c.719A>G C.A719G K240R p.(Lys240Arg) c.721A>T C.A721T S241C p.(Ser241Cys) c.722G>T C.G722T S241I p.(Ser241Ile) c.722G>C C.G722C S241T p.(Ser241Thr) c.724A>C C.A724C I242L p.(Ile242Leu) Petition 870260032676, dated 08 / 04 / 2026, page 105 / 370 95 / 305 Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) c.726C>G C.C726G I242M p.(Ile242Met) c.725T>G C.T725G I242S p. C.T727A L243M p.(Leu243Met) c.728T>C C.T728C L243S p.(Leu243Ser) c.727T>G C.T727G L243V p.(Leu243Val) c.731A>C C.A731A. c.732C>G C.C732G D244E p.(Asp244Glu) c.731A>G C.A731G D244G p.(Asp244Gly) c.731A>T C.A731T D244V p.(Asp244Val) c.730G>T D244YD. p.(Asp244Tyr) c.735G>C C.G735C W245C p.(Trp245Cys) c.736A>G C.A736G T246A p.(Thr246Ala) c.737C>T C.C737T T246I p.6(Thr27C)c. C.C737A T246K p.(Thr246Lys) c.737C>G C.C737G T246R p.(Thr246Arg) c.739T>G C.T739G S247A p.(Ser247Ala) c.740C>T C.C740S p.(Thr246Lys) c.739T>A C.T739A S247T p.(Ser247Thr) c.740C>A C.C740A S247Y p.(Ser247Tyr) c.743T>G C.T743G F248C p.(Phe248Cys) c.7 C4T>A F244L. p.(Phe248Leu) c.742T>G C.T742G F248V p.(Phe248Val) c.743T>A C.T743A F248Y p.(Phe248Tyr) c.745A>G C.A745G N249D p.(Aspn24) Petition 870260032676, dated 08 / 04 / 2026, page 106 / 370 96 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.745A>C C.A745C N249H p.(Asn249His) c.746A>T C.A746T N249I p.(Asn249Ile) c.746A>G C.A746G N249S p.(Asn249Ser) c.746A>C C.A746C N249T p.(Asn249Thr) c.745A>T C.A745T N249Y p.(Asn249Tyr) c.748C>G C.C748G Q250E p.(Gln250Glu) c.749A>T C.A749T Q250L p.(Gln250Leu) c.752A>G C.A752G E251G p.(Glu251Gly) c.751G>A C.G751A E251K p.(Glu251Lys) c.751G>C C.G751C E251Q p.(Glu251Gln) c.752A>T C.A752T E251V p.(Glu251Val) c.754A>G C.A754G R252G p.(Arg252Gly) c.757A>T C.A757T I253F p.(Ile253Phe) c.758T>A C.T758A I253N p.(Ile253Asn) c.757A>G C.A757G I253V p.(Ile253Val) c.761T>C C.T761C V254A p.(Val254Ala) c.761T>A C.T761A V254D p.(Val254Asp) c.760G>T C.G760T V254F p.(Val254Phe) c.761T>G C.T761G V254G p.(Val254Gly) c.764A>C C.A764C D255A p.(Asp255Ala) c.765T>A C.T765A D255E p.(Asp255Glu) c.763G>C C.G763C D255H p.(Asp255His) c.763G>A C.G763A D255N p.(Asp255Asn) c.764A>T C.A764T D255V p.(Asp255Val) Petition 870260032676, dated 08 / 04 / 2026, page 107 / 370 97 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.763G>T C.G763T D255Y p.(Asp255Tyr) c.767T>A C.T767A V256D p.(Val256Asp) c.767T>G C.T767G V256G p.(Val256Gly) c.766G>C C.G766C V256L p.(Val256Leu) c.769G>T C.G769T A257S p.(Ala257Ser) c.773G>A C.G773A G258E p.(Gly258Glu) c.775C>G C.C775G P259A p.(Pro259Ala) c.775C>A C.C775A P259T p.(Pro259Thr) c.778G>T C.G778T G260W p.(Gly260Trp) c.782G>C C.G782C G261A p.(Gly261Ala) c.787A>C C.A787C N263H p.(Asn263His) c.788A>C C.A788C N263T p.(Asn263Thr) c.790G>C C.G790C D264H p.(Asp264His) c.790G>A C.G790A D264N p.(Asp264Asn) c.793C>G C.C793G P265A p.(Pro265Ala) c.794C>A C.C794A P265Q p.(Pro265Gln) c.799A>T C.A799T M267L p.(Met267Leu) c.799A>G C.A799G M267V p.(Met267Val) c.804A>T C.A804T L268F p.(Leu268Phe) c.802T>A C.T802A L268I p.(Leu268Ile) c.805G>C C.G805C V269L p.(Val269Leu) c.808A>C C.A808C I270L p.(Ile270Leu) c.809T>G C.T809G I270S p.(Ile270Ser) c.808A>G C.A808G I270V p.(Ile270Val) Petition 870260032676, dated 08 / 04 / 2026, page 108 / 370 98 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.814A>G C.A814G N272D p.(Asn272Asp) c.818T>A C.T818A F273Y p.(Phe273Tyr) c.823C>A C.C823A L275I p.(Leu275Ile) c.830G>T C.G830T W277L p.(Trp277Leu) c.833A>T C.A833T N278I p.(Asn278Ile) c.839A>T C.A839T Q280L p.(Gln280Leu) c.839A>G C.A839G Q280R p.(Gln280Arg) c.842T>C C.T842C V281A p.(Val281Ala) c.842T>A C.T842A V281E p.(Val281Glu) c.842T>G C.T842G V281G p.(Val281Gly) c.841G>C C.G841C V281L p.(Val281Leu) c.844A>T C.A844T T282S p.(Thr282Ser) c.847C>G C.C847G Q283E p.(Gln283Glu) c.849G>C C.G849C Q283H p.(Gln283His) c.848A>T C.A848T Q283L p.(Gln283Leu) c.852G>C C.G852C M284I p.(Met284Ile) c.850A>T C.A850T M284L p.(Met284Leu) c.854C>G C.C854G A285G p.(Ala285Gly) c.853G>A C.G853A A285T p.(Ala285Thr) c.854C>T C.C854T A285V p.(Ala285Val) c.856C>T C.C856T L286F p.(Leu286Phe) c.857T>A C.T857A L286H p.(Leu286His) c.856C>G C.C856G L286V p.(Leu286Val) c.863C>G C.C863G A288G p.(Ala288Gly) Petition 870260032676, dated 08 / 04 / 2026, page 109 / 370 99 / 305 Table 2 Nucleotide change Nucleotide change Protein change (1 Letter) Protein change (3 Letters) c.862G>T C.G862T A288S p.(Ala288Ser) c.863C>T C.C863T A288V p. C.A865C I289L p.(Ile289Leu) c.866T>C c.T866C I289T p.(Ile289Thr) c.865A>G C.A865G I289V p.(Ile289Val) c.872C>G C.C872G. c.875C>G C.C875G A292G p.(Ala292Gly) c.874G>T C.G874T A292S p.(Ala292Ser) c.882A>T C.A882T L294F p.(Leu294Phe) c.8 C80T>A L294I L294I p.(Leu294Ile) c.880T>G C.T880G L294V p.(Leu294Val) c.883T>A C.T883A F295I p.(Phe295Ile) c.884T>C C.T884C F295S p.(Phe295G) c. C.T883G F295V p.(Phe295Val) c.884T>A C.T884A F295Y p.(Phe295Tyr) c.889T>A C.T889A S297T p.(Ser297Thr) c.892A>G C.Asp. c.893A>T C.A893T N298I p.(Asn298Ile) c.893A>C C.A893C N298T p.(Asn298Thr) c.895G>C C.G895C D299H p.(Asp299His). p.(Asp299Asn) c.898C>A C.C898A L300I p.(Leu300Ile) c.898C>G C.C898G L300V p.(Leu300Val) c.904C>G C.C904G H302D p.(His302) Petition 870260032676, dated 08 / 04 / 2026, page 110 / 370 100 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.905A>T C.A905T H302L p.(His302Leu) c.904C>A C.C904A H302N p.(His302Asn) c.904C>T c.C904T H302Y p.(His302Tyr) c.908T>G C.T908G I303S p.(Ile303Ser) c.911G>T C.G911T S304I p.(Ser304Ile) c.916C>G C.C916G Q306E p.(Gln306Glu) c.917A>T C.A917T Q306L p.(Gln306Leu) c.917A>C C.A917C Q306P p.(Gln306Pro) c.920C>A C.C920A A307D p.(Ala307Asp) c.920C>G C.C920G A307G p.(Ala307Gly) c.919G>C C.G919C A307P p.(Ala307Pro) c.919G>T C.G919T A307S p.(Ala307Ser) c.920C>T C.C920T A307V p.(Ala307Val) c.923A>T C.A923T K308I p.(Lys308Ile) c.922A>C C.A922C K308Q p.(Lys308Gln) c.923A>G C.A923G K308R p.(Lys308Arg) c.926C>A C.C926A A309D p.(Ala309Asp) c.925G>A C.G925A A309T p.(Ala309Thr) c.928C>A C.C928A L310I p.(Leu310Ile) c.931C>A C.C931A L311I p.(Leu311Ile) c.934C>G C.C934G Q312E p.(Gln312Glu) c.934C>A C.C934A Q312K p.(Gln312Lys) c.935A>T C.A935T Q312L p.(Gln312Leu) c.939T>A C.T939A D313E p.(Asp313Glu) Petition 870260032676, dated 08 / 04 / 2026, page 111 / 370 101 / 305 Table 2 Nucleotide mutation Nucleotide mutation Protein mutation (1 Letra) Protein mutation (3 Letras) c.938A>T C.A938T D313V p.(Asp313Val) c.940A>G C.A940G K314E p.(Lys314Glu) c.941A>T C.A941T K314M p.(Lys314Met) c.942G>C C.G942C K314N p.(Lys314Asn) c.941A>C C.A941C K314T p.(Lys314Thr) c.944A>C C.A944C D315A p.(Asp315Ala) c.944A>G C.A944G D315G p.(Asp315Gly) c.943G>C C.G943C D315H p.(Asp315His) c.943G>A C.G943A D315N p.(Asp315Asn) c.944A>T C.A944T D315V p.(Asp315Val) c.943G>T C.G943T D315Y p.(Asp315Tyr) c.947T>C C.T947C V316A p.(Val316Ala) c.946G>C C.G946C V316L p.(Val316Leu) c.949A>C C.A949C I317L p.(Ile317Leu) c.951T>G C.T951G I317M p.(Ile317Met) c.949A>G C.A949G I317V p.(Ile317Val) c.953C>A C.C953A A318D p.(Ala318Asp) c.952G>C C.G952C A318P p.(Ala318Pro) c.952G>A C.G952A A318T p.(Ala318Thr) c.953C>T C.C953T A318V p.(Ala318Val) c.957C>G C.C957G I319M p.(Ile319Met) c.959A>G C.A959G N320S p.(Asn320Ser) c.959A>C C.A959C N320T p.(Asn320Thr) c.961C>A C.C961A Q321K p.(Gln321Lys) Petition 870260032676, dated 08 / 04 / 2026, page 112 / 370 102 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.965A>C C.A965C D322A p.(Asp322Ala) c.965A>T C.A965T D322V p.(Asp322Val) c.970T>G C.T970G L324V p.(Leu324Val) c.971T>G C.T971G L324W p.(Leu324Trp) c.974G>C C.G974C G325A p.(Gly325Ala) c.973G>T C.G973T G325C p.(Gly325Cys) c.974G>T C.G974T G325V p.(Gly325Val) c.976A>G C.A976G K326E p.(Lys326Glu) c.977A>T C.A977T K326M p.(Lys326Met) c.976A>C C.A976C K326Q p.(Lys326Gln) c.977A>G C.A977G K326R p.(Lys326Arg) c.977A>C C.A977C K326T p.(Lys326Thr) c.981A>T C.A981T Q327H p.(Gln327His) c.980A>C C.A980C Q327P p.(Gln327Pro) c.986A>G C.A986G Y329C p.(Tyr329Cys) c.985T>G C.T985G Y329D p.(Tyr329Asp) c.986A>T C.A986T Y329F p.(Tyr329Phe) c.985T>C C.T985C Y329H p.(Tyr329His) c.985T>A C.T985A Y329N p.(Tyr329Asn) c.988C>G C.C988G Q330E p.(Gln330Glu) c.990G>C C.G990C Q330H p.(Gln330His) c.988C>A C.C988A Q330K p.(Gln330Lys) c.992T>A C.T992A L331H p.(Leu331His) c.992T>C C.T992C L331P p.(Leu331Pro) Petition 870260032676, dated 08 / 04 / 2026, page 113 / 370 103 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.992T>G C.T992G L331R p.(Leu331Arg) c.991C>G C.C991G L331V p.(Leu331Val) c.994A>G C.A994G R332G p.(Arg332Gly) c.995G>T C.G995T R332I p.(Arg332Ile) c.996A>T C.A996T R332S p.(Arg332Ser) c.995G>C C.G995C R332T p.(Arg332Thr) c.997C>G C.C997G Q333E p.(Gln333Glu) c.998A>T C.A998T Q333L p.(Gln333Leu) c.998A>C C.A998C Q333P p.(Gln333Pro) c.1000G>C C.G1000C G334R p.(Gly334Arg) c.1001G>T C.G1001T G334V p.(Gly334Val) c.1004A>C C.A1004C D335A p.(Asp335Ala) c.1005C>G C.C1005G D335E p.(Asp335Glu) c.1004A>G C.A1004G D335G p.(Asp335Gly) c.1004A>T C.A1004T D335V p.(Asp335Val) c.1003G>T C.G1003T D335Y p.(Asp335Tyr) c.1006A>G C.A1006G N336D p.(Asn336Asp) c.1007A>T C.A1007T N336I p.(Asn336Ile) c.1007A>G C.A1007G N336S p.(Asn336Ser) c.1007A>C C.A1007C N336T p.(Asn336Thr) c.1006A>T C.A1006T N336Y p.(Asn336Tyr) c.1010T>G C.T1010G F337C p.(Phe337Cys) c.1011T>A C.T1011A F337L p.(Phe337Leu) c.1009T>G C.T1009G F337V p.(Phe337Val). Petition 870260032676, dated 08 / 04 / 2026, page 114 / 370 104 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.1010T>A C.T1010A F337Y p.(Phe337Tyr) c.1013A>C C.A1013C E338A p.(Glu338Ala) c.1014A>T C.A1014T E338D p.(Glu338Asp) c.1013A>G C.A1013G E338G p.(Glu338Gly) c.1015G>A C.G1015A V339M p.(Val339Met) c.1022A>C C.A1022C E341A p.(Glu341Ala) c.1021G>C C.G1021C E341Q p.(Glu341Gln) c.1027C>G C.C1027G P343A p.(Pro343Ala) c.1027C>T C.C1027T P343S p.(Pro343Ser) c.1030C>T C.C1030T L344F p.(Leu344Phe) c.1031T>G C.T1031G L344R p.(Leu344Arg) c.1030C>G C.C1030G L344V p.(Leu344Val) c.1037G>C C.G1037C G346A p.(Gly346Ala) c.1036G>T C.G1036T G346C p.(Gly346Cys) c.1037G>A C.G1037A G346D p.(Gly346Asp) c.1037G>T C.G1037T G346V p.(Gly346Val) c.1039T>A C.T1039A L347I p.(Leu347Ile) c.1043C>A C.C1043A A348D p.(Ala348Asp) c.1047G>C C.G1047C W349C p.(Trp349Cys) c.1046G>T C.G1046T W349L p.(Trp349Leu) c.1049C>G C.C1049G A350G p.(Ala350Gly) c.1048G>T C.G1048T A350S p.(Ala350Ser) c.1048G>A C.G1048A A350T p.(Ala350Thr) c.1049C>T C.C1049T A350V p.(Ala350Val). Petition 870260032676, dated 08 / 04 / 2026, p. 115 / 370 105 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.1052T>C C.T1052C V351A p.(Val351Ala) c.1052T>A C.T1052A V351E p.(Val351Glu) c.1054G>T C.G1054T A352S p.(Ala352Ser) c.1054G>A C.G1054A A352T p.(Ala352Thr) c.1058T>A C.T1058A M353K p.(Met353Lys) c.1057A>T C.A1057T M353L p.(Met353Leu) c.1058T>C C.T1058C M353T p.(Met353Thr) c.1061T>G C.T1061G I354R p.(Ile354Arg) c.1063A>G C.A1063G N355D p.(Asn355Asp) c.1063A>C C.A1063C N355H p.(Asn355His) c.1064A>G C.A1064G N355S p.(Asn355Ser) c.1063A>T C.A1063T N355Y p.(Asn355Tyr) c.1067G>T C.G1067T R356L p.(Arg356Leu) c.1069C>G C.C1069G Q357E p.(Gln357Glu) c.1075A>T C.A1075T I359F p.(Ile359Phe) c.1075A>C C.A1075C I359L p.(Ile359Leu) c.1076T>A C.T1076A I359N p.(Ile359Asn) c.1076T>G C.T1076G I359S p.(Ile359Ser) c.1075A>G C.A1075G I359V p.(Ile359Val) c.1084C>G C.C1084G P362A p.(Pro362Ala) c.1085C>A C.C1085A P362H p.(Pro362His) c.1085C>G C.C1085G P362R p.(Pro362Arg) c.1084C>T C.C1084T P362S p.(Pro362Ser) c.1087C>G C.C1087G R363G p.(Arg363Gly). Petition 870260032676, dated 08 / 04 / 2026, page 116 / 370 106 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.1088G>T c.G1088T R363L p.(Arg363Leu) c.1087C>A c.C1087A R363S p.(Arg363Ser) c.1091C>G c.C1091G S364C p.(Ser364Cys) c.1090T>C c.T1090C S364P p.(Ser364Pro) c.1093T>G c.T1093G Y365D p.(Tyr365Asp) c.1094A>T c.A1094T Y365F p.(Tyr365Phe) c.1093T>A c.T1093A Y365N p.(Tyr365Asn) c.1094A>C c.A1094C Y365S p.(Tyr365Ser) c.1097C>T c.C1097T T366I p.(Thr366Ile) c.1097C>A c.C1097A T366N p.(Thr366Asn) c.1096A>C c.A1096C T366P p.(Thr366Pro) c.1096A>T c.A1096T T366S p.(Thr366Ser) c.1099A>T c.A1099T I367F p.(Ile367Phe) c.1099A>C c.A1099C I367L p.(Ile367Leu) c.1101C>G c.C1101G I367M p.(Ile367Met) c.1103C>G c.C1103G A368G p.(Ala368Gly) c.1102G>C c.G1102C A368P p.(Ala368Pro) c.1106T>C c.T1106C V369A p.(Val369Ala) c.1105G>T c.G1105T V369F p.(Val369Phe) c.1106T>G c.T1106G V369G p.(Val369Gly) c.1105G>A c.G1105A V369I p.(Val369Ile) c.1105G>C c.G1105C V369L p.(Val369Leu) c.1109C>A c.C1109A A370D p.(Ala370Asp) c.1109C>G c.C1109G A370G p.(Ala370Gly). Petition 870260032676, dated 08 / 04 / 2026, p. 117 / 370 107 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.1108G>C c.G1108C A370P p.(Ala370Pro) c.1108G>A c.G1108A A370T p.(Ala370Thr) c.1109C>T c.C1109T A370V p.(Ala370Val) c.1112C>G c.C1112G S371C p.(Ser371Cys) c.1111T>A c.T1111A S371T p.(Ser371Thr) c.1118G>C c.G1118C G373A p.(Gly373Ala) c.1117G>T c.G1117T G373C p.(Gly373Cys) c.1120A>G c.A1120G K374E p.(Lys374Glu) c.1121A>T c.A1121T K374I p.(Lys374Ile) c.1121A>G c.A1121G K374R p.(Lys374Arg) c.1121A>C c.A1121C K374T p.(Lys374Thr) c.1123G>C c.G1123C G375R p.(Gly375Arg) c.1127T>A c.T1127A V376E p.(Val376Glu) c.1127T>G c.T1127G V376G p.(Val376Gly) c.1126G>C c.G1126C V376L p.(Val376Leu) c.1126G>A c.G1126A V376M p.(Val376Met) c.1130C>G c.C1130G A377G p.(Ala377Gly) c.1129G>C c.G1129C A377P p.(Ala377Pro) c.1129G>T c.G1129T A377S p.(Ala377Ser) c.1129G>A c.G1129A A377T p.(Ala377Thr) c.1135A>G c.A1135G N379D p.(Asn379Asp) c.1136A>T c.A1136T N379I p.(Asn379Ile) c.1137T>A c.T1137A N379K p.(Asn379Lys) c.1136A>C c.A1136C N379T p.(Asn379Thr). Petition 870260032676, dated 08 / 04 / 2026, p. 118 / 370 108 / 305 Table 2 Nucleotide change Nucleotide change Protein change (1 letter) Protein change (3 letters) c.1138C>G c.C1138G P380A p.(Pro380Ala) c.1139C>A c.C1139A p380H(H. c.1139C>G c.C1139G P380R p.(Pro380Arg) c.1138C>A c.C1138A P380T p.(Pro380Thr) c.1142C>A c.C1142A A381D p.(Ala381Asp) c. F383C p.(Phe383Cys) c.1147T>A c.T1147A F383I p.(Phe383Ile) c.1148T>A c.T1148A F383Y p.(Phe383Tyr) c.1150A>T c.A1150F IP483I(Phe383I) c.1152C>G c.C1152G I384M p.(Ile384Met) c.1151T>C c.T1151C I384T p.(Ile384Thr) c.1154C>T c.C1154T T385I p.(Thr38Ile) c.G>1518G>C. Q386H p.(Gln386His) c.1156C>A c.C1156A Q386K p.(Gln386Lys) c.1157A>T c.A1157T Q386L p.(Gln386Leu) c.1159C>T c.T c.1160T>A c.T1160A L387H p.(Leu387His) c.1159C>A c.C1159A L387I p.(Leu387Ile) c.1160T>G c.T1160G L387R p.(Leu387Arg)c. L388F p.(Leu388Phe) c.1163T>A c.T1163A L388H p.(Leu388His) c.1162C>A c.C1162A L388I p.(Leu388Ile) c.1163T>G c.T1163R L383G p.(Leu388Arg) c.1162C>G c.C1162G L388V p.(Leu388Val). Petition 870260032676, dated 08 / 04 / 2026, p. 119 / 370 109 / 305 Table 2 Nucleotide mutation Nucleotide mutation Protein mutation (1 Letra) Protein mutation (3 Letras) c.1172A>T c.A1172T K391I p.(Lys391Ile) c.1173A>T c.A1173T K391N p.(Lys391Asn) c.1171A>C c.A1171C K391Q p.(Lys391Gln) c.1172A>G c.A1172G K391R p.(Lys391Arg) c.1174A>G c.A1174G R392G p.(Arg392Gly) c.1175G>A c.G1175A R392K p.(Arg392Lys) c.1175G>T c.G1175T R392M p.(Arg392Met) c.1174A>T c.A1174T R392W p.(Arg392Trp) c.1177A>G c.A1177G K393E p.(Lys393Glu) c.1179G>C c.G1179C K393N p.(Lys393Asn) c.1177A>C c.A1177C K393Q p.(Lys393Gln) c.1178A>C c.A1178C K393T p.(Lys393Thr) c.1180C>A c.C1180A L394I p.(Leu394Ile) c.1181T>A c.T1181A L394Q p.(Leu394Gln) c.1181T>G c.T1181G L394R p.(Leu394Arg) c.1183G>C c.G1183C G395R p.(Gly395Arg) c.1187T>G c.T1187G F396C p.(Phe396Cys) c.1186T>A c.T1186A F396I p.(Phe396Ile) c.1188C>G c.C1188G F396L p.(Phe396Leu) c.1186T>G c.T1186G F396V p.(Phe396Val) c.1190A>G c.A1190G Y397C p.(Tyr397Cys) c.1190A>T c.A1190T Y397F p.(Tyr397Phe) c.1189T>C c.T1189C Y397H p.(Tyr397His) c.1189T>A c.T1189A Y397N p.(Tyr397Asn). Petition 870260032676, dated 08 / 04 / 2026, pp. 120 / 370 110 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.1190A>C c.A1190C Y397S p.(Tyr397Ser) c.1193A>G C.A1193G E398G p.(Glu398Gly) c.1192G>C c.G1192C E398Q p.(Glu398Gln) c.1195T>G c.T1195G W399G p.(Trp399Gly) c.1195T>A c.T1195A W399R p.(Trp399Arg) c.1198A>G c.A1198G T400A p.(Thr400Ala) c.1199C>T c.C1199T T400I p.(Thr400Ile) c.1199C>A c.C1199A T400N p.(Thr400Asn) c.1198A>C c.A1198C T400P p.(Thr400Pro) c.1198A>T c.A1198T T400S p.(Thr400Ser) c.1201T>G c.T1201G S401A p.(Ser401Ala) c.1202C>T c.C1202T S401L p.(Ser401Leu) c.1201T>A c.T1201A S401T p.(Ser401Thr) c.1204A>G c.A1204G R402G p.(Arg402Gly) c.1205G>T c.G1205T R402M p.(Arg402Met) c.1206G>C c.G1206C R402S p.(Arg402Ser) c.1205G>C c.G1205C R402T p.(Arg402Thr) c.1204A>T c.A1204T R402W p.(Arg402Trp) c.1209A>T c.A1209T L403F p.(Leu403Phe) c.1207T>G c.T1207G L403V p.(Leu403Val) c.1210A>G c.A1210G R404G p.(Arg404Gly) c.1211G>T c.G1211T R404I p.(Arg404Ile) c.1211G>A c.G1211A R404K p.(Arg404Lys) c.1212A>T c.A1212T R404S p.(Arg404Ser). Petition 870260032676, dated 08 / 04 / 2026, page 121 / 370 111 / 305 Table 2 Mudança de nucleotídeos Mudança de nucleotídeos Mudança de proteína (1 Letra) Mudança de Proteína (3 Letras) c.1211G>C c.G1211C R404T p.(Arg404Thr) c.1213A>G c.A1213G S405G p.(Ser405Gly) c.1216C>G c.C1216G H406D p.(His406Asp) c.1217A>T c.A1217T H406L p.(His406Leu) c.1218C>G c.C1218G H406Q p.(His406Gln) c.1219A>T c.A1219T I407L p.(Ile407Leu) c.1221A>G c.A1221G I407M p.(Ile407Met) c.1220T>C c.T1220C I407T p.(Ile407Thr) c.1222A>G c.A1222G N408D p.(Asn408Asp) c.1222A>C c.A1222C N408H p.(Asn408His) c.1223A>C c.A1223C N408T p.(Asn408Thr) c.1226C>T c.C1226T P409L p.(Pro409Leu) c.1228A>T c.A1228T T410S p.(Thr410Ser) c.1232G>C c.G1232C G411A p.(Gly411Ala) c.1231G>T c.G1231T G411C p.(Gly411Cys) c.1232G>T c.G1232T G411V p.(Gly411Val) c.1234A>G c.A1234G T412A p.(Thr412Ala) c.1235C>T c.C1235T T412I p.(Thr412Ile) c.1234A>T c.A1234T T412S p.(Thr412Ser) c.1237G>T c.G1237T V413F p.(Val413Phe) c.1238T>G c.T1238G V413G p.(Val413Gly) c.1237G>A c.G1237A V413I p.(Val413Ile) c.1242G>C c.G1242C L414F p.(Leu414Phe) c.1240T>G c.T1240G L414V p.(Leu414Val). Petition 870260032676, dated 08 / 04 / 2026, page 122 / 370 112 / 305 Table 2 Nucleotide change Nucleotide change Protein change (1 letter) Protein change (3 letters) c.1244T>A C.T1244A L415H p.(Leu415His) c.1243C>A C.C1243A p.Ileu4151 c.1246C>G C.C1246G Q416E p.(Gln416Glu) c.1248G>C C.G1248C Q416H p.(Gln416His) c.1247A>T C.A1247T Q416L p.(Gln416Le)c>129Cu. C.C1249A L417I p.(Leu417Ile) c.1253A>C C.A1253C E418A p.(Glu418Ala) c.1254A>T C.A1254T E418D p.(Glu418Asp) c.1252G>A C.Glu418K p.(Glu418Lys) c.1252G>C C.G1252C E418Q p.(Glu418Gln) c.1256A>T C.A1256T N419I p.(Asn419Ile) c.1256A>G C.A1256G N419Sc. c.1256A>C C.A1256C N419T p.(Asn419Thr) c.1255A>T C.A1255T N419Y p.(Asn419Tyr) c.1259C>A C.C1259A T420K p.(Thr444)c>25A>C. C.A1258C T420P p.(Thr420Pro) c.1259C>G C.C1259G T420R p.(Thr420Arg) c.1258A>T C.A1258T T420S p.(Thr420Ser) c.126 C320C>C321G13I. p.(Met421Ile) c.1262T>A C.T1262A M421K p.(Met421Lys) c.1261A>T C.A1261T M421L p.(Met421Leu) c.1262T>G C.T1262G M42R p.Met(Arg41) c.1262T>C C.T1262C M421T p.(Met421Thr) c.1265A>C C.A1265C Q422P p.(Gln422Pro). Petition 870260032676, dated 08 / 04 / 2026, p. 123 / 370 113 / 305 Table 2 Nucleotide Change Nucleotide Change Protein Change (1 Letter) Protein Change (3 Letters) c.1269G>C c.G1269C M423I p.(Met423Ile) c.1268T>A c.T1268A M423K p.(Met423Lys) c.1267A>T c.A1267T M423L p.(Met423Leu) c.1268T>C c.T1268C M423T p.(Met423Thr) c.1271C>T c.C1271T S424L p.(Ser424Leu) c.1275A>T c.A1275T L425F p.(Leu425Phe) c.1279G>A c.G1279A D427N p.(Asp427Asn) c.1286T>G c.T1286G L429R p.(Leu429Arg)

[0094] Accordingly, in several embodiments, migalastate is used to treat Fabry disease and / or enhance α-Gal A activity in a patient having a GLA mutation selected from the group consisting of the nucleotide changes presented in Table 2. In several embodiments, these α-Gal A mutations are relative to the nucleic sequence shown in SEQ ID NO: 3.

[0095] Additional susceptible prophetic mutations identified include V22G, A29D, D33H, N34H, G35A, R38S, N53K, N53Y, Q57R, F69L, G80V, Y88C, Y88S, M96V, Q107R, R112L, V124G, H125Y, I133M, I133F, A143V, Y152D, Y152N, D155E, A156S, Q157H, F159C, A160D, D165N, F169I, G171S, L180V, D182G, L189F, T194A, R196T, W204L, W204G, W209R, N215I, Y216S, I219L, N224T, N228D, S238G, I239M, K240N, Q250K, A257V, A257T, P259Q, P259S, G271A, L275V, S276T, N278Y, M290V, M290T, A291S, I303T, I303V, K308E, L310V, N320H, D322H, P323T, Q330P, F337S, E338V, V339A, P343T, E358Q, G360A, G360R, G375A, P380L, K391E, R392T, L394P, N408Y, G411S, T412P and N419D. Petition 870260032676, dated 08 / 04 / 2026, page 124 / 370 114 / 305 These mutations are also presented in Table 3 with their corresponding nucleotide changes.

[0096] Accordingly, in one or more embodiments, migalastate is used to treat Fabry disease and / or enhance α-Gal A activity in a patient having an α-Gal A mutation selected from the group consisting of the mutations presented in Table 3. In several embodiments, these α-Gal A mutations are relative to the amino acid sequence shown in SEQ ID NO: 2.

[0097] Exemplary nucleotide changes associated with these new mutations are shown in Table 3 below: Table 3 Nucleotide Change Protein Change (1 Letter) c.65T>G V22G c.86C>A A29D c.97G>C D33H c.100A>C N34H c.104G>C G35A c.114G>C R38S c.159C>G or c.159C>A N53K c.157A>T N53Y c.170A>G Q57R c.207C>A or c.207C>G F69L c.239G>T G80V c.263A>G Y88C c.263A>C Y88S c.286A>G M96V c.320A>G Q107R Petition 870260032676, dated 08 / 04 / 2026, p. 125 / 370 115 / 305 Table 3 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.335G>T R112L c.371T>G V124G c.373C>T H125Y c.399T>G I133M c.397A>T I133F c.428C>T A143V c.454T>G Y152D c.454T>A Y152N c.465T>A ou c.465T>G D155E c.466G>T A156S c.471G>C ou c.471G>T Q157H c.476T>G F159C c.479C>A A160D c.493G>A D165N c.505T>A F169I c.511G>A G171S c.538T>G L180V c.545A>G D182G c.567G>C ou c.567G>T L189F c.580A>G T194A c.587G>C R196T c.611G>T W204L c.610T>G W204G c.625T>A W209R c.644A>T N215I Petição 870260032676, de 08 / 04 / 2026, pág. 126 / 370 116 / 305 Tabela 3 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.647A>C Y216S c.655A>C I219L c.671A>C N224T c.682A>G N228D c.712A>G S238G c.717A>G I239M c.720G>C ou c.720G>T K240N c.748C>A Q250K c.770C>T A257V c.769G>A A257T c.776C>A P259Q c.775C>T P259S c.812G>C G271A c.823C>G L275V c.827G>C S276T c.832A>T N278Y c.868A>G M290V c.869T>C M290T c.871G>T A291S c.908T>C I303T c.907A>G I303V c.922A>G K308E c.928C>G L310V c.958A>C N320H c.964G>C D322H Petição 870260032676, de 08 / 04 / 2026, pág. 127 / 370 117 / 305 Tabela 3 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.967C>A P323T c.989A>C Q330P c.1010T>C F337S c.1013A>T E338V c.1016T>C V339A c.1027C>A P343T c.1072G>C E358Q c.1079G>C G360A c.1078G>C G360R c.1124G>C G375A c.1139C>T P380L c.1171A>G K391E c.1175G>C R392T c.1181T>C L394P c.1222A>T N408Y c.1231G>A G411S c.1234A>C T412P c.1255A>G N419D

[0098] Accordingly, in several embodiments, migalastate is used to treat Fabry disease and / or enhance α-Gal A activity in a patient having a GLA mutation selected from the group consisting of the nucleotide changes presented in Table 3. In several embodiments, these α-Gal A mutations are relative to the nucleic sequence shown in SEQ ID NO: 3.

[0099] Although the susceptible mutations presented in Table 2 and Table 3 were initially assessed as prophetic susceptible mutations Petition 870260032676, dated 08 / 04 / 2026, page 128 / 370 118 / 305 by the HEK assay, patients subsequently identified have since presented with several of these mutations. Accordingly, the mutations listed in Table 4 are now susceptible mutations associated with patients, thus confirming that the prognostic mutations described here can subsequently present in patients and that such patients can be treated with migalastat. Table 4 Nucleotide change Protein change (1 Letter) c.23T>A L8Q c.65T>G V22G c.86C>A A29D c.97G>C D33H c.100A>C N34H c.104G>C G35A c.114G>C c.G>C G35A c.114G>C c. c.159C>A N53K c.157A>T N53Y c.170A>G Q57R c.207C>A ou c.207C>G F69L c.239G>T G80V c.263A>G Y88C c.263A>C Y88S c.286A>G Q307R>G. c.335G>T R112L c.371T>G V124G c.373C>T H125Y Petition 870260032676, of 08 / 04 / 2026, p. 129 / 370 119 / 305 Table 4 Nucleotide change Protein change (1 Letter) c.399T>G I133M c.397A>T I133F c.428C>T A143V c.454T>G Y152D c.454T>A Y152N c.455A>C Y152S>A Y152N c.455A>C Y152S c. D155E c.466G>T A156S c.471G>C or c.471G>T Q157H c.476T>G F159C c.479C>A A160D c.493G>A D165N c.505T>A F169I c.5117G>A c.G188V> LG. c.545A>G D182G c.551A>C Y184S c.567G>C or c.567G>T L189F c.580A>G T194A c.587G>C R196T c.598T>A Y200N c.611G>T W204L c.G. c.625T>A W209R c.644A>T N215I Petition 870260032676, dated 08 / 04 / 2026, pp. 130 / 370 120 / 305 Table 4 Nucleotide Change Protein Change (1 Letter) c.647A>C Y216S c.655A>C I219L c.664T>G Y222D c.671A>C N224T c.682A>G N228D c.712A>G S238G c.717A>G I239M c.720G>C or c.720G>T K240N c.748C>A Q250K c.770C>T A257V c.769G>A A257T c.776C>A P259Q c.775C>T P259S c.812G>C G271A c.823C>G L275V c.827G>C S276T c.832A>T N278Y c.868A>G M290V c.869T>C M290T c.871G>T A291S c.908T>C I303T c.907A>G I303V c.922A>G K308E c.928C>G L310V c.958A>C N320H Petition 870260032676, dated 08 / 04 / 2026, pp. 131 / 370 121 / 305 Table 4 Nucleotide Change Protein Change (1 Letter) c.964G>C D322H c.967C>A P323T c.973G>T G325C c.989A>C Q330P c.1010T>C F337S c.1013A>T E338V c.1016T>C V339A c.1027C>A P343T c.1072G>C E358Q c.1079G>C G360A c.1078G>C G360R c.1093T>A Y365N c.1124G>C G375A c.1139C>T P380L c.1162C>T L388F c.1171A>G K391E c.1175G>C R392T c.1181T>C L394P c.1181T>G L394R c.1222A>T N408Y c.1231G>A G411S c.1234A>C T412P c.1255A>G N419D

[0100] In addition to the susceptible prognostic mutations identified above in Tables 2 and 3, several new mutations were Petition 870260032676, dated 08 / 04 / 2026, p. 132 / 370 122 / 305 identified and determined to be mutations that are not amenable to migalastat therapy.

[0101] As described above, those mutations that were not found to be susceptible to the HEK assay were labeled as non-susceptible protein mutations. When multiple different nucleotide changes within a single codon led to the same amino acid residue substitution at that position, the protein sequence change was listed as a single entry with alternative nucleotide changes.

[0102] The identified non-susceptible prophetic mutations include Q2E, Q2K, Q2L, Q2P, Q2R, Q2H, L3M, L3Q, L3R, R4G, R4W, R4K, R4T, R4M, R4S, N5I, N5Y, N5H, N5T, N5S, P6A, E7Q, E7A, E7G, L8R, L8V, H9D, H9P, H9N, G11A, C12F, C12W, A13S, A13V, L14R, L14I, A15V, A15S, L16R, L16I, L16F, R17L, F18V, F18Y, L19M, L19V, L19R, A20S, A20T, L21I, L21V, V22D, S23A, S23C, S23Y, S23F, W24L, D25G, D25Y, D25A, D25E, D25V, D25N, I26F, I26L, I26M, I26S, I26T, I26V, P27H, P27R, G28A, G28V, A29S, A29T, R30I, R30K, R30S, R30T, A31T, A31E, A31G, A31P, A31S, D33N, N34I, N34Y, R38K, R38T, T39P, P40T, T41P, G43C, W44G, W44L, W44R, W44S, L45Q, W47S, E48G, E48V, R49H, F50I, F50L, F50S, F50V, M51L, C52F, L54I, D55N, C56R, Q57E, Q57H, Q57K, Q57P, E58A, E58G, E58Q, E58D, E58V, D61A, D61G, D61H, D61N, D61Y, S62T, C63F, C63G, C63W, I64F, I64M, I64N, I64S, I64T, E66A, K67R, L68V, L68H, L68P, L68R, F69V, F69C, F69S, M70V, M70T, E71K, M72K, A73P, A73G, E74Q, E74A, L75V, L75H, L75I, L75R, M76K, M76L, M76I, V77F, V77A,V77G, V77D, S78T, S78A, G80R, W81G, K82Q, D83Y, D83H, G85V, Y86N, Y86S, E87K, E87A, E87V, E87Q, Y88F, L89I, C90F, C90G, C90S, I91V, I91N, D92A, D92E, D93A, D93H, C94R, C94W, W95R, M96K, M96R, A97G, P98A, P98S, P98T, Q99H, Q99K, R100G, R100I, R100S, D101N, D101Y, E103A, E103D, E103G, E103K, E103V, G104C, G104R, R105S, Q107P, A108G, A108P, Petition 870260032676, dated 08 / 04 / 2026, page 133 / 370 123 / 305 A108S, D109V, P110H, P110S, Q111E, Q111H, Q111R, Q111K, Q111L, Q111P, R112P, F113C, P114A, P114H, P114S, P114T, P114R, H115L, H115P, H115Q, H115R, H115Y, G116W, G116A, G116E, I117F, I117L, I117N, I117V, R118G, R118P, R118S, R118L, R118H, Q119E, Q119H, Q119K, Q119L, Q119P, L120I, L120Q, L120R, A121S, A121D, A121G, N122D, N122H, N122I, N122K, N122S, N122T, N122Y, Y123H, V124L, V124A, V124F, H125Q, S126T, S126R, S126N, K127Q, K127T, K127R, K127I, K127N, G128R, G128V, L129M, L129Q, L129R, K130E, K130T, L131Q, L131I, L131R, G132W, G132V, I133S, Y134N, Y134C, Y134F, A135P, D136G, V137F, G138V, N139D, T141P, T141A, C142S, C142G, C142F, A143S, F145I, G147W, G147V, S148I, F149I, F149V, F149Y, F149L, F149S, G150A, G150R, Y151H, Y151N, Y151F, D153E, D153G, I154F, I154L, I154M, I154N, I154S, I154T, I154V, D155A, D155G, D155N, D155V, D155Y, A156P, Q157R, T158P, F159S, A160P, D161A, D161E, D161G, G163A, G163E, G163R, V164E, L166P, L166R, L167R, K168Q, K168E, K168I, K168T, D170A, D170E, D170Y, Y173D, Y173N, C174F, C174S, C174W, C174Y, D175A, S176G, S176I, S176N, S176T, E178D, E178V, N179D, N179H, N179I, N179K, N179S, N179T, N179Y, A181S, A181E, A181G, D182N, D182H, Y184D, K185R, H186R, M187K, L189M, L189W, A190P, L191R, N192Y, N192I, R193K, R193S, G195A, G195D, S197R, I198F, I198L, I198N, I198V, Y200D, Y200F, Y200H, C202F, C202G, C202S, P205A, P205H, Y207D, Y207N, M208I, M208L, M208T, M208V, W209L, W209S, P210A, P210R, F211I, Q212E, Q212K, Q212L, Q212R, K213T, I219V, R220G, Y222F, C223S, C223F, C223W, N224K, N224Y, N224I, H225N, H225Y, H225P, H225L, H225Q, W226G, W226S, W226L, R227L, N228Y, N228K, F229V, F229C, A230S, D231H, D231Y, D231A, D231E, I232N, I232F, D233N, D233H, D233Y, D234N, D234H, D234A, D234G, S235P, W236G, W236S, K237E, K237N, K237Q, K237R, K237T, I239K, I239R, I239V, K240Q, K240T, S241G, S241N, S241R, W245R, W245S, Petition 870260032676, dated 08 / 04 / 2026, page 134 / 370 124 / 305 T246P, T246S, F248I, F248S, E251A, E251D, R252I, R252K, R252S, I253M, I253L, V254I, V254L, D255G, V256F, V256I, V256A, G258A, G260R, G260V, W262R, W262G, W262S, N263D, N263I, N263K, N263Y, D264E, D264G, P265T, D266G, M267K, L268V, V269G, I270F, I270N, G271R, N272H, N272Y, N272T, N272I, F273I, F273V, F273S, F273C, G274R, G274C, G274D, G274A, L275P, L275R, S276C, S276I, S276R, W277R, W277S, N278H, N278D, N278T, N278S, N278K, Q279L, Q279P, Q280E, Q280P, V281I, T282P, Q283K, M284R, M284K, A285S, L286I, L286R, L286P, W287S, A288T, I289N, I289M, M290R, M290K, A291D, A291V, A292D, P293R, F295L, M296R, M296K, S297P, S297Y, S297A, N298Y, D299A, D299V, D299Y, L300R, H302P, H302Q, H302R, I303L, I303M, S304G, S304C, S304R, P305A, P305H, P305L, P305R, P305S, P305T, Q306H, Q306K, Q306R, K308T, A309G, A309S, L310H, L310P, L311H, D313H, D313N, D313A, K314Q, K314R, D315E, A318G, A318S, I319S, I319L, I319V, I319N, N320D, Q321P, D322Y, D322G, P323A, P323H, P323L, P323S, L324M, L324F, L324S, Q327R, Y329S, Q330L, L331I, L331F, R332K, Q333H, Q333K, G334A, D335H, D335N, N336H, N336K, F337I, E338Q, V339L, W340G, W340L, W340S W340C, E341V, E341G, P343R, P343H, L344I, L344H, S345L, S345T, S345A, G346S, G346R, L347V, L347S, L347F, A348T, A348S, A348G, A348V, W349G, A350D, V351I, V351L, V351G, M353I, M353V, M353R, I354M, I354L, I354V, I354T, N355I, N355T, Q357L, Q357P, Q357H, Q357R, Q357K, E358V, I359M, G360V G361V, S364T, S364A, S364Y, S364F, Y365C, Y365H, T366A, I367V, I367N, I367T, I367S, A368S, A368E, A368V, V369D, A370S, S371A, S371F, S371P, S371Y, L372M, L372V, G373V, K374N, K374Q, G375V, V376A, A377V, C378F, C378G, C378W, N379H, N379S, N379Y, P380S, A381P A381S, A381T, A381G, A381V, C382F, C382G, C382S, F383L, F383S F383V, I384L, I384S, I384V, T385K, T385R, T385S, Q386E, Q386R, L387P, L387V, P389H, P389S, P389T, V390A, V390E, V390G, V390L, R392S, Petition 870260032676, dated 08 / 04 / 2026, page 135 / 370 125 / 305 K393M, K393R, L394V, G395V, G395W, F396S, Y397D, E398D, E398V, W399C, W399L, S401P, R402K, L403I, S405C, S405I, S405N, S405T, H406N, H406P, H406Y, N408I, N408K, N408S, P409H, P409R, T410R, G411R, V413A, V413D, V413L, L414M, L414W, L415R, L415V, Q416K, Q416R, L417Q, L417V, E418V, N419H, N419K, T420A, T420I, Q422E, Q422H, Q422K, Q422L, Q422R, M423R, M423V, S424A, S424P, S424T, L425I, L425S, L425V, K426E, K426Q, K426T, K426I, K426N, K426R, D427A, D427H, D427Y, D427E, D427G, D427V, L428F, L428S, L428I, L428V, L429I, L429V, L429F, L429H, and L429P. These mutations are also presented in Table 5 with their corresponding nucleotide changes.

[0103] Exemplary nucleotide changes associated with these new mutations are shown in Table 5 below: Table 5 Nucleotide Change Protein Change (1 Letter) c.4C>G Q2E c.4C>A Q2K c.5A>T Q2L c.5A>C Q2P c.5A>G Q2R c.6G>C Q2H c.7C>A L3M c.8T>A L3Q c.8T>G L3R c.10A>G R4G c.10A>T R4W c.11G>A R4K c.11G>C R4T c.11G>T R4M Petition 870260032676, dated 08 / 04 / 2026, pp. 136 / 370 126 / 305 Table 5 Nucleotide Change Protein Change (1 Letter) c.12G>C R4S c.14A>T N5I c.13A>T N5Y c.13A>C N5H c.14A>C N5T c.14A>G N5S c.16C>G P6A c.19G>C E7Q c.20A>C E7A c.20A>G E7G c.23T>G L8R c.22C>G L8V c.25C>G H9D c.26A>C H9P c.25C>A H9N c.32G>C G11A c.35G>T C12F c.36C>G C12W c.37G>T A13S c.38C>T A13V c.41T>G L14R c.40C>A L14I c.44C>T A15V c.43G>T A15S c.47T>G L16R Petition 870260032676, dated 08 / 04 / 2026, pp. 137 / 370 127 / 305 Table 5 Nucleotide change Protein change (1 Letter) c.46C>A L16I c.46C>T L16F c.50G>T R17L c.52T>G F18V c.53T>A F18Y c.55C>A L19M c.55C>G L15T>A L19M c.55C>G L19V c. A20S c.58G>A A20T c.61C>A L21I c.61C>G L21V c.65T>A V22D c.67T>G S23A c.68C>G S23C c.68C>A S23Y c.68C>T S23F c.71G>T c.24L W24G>A>G. c.73G>T D25Y c.74A>C D25A c.75C>G D25E c.74A>T D25V c.73G>A D25N c.76A>T I26F Petition 870260032676, of 08 / 04 / 2026, p. 138 / 370 128 / 305 Table 5 Nucleotide change Protein change (1 Letter) c.76A>C I26L c.78C>G I26M c.77T>G I26S c.77T>C I26T c.76A>G I26V c.80C>A P27H c.80C>G P27R c.27G>G>G. G28V c.85G>T A29S c.85G>A A29T c.89G>T R30I c.89G>A R30K c.90A>T R30S c.89G>C R30T c.91G>A A31T c.92C>A A31E c.92C>G A31G>A31G>A31G. c.91G>T A31S c.97G>A D33N c.101A>T N34I c.100A>T N34Y c.113G>A R38K c.113G>C R38T Petition 870260032676, of 08 / 04 / 2026, p. 139 / 370 129 / 305 Table 5 Nucleotide change Protein change (1 Letter) c.115A>C T39P c.118C>A P40T c.121A>C T41P c.127G>T G43C c.130T>G W44G c.131G>T W44L c.130T>A W44G>C. W44S c.134T>A L45Q c.140G>C W47S c.143A>G E48G c.143A>T E48V c.146G>A R49H c.148T>A F50I c.148T>C or c.150C>G or c.150C>A F150C>C. c.148T>G F50V c.151A>T M51L c.155G>T C52F c.160C>A L54I c.163G>A D55N c.166T>C C56R c.169C>G Q57E c.171G>C Q57H c.1A Q59K>K Petition 870260032676, of 08 / 04 / 2026, p. 140 / 370 130 / 305 Table 5 Nucleotide change Protein change (1 Letter) c.170A>C Q57P c.173A>C E58A c.173A>G E58G c.172G>C E58Q c.174A>T E58D c.173A>T E58V c.182A>T E58D c.173A>T E58V c.182A>C>G. D61G c.181G>C D61H c.181G>A D61N c.181G>T D61Y c.184T>A S62T c.188G>T C63F c.187T>G C63G c.189C>G C63W c.190A>T I64F c.194M>C. c.191T>A I64N c.191T>G I64S c.191T>C I64T c.197A>C E66A c.200A>G K67R c.202C>G L68V c.203T>A L68H c.203T>C L68P Petition 870260032676, dated 08 / 04 / 2026, page 141 / 370 131 / 305 Table 5 Nucleotide Change Protein Change (1 Letter) c.203T>G L68R c.205T>G F69V c.206T>G F69C c.206T>C F69S c.208A>G M70V c.209T>C M70T c.211G>A E71K c.215T>A M72K c.217G>C A73P c.218C>G A73G c.220G>C E74Q c.221A>C E74A c.223C>G L75V c.224T>A L75H c.223C>A L75I c.224T>G L75R c.227T>A M76K c.226A>T M76L c.228G>C or c.228G>A or c.228G>T M76I c.229G>T V77F c.230T>C V77A c.230T>G V77G c.230T>A V77D c.232T>A S78T c.232T>G S78A Petition 870260032676, dated 08 / 04 / 2026, page 142 / 370 132 / 305 Table 5 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.238G>C G80R c.241T>G W81G c.244A>C K82Q c.247G>T D83Y c.247G>C D83H c.254G>T G85V c.256T>A Y86N c.257A>C Y86S c.259G>A E87K c.260A>C E87A c.260A>T E87V c.259G>C E87Q c.263A>T Y88F c.265C>A L89I c.269G>T C90F c.268T>G C90G c.268T>A C90S c.271A>G I91V c.272T>A I91N c.275A>C D92A c.276T>A D92E c.278A>C D93A c.277G>C D93H c.280T>C C94R c.282T>G C94W Petição 870260032676, de 08 / 04 / 2026, pág. 143 / 370 133 / 305 Tabela 5 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.283T>A W95R c.287T>A M96K c.287T>G M96R c.290C>G A97G c.292C>G P98A c.292C>T P98S c.292C>A P98T c.297A>T Q99H c.295C>A Q99K c.298A>G R100G c.299G>T R100I c.300A>T R100S c.301G>A D101N c.301G>T D101Y c.308A>C E103A c.309A>T E103D c.308A>G E103G c.307G>A E103K c.308A>T E103V c.310G>T G104C c.310G>C G104R c.315A>T R105S c.320A>C Q107P c.323C>G A108G c.322G>C A108P Petição 870260032676, de 08 / 04 / 2026, pág. 144 / 370 134 / 305 Tabela 5 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.322G>T A108S c.326A>T D109V c.329C>A P110H c.328C>T P110S c.331C>G Q111E c.333G>C Q111H c.332A>G Q111R c.331C>A Q111K c.332A>T Q111L c.332A>C Q111P c.335G>C R112P c.338T>G F113C c.340C>G P114A c.341C>A P114H c.340C>T P114S c.340C>A P114T c.341C>G P114R c.344A>T H115L c.344A>C H115P c.345T>A H115Q c.344A>G H115R c.343C>T H115Y c.346G>T G116W c.347G>C G116A c.347G>A G116E Petição 870260032676, de 08 / 04 / 2026, pág. 145 / 370 135 / 305 Tabela 5 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.349A>T I117F c.349A>C I117L c.350T>A I117N c.349A>G I117V c.352C>G R118G c.353G>C R118P c.352C>A R118S c.353G>T R118L c.353G>A R118H c.355C>G Q119E c.357G>C Q119H c.355C>A Q119K c.356A>T Q119L c.356A>C Q119P c.358C>A L120I c.359T>A L120Q c.359T>G L120R c.361G>T A121S c.362C>A A121D c.362C>G A121G c.364A>G N122D c.364A>C N122H c.365A>T N122I c.366T>A N122K c.365A>G N122S Petição 870260032676, de 08 / 04 / 2026, pág. 146 / 370 136 / 305 Tabela 5 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.365A>C N122T c.364A>T N122Y c.367T>C Y123H c.370G>C V124L c.371T>C V124A c.370G>T V124F c.375C>G H125Q c.377G>C S126T c.378C>G S126R c.377G>A S126N c.379A>C K127Q c.380A>C K127T c.380A>G K127R c.380A>T K127I c.381A>T K127N c.382G>C G128R c.383G>T G128V c.385C>A L129M c.386T>A L129Q c.386T>G L129R c.388A>G K130E c.389A>C K130T c.392T>A L131Q c.391C>A L131I c.392T>G L131R Petition 870260032676, dated 08 / 04 / 2026, pp. 147 / 370 137 / 305 Table 5 Nucleotide Change Protein Change (1 Letter) c.394G>T G132W c.395G>T G132V c.398T>G I133S c.400T>A Y134N c.401A>G Y134C c.401A>T Y134F c.403G>C A135P c.407A>G D136G c.409G>T V137F c.413G>T G138V c.415A>G N139D c.421A>C T141P c.421A>G T141A c.424T>A C142S c.424T>G C142G c.425G>T C142F c.427G>T A143S c.433T>A F145I c.439G>T G147W c.440G>T G147V c.443G>T S148I c.445T>A F149I c.445T>G F149V c.446T>A F149Y c.447T>A F149L Petition 870260032676, dated 08 / 04 / 2026, pp. 148 / 370 138 / 305 Table 5 Nucleotide change Protein change (1 Letter) c.446T>C F149S c.449G>C G150A c.448G>C G150R c.451T>C Y151H c.451T>A Y151N c.452A>T Y151F c.G. c.458A>G D153G c.460A>T I154F c.460A>C I154L c.462T>G I154M c.461T>A I154N c.461T>G I154S c.461T>C I154T c.460A>G I154V>C D454A>C. c.464A>G D155G c.463G>A D155N c.464A>T D155V c.463G>T D155Y c.466G>C A156P c.470A>G Q157R c.472A>C T158P c.476T>C F159G>C c. Petition 870260032676, of 08 / 04 / 2026, p. 149 / 370 139 / 305 Table 5 Nucleotide change Protein change (1 Letter) c.482A>C D161A c.483C>G D161E c.482A>G D161G c.488G>C G163A c.488G>A G163E c.487G>C G163R>A V. c.497T>C L166P c.497T>G L166R c.500T>G L167R c.502A>C K168Q c.502A>G K168E c.503A>T K168I c.503A>C K168T c.509A>C D170A>A D1170E>A. c.508G>T D170Y c.517T>G Y173D c.517T>A Y173N c.521G>T C174F c.520T>A C174S c.522T>G C174W c.521G>A C174Y c.524A>C D175A>G c176A>G. Petition 870260032676, dated 08 / 04 / 2026, pp. 150 / 370 140 / 305 Table 5 Nucleotide Change Protein Change (1 Letter) c.527G>T S176I c.527G>A S176N c.527G>C S176T c.534A>T E178D c.533A>T E178V c.535A>G N179D c.535A>C N179H c.536A>T N179I c.537T>A N179K c.536A>G N179S c.536A>C N179T c.535A>T N179Y c.541G>T A181S c.542C>A A181E c.542C>G A181G c.544G>A D182N c.544G>C D182H c.550T>G Y184D c.554A>G K185R c.557A>G H186R c.560T>A M187K c.565T>A L189M c.566T>G L189W c.568G>C A190P c.572T>G L191R Petition 870260032676, dated 08 / 04 / 2026, pp. 151 / 370 141 / 305 Table 5 Nucleotide change Protein change (1 Letter) c.574A>T N192Y c.575A>T N192I c.578G>A R193K c.579G>C R193S c.584G>C G195A c.584G>A c.584G>C G195A c.584G>A c.574G>C G195A c.584G>A c. ou c.591C>A S197R c.592A>T I198F c.592A>C I198L c.593T>A I198N c.592A>G I198V c.598T>G Y200D c.599A>T Y200F c.598T> c.C.Y2020G>T Y602F. c.604T>G C202G c.604T>A C202S c.613C>G P205A c.614C>A P205H c.619T>G Y207D c.619T>A Y207N c.624G>C M208I c.622A>T M628L>T>C. c.622A>G M208V Petition 870260032676, of 08 / 04 / 2026, p. 152 / 370 142 / 305 Table 5 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.626G>T W209L c.626G>C W209S c.628C>G P210A c.629C>G P210R c.631T>A F211I c.634C>G Q212E c.634C>A Q212K c.635A>T Q212L c.635A>G Q212R c.638A>C K213T c.655A>G I219V c.658C>G R220G c.665A>T Y222F c.667T>A ou c.668G>C C223S c.668G>T C223F c.669C>G C223W c.672T>A N224K c.670A>T N224Y c.671A>T N224I c.673C>A H225N c.673C>T H225Y c.674A>C H225P c.674A>T H225L c.675C>G H225Q c.676T>G W226G Petição 870260032676, de 08 / 04 / 2026, pág. 153 / 370 143 / 305 Tabela 5 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.677G>C W226S c.677G>T W226L c.680G>T R227L c.682A>T N228Y c.684T>A N228K c.685T>G F229V c.686T>G F229C c.688G>T A230S c.691G>C D231H c.691G>T D231Y c.692A>C D231A c.693C>G D231E c.695T>A I232N c.694A>T I232F c.697G>A D233N c.697G>C D233H c.697G>T D233Y c.700G>A D234N c.700G>C D234H c.701A>C D234A c.701A>G D234G c.703T>C S235P c.706T>G W236G c.707G>C W236S c.709A>G K237E Petition 870260032676, dated 08 / 04 / 2026, page 154 / 370 144 / 305 Table 5 Nucleotide change Protein change (1 Letter) c.711A>T K237N c.709A>C K237Q c.710A>G K237R c.710A>C K237T c.716T>A I239K c.716T>G I239R c.715A>G I239V c.718A>C K240Q c.719A>C K240T c.721A>G S241G c.722G>A S241N c.723T>A S241R c.733T>A W245R c.734G>C W245S c.736A>C T246P c.736A>T T246S c.742T>A F248I c.743T>C F248S c.752A>C E251A c.753G>C E251D c.755G>T R252I c.755G>A R252K c.756A>T R252S c.759T>G I253M c.757A>C I253L Petition 870260032676, dated 08 / 04 / 2026, pp. 155 / 370 145 / 305 Table 5 Nucleotide mutation Protein mutation (1 Letra) c.760G>A V254I c.760G>C V254L c.764A>G D255G c.766G>T V256F c.766G>A V256I c.767T>C V256A c.773G>C G258A c.778G>C ou c.778G>A G260R ​​c.779G>T G260V c.784T>A ou c.784T>C W262R c.784T>G W262G c.785G>C W262S c.787A>G N263D c.788A>T N263I c.789T>A ou c.789T>G N263K c.787A>T N263Y c.792C>G D264E c.791A>G D264G c.793C>A P265T c.797A>G D266G c.800T>A M267K c.802T>G L268V c.806T>G V269G c.808A>T I270F c.809T>A I270N Petition 870260032676, dated 04 / 08 / 2026, pág. 156 / 370 146 / 305 Table 5 Nucleotide Change Protein Change (1 Letter) c.811G>C G271R c.814A>C N272H c.814A>T N272Y c.815A>C N272T c.815A>T N272I c.817T>A F273I c.817T>G F273V c.818T>C F273S c.818T>G F273C c.820G>C G274R c.820G>T G274C c.821G>A G274D c.821G>C G274A c.824T>C L275P c.824T>G L275R c.826A>T S276C c.827G>T S276I c.828C>A or c.828C>G S276R c.829T>A W277R c.830G>C W277S c.832A>C N278H c.832A>G N278D c.833A>C N278T c.833A>G N278S c.834T>G or c.834T>A N278K Petition 870260032676, dated 08 / 04 / 2026, pp. 157 / 370 147 / 305 Table 5 Nucleotide Change Protein Change (1 Letter) c.836A>T Q279L c.836A>C Q279P c.838C>G Q280E c.839A>C Q280P c.841G>A V281I c.844A>C T282P c.847C>A Q283K c.851T>G M284R c.851T>A M284K c.853G>T A285S c.856C>A L286I c.857T>G L286R c.857T>C L286P c.860G>C W287S c.862G>A A288T c.866T>A I289N c.867C>G I289M c.869T>G M290R c.869T>A M290K c.872C>A A291D c.872C>T A291V c.875C>A A292D c.878C>G P293R c.885C>G F295L c.887T>G M296R Petition 870260032676, dated 08 / 04 / 2026, pp. 158 / 370 148 / 305 Table 5 Nucleotide Change Protein Change (1 Letter) c.887T>A M296K c.889T>C S297P c.890C>A S297Y c.889T>G S297A c.892A>T N298Y c.896A>C D299A c.896A>T D299V c.895G>T D299Y c.899T>G L300R c.905A>C H302P c.906C>G H302Q c.905A>G H302R c.907A>C I303L c.909C>G I303M c.910A>G S304G c.910A>T S304C c.912C>G S304R c.913C>G P305A c.914C>A P305H c.914C>T P305L c.914C>G P305R c.913C>T P305S c.913C>A P305T c.918A>T Q306H c.916C>A Q306K Petition 870260032676, dated 08 / 04 / 2026, pp. 159 / 370 149 / 305 Table 5 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.917A>G Q306R c.923A>C K308T c.926C>G A309G c.925G>T A309S c.929T>A L310H c.929T>C L310P c.932T>A L311H c.937G>C D313H c.937G>A D313N c.938A>C D313A c.940A>C K314Q c.941A>G K314R c.945C>G D315E c.953C>G A318G c.952G>T A318S c.956T>G I319S c.955A>C I319L c.955A>G I319V c.956T>A I319N c.958A>G N320D c.962A>C Q321P c.964G>T D322Y c.965A>G D322G c.967C>G P323A c.968C>A P323H Petição 870260032676, de 08 / 04 / 2026, pág. 160 / 370 150 / 305 Tabela 5 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.968C>T P323L c.967C>T P323S c.970T>A L324M c.972G>C L324F c.971T>C L324S c.980A>G Q327R c.986A>C Y329S c.989A>T Q330L c.991C>A L331I c.991C>T L331F c.995G>A R332K c.999G>C Q333H c.997C>A Q333K c.1001G>C G334A c.1003G>C D335H c.1003G>A D335N c.1006A>C N336H c.1008C>G N336K c.1009T>A F337I c.1012G>C E338Q c.1015G>C V339L c.1018T>G W340G c.1019G>T W340L c.1019G>C W340S c.1020G>C W340C Petition 870260032676, dated 08 / 04 / 2026, pp. 161 / 370 151 / 305 Table 5 Nucleotide Change Protein Change (1 Letter) c.1022A>T E341V c.1022A>G E341G c.1028C>G P343R c.1028C>A P343H c.1030C>A L344I c.1031T>A L344H c.1034C>T S345L c.1033T>A S345T c.1033T>G S345A c.1036G>A G346S c.1036G>C G346R c.1039T>G L347V c.1040T>C L347S c.1041A>T L347F c.1042G>A A348T c.1042G>T A348S c.1043C>G A348G c.1043C>T A348V c.1045T>G W349G c.1049C>A A350D c.1051G>A V351I c.1051G>C V351L c.1052T>G V351G c.1059G>C M353I c.1057A>G M353V Petition 870260032676, dated 08 / 04 / 2026, page 162 / 370 152 / 305 Table 5 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.1058T>G M353R c.1062A>G I354M c.1060A>T I354L c.1060A>G I354V c.1061T>C I354T c.1064A>T N355I c.1064A>C N355T c.1070A>T Q357L c.1070A>C Q357P c.1071G>C Q357H c.1070A>G Q357R c.1069C>A Q357K c.1073A>T E358V c.1077T>G I359M c.1079G>T G360V c.1082G>T G361V c.1090T>A S364T c.1090T>G S364A c.1091C>A S364Y c.1091C>T S364F c.1094A>G Y365C c.1093T>C Y365H c.1096A>G T366A c.1099A>G I367V c.1100T>A I367N Petição 870260032676, de 08 / 04 / 2026, pág. 163 / 370 153 / 305 Tabela 5 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.1100T>C I367T c.1100T>G I367S c.1102G>T A368S c.1103C>A A368E c.1103C>T A368V c.1106T>A V369D c.1108G>T A370S c.1111T>G S371A c.1112C>T S371F c.1111T>C S371P c.1112C>A S371Y c.1114C>A L372M c.1114C>G L372V c.1118G>T G373V c.1122A>T K374N c.1120A>C K374Q c.1124G>T G375V c.1127T>C V376A c.1130C>T A377V c.1133G>T C378F c.1132T>G C378G c.1134T>G C378W c.1135A>C N379H c.1136A>G N379S c.1135A>T N379Y Petição 870260032676, de 08 / 04 / 2026, pág. 164 / 370 154 / 305 Tabela 5 Nucleotide change Protein change (1 Letter) c.1138C>T P380S c.1141G>C A381P c.1141G>T A381S c.1141G>A A381T c.1142C>G A381G c.1142C>T>G A381G c.1142C>T>G. C382F c.1144T>G C382G c.1144T>A C382S c.1147T>C or c.1149C>G or c.1149C>A F383L c.1148T>C F383S c.1147T>G F383V c.150A C>151L>IG. I384S c.1150A>G I384V c.1154C>A T385K c.1154C>G T385R c.1153A>T T385S c.1156C>G Q386E c.1157A>G Q386R c.1160T>C L387A>G Q386R c. c.1166C>A P389H c.1165C>T P389S c.1165C>A P389T Petition 870260032676, of 08 / 04 / 2026, p. 165 / 370 155 / 305 Table 5 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.1169T>C V390A c.1169T>A V390E c.1169T>G V390G c.1168G>C V390L c.1176G>C R392S c.1178A>T K393M c.1178A>G K393R c.1180C>G L394V c.1184G>T G395V c.1183G>T G395W c.1187T>C F396S c.1189T>G Y397D c.1194A>T E398D c.1193A>T E398V c.1197G>C W399C c.1196G>T W399L c.1201T>C S401P c.1205G>A R402K c.1207T>A L403I c.1213A>T S405C c.1214G>T S405I c.1214G>A S405N c.1214G>C S405T c.1216C>A H406N c.1217A>C H406P Petição 870260032676, de 08 / 04 / 2026, pág. 166 / 370 156 / 305 Tabela 5 Nucleotide change Protein change (1 Letter) c.1216C>T H406Y c.1223A>T N408I c.1224T>A N408K c.1223A>G N408S c.1226C>A P409H c.1226C>G PG1299 c. T410R c.1231G>C G411R c.1238T>C V413A c.1238T>A V413D c.1237G>C V413L c.1240T>A L414M c.1241T>G L414W c.1244T>RG L415G L414V>C. c.1246C>A Q416K c.1247A>G Q416R c.1250T>A L417Q c.1249C>G L417V c.1253A>T E418V c.1255A>C N419H c.1257T>A N419K c.G T2420A c.1259C>T T420I c.1264C>G Q422E Petition 870260032676, of 08 / 04 / 2026, p. 167 / 370 157 / 305 Table 5 Nucleotide Change Protein Change (1 Letter) c.1266G>C Q422H c.1264C>A Q422K c.1265A>T Q422L c.1265A>G Q422R c.1268T>G M423R c.1267A>G M423V c.1270T>G S424A c.1270T>C S424P c.1270T>A S424T c.1273T>A L425I c.1274T>C L425S c.1273T>G L425V c.1276A>G K426E c.1276A>C K426Q c.1277A>C K426T c.1277A>T K426I c.1278A>T K426N c.1277A>G K426R c.1280A>C D427A c.1279G>C D427H c.1279G>T D427Y c.1281C>G D427E c.1280A>G D427G c.1280A>T D427V c.1284A>T L428F Petition 870260032676, dated 08 / 04 / 2026, pp. 168 / 370 158 / 305 Table 5 Nucleotide Change Protein Change (1 Letter) c.1283T>C L428S c.1282T>A L428I c.1282T>G L428V c.1285C>A L429I c.1285C>G L429V c.1285C>T L429F c.1286T>A L429H c.1286T>C L429P

[0104] Although non-susceptible mutations presented in Table 5 initially showed non-susceptible prognostic mutations assessed by the HEK assay; however, the patients subsequently identified have since presented with several of these mutations. Accordingly, the mutations listed in Table 6 are now susceptible mutations associated with the patients, thus confirming that the prognostic mutations described here can subsequently present in patients. Table 6 Nucleotide Change Protein Change (1 Letter) c.47T>G L16R c.146G>A R49H c.148T>C or c.150C>G or c.150C>A F50L c.155G>T C52F c.188G>T C63F c.206T>C F69S c.208A>G M70V Petition 870260032676, dated 08 / 04 / 2026, pp. 169 / 370 159 / 305 Table 6 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.228G>C ou c.228G>A ou c.228G>T M76I c.241T>G W81G c.254G>T G85V c.338T>G F113C c.346G>T G116W c.359T>G L120R c.383G>T G128V c.386T>G L129R c.388A>G K130E c.389A>C K130T c.392T>A L131Q c.409G>T V137F c.421A>G T141A c.424T>A C142S c.440G>T G147V c.443G>T S148I c.476T>C F159S c.478G>C A160P c.487G>C G163R c.497T>C L166P c.502A>C K168Q c.550T>G Y184D c.574A>T N192Y c.605G>T C202F c.613C>G P205A Petição 870260032676, de 08 / 04 / 2026, pág. 170 / 370 160 / 305 Tabela 6 Mudança de nucleotídeos Mudança de proteína (1 Letra) c.667T>A ou c.668G>C C223S c.668G>T C223F c.674A>C H225P c.676T>G W226G c.680G>T R227L c.685T>G F229V c.691G>T D231Y c.692A>C D231A c.700G>A D234N c.701A>G D234G c.706T>G W236G c.743T>C F248S c.778G>C ou c.778G>A G260R c.784T>A ou c.784T>C W262R c.785G>C W262S c.787A>G N263D c.789T>A ou c.789T>G N263K c.793C>A P265T c.797A>G D266G c.808A>T I270F c.815A>C N272T c.815A>T N272I c.818T>C F273S c.820G>C G274R c.820G>T G274C Petição 870260032676, de 08 / 04 / 2026, pág. 171 / 370 161 / 305 Tabela 6 Nucleotide Change Protein Change (1 Letter) c.821G>A G274D c.826A>T S276C c.827G>T S276I c.828C>A or c.828C>G S276R c.834T>G or c.834T>A N278K c.857T>C L286P c.887T>A M296K c.889T>C S297P c.890C>A S297Y c.896A>T D299V c.929T>C L310P c.980A>G Q327R c.1019G>C W340S c.1022A>G E341G c.1058T>G M353R c.1124G>T G375V c.1133G>T C378F c.1147T>C or c.1149C>G or c.1149C>A F383L c.1160T>C L387P c.1165C>T P389S

[0105] Furthermore, several embodiments of the present invention provide PCs for the treatment of Fabry disease in a patient having a mutation in the gene encoding α-Gal A, wherein the patient is identified as having a missense mutation in a human α-Gal A encoded by a nucleic acid sequence established in SEQ ID NO: 1 and / or SEQ ID NO: 3. Another aspect of the invention concerns Petition 870260032676, dated 08 / 04 / 2026, pp. 172 / 370 162 / 305 relates to a method of treating a patient diagnosed with Fabry disease. In one or more embodiments, the method comprises administering to a patient a therapeutically effective dose of an α-Gal A PC. In further embodiments, the patient has a missense mutation in the nucleic acid sequence encoding α-Gal A. Another aspect of the invention relates to a method of enhancing α-Gal A in a patient diagnosed with or suspected of having Fabry disease. In one or more embodiments, the method comprises administering to a patient a therapeutically effective dose of an α-Gal A PC, wherein the patient has a mutant α-Gal A encoded by a nucleic acid sequence having a missense mutation with respect to SEQ ID NO: 1 and / or SEQ ID NO: 3. Further details and embodiments of these uses and methods follow below.Any embodiment relating to a method of treating a patient with Fabry disease, a method of enhancing α-Gal A in a patient diagnosed with or suspected of having Fabry disease, use of a pharmacological chaperone for α-Gal A for the manufacture of a medicament to treat a patient diagnosed with Fabry disease, or with a pharmacological chaperone for α-Gal A for use in treating a patient diagnosed with Fabry disease where the patient is identified as having a missense mutation in a human α-Gal A encoded by a nucleic acid sequence established in SEQ ID NO: 1 and / or SEQ ID NO: 3, may be combined with any of the other embodiments of the invention, for example, embodiments relating to PCs and their appropriate dosages.

[0106] In one or more modalities, the patient may have other mutations in their GLA gene. For example, there may be mutations in the intron region that may or may not affect the resulting α-Gal A enzyme. Thus, in one or more modalities, the patient has mutant α-Gal A encoded by a nucleic acid sequence having at least 95, 96, 97, 98, 99, Petition 870260032676, dated 08 / 04 / 2026, pp. 173 / 370 163 / 305 99.1, 99.2, 99.3, 99.4, 99.5, 99.6, 99.7, 99.8 or 99.9% identity with SEQ ID NO: 1. Furthermore, the patient may have one or more additional mutations in the coding region of the GLA gene. Thus, in one or more embodiments, the patient has a mutant α-Gal A encoded by a nucleic acid sequence having at least 95, 96, 97, 98, 99, 99.1, 99.2, 99.3, 99.4, 99.5, 99.6, 99.7, 99.8, or 99.9% identity with SEQ ID NO: 3. Furthermore, in one or more embodiments, the patient has 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 30 mutations relative to SEQ ID NO: 1 or SEQ ID NO: 3. It is also noted that some nucleic acid mutations in SEQ ID NO: 1 or SEQ ID NO: 3 may result in no amino acid change for the resulting protein, as multiple amino acids are encoded by multiple nucleic acid sequences. nuclei.Again, any of these embodiments can be combined with any of the other embodiments of the invention, for example embodiments relating to susceptible mutations, PCs and their appropriate dosages.

[0107] In several embodiments, a pharmacological reference table is provided that includes one or more of the mutations disclosed herein. In one or more embodiments, the pharmacological reference table includes one or more of the mutations in Table 2. In one or more embodiments, the pharmacological reference table includes all mutations in Table 2. In one or more embodiments, the pharmacological reference table includes one or more of the mutations in Table 1. In one or more embodiments, the pharmacological reference table includes all mutations in Table 1. In one or more embodiments, the pharmacological reference table includes one or more of the mutations in Table 1 and one or more of the mutations in Table 2. In one or more embodiments, the pharmacological reference table includes all mutations in Table 1 and one or more of the mutations in Table 2. In one or more embodiments, the pharmacological reference table includes one or more of the mutations in Table 1 and all mutations in Table 2. Petition 870260032676, dated 08 / 04 / 2026, pp. 174 / 370 164 / 305 In one or more modalities, the pharmacological reference table includes all mutations in Table 1 and all mutations in Table 2.

[0108] As described above, the pharmacological reference table can be any publicly accessible written or electronic record. In one or more embodiments, the pharmacological reference table is a written record. In one or more embodiments, the pharmacological reference table is provided on a product label for a migalastat product, such as a migalastat product approved by a U.S. regulatory agency or other for the treatment of Fabry disease. In one or more embodiments, the pharmacological reference table is provided on a product label for GALAFOLD®. In one or more embodiments, the pharmacological reference table is an electronic record. In one or more embodiments, the pharmacological reference table is provided on a website.In one or more embodiments, the website is associated with a migalastat product, such as a migalastat product approved by a U.S. regulatory agency or other agency for the treatment of Fabry disease. In one or more embodiments, the pharmacological reference table is provided at www.galafoldamenabilitytable.com. In one or more embodiments, the pharmacological reference table is provided at www.fabrygenevariantsearch.com.

[0109] Several embodiments also relate to a data store including a pharmacological reference table as described herein. Such a data store may include an electronic search function to determine whether a particular mutation is included in the pharmacological reference table. In one or more embodiments, the data store and the optional search function are provided on a website. In one or more embodiments, the data store and the optional search function are Petition 870260032676, dated 08 / 04 / 2026, pp. 175 / 370 165 / 305 provided on an electronic storage medium. Examples of such electronic storage media include, but are not limited to, compact discs (CDs), digital versatile discs (DVDs), hard drives, and pen drives. Pharmacological chaperones

[0110] The binding of small molecule enzyme inhibitors associated with LSDs can increase the stability of both the mutant enzyme and the corresponding wild-type enzyme (see U.S. Pat. Nos. 6,274,597; 6,583,158; 6,589,964; 6,599,919; 6,916,829 and 7,141,582, all incorporated herein by reference). In particular, administration of small molecule glucose and galactose derivatives, which are specific, selective competitive inhibitors for various target lysosomal enzymes, effectively increased enzyme stability in cells in vitro and thus increased enzyme trafficking to the lysosome. Thus, by increasing the amount of enzyme in the lysosome, the hydrolysis of enzyme substrates is expected to increase. The original theory behind this strategy was as follows: since the mutant enzyme protein is unstable in the ER (Ishii et al., Biochem. Biophys. Res. Comm.(1996; 220: 812-815), the enzymatic protein is slowed down in the normal transport pathway (ER—Golgi apparatus—endosomes—lysosome) and prematurely degraded. Therefore, a compound that binds to and increases the stability of a mutant enzyme can serve as a “chaperone” for the enzyme and increase the amount that can exit the ER and move to the lysosomes. Additionally, because the folding and trafficking of some wild-type proteins are incomplete, with up to 70% of some wild-type proteins being degraded in some cases before reaching their final cellular location, chaperones can be used to stabilize wild-type enzymes and increase the amount of enzyme that can exit the ER and be transported to the lysosomes. Petition 870260032676, dated 08 / 04 / 2026, pp. 176 / 370 166 / 305

[0111] In one or more embodiments, the pharmacological chaperone comprises migalastat or a salt thereof. The compound migalastat, also known as 1-deoxygalactonojirimycin (1-DGJ) or (2R,3S,4R,5S)-2-(hydroxymethyl)piperidine-3,4,5-triol, is a compound having the following chemical formula: Migalastate-free base

[0112] As discussed herein, pharmaceutically acceptable salts of migalastat can also be used in the present invention. When a salt of migalastat is used, the dosage of the salt will be adjusted such that the dose of migalastat received by the patient is equivalent to the amount that would have been received if the free base of migalastat had been used. An example of a pharmaceutically acceptable salt of migalastat is migalastat HCl: Migalastate HCl

[0113] Migalastat is a low molecular weight iminosugar and is an analog of terminal galactose of GL-3. In vitro and in vivo pharmacological studies have demonstrated that migalastat acts as a pharmacological chaperone, binding selectively and reversibly, with high Petition 870260032676, dated 08 / 04 / 2026, pp. 177 / 370 167 / 305 affinity, to the active site of wild-type α-Gal A and specific mutant forms of α-Gal A. Migalastate binding stabilizes these mutant forms of α-Gal A in the endoplasmic reticulum, facilitating their appropriate trafficking to lysosomes where migalastate dissociation allows α-Gal A to reduce the level of GL-3 and other substrates.

[0114] In one specific embodiment, the PC comprises migalastate or its salt. In additional embodiments, the PC comprises migalastate hydrochloride.

[0115] Any of these PCs for α-Gal A can be used in combination with any of the other embodiments of the invention, for example, embodiments relating to a method of treating a patient with Fabry disease, a method of enhancing α-Gal A in a patient diagnosed with or suspected of having Fabry disease, use of a pharmacological chaperone for α-Gal A for the manufacture of a medicament to treat a patient diagnosed with Fabry disease or with a pharmacological chaperone for α-Gal A for use in treating a patient diagnosed with Fabry disease as well as embodiments relating to appropriate doses of PCs, susceptible mutations and with the treatment of a Fabry patient having certain mutations in the nucleic acid sequence encoding α-Gal A. Dosage, Formulation and Administration

[0116] In one or more embodiments, the Fabry patient receives migalastat or its salt at a frequency of once every other day (also referred to as “QOD”). In several embodiments, the doses described herein relate to migalastat hydrochloride or an equivalent dose of migalastat or a salt thereof other than the hydrochloride salt. In some embodiments, these doses relate to the free base of migalastat. In alternative embodiments, these doses relate to a salt of migalastat. In additional embodiments, the salt of migalastat is Petition 870260032676, dated 08 / 04 / 2026, pp. 178 / 370 168 / 305 migalastat hydrochloride. The administration of migalastat or a migalastat salt is referred to herein as “migalastat therapy”.

[0117] The effective amount of migalastat or its salt may be in the range of about 100 mg FBE to about 150 mg FBE. Exemplary doses include about 100 mg FBE, about 105 mg FBE, about 110 mg FBE, about 115 mg FBE, about 120 mg FBE, about 123 mg FBE, about 125 mg FBE, about 130 mg FBE, about 135 mg FBE, about 140 mg FBE, about 145 mg FBE or about 150 mg FBE.

[0118] It is again noted that 150 mg of migalastat hydrochloride is equivalent to 123 mg of the free base form of migalastat. Thus, in one or more embodiments, the dose is 150 mg of migalastat hydrochloride or an equivalent dose of migalastat or a salt thereof other than the hydrochloride salt, administered at a frequency of once every other day. As set forth above, this dose is referred to as 123 mg of migalastat FBE. In additional embodiments, the dose is 150 mg of migalastat hydrochloride administered at a frequency of once every other day. In other embodiments, the dose is 123 mg of migalastat free base administered at a frequency of once every other day.

[0119] In various embodiments, the effective amount is about 122 mg, about 128 mg, about 134 mg, about 140 mg, about 146 mg, about 150 mg, about 152 mg, about 159 mg, about 165 mg, about 171 mg, about 177 mg or about 183 mg of migalastat hydrochloride.

[0120] Accordingly, in several modalities, migalastat therapy includes administering 123 mg of FBE at a frequency of once every other day, such as 150 mg of migalastat hydrochloride every other day. Petition 870260032676, dated 08 / 04 / 2026, pp. 179 / 370 169 / 305

[0121] Migalastat or its salt may be administered over a period of time. In one or more embodiments, migalastat or its salt is administered for a duration of at least 28 days, such as at least 30, 60, or 90 days, or at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 20, 24, 30, or 36 months, or at least 1, 2, 3, 4, or 5 years. In several embodiments, migalastat therapy is long-term migalastat therapy of at least 6 months, such as at least 6, 7, 8, 9, 10, 11, 12, 16, 20, 24, 30, or 36 months, or at least 1, 2, 3, 4, or 5 years.

[0122] The administration of migalastat or its salt according to the present invention may be in a formulation suitable for any route of administration, but is preferably administered in an oral dosage form such as a tablet, capsule or solution. As an example, the patient orally receives capsules each containing 150 mg of migalastat hydrochloride or an equivalent dose of migalastat or a salt thereof other than the hydrochloride salt.

[0123] In some embodiments, the PC (e.g., migalastat or its salt) is administered orally. In one or more embodiments, the PC (e.g., migalastat or its salt) is administered by injection. The PC may be accompanied by a pharmaceutically acceptable carrier, which may depend on the method of administration.

[0124] In one or more embodiments, PC (e.g., migalastat or its salt) is administered as monotherapy and may be in a form suitable for any route of administration, including, e.g., orally in the form of tablets or capsules or liquid or in sterile aqueous solution for injection. In other embodiments, PC is provided as a dry lyophilized powder to be added to the replacement enzyme formulation during or immediately after reconstitution to prevent enzyme aggregation in vitro prior to administration. Petition 870260032676, dated 08 / 04 / 2026, pp. 180 / 370 170 / 305

[0125] When PC (e.g., migalastate or its salt) is formulated for oral administration, tablets or capsules may be prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g., pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropylmethylcellulose); fillers (e.g., lactose, microcrystalline cellulose or calcium hydrogen phosphate); lubricants (e.g., magnesium stearate, talc or silica); disintegrants (e.g., potato starch or sodium starch glycolate); or wetting agents (e.g., sodium lauryl sulfate). Tablets may be coated by methods well known in the art. Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or may be presented as a dry product for mixing with water or another suitable vehicle before use.Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, cellulose derivatives, or edible hydrogenated fats); emulsifying agents (e.g., lecithin or acacia); non-aqueous carriers (e.g., almond oil, oily esters, ethyl alcohol, or fractionated vegetable oils); and preservatives (e.g., methyl or propyl p-hydroxybenzoates or sorbic acid). The preparations may also contain buffering salts, flavoring agents, colorings, and sweeteners as appropriate. Preparations for oral administration may be suitably formulated to provide controlled release of the active chaperone compound.

[0126] Pharmaceutical formulations of PC (e.g., migalastat or its salt) suitable for parenteral / injectable use generally include sterile aqueous solutions (where water-soluble) or sterile dispersions and powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases, the dosage form must be sterile and must Petition 870260032676, dated 08 / 04 / 2026, pp. 181 / 370 171 / 305 must be fluid to the extent that easy syringeability exists. It must be stable under manufacturing and storage conditions and must be protected against the contaminating action of microorganisms such as bacteria and fungi. The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol and polyethylene glycol and the like), suitable mixtures thereof, or vegetable oils. Appropriate fluidity may be maintained, for example, by the use of a coating such as lecithin, by maintaining the required particle size in the case of dispersion, and by the use of surfactants. Prevention of microbial action may be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, benzyl alcohol, sorbic acid and the like. In many cases it will be reasonable to include isotonic agents, for example, sugars or sodium chloride.Prolonged absorption of injectable compositions can be achieved by using absorption-delaying agents in the compositions, for example, aluminum monostearate and gelatin.

[0127] Sterile injectable solutions are prepared by incorporating the purified enzyme (if any) and the PC (e.g., migalastate or its salt) in the required quantity into the appropriate solvent with several of the other ingredients listed above, as required, followed by sterilization by filtration or terminal. Generally, dispersions are prepared by incorporating the various sterilized active ingredients into a sterile vehicle containing the basic dispersion medium and the other required ingredients from those listed above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred preparation methods are vacuum drying and the lyophilization technique, which yield a powder of the active ingredient plus any desired additional ingredient from its previously sterilized solution by filtration. Petition 870260032676, dated 08 / 04 / 2026, pp. 182 / 370 172 / 305

[0128] The formulation may contain an excipient. Pharmaceutically acceptable excipients that may be included in the formulation are buffers such as citrate buffer, phosphate buffer, acetate buffer and bicarbonate buffer, amino acids, urea, alcohols, ascorbic acid and phospholipids; proteins such as serum albumin, collagen and gelatin; salts such as EDTA or EGTA and sodium chloride; liposomes; polyvinylpyrrolidone; sugars such as dextran, mannitol, sorbitol and glycerol; propylene glycol and polyethylene glycol (e.g., PEG-4000, PEG-6000); glycerol; glycine or other amino acids; and lipids. Buffering systems for use with the formulations include citrate, acetate, bicarbonate, and phosphate buffers. Phosphate buffer is a preferred embodiment.

[0129] The route of administration of the chaperone compound may be oral or parenteral, including intravenous, subcutaneous, intra-arterial, intraperitoneal, ophthalmic, intramuscular, buccal, rectal, vaginal, intraorbital, intracerebral, intradermal, intracranial, intraspinal, intraventricular, intrathecal, intracisternal, intracapsular, intrapulmonary, intranasal, transmucosal, transdermal or by inhalation.

[0130] The administration of the above-described parenteral formulations of the chaperone compound can be by periodic bolus injections of the preparation or can be administered intravenously or intraperitoneally from a reservoir that is external (e.g., an IV bag) or internal (e.g., a bioerodible implant).

[0131] The embodiments relating to pharmaceutical formulations and administration can be combined with any of the other embodiments of the invention, for example embodiments relating to methods of treating patients with Fabry disease, use of a pharmacological chaperone for α-Gal A for the manufacture of a medicament to treat a patient diagnosed with Fabry disease or with a pharmacological chaperone for α-Gal A for use in treating a Petition 870260032676, dated 08 / 04 / 2026, pp. 183 / 370 173 / 305 patient diagnosed with Fabry disease as well as modalities relating to susceptible mutations, PCs and their appropriate dosages.

[0132] In one or more modalities, the PC (e.g., migalastat or its salt) is administered in combination with ERT. ERT increases the amount of protein by exogenously introducing a wild-type or biologically functional enzyme via infusion. This therapy has been developed for many genetic disorders, including LSDs such as Fabry disease, as referenced above. After infusion, the exogenous enzyme is expected to be absorbed by tissues through a non-specific or receptor-specific mechanism. In general, absorption efficacy is not high, and the circulation time of the exogenous protein is short. Additionally, the exogenous protein is unstable and subject to rapid intracellular degradation, as well as having the potential for adverse immunological reactions with subsequent treatments. In one or more modalities, the chaperone is administered at the same time as the replacement enzyme (e.g., α-Gal A replacement).In some embodiments, the chaperone is co-formulated with the replacement enzyme (e.g., replacement α-Gal A).

[0133] Throughout this descriptive report, references to “an embodiment,” “certain embodiments,” “various embodiments,” “one or more embodiments,” or “an embodiment” mean that a particular feature, structure, material, or resource described in connection with the embodiment is included in at least one embodiment of the invention. Thus, the appearances of phrases such as “in one or more embodiments,” “in certain embodiments,” “in various embodiments,” “in an embodiment,” or “in an embodiment” in various places throughout this descriptive report do not necessarily refer to the same embodiment of the invention. Furthermore, the features, structures, Petition 870260032676, dated 08 / 04 / 2026, pp. 184 / 370 174 / 305 particular materials or resources may be combined in any suitable manner in one or more modalities.

[0134] Although the invention has been described herein with reference to particular embodiments, it should be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It will be evident to those skilled in the art that various modifications and variations can be made to the method and device of the present invention without departing from the spirit and scope of the invention. Thus, it is intended that the present invention includes modifications and variations that are within the scope of the appended claims and their equivalents. EXAMPLE: Effect of Migalastat on α-Gal A Mutations

[0135] α-Gal A activity was measured in lysates prepared from HEK-293 cells transiently transfected with the indicated mutant form of α-Gal A and incubated in the absence or presence of 10 μM migalastat for 5 days. α-Gal A activity is expressed as the nmoles of free 4-MU released per milligram of protein per hour (nmol / mg / hr). Baseline α-Gal A activity and α-Gal A activity after incubation with 10 μM migalastat were additionally expressed as a percentage of baseline wild-type α-Gal A activity (% WT). The wild-type α-Gal A activity used to calculate these percentages was the average activity measured in lysates from transfected wild-type cells, incubated in the absence of migalastate, measured in parallel.

[0136] The results of the α-Gal A activity test for the new mutations presented in Table 2 are shown in Table 7 below: Petition 870260032676, dated 08 / 04 / 2026, pp. 185 / 370 175 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalastat at 10 μM (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalastat at 10 μM (% WT) Absolute Increase (% WT) Relative Increase N5D 26578 ± 1944 34661 ± 1816 0.0017 74.9 ± 5.1 98.9 ± 5.5 24.1 1.3 N5K 22221 ± 753 27689±9550.0002 58.6±2.673±3.314.41.3 P6L ± 825 22316± 1261 0.001 3 49.4 ± 2.2 64.8 ± 4.3 15.4 1.3 P6R 24240 ± 1350 32919± 1593 0.000 3 70.1 ± 4.2 94.1 ± 3.6 24.0 1.4 P6S 34848 ± 1440 43046 ± 1713 0.000 9 82 ± 2.9 101.5 ± 3.7 19.5 1.2 P6T 30926 ± 1479 37354 ± 1577 0.007 7 88.3 ± 3.3 108 ± 5.1 19.7 1.2 E7D 31325± 1280 39271 ± 1669 0.000 5 77.6 ± 2.3 97.2 ± 3 19.6 1.3 E7K 18705± 801 25316 ± 1403 0.000 1 55.2 ± 3.1 75.4 ± 5.7 20.2 1.4 Petition 870260032676, dated 08 / 04 / 2026, pp. 186 / 370 176 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 μM (% WT) Absolute Increase (% WT) Relative Increase E7V 25273 ± 1376 30825 ± 1805 0.019 3 74.7 ± 2.8 91.6 ± 4.3 16.9 1.2 L8I 21345 ± 1469 26036 ± 1514 0.009 0 67.5 ± 4.2 82.4 ± 4.3 14.9 1.2 L8P 19934 ± 3444 25868 ± 4321 0.002 8 55.1 ± 6.9 72.3 ± 8.5 17.2 1.3 L8Q 18234 ± 1818 22878 ± 1755 0.005 3 57.5 ± 5.4 72.3 ± 5.1 14.7 1.3 H9L 26490 ± 1295 36318± 2304 0.000 3 75.9 ± 5.5 107.8 ± 11.2 31.9 1.4 H9Q 20382 ± 918 27072 ± 1062 0.000 1 57.3 ± 2.9 78.2 ± 5.6 20.9 1.3 H9R 21497 ± 2019 27866 ± 1854 0.004 2 56.2 ± 4.2 75.2 ± 5.4 19.0 1.3 H9Y 27713 ± 2168 33834 ± 2369 0.009 0 81.9 ± 8.5 101 ± 10 19.1 1.2 L10 M 19028 ± 958 26110 ± 1344 0.000 1 55.1 ± 4.1 78.3 ± 6.8 23.2 1.4 Petition 870260032676, dated 08 / 04 / 2026, pages 187 / 370 177 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) a 10 μΜ (% WT) Absolute amount (% WT) Relative amount L10P 21054 ± 1238 26571 ± 1812 0.004 2 68.3 ± 3.9 85.9 ± 5.5 17.5 1.3 L154 Q 154 ± 279 1583 0.001 3 47.8 ± 3.3 67.3 ± 5.4 19.5 1.4 L10 R 15760± 920 24293 ± 2170 0.001 7 51.9 ± 3.3 78.9 ± 7.7 7.7 2015 ± 175 L 683 23595 ± 1256 0.000 1 49.5 ± 2.6 68.8 ± 6.1 19.3 1.4 G11 C 34393 ± 2207 43933 ± 3128 0.004 9 111.9 71.3 ± 40.3 ± 40.3 1.3 G11 D 13315 ± 1237 18851 ± 1704 0.014 2 43.9 ± 4.3 61.3 ± 5.8 17.3 1.4 G11 R 32525 ± 2047 41260± 3644 R 134.3 ± 12.7 29.1 1.3 G11 S 28169 ± 1641 38524 ± 3460 0.007 2 91 ± 4.9 122.9 ± 10.8 31.9 1.4 G11 V 39507 ± 1757 ± 1757 ± 1695 0.001 0 121.8 ± 7 153 ± 9.2 31.3 1.2 Petition 870260032676, dated 08 / 04 / 2026, pages 188 / 370 178 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalast (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 μM Migalast (% WT) Absolute Increase (% WT) Relative Increase C12 G 14560 ± 1307 21780 ± 2916 0.023 4 44.4 ± 3.1 64.7 ± 6.9 20.3 1.5 C12 R 10869 ± 1110 16596±2243 0.012 8 32.9±2.6 49.1±5.3 16.2 1.5 C12 S 15741±1462 23071±2829 0.021 9 47.6±3.2 68.6±6.4 21.0 1.5 C12 Y 32218 ± 2218 38717± 2744 0.033 9 99.8 ± 5.9 118.6 ± 7.4 18.9 1.2 A13 E 16631 ± 1310 23633 ± 2424 0.008 3 51.2 ± 3.5 71.5 ± 6 20.2 1.4 A13 G 21739 ± 1693 27200 ± 2187 0.036 0 67 ± 4.3 83.6 ± 5.5 16.6 1.3 L14F 30970 ± 2383 38206 ± 2599 0.028 3 97.4 ± 5.3 122.1 ± 7.4 24.7 1.2 L14 H 1316 ± 125 3166 ± 428 0.002 2 3.8 ± 0.2 8.8 ± 1 5.0 2.4 L14V 25550 ± 1778 31818 ± 1959 0.024 9 82.5 ± 5.2 101.6 ± 5.1 19.1 1.3 Petition 870260032676, dated 08 / 04 / 2026, pp. 189 / 370 179 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 µΜ (% WT) Absolute value (% WT) Relative value R17 C 33909 ± 1965 48618± 2267 0.000 1 97.2 ± 5.8 140.5 ± 8.4 43.3 1.4 G ± 2273 0.002 8 117 ± 7.1 145.2 ± 6.2 28.2 1.3 P 1526 45995 ± 2671 0.000 1 80.6 ± 4.7 133.4 ± 9.9 52.8 1.6 R17 S 28809 ± 1251 42089 ± 1807 0.000 1 82.1 ± 1.43.6 1.5 F18I 38335 ± 2361 49150± 2675 0.002 6 113.3 ± 8 146.5 ± 10.7 33.2 1.3 F18L 22788 ± 1848 27677 2429 ± 0.030.797 97.1 ± 6.6 17.5 1.2 A20 G 8349 ± 475 10555± 783 0.006 7 30.2 ± 1.5 37.4 ± 2.4 7.2 1.3 L21 H 17203 ± 1913 ± 3891 2015 ± 2015 47.2 ± 4.5 66.1 ± 5.8 19.0 1.4 Petition 870260032676, dated 08 / 04 / 2026, pages 190 / 370 180 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) a 10 μΜ (% WT) Absolute amount (% WT) Relative amount V22 A 15790± 1037 22194± 2010 0.007 7 43.9 ± 2.5 61.2 ± 5.1 17.3 1.4 V292 F 2458 0.033 9 83.5 ± 4.6 102.5 ± 5.7 19.0 1.2 V22I 27969 ± 1731 43104± 3250 0.000 3 75.7 ± 4.1 116.4 83.5 ± 2.25 L 27041 ± 1471 38357 ± 3293 0.008 3 74.7 ± 3.6 105.8 ± 8.9 31.1 1.4 S23 P 28512 ± 2197 38609 ± 2917 0.006 7 88.2 ± 1.5 ± 19.9 5.7 31.0 1.4 S23 T 32295 ± 2128 40230 ± 2181 0.005 7 90.2 ± 5.1 112.8 ± 5.4 22.6 1.3 W24 S 13019 ± 845 1842 1.02 2.5 56.7 ± 4 16.7 1.4 D25 H 30857 ± 1142 37503 ± 1794 0.005 3 94.9 ± 3.9 115.8 ± 6.5 20.9 1.2 I26N 32979 ± 4194 ± 4046 ± 4046 0.038 2 75.5 ± 4.2 97.3 ± 7.3 21.8 1.3 Petition 870260032676, dated 08 / 04 / 2026, pp. 191 / 370 181 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalastat at 10 μM (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalastat at 10 μM (% WT) Absolute Increase (% WT) Relative Increase P27A 19346 ± 1192 27202 ± 1150 0.000 1 51.9 ± 3.2 72.6 ± 2.3 20.7 1.4 P27L 26913 ± 1947 32775 ± 1415 0.003 0 72.4 ± 5.4 90 ± 5.3 17.6 1.2 P27 S 28366 ± 1590 38366 ± 1767 0.000 3 70.4 ± 3.3 95.3 ± 3.6 24.9 1.4 P27 T 26456 ± 954 34628 ± 1113 0.000 1 62.4 ± 2.4 81.9 ± 3.2 19.5 1.3 G28 E 27350 ± 1663 34034 ± 2028 0.002 4 73.8 ± 4.5 91.1 ± 4.6 17.2 1.2 G28 R 26315± 1950 32315± 1988 0.006 2 71.5 ± 5.7 87.6 ± 5.4 16.1 1.2 G28 W 27378 ± 1600 36559 ± 1783 0.000 3 74 ± 4.4 97.9 ± 4.2 23.9 1.3 A29 G 15101 ± 1719 18785± 1854 0.014 7 44.5 ± 4.2 55.1 ± 4.4 10.6 1.2 A29 P 4738 ± 402 6987 ± 388 0.000 3 14 ± 1 20.6 ± 0.6 6.6 1.5 Petition 870260032676, dated 08 / 04 / 2026, pp. 192 / 370 182 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) a 10 μΜ (% WT) Absolute amount (% WT) Relative amount A29 V 18656± 1649 22884 ± 1713 0.038 2 55.7 ± 4.3 68.2 ± 4.4 12.5 1.2 R303 G 2130 ± 2730 ± 1888 0.005 3 65.4 ± 5.2 80.7 ± 4 15.3 1.3 L32 M 23345 ± 1826 30767 ± 2014 0.006 7 66.9 ± 3.8 89.4 ± 4.5 2.23 23 L32 5733 ± 357 0.000 1 0.7 ± 0.1 16.9 ± 1.1 16.2 25.2 L32 R 15594 ± 1339 24030 ± 1883 0.003 3 45.4 ± 3.9 70.6 2.5 L 17391 ± 1265 25028 ± 1678 0.001 8 51.2 ± 3.7 73.7 ± 4.7 22.5 1.4 D33 A 21613 ± 1926 37153± 2439 0.000 1 5.51 ± 3.5 ± 3.5 39.4 1.7 D33 E 32178 ± 2816 44926 ± 3037 0.001 0 81.8 ± 5.9 116.8 ± 7.1 34.9 1.4 D33 V 8815 ± 815 28371 ± 2720 ± 1.203 1.7 71 ± 4.2 48.7 3.2 Petition 870260032676, dated 08 / 04 / 2026, pp. 193 / 370 183 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 μΜ (% WT) Absolute amount (% WT) Relative amount L36 M 29476 ± 1787 37839 ± 2103 0.003 0 75.8 ± 4.5 97.4 ± 5.7 21.6 1.3 L3 2152 0.000 1 87.7 ± 8.1 118.1 ± 7.7 30.4 1.4 A37 E 17508± 1781 22216± 922 0.003 9 51.1 ± 3.2 68.6 ± 3.17 ± 3.35 G 1634 26374 ± 1068 0.001 1 59.5 ± 3.1 81.2 ± 3.3 21.7 1.3 A37 S 28548 ± 1621 36678 ± 2507 0.009 0 68.28 ± 2.87.5. 1.3 R38 G 20871 ± 1596 26474 ± ​​1182 0.001 7 59.2 ± 3.2 76.8 ± 3.1 17.5 1.3 R38 M 27519 ± 2289 33201 ± 1837 0.010 4.82 ± 4.26 105.3 ± 8.7 23.2 1.2 R38 W 13728 ± 1660 19031 ± 797 0.002 6 39.4 ± 3.1 58.3 ± 2 18.9 1.4 T39 A 14133 ± 23.2 1.30 58 ± 2.5 92.9 ± 4.5 35.0 1.6 Petition 870260032676, dated 08 / 04 / 2026, pp. 194 / 370 184 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalastat at 10 μM (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalastat at 10 μM (% WT) Absolute Increase (% WT) Relative Increase T39 K 14243 ± 982 19261 ± 1065 0.001 0 57.9 ± 3.6 78 ± 3.4 20.1 1.4 T39 M 18868 ± 1035 29341 ± 1094 0.000 1 42.9 ± 2.6 66.7 ± 3.3 23.8 1.6 T39 R 16386± 946 19594± 1257 0.004 9 66.6 ± 3.3 79.3 ± 4.2 12.7 1.2 T39 S 22746 ± 1704 30290 ± 1697 0.001 0 68.8 ± 3.9 98.5 ± 10.1 29.6 1.3 T41 A 23027 ± 1729 35730 ± 2325 0.000 1 93.8 ± 6.4 144.3 ± 7.5 50.5 1.6 T41 N 15106± 1455 27001 ± 1828 0.000 1 61.7 ± 5.7 109.4 ± 6.3 47.7 1.8 T41 S 36978 ± 1637 47987 ± 2574 0.000 1 83 ± 3.1 108.3 ± 5.2 25.2 1.3 G43 A 547 ± 39 9152 ± 903 0.000 1 2.1 ± 0.2 35.6 ± 4.2 33.6 16.7 L45 M 10167 ± 738 15884 ± 1038 0.000 1 35.4 ± 3.2 55.3 ± 4.8 20.0 1.6 Petition 870260032676, dated 08 / 04 / 2026, pp. 195 / 370 185 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalast (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 μM Migalast (% WT) Absolute Increase (% WT) Relative Increase L45V 7728 ± 553 12995 ± 870 0.000 1 27 ± 2.4 45.5 ± 4.1 18.5 1.7 H46 D 5064 ± 346 12824 ± 844 0.000 1 17.5 ± 1.4 44.8 ± 3.9 27.3 2.5 H46 N 4890 ± 293 16015± 971 0.000 1 16.9 ± 1.3 55.9 ± 4.6 39.0 3.3 H46 Q 5784 ± 357 12138± 771 0.000 1 20 ± 1.5 42.4 ± 3.6 22.4 2.1 E48 A 1795 ± 172 7438 ± 547 0.000 1 7.4 ± 1 29.1 ± 2.7 21.7 4.1 F50 Y 756 ± 43 15051 ± 1103 0.000 1 2.4 ± 0.2 46.3 ± 4.9 43.9 19.9 M51 R 14619 ± 996 18178± 722 0.003 9 53.3 ± 4 65.5 ± 2.8 12.1 1.2 M51 T 9539 ± 615 17742 ± 498 0.000 1 37.8 ± 2.1 71.1 ± 2.2 33.3 1.9 M51 V 8888 ± 629 12943± 674 0.000 1 34.1 ± 2.8 49.2 ± 3.1 15.1 1.5 Petition 870260032676, dated 08 / 04 / 2026, pp. 196 / 370 186 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalastat at 10 μM (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalastat at 10 μM (% WT) Absolute Increase (% WT) Relative Increase N53 H 4889 ± 672 10065 ± 346 0.000 1 19.2 ± 2.3 40.3 ± 1.4 21.1 2.1 N53I 12636 ± 1899 20010± 2488 0.000 6 35 ± 3 57.2 ± 3.8 22.2 1.6 N53 S 15799± 1945 25411 ± 2907 0.000 7 47.3 ± 3.7 75.3 ± 4.1 28.0 1.6 N53 T 16203 ± 1515 26147± 2763 0.000 1 49.4 ± 3.1 78.4 ± 4.1 29.0 1.6 L54 H BLD 6158 ± 377 0.000 1 N / A 17.5 ± 0.8 17.5 NC L54 R 15536± 1823 23973 ± 743 0.000 1 44.4 ± 4.6 70.1 ± 3.1 25.8 1.5 L54V 24595 ± 2022 30741 ± 1942 0.004 5 69.6 ± 4 87.9 ± 4.5 18.4 1.3 D55 A 16170 ± 1627 21497± 801 0.001 0 47 ± 4.6 63.3 ± 3.4 16.3 1.3 D55 E 16212 ± 1607 22237 ± 896 0.000 2 47 ± 4.3 66.2 ± 4.6 19.2 1.4 Petition 870260032676, dated 08 / 04 / 2026, pp. 197 / 370 187 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 μM (% WT) Absolute Increase (% WT) Relative Increase D55 H 9076 ± 1049 16638 ± 569 0.000 1 27.3 ± 3 50.4 ± 2.9 23.1 1.8 D55 Y 2268 ± 94 9956 ± 562 0.000 1 7.5 ± 0.6 32.1 ± 1.9 24.5 4.4 C56 W BLD 1854 ± 140 0.000 1 N / A 5.6 ± 0.4 5.6 NC E58 K 11757 ± 839 18105± 1138 0.000 1 37.2 ± 2.7 57.6 ± 4.2 20.5 1.5 E59 A 17204 ± 1538 21575± 1115 0.001 4 47 ± 3.9 58.9 ± 2.2 11.9 1.3 E59 D 22266 ± 1484 28238 ± 1077 0.000 5 69.7 ± 3.8 89.5 ± 3.5 19.8 1.3 E59 G 4551 ± 506 12357± 924 0.000 1 12.4 ± 0.9 35.1 ± 1.6 22.7 2.7 E59 Q 13611 ± 1152 18673± 1404 0.001 1 42.7 ± 3.2 58.8 ± 3.9 16.0 1.4 E59 V 2072 ± 168 7546 ± 732 0.000 1 6.7 ± 0.6 24.4 ± 2.8 17.8 3.6 Petition 870260032676, dated 08 / 04 / 2026, pp. 198 / 370 188 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 μM (% WT) Absolute Increase (% WT) Relative Increase P60 A 19972 ± 1596 26820 ± 1669 0.000 6 54.9 ± 4 73.2 ± 3 18.3 1.3 P60 Q 15470 ± 799 26238 ± 1132 0.000 1 48.7 ± 2 82.7 ± 2.9 34.0 1.7 P60 R 10622 ± 882 17095± 698 0.000 1 30 ± 2.1 48.8 ± 2 18.8 1.6 D61 E 29588 ± 1345 37109± 2077 0.004 9 97.9 ± 6 119.2 ± 5 21.4 1.3 D61 V 15741 ± 668 21299± 748 0.000 1 54.8 ± 2.9 74.8 ± 3.9 20.0 1.4 S62 A 31726 ± 1779 38602 ± 2163 0.003 0 95.2 ± 3.8 115.5 ± 4.2 20.2 1.2 S62 C 12299 ± 669 16978± 1074 0.000 6 41.3 ± 1.9 58.2 ± 4.6 16.9 1.4 S62 F 10360± 706 15534± 903 0.000 2 34.5 ± 1.7 52.6 ± 3 18.1 1.5 S62 P 245 ± 39 6945 ± 844 0.000 1 0.7 ± 0.1 19.3 ± 1.6 18.6 28.3 Petition 870260032676, dated 08 / 04 / 2026, pp. 199 / 370 189 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalast (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 μM Migalast (% WT) Absolute Increase (% WT) Relative Increase S62 Y 12108 ± 1047 19476 ± 875 0.000 1 40 ± 2.4 66.7 ± 3.7 26.7 1.6 I64L 229 ± 32 8452 ± 484 0.000 1 0.7 ± 0.1 24.3 ± 1.2 23.6 36.9 I64V 18259 ± 1030 27706 ± 637 0.000 1 54.5 ± 3.2 82.7 ± 2.6 28.2 1.5 S65 C 26986 ± 2021 35417± 2097 0.002 2 61.1 ± 2.3 81 ± 1.9 19.9 1.3 S65 G 19996± 2296 33127± 2448 0.000 5 64 ± 7.4 105.3 ± 7.1 41.3 1.7 S65 R 37555 ± 2042 45657 ± 2084 0.005 3 87.1 ± 4 105.7 ± 2.4 18.5 1.2 E66 D 24426 ± 1399 30874 ± 1190 0.000 7 56.4 ± 2 72.2 ± 2.3 15.8 1.3 E66 V 10943 ± 1124 15435± 1251 0.000 7 24.7 ± 1.7 35.2 ± 1.7 10.5 1.4 K67 E 30290 ± 1420 46106 ± 1265 0.000 1 70.7 ± 2.7 108.2 ± 2.8 37.6 1.5 Petition 870260032676, dated 08 / 04 / 2026, pp. 200 / 370 190 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalastat at 10 μM (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalastat at 10 μM (% WT) Absolute Increase (% WT) Relative Increase K67 M 22374 ± 1366 33812 ± 1237 0.000 1 53.3 ± 2.9 81.1 ± 2.6 27.8 1.5 K67 N 30951 ± 2447 48271 ± 1855 0.000 1 73.9 ± 5.6 115.9 ± 4.1 42.0 1.6 K67 Q 33571 ± 1439 48101 ± 1363 0.000 1 78.2 ± 2.3 113.2 ± 3.4 35.0 1.4 K67 T 29063 ± 2114 42744 ± 1271 0.000 1 69.3 ± 4.9 102.5 ± 2.6 33.2 1.5 L68I 1191 ± 125 9012 ± 534 0.000 1 2.8 ± 0.3 21.5 ± 1.1 18.7 7.6 F69I 376 ± 38 10829± 488 0.000 1 0.9 ± 0.1 25.4 ± 0.8 24.5 28.8 F69 Y 1500 ± 119 18806± 1141 0.000 1 3.3 ± 0.2 40.7 ± 2.2 37.4 12.5 M70I 24534 ± 1064 32895 ± 1518 0.000 1 60.7 ± 2.7 82.2 ± 4.6 21.5 1.3 M70 K 25582 ± 1732 38457 ± 1757 0.000 1 62.5 ± 3 94.9 ± 4.1 32.5 1.5 Petition 870260032676, dated 08 / 04 / 2026, pages 201 / 370 191 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 μM (% WT) Absolute Increase (% WT) Relative Increase M70 L 26515± 1172 31930± 1211 0.002 4 63.9 ± 1.4 78.4 ± 3.4 14.5 1.2 M70 R 27578 ± 2110 42595 ± 1951 0.000 1 59.4 ± 4 93 ± 5 33.6 1.5 E71 A 23766 ± 1537 32700 ± 1312 0.000 1 59.3 ± 4.5 81.1 ± 3.6 21.8 1.4 E71 D 26962 ± 1987 36176± 2174 0.000 9 61.1 ± 2.5 82.7 ± 3.1 21.7 1.3 E71 G 22820 ± 1979 32128± 878 0.000 1 54.7 ± 3 80.3 ± 3.4 25.6 1.4 E71 1 62.8 ± 2.8 85.3 ± 3.8 22.4 1.3 M72 L 8208 ± 664 23988 ± 1422 0.000 1 18.5 ± 1.1 54.9 ± 2.1 36.4 2.9 M72 T 25205 ± 1791 32476 ± 2471 0.020 6 57 ± 2.4 73.4 ± 3.3 16.5 1.3 Petition 870260032676, dated 08 / 04 / 2026, p. 202 / 370 192 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 μΜ (% WT) Absolute amplitude (% WT) Relative amplitude A73 S 23566 ± 1631 31993± 1944 0.003 3 53.7 ± 2.9 73.3 ± 3 19.6 1.4 A73 T 2379 ± 2393 ± 21939 1642 0.028 3 53.6 ± 3.3 66 ± 2.2 12.4 1.2 E74 D 28411 ± 1782 39202 ± 2134 0.000 3 69.6 ± 2.7 96.8 ± 2.7 2.7 2.74 G 1447 33068 ± 1675 0.000 2 58.8 ± 2.8 82.9 ± 3.5 24.2 1.4 E74 K 23026 ± 2084 27539 ± 1592 0.019 3 52.4 ± 16.4 ± 3.16. 1.2 E74 V 20975 ± 1489 25386 ± 1823 0.023 4 51.6 ± 3.1 63.2 ± 4.1 11.6 1.2 L75F 25253 ± 1313 30602 ± 1493 0.004 2.635 ± 3.66 76.7 ± 3.1 13.3 1.2 L75P 4084 ± 434 5513 ± 287 0.011 1 9.7 ± 0.9 13.6 ± 1 3.9 1.4 M76 V 11543 ± 644 20077 1.2 51.3 ± 2.6 21.3 1.7 Petition 870260032676, dated 08 / 04 / 2026, pp. 203 / 370 193 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 μM (% WT) Absolute Increase (% WT) Relative Increase V77I 29128 ± 1593 36588 ± 2669 0.036 0.72 ± 3.8 87.4 ± 2.9 15.4 1.3 V77L 29482 ± 1970 35834 ± 1940 0.017 4 77 ± 5.5 92.8 ± 3.2 15.7 1.2 S78L 27575 ± 1856 34892 ± 1683 0.002 4 68.9 ± 2.5 89.4 ± 3.2 20.5 1.3 S78 P 2263 ± 319 3971 ± 333 0.001 4 5.4 ± 0.7 9.7 ± 0.5 4.3 1.8 E79 A 24732 ± 1717 33721 ± 1802 0.001 1 72 ± 4.8 100.2 ± 6.9 28.3 1.4 E79 D 38422 ± 3185 51309± 3083 0.000 8 112.5 ± 9.3 153.4 ± 11.9 40.8 1.3 E79 G 23729 ± 2129 34762 ± 2171 0.000 5 68.9 ± 5.6 104.1 ± 8.5 35.2 1.5 E79 K 12002 ± 931 19360± 953 0.000 1 29.9 ± 1.3 50.5 ± 3 20.6 1.6 E79 Q 31940 ± 2387 44470 ± 3000 0.000 7 92.6 ± 6.2 134 ± 11.8 41.4 1.4 Petition 870260032676, dated 08 / 04 / 2026, pp. 204 / 370 194 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase E79 V 3360 ± 551 8915 ± 565 0.000 1 9.8 ± 1.5 26.3 ± 1.9 16.6 2.7 G80 A 12723 ± 1236 21243 ± 1698 0.000 1 35.3 ± 3.2 60.7 ± 5.7 25.4 1.7 G80 C 4279 ± 732 8085 ± 487 0.000 5 12.5 ± 2 24 ± 1.6 11.5 1.9 G80 S 14825 ± 1175 24788 ± 1376 0.000 1 43.2 ± 3.3 73.8 ± 5.1 30.6 1.7 W81 L BLD 1190 ± 99 0.000 1 N / A 4.4 ± 0.3 4.4 NC K82 E 7610 ± 608 10952 ± 967 0.010 0 30.7 ± 2.3 43.7 ± 3.2 12.9 1.4 K82 M 19592 ± 1306 25993 ± 2122 0.026 6 72.6 ± 4 94.8 ± 5.2 22.3 1.3 K82 N 11724 ± 855 17397± 1132 0.000 5 43.5 ± 2.6 63.9 ± 2.5 20.4 1.5 K82 R 22252 ± 1312 27326 ± 1986 0.045 5 83.6 ± 4.2 101.4 ± 5.6 17.7 1.2 Petition 870260032676, dated 08 / 04 / 2026, pages 205 / 370 195 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase K82 T 13117 ± 769 17594 ± 1185 0.002 6 49.2 ± 2.4 65.5 ± 3.5 16.3 1.3 D83 A 19999 ± 1698 24545 ± 1346 0.006 7 65.6 ± 3.9 81 ± 2.6 15.4 1.2 D83 E 26423 ± 1478 41691 ± 3309 0.000 7 76.3 ± 3.5 120.2 ± 9 43.9 1.6 D83 G 16734 ± 1241 21951 ± 1455 0.004 9 54.7 ± 2.5 72 ± 3 17.3 1.3 D83 V 14758 ± 1130 25238 ± 1768 0.000 1 45.8 ± 2.2 78.5 ± 3.9 32.7 1.7 A84 E 9978 ± 952 16862 ± 1319 0.000 3 27.7 ± 1.8 48.6 ± 3.9 20.9 1.7 A84 G 9870 ± 942 18181 ± 1377 0.000 1 28.6 ± 2.3 52.4 ± 3.3 23.9 1.8 A84 P 180 ± 47 1255 ± 141 0.000 1 0.6 ± 0.2 3.9 ± 0.4 3.3 7.0 A84 S 27798 ± 2763 36913 ± 2263 0.004 2 84.8 ± 5 116.1 ± 5.6 31.3 1.3 Petition 870260032676, dated 08 / 04 / 2026, pp. 206 / 370 196 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase A84 T 16960 ± 1350 23585 ± 2022 0.007 2 48.8 ± 2.7 69.3 ± 6 20.5 1.4 A84 V 34751 ± 2600 41833 ± 2901 0.045 5 94.9 ± 4.5 115.4 ± 6 20.5 1.2 G85 A 3114 ± 442 8107 ± 550 0.000 1 7.9 ± 0.9 20.8 ± 1.2 12.9 2.6 G85 C 926 ± 66 3079 ± 427 0.000 1 2.4 ± 0.2 7.5 ± 0.8 5.1 3.3 G85 R 9145 ± 1128 13622 ± 1053 0.003 9 22.5 ± 2.2 33.7 ± 1.5 11.2 1.5 Y86 F 12275 ± 707 16114± 468 0.000 2 31 ± 1.7 41 ± 1.7 10.0 1.3 E87 G 16130 ± 877 20394 ± 867 0.000 8 41 ± 2.6 52 ± 3 11.0 1.3 Y88 H 11199 ± 689 16074± 612 0.000 1 28.4 ± 1.3 41.5 ± 1.6 13.1 1.4 Y88 N 5381 ± 557 7561 ± 298 0.000 1 13.5 ± 1.1 19.5 ± 0.9 6.0 1.4 Petition 870260032676, dated 08 / 04 / 2026, pages 207 / 370 197 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase L89V 26558 ± 1501 33849 ± 1243 0.000 5 63.4 ± 4.6 80.7 ± 4.4 17.3 1.3 I91F 353 ± 36 3846 ± 338 0.000 1 1 ± 0.1 9.7 ± 0.5 8.7 10.9 I91L 17057 ± 1308 28279 ± 1631 0.000 1 54.3 ± 6 91.4 ± 9.9 37.0 1.7 I91M 19360± 1837 32190± 1335 0.000 1 47.9 ± 3.4 82.4 ± 3.8 34.5 1.7 I91S 946 ± 38 3966 ± 176 0.000 1 2.5 ± 0.2 10.2 ± 0.6 7.7 4.2 M96 L 24584 ± 1414 37462 ± 1866 0.000 1 61.8 ± 2.8 93.8 ± 3.1 32.0 1.5 M96 T 12103 ± 1633 18415± 1827 0.003 3 30.3 ± 3.3 46.7 ± 3.4 16.4 1.5 A97 D 17634 ± 1789 29319± 4081 0.003 9 45 ± 3.4 74.5 ± 9.5 29.5 1.7 A97 S 21262 ± 1383 27841 ± 2335 0.012 8 55.7 ± 3.7 70.9 ± 4.2 15.1 1.3 Petition 870260032676, dated 08 / 04 / 2026, pp. 208 / 370 198 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase A97 T 11157 ± 776 19875 ± 1502 0.000 1 29.4 ± 2.2 50.9 ± 2.7 21.4 1.8 P98 H 21896 ± 1232 29920 ± 1808 0.001 3 60.8 ± 3.1 83.4 ± 4.6 22.5 1.4 P98L 24223 ± 1555 31835± 2399 0.007 2 69 ± 5.5 88.5 ± 6.3 19.6 1.3 P98 R 24969 ± 1730 31289± 2550 0.040 5 69.4 ± 4 85.8 ± 5.8 16.4 1.3 Q99 E 25264 ± 1668 34635 ± 3117 0.010 4 70.3 ± 4.1 95.8 ± 7.9 25.5 1.4 Q99 L 23382 ± 1548 33479 ± 2746 0.001 2 65.9 ± 5.1 93.4 ± 7.3 27.4 1.4 Q99 P 3034 ± 340 9885 ± 794 0.000 1 8.8 ± 1.2 28 ± 2.4 19.1 3.3 Q99 R 32963 ± 1757 41024± 3001 0.019 3 93.4 ± 6.3 114.8 ± 8 21.4 1.2 D10 1A 10144 ± 1069 14707 ± 1289 0.004 9 23.9 ± 3 34.1 ± 3.3 10.2 1.5 Petition 870260032676, dated 08 / 04 / 2026, pages 209 / 370 199 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase D10 1E 10465 ± 624 14682 ± 993 0.001 0 23.9 ± 1.6 34 ± 2.8 10.1 1.4 D10 1G 18091 ± 1103 23672 ± 1428 0.003 3 41.8 ± 3.1 54.5 ± 3.8 12.7 1.3 D10 1H 7311 ± 556 10493± 561 0.000 2 16.5 ± 1.2 23.8 ± 1.3 7.3 1.4 D10 1V 3368 ± 179 7489 ± 936 0.000 1 7.8 ± 0.5 18 ± 2.6 10.2 2.2 S102 A 17330 ± 2084 26790 ± 1958 0.001 8 42.6 ± 3.5 69.9 ± 5.1 27.3 1.6 S102 P 27252 ± 1778 35885 ± 2754 0.011 1 69.4 ± 3.4 91.7 ± 5 22.3 1.3 S102 T 22123 ± 2319 29662 ± 2559 0.033 9 56.4 ± 5.2 76.9 ± 6.2 20.5 1.3 G10 4A 5271 ± 397 19670± 1202 0.000 1 14.8 ± 1 55.2 ± 3 40.4 3.7 G10 4D 14123 ± 1096 24797 ± 1771 0.000 1 39.3 ± 2.6 69.8 ± 4.7 30.5 1.8 Petition 870260032676, dated 08 / 04 / 2026, pp. 210 / 370 200 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalastat at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalastat at 10 pM (% WT) Absolute Increase (% WT) Relative Increase G10 4S 5720 ± 464 22242 ± 1000 0.000 1 17.9 ± 1.8 69.8 ± 5.8 52.0 3.9 R10 5G 16513 ± 681 22993 ± 1042 0.000 1 38 ± 2.1 53.3 ± 3.5 15.3 1.4 R10 5I 9696 ± 798 12128± 1157 0.015 8 33.4 ± 2.2 41.6 ± 3.1 8.2 1.3 R10 5K 25495 ± 1793 31647± 2251 0.036 0 76.2 ± 2.9 96.7 ± 5.2 20.5 1.2 R10 5T 12553± 603 17062 ± 1134 0.002 0 44 ± 2.2 59.6 ± 3.9 15.6 1.4 L106 H 856 ± 58 3009 ± 399 0.000 1 3 ± 0.2 10.2 ± 1.1 7.3 3.5 L106 I 13485 ± 1014 20120± 1416 0.000 2 46.4 ± 2.7 70 ± 4.7 23.6 1.5 L106 P 8835 ± 878 16075± 1039 0.000 1 30.7 ± 2.7 56.5 ± 3.9 25.8 1.8 L106 V 15393± 1288 20991 ± 1611 0.003 3 53.6 ± 4.3 73.4 ± 5.9 19.8 1.4 Petition 870260032676, dated 08 / 04 / 2026, pages 211 / 370 201 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase Q10 7E 13148 ± 985 16149 ± 1059 0.011 1 45.7 ± 3.1 56.2 ± 3.3 10.4 1.2 Q10 7H 12307 ± 487 14822 ± 384 0.000 1 41.7 ± 1.5 50.8 ± 2 9.1 1.2 Q10 7K 14579 ± 2689 20402 ± 3399 0.012 8 38.2 ± 3.9 54.6 ± 4.8 16.4 1.4 A108 E 11629 ± 835 15648± 1305 0.011 1 38.4 ± 2.6 52.6 ± 4.6 14.2 1.4 A108 V 4914 ± 799 17249± 2284 0.000 1 13.3 ± 1.7 47.7 ± 4.6 34.4 3.5 D10 9A 6345 ± 1034 13742 ± 1780 0.000 2 17.5 ± 2.2 38 ± 3.7 20.4 2.2 D10 9E 13839± 1179 16926± 1156 0.014 7 41.3 ± 3.4 50.6 ± 3.6 9.3 1.2 D10 9H 7540 ± 684 16483± 1317 0.000 1 24.6 ± 1.7 54.6 ± 3.5 30.0 2.2 D10 9N 1475±83 12358± 973 0.000 1 5 ± 0.3 41.5 ± 2.8 36.5 8.4 Petition 870260032676, dated 08 / 04 / 2026, pp. 212 / 370 202 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration D10 9Y 212 ± 30 2530 ± 415 0.000 1 0.7 ± 0.1 8.2 ± 1.1 7.5 11.9 P110 T 0.004 9 62.6 ± 5.9 81.2 ± 6.5 18.6 1.3 F113 V 341 ± 41 3614 ± 596 0.000 1 1.1 ± 0.1 10.3 ± 1 9.2 10.6 F113 Y BLD 180 ± 180 ± 109 N / A 4.4 ± 0.3 4.4 NC P114 L 6229 ± 901 7973 ± 626 0.006 2 18.3 ± 2.1 23.7 ± 1.3 5.4 1.3 H11 5D 10284 ± 1141 ± 1141 ± 1.4028 30.7 ± 2.9 44.8 ± 3 14.1 1.5 H11 5N 13745 ± 890 23018± 1098 0.000 1 44.9 ± 2.5 75 ± 2.5 30.1 1.7 G11 6R 192 143 ± 145 ± 145 0.000 1 5.4 ± 0.3 15.4 ± 1.5 9.9 2.7 I117 M 20226 ± 1373 31280± 1153 0.000 1 54.2 ± 3.9 83.5 ± 3.6 29.4 1.6 Petition 870260032676, dated 08 / 04 / 2026, pp. 213 / 370 203 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase I117 T 1607 ±54 3303 ± 308 0.000 1 4.3 ± 0.2 9 ± 0.9 4.7 2.1 A121 V 7301 ± 253 26639 ± 1124 0.000 1 21.5 ± 1.2 78.2 ± 4.2 56.7 3.7 Y123 D 15093± 815 18723± 1237 0.008 3 43.4 ± 1.6 53.6 ± 2.7 10.2 1.2 Y123 F 22066 ± 1408 33544 ± 1384 0.000 1 63.6 ± 3.3 97.4 ± 3.4 33.8 1.5 Y123 N 13817 ± 816 20466 ± 846 0.000 1 40.9 ± 3.2 60.6 ± 4.1 19.7 1.5 Y123 S 14556 ± 986 21255± 1484 0.000 8 41.7 ± 2.1 61 ± 3.6 19.3 1.5 V124 I 32074 ± 1858 43288 ± 2179 0.000 3 80.7 ± 2 111.3 ± 4.5 30.6 1.4 H12 5D 995±106 3282 ± 375 0.000 1 2.3 ± 0.2 8.8 ± 1.4 6.5 3.3 H12 5N 14162 ± 994 20228 ± 1240 0.000 6 33.5 ± 1.8 48.4 ± 2.7 14.9 1.4 Petition 870260032676, dated 08 / 04 / 2026, pp. 214 / 370 204 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase H12 5R 14738 ± 699 24004 ± 987 0.000 1 36 ± 1.2 59.1 ± 1.9 23.0 1.6 S126 C 7046 ± 488 10050± 554 0.000 4 16.9 ± 1.1 24.5 ± 1.5 7.5 1.4 S126 I 28685 ± 1923 35340 ± 2027 0.023 4 69.8 ± 5.1 85.9 ± 5.3 16.0 1.2 K127 E 8968 ± 519 11003± 768 0.014 7 25.8 ± 1.1 32.2 ± 2.3 6.4 1.2 G12 8A 8484 ± 872 10204± ​​703 0.031 9 20.8 ± 2 25.9 ± 2.3 5.1 1.2 L129 V 12614 ± 1265 19488± 1603 0.001 2 31.8 ± 3.3 48.1 ± 4.5 16.4 1.5 K130 M 12335 ± 890 16496± 921 0.002 0 30.5 ± 2.1 41.4 ± 2.6 10.9 1.3 K130 N 8597 ± 678 12595± 989 0.001 7 21.5 ± 1.9 31.5 ± 3 10.1 1.5 K130 Q 11880 ± 450 16001 ± 701 0.000 1 35.8 ± 2.6 47.8 ± 3.1 12.0 1.4 Petition 870260032676, dated 08 / 04 / 2026, pages 215 / 370 205 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase L131 V 18644 ± 1664 24913 ± 3151 0.031 9 40.5 ± 2.8 53.2 ± 5.3 12.7 1.3 I133 L 24431 ± 1181 31550± 1420 0.000 4 60.7 ± 2.7 78.2 ± 3.1 17.5 1.3 I133 T 4362 ± 397 10255± 335 0.000 1 10.8 ± 1 25.8 ± 1.1 15.0 2.4 I133 V 38738 ± 1624 47299 ± 1885 0.000 7 96.2 ± 3.7 118.1 ± 5.1 21.9 1.2 A135 E 10143 ± 752 12954± 678 0.004 5 25.1 ± 1.5 32.5 ± 1.6 7.4 1.3 A135 G 29959 ± 2193 36552 ± 2309 0.020 6 73.9 ± 3.8 90 ± 3.6 16.1 1.2 A135 S 16777 ± 897 21383± 1125 0.002 0 45.6 ± 2.9 57.9 ± 3.2 12.2 1.3 A135 T 7906 ± 694 18890± 2092 0.000 1 17.4 ± 1.3 40.5 ± 3.4 23.2 2.4 D13 6A 8054 ± 482 12166 ± 927 0.000 1 20.4 ± 1.1 29.8 ± 1 9.4 1.5 Petition 870260032676, dated 08 / 04 / 2026, pp. 216 / 370 206 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration D13 6N 5079 ± 248 9827 ± 630 0.000 1 13 ± 0.8 24.2 ± 0.9 11.2 1.9 D13 6V 6V 3779 0.000 1 42.2 ± 1.7 116.4 ± 5.5 74.2 2.8 V137 A 22393 ± 1429 40016± 2785 0.000 1 61.1 ± 4.6 106.6 5.41 ± 1.38 V137 516 ± 80 4757 ± 618 0.000 1 1.4 ± 0.2 13 ± 1.6 11.6 9.2 V137 G 16515± 1170 36258 ± 1701 0.000 1 45.9 ± 4.29 ± 2.2.2.2.5 V137 I 12148 ± 597 21313± 987 0.000 1 32.8 ± 1.6 57.4 ± 2.5 24.7 1.8 V137 L 15359± 656 19794± 1475 0.004 51.36 ± 3.5 3.7 11.7 1.3 G13 8A 4768 ± 480 11112 ± 732 0.000 1 14.4 ± 1.1 34.5 ± 1.5 20.1 2.3 N13 9H 29115 ± 2336 40.0678 3.020 ± 4.000 73.1 ± 5.4 101.2 ± 7.1 28.1 1.4 Petition 870260032676, dated 08 / 04 / 2026, pp. 217 / 370 207 / 305 Table 7 Mutant form of α- Gal 10 pM (% WT) Absol ute increase (% WT) Relative increase N13 9I 17180 ± 1455 26326 ± 1627 0.000 1 51.8 ± 5.1 78.3 ± 4.5 26.4 1.5 N13 9K 33797 ± 2244 45090 ± 2667 0.002 2 93.6 ± 5.8 127.4 ± 8.8 33.8 1.3 N13 9Y 19998± 1682 24303 ± 2079 0.040 5 52.3 ± 3.8 64 ± 5.2 11.7 1.2 K140 E 26053 ± 1925 46670 ± 2685 0.000 1 72.6 ± 5.8 132.1 ± 9 59.5 1.8 K140 I 15415 ± 1294 32440 ± 2092 0.000 1 42.7 ± 3.3 92.1 ± 7.1 49.4 2.1 K140 N 40575 ± 2928 54681 ± 3030 0.001 3 113.8 ± 9.5 154.1 ± 11.1 40.3 1.4 K140 Q 42995 ± 3236 59162 ± 3600 0.000 9 123.2 ± 12.1 165.7 ± 9.7 42.5 1.4 K140 R 50348 ± 3558 62820 ± 3401 0.012 0 141.5 ± 12 180.9 ± 15 39.4 1.3 T141 S 22602 ± 2254 34806 ± 2770 0.001 8 63.8 ± 7.1 98.2 ± 9.1 34.4 1.5 Petition 870260032676, dated 08 / 04 / 2026, pp. 218 / 370 208 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase A143 E 7681 ± 439 11458 ± 884 0.001 5 25.9 ± 1.5 37.3 ± 1.8 11.4 1.5 A143 G 20419 ± 1260 36821 ± 2997 0.000 1 67.8 ± 3.4 119.7 ± 5.9 51.9 1.8 G14 4A 20304 ± 1590 27268 ± 1039 0.001 1 44.9 ± 3.6 60.4 ± 2.8 15.5 1.3 G14 4C 759 ± 69 2988 ± 262 0.000 1 2.5 ± 0.2 9.5 ± 0.8 7.1 3.9 G14 4R 10574 ± 838 21406± 1764 0.000 1 35.7 ± 2.8 73.4 ± 6.5 37.7 2.0 G14 4S 14190 ± 967 23153± 1847 0.000 3 47.6 ± 2.4 78 ± 5.6 30.4 1.6 F145 C 768 ± 54 11083± 678 0.000 1 2.1 ± 0.2 27.8 ± 0.8 25.7 14.4 F145 L 5455 ± 412 29794 ± 1799 0.000 1 13.9 ± 0.8 75.7 ± 2.9 61.8 5.5 F145 V BLD 2359 ± 333 0.000 1 N / A 5.7 ± 0.6 5.7 NC Petition 870260032676, dated 08 / 04 / 2026, pp. 219 / 370 209 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase F145 Y 41985 ± 2942 51524 ± 2970 0.014 7 108.1 ± 6.2 131.7 ± 5.1 23.5 1.2 P146 A 15393 ± 1271 25029 ± 1628 0.000 2 38.7 ± 2.5 64.1 ± 4.4 25.4 1.6 P146 H 3220 ± 211 11903± 844 0.000 1 8.5 ± 0.7 30.2 ± 2.1 21.8 3.7 P146 L 9940 ± 899 14540± 903 0.000 9 24.7 ± 1.8 37.1 ± 2.2 12.4 1.5 P146 T 13711 ± 1154 24123± 2081 0.000 4 33.6 ± 1.5 58.6 ± 2.4 25.0 1.8 G14 7A BLD 1159 ± 74 0.000 1 N / A 3 ± 0.2 3.0 NC S148 C 11927 ± 1020 19343± 919 0.000 1 30.2 ± 2.2 49.5 ± 2 19.3 1.6 S148 G 435 ± 55 4879 ± 263 0.000 1 1.1 ± 0.1 12.9 ± 1 11.8 11.2 S148 T 24827 ± 1221 30620 ± 813 0.000 6 66.5 ± 3.8 82.4 ± 3.7 15.9 1.2 Petition 870260032676, dated 08 / 04 / 2026, pages 220 / 370 210 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase F149 C 15198 ± 1188 19032 ± 1272 0.030 147 ± 4.4 60.9 ± 6.4 13.9 1.3 G15 0E 18804 ± 1070 22710± 1059 0.012 0 61.5 ± 6.6 73.8 ± 7 12.3 1.2 G15 0V 1080±63 4639 ± 361 0.000 1 2.9 ± 0.1 12.1 ± 0.7 9.2 4.3 Y151 C 11271 ± 579 15859± 752 0.000 1 32.4 ± 1.5 45.6 ± 2 13.2 1.4 Y151 D 10673± 604 15196± 1025 0.000 6 29.3 ± 1.7 40.8 ± 2.2 11.5 1.4 Y151 S 30047 ± 1943 37527 ± 2003 0.006 7 84.8 ± 4.2 107 ± 4.9 22.2 1.3 Y152 F 18675± 907 23612 ± 1095 0.001 3 45.4 ± 2.6 56.8 ± 2.7 11.4 1.3 Y152 S 9917 ± 917 16642 ± 1218 0.000 2 27.1 ± 1.7 46.7 ± 2.6 19.6 1.7 D15 3A 22606 ± 1445 30854 ± 1997 0.002 8 60.1 ± 2.4 81.6 ± 2.3 21.6 1.4 Petition 870260032676, dated 08 / 04 / 2026, pp. 221 / 370 211 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration D15 3H 23578 ± 1741 31052 ± 1774 0.003 0 60.5 ± 2.2 81 ± 2.1 20.5 1.3 D1 ± 1551 0.000 1 65.6 ± 2.8 89.7 ± 4.4 24.1 1.3 D15 3V 7357 ± 1139 16301 ± 766 0.000 ± 1299 22535 ± 1174 0.000 1 29.1 ± 3.1 52.4 ± 2.8 23.3 1.8 A156 G 17406 ± 1187 23415± 1710 0.003 3 46.7 ± 3.36 ± 3.6 1.4 Q15 7E 28269 ± 1306 37204 ± 2126 0.000 7 77.4 ± 4.1 101.5 ± 6.1 24.1 1.3 Q15 7K 9815 ± 1083 31331 ± 2428 ± 20.01 ± 2401 1.8 79.7 ± 5 55.6 3.2 Q15 7L 5734 ± 700 28942 ± 2013 0.000 1 14.3 ± 1.5 74.4 ± 4.3 60.2 5.1 Q15 7P 3887 ± 2887 ± 2878 0.000 1 9 ± 1 49.6 ± 3.4 40.6 5.4 Petition 870260032676, dated 08 / 04 / 2026, pp. 222 / 370 212 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration T158 A 14835 ± 1107 25678 ± 1673 0.000 1 38.6 ± 2.5 67.3 ± 3.1 28.7 1.7 T1 ± 1695 0.004 2 49 ± 2.7 67.8 ± 3.4 18.8 1.4 T158 N 1906 ± 106 5991 ± 499 0.000 1 5.4 ± 0.2 18.2 ± 2 12.8 3.1 T1053 ± 2173 S 39060 ± 2937 0.016 9 79.3 ± 4 99.1 ± 5.6 19.8 1.3 F159 I 21543 ± 1754 29402 ± 1960 0.005 7 64.7 ± 3.5 89.3 .414 L 22840 ± 1245 31357± 1408 0.000 1 75.6 ± 8.4 103.6 ± 10.7 28.0 1.4 F159 V 16474 ± ​​1048 26241 ± 1907 0.00 ± 159.80. 4.8 29.8 1.6 F159 Y 2573 ± 301 10052 ± 825 0.000 1 7.7 ± 0.7 30.1 ± 1.7 22.4 3.9 A160 G 13634 ± 2705 196437 ± 30.77 ± 30.351 3.7 54.1 ± 5.3 19.0 1.4 Petition 870260032676, dated 08 / 04 / 2026, pp. 223 / 370 213 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase A160 S 18308 ± 685 27775 ± 1478 0.000 1 56 ± 3.1 85.9 ± 6.3 29.9 1.5 A160 T 20193 ± 1713 29082 ± 1980 0.000 1 59.6 ± 3.5 90.9 ± 8.1 31.3 1.4 A160 V 15511 ± 1847 22124± 1885 0.001 3 44.1 ± 2.7 66 ± 4.8 21.9 1.4 D16 1H 21949 ± 2587 26457 ± 2512 0.002 6 61.5 ± 2.9 77 ± 3.8 15.5 1.2 D16 1N 19553± 2838 24298 ± 3201 0.006 2 54.5 ± 4.3 68.7 ± 4.9 14.1 1.2 D16 1V 13728 ± 1344 19117± 2241 0.005 7 43.7 ± 1.7 59.7 ± 2.7 16.0 1.4 D16 1Y 11060 ± 1571 21231 ± 2136 0.000 1 31 ± 2.5 63.1 ± 4.6 32.1 1.9 W16 2S 653 ± 38 3019 ± 210 0.000 1 2.6 ± 0.2 11.8 ± 0.8 9.2 4.6 V164 A 6491 ± 691 8468 ± 832 0.014 7 24.5 ± 1.8 32 ± 2.2 7.5 1.3 Petition 870260032676, dated 08 / 04 / 2026, pp. 224 / 370 214 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute amount (% WT) Relative amount V164 I 12164 ± 1271 23219± 2640 0.000 3 45.1 ± 3.4 87.1 ± 8.2 41.9 1.9 V1645 L ± 1952 0.000 1 51.2 ± 3.8 86.2 ± 5.2 35.0 1.7 D16 5A 271 ± 30 1397 ± 86 0.000 1 1 ± 0.1 5.4 ± 0.3 4.4 5.2 E 288 0.000 1 5.4 ± 0.2 23.8 ± 1.6 18.4 4.4 L166 M 15603± 1630 27922 ± 1578 0.000 1 55.2 ± 4.5 104 ± 7.3 8.8 L166 ± 1566 325 14720± 616 0.000 1 18.4 ± 1.2 47.6 ± 1.9 29.2 2.6 L167 I 14763 ± 942 22948 ± 1321 0.000 1 46.8 ± 2.27 ± 2.27.26. F169 C 6861 ± 977 16396± 1516 0.000 1 18.1 ± 2 44.9 ± 2.3 26.9 2.4 F169 L 15588± 1463 26527 ± 1806 0.000 18.47 ± 2.32 3.2 34.5 1.7 Petition 870260032676, dated 08 / 04 / 2026, pages 225 / 370 215 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase F169 V 2870 ± 239 16145 ± 1680 0.000 1 10.2 ± 0.9 53 ± 2.1 42.8 5.6 F169 Y 14358 ± 1768 23459 ± 2391 0.000 3 45.3 ± 2.8 75.5 ± 3.6 30.2 1.6 G17 1A 19081 ± 1801 27514± 2486 0.003 0 57.6 ± 2.8 84 ± 5.7 26.4 1.4 G17 1V 856 ± 62 3111 ± 411 0.000 1 2.8 ± 0.2 9.2 ± 0.9 6.4 3.6 Y173 C 17669± 1240 27924 ± 1225 0.000 1 51.1 ± 3.6 80.5 ± 3.3 29.3 1.6 Y173 F 26479 ± 1523 33158± 657 0.000 4 76.5 ± 4.2 97.7 ± 4.7 21.2 1.3 Y173 H 21234 ± 879 27455 ± 1147 0.000 2 61.9 ± 3.4 80.2 ± 4.6 18.3 1.3 Y173 S 21751 ± 1625 26270 ± 994 0.000 7 61.4 ± 3.3 76.2 ± 3.3 14.8 1.2 D17 5G 23065 ± 2315 28273 ± 1968 0.012 8 74.7 ± 6.7 92.8 ± 6.2 18.1 1.2 Petition 870260032676, dated 08 / 04 / 2026, pp. 226 / 370 216 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase D17 5H 18529 ± 1174 26201 ± 994 0.000 1 60.7 ± 3.4 87.1 ± 3.9 26.4 1.4 D17 5V 10430 ± 915 16384±1039 0.000 1 33.7±2.2 53.5±2.5 19.7 1.6 D17 5Y 8991±838 15923±778 0.000 1 29.4±2.4 52.3±1.9 22.9 1.8 C 20097 ± 1126 24777 ± 960 0.006 7 63.3 ± 3.9 79.5 ± 5.1 16.2 1.2 S176 R 22675 ± 886 30159± 1226 0.000 1 66.3 ± 2 88.3 ± 3.3 22.0 1.3 L177 F 15605± 911 28893 ± 1210 0.000 1 45.3 ± 2.1 84 ± 2.3 38.7 1.9 L177 M 23730 ± 946 33080 ± 829 0.000 1 69.5 ± 2.3 97.4 ± 2.7 27.9 1.4 L177 S 17445 ± 533 29868 ± 1909 0.000 1 51.4 ± 1.7 87.2 ± 4.5 35.9 1.7 L177 V 23616 ± 1282 31347 ± 1132 0.000 1 68.9 ± 3.2 91.8 ± 2.8 22.9 1.3 Petition 870260032676, dated 08 / 04 / 2026, pages 227 / 370 217 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute amount (% WT) Relative amount L177 W 17321 ± 1025 30075 ± 867 0.000 1 50.5 ± 2.6 88.2 ± 2 37.6 1.7 E178 A 2326 0.048 1 70.3 ± 4.9 84.8 ± 6.8 14.5 1.2 E178 G 17470 ± 2323 26566 ± 4263 0.021 9 43.1 ± 4.7 61.7 6.41 ± 8.68 K. 25584 ± 1225 31222 ± 1660 0.007 7 74.5 ± 3.4 90.9 ± 4.8 16.4 1.2 E178 Q 23272 ± 1501 29671 ± 1733 0.006 28.65 ± 4.5 ± 4.5 18.3 1.3 L180 M 35987 ± 2266 47587 ± 2132 0.000 2 93.4 ± 6.6 122.9 ± 5.5 29.5 1.3 L180 S 5625 ± 604 18335 ± 0.0604 ± 10.54 1.5 50.9 ± 2.3 35.5 3.3 A181 P 10948 ± 725 21274± 1279 0.000 1 31.7 ± 2 61.5 ± 3.3 29.8 1.9 A181 T 0.001 2 52.1 ± 2.7 71.3 ± 4.6 19.2 1.4 Petition 870260032676, dated 08 / 04 / 2026, pages 228 / 370 218 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration A181 V 26667 ± 1945 32358 ± 2863 0.033 9 79.1 ± 3.5 93.2 ± 5.3 14.2 1.2 D1 44436 ± 3828 0.009 6 101.5 ± 5.7 133.3 ± 8.2 31.8 1.3 D18 2E 28082 ± 2023 38956 ± 2806 0.001 1 84.8 ± 417 ± 14.3.4 D18 2V 26881 ± 2166 42107± 3524 0.000 5 80.2 ± 4.2 124.8 ± 6.9 44.7 1.6 D18 2Y 28377 ± 2226 39247 3250 ± 0.000 8.47 ± 4.46 116.5 ± 6.4 31.9 1.4 Y184 F 26088 ± 1334 36815± 2009 0.000 2 77.9 ± 4.4 109.7 ± 5.8 31.8 1.4 Y184 H 0.000 1 30.2 ± 2.9 48.6 ± 3.5 18.4 1.6 Y184 S 5213 ± 371 13965± 799 0.000 1 15.4 ± 1 40.6 ± 1.6 25.2 2.7 K M 44387 ± 2696 0.001 4 75.1 ± 4.6 102.9 ± 9 27.8 1.3 Petition 870260032676, dated 08 / 04 / 2026, pp. 229 / 370 219 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase K185 N 833 ± 38 10540 ± 618 0.000 1 1.9 ± 0.1 24.4 ± 1.9 22.5 12.7 K185 Q 14992 ± 947 25543 ± 1463 0.000 1 43.6 ± 2.2 74.5 ± 2.9 30.9 1.7 K185 T 32028 ± 1167 39805 ± 2259 0.002 4 73.6 ± 4.4 92.6 ± 7.8 19.0 1.2 H18 6D 26924 ± 2047 34055 ± 1657 0.006 7 60 ± 4.1 78.2 ± 5.2 18.2 1.3 H18 6L 31615± 1833 42145± 2540 0.000 9 70.4 ± 3.4 97.5 ± 8.2 27.1 1.3 H18 6N 28175 ± 1462 39509 ± 1885 0.000 1 63.5 ± 3.1 90.3 ± 5.8 26.8 1.4 H18 6Q 28845 ± 2365 38865 ± 2966 0.012 0 76.9 ± 4.3 105.3 ± 7 28.5 1.4 H18 6Y 37644 ± 2421 53613± 2581 0.000 1 83.8 ± 4.5 123.6 ± 8.9 39.8 1.4 M18 7L 1924 ±64 12810± 929 0.000 1 5.3 ± 0.2 34.5 ± 1.9 29.2 6.7 Petition 870260032676, dated 08 / 04 / 2026, pp. 230 / 370 220 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase S188 A 22589 ± 1833 32197 ± 2515 0.007 2 60.6 ± 4 86.3 ± 4.9 25.7 1.4 S188 C 18465 ± 1552 25569 ± 2083 0.003 3 50.1 ± 3.7 68.6 ± 4.3 18.5 1.4 S188 F 7746 ± 839 21273± 1477 0.000 1 20.7 ± 2 57.1 ± 2.8 36.4 2.8 S188 P BLD 1159 ± 61 0.000 1 N / A 3.2 ± 0.2 3.2 NC S188 T 17041 ± 1389 26198± 2461 0.000 4 45.4 ± 2.5 69.5 ± 4.5 24.0 1.5 S188 Y 12244 ± 1167 23849 ± 1725 0.000 1 32.6 ± 2.6 64.1 ± 3.5 31.5 2.0 L189 S 23204 ± 1213 29510± 1181 0.000 7 72.6 ± 3.1 92.7 ± 3.2 20.1 1.3 L189 V 25544 ± 1758 32031 ± 1633 0.004 9 79.9 ± 5.1 100.1 ± 3.9 20.2 1.3 A190 D 7141 ± 423 15887± 1308 0.000 1 22.1 ± 1 49 ± 3.4 26.9 2.2 Petition 870260032676, dated 08 / 04 / 2026, pp. 231 / 370 221 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase A190 G 24299 ± 2173 34126 ± 2992 0.003 0 70.5 ± 7.3 97.9 ± 9.8 27.4 1.4 A190 S 27316 ± 1369 35787 ± 2235 0.002 6 84.5 ± 3.2 110.6 ± 5.5 26.1 1.3 A190 T 8600 ± 733 18373± 795 0.000 1 26.3 ± 2 57 ± 1.9 30.7 2.1 A190 V 12542 ± 1642 27078 ± 2910 0.000 1 36.8 ± 5.1 77.9 ± 9.5 41.2 2.2 L191 M 19968± 2010 34977 ± 3072 0.000 1 58.4 ± 6.6 100.2 ± 9.8 41.7 1.8 L191 V 24068 ± 1533 37342 ± 2569 0.000 1 71.1 ± 4.7 110.2 ± 7.9 39.1 1.6 N19 2D 9035 ± 886 28923 ± 1892 0.000 1 25.9 ± 3 81.5 ± 6.7 55.6 3.2 N19 2H 3103 ± 402 8765 ± 935 0.000 1 8.6 ± 1.1 24.9 ± 3 16.4 2.8 N19 2K 8005 ± 776 22845 ± 1943 0.000 1 26.3 ± 1.7 76.8 ± 5.6 50.5 2.9 Petition 870260032676, dated 08 / 04 / 2026, pp. 232 / 370 222 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration N19 2S 2470 ± 217 4712 ± 843 0.000 3 8.3 ± 0.6 15 ± 1.9 6.6 1.9 N19 2T 0.000 1 10.1 ± 0.7 23.5 ± 4 13.4 2.2 R19 3G 20819 ± 1615 32498 ± 2580 0.000 9 64.7 ± 4.1 102.7 ± 7.8 38.0 17.3 M ± 353 M 2087 34818± 2049 0.007 7 68.2 ± 2.7 89.4 ± 5.4 21.2 1.3 R19 3T 27863 ± 1953 38519± 2880 0.005 3 70.7 3.69 ± 9.68 ± 1.4 R19 3W 10407 ± 919 21063± 1562 0.000 1 32 ± 2.4 66.6 ± 4.6 34.6 2.0 T194 N 753 ± 80 5923 ± 816 0.000 1.20 ± 2.27 ± 2.3 15.1 7.9 T194 P 951 ± 71 8134 ± 602 0.000 1 2.6 ± 0.3 21.2 ± 1.6 18.6 8.6 T194 S 27831 ± 2308 44208 ± 28890 395 ± 695 112.1 ± 6.2 42.6 1.6 Petition 870260032676, dated 08 / 04 / 2026, pages 233 / 370 223 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase G19 5C 8165 ± 500 13240 ± 568 0.000 1 24.6 ± 2.4 39.6 ± 3 15.0 1.6 G19 5R 15572 ± 893 30415±1008 0.000 1 46±3.5 89.4±4.8 43.4 2.0 G19 5S 20112±883 25947±1235 0.000 1 60.5±5 78±6.6 17.5 1.3 R19 6I 12764 ± 1241 25303 ± 3386 0.000 3 30.6 ± 1.8 59.6 ± 5 29.0 2.0 R19 6K 27718 ± 2086 38090 ± 2117 0.000 9 69.8 ± 2.9 97.6 ± 3.2 27.8 1.4 S197 C 4181 ± 151 7035 ± 598 0.000 2 11.7 ± 0.8 18.3 ± 1 6.5 1.7 S197 G 27255 ± 1639 33018± 1986 0.024 9 72.3 ± 2.1 88.4 ± 3.7 16.1 1.2 S197 I 9277 ± 581 18272 ± 1006 0.000 1 25.2 ± 1.3 49.5 ± 2.1 24.3 2.0 S197 N 23664 ± 1103 30051 ± 1440 0.000 6 56.9 ± 2.5 72.1 ± 3.3 15.2 1.3 Petition 870260032676, dated 08 / 04 / 2026, pp. 234 / 370 224 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase S197 T 24022 ± 1698 33425 ± 1713 0.000 1 57.6 ± 3.9 79.9 ± 3.6 22.3 1.4 I198 M 29416 ± 1526 41174± 2420 0.000 2 82.3 ± 6.7 113.7 ± 8 31.4 1.4 I198 S 1296±63 8455 ± 513 0.000 1 3.6 ± 0.3 22.8 ± 1.3 19.2 6.5 V199 E 5470 ± 293 15458± 855 0.000 1 15.2 ± 1.1 41.5 ± 1.9 26.2 2.8 V199 L 23090 ± 1117 41654 ± 2281 0.000 1 64.4 ± 4.6 113.2 ± 6.6 48.8 1.8 Y200 N 3364 ± 193 17117± 1368 0.000 1 9.5 ± 0.8 46.8 ± 3.5 37.3 5.1 Y200 S 514 ± 47 8573 ± 601 0.000 1 1.4 ± 0.1 24.4 ± 1.5 22.9 16.7 S201 A 37974 ± 2291 47325 ± 1754 0.002 4 90.6 ± 5 113.1 ± 3.3 22.5 1.3 S201 C 10947 ± 594 23033 ± 1510 0.000 1 33.3 ± 2 71.2 ± 6 37.9 2.1 Petition 870260032676, dated 08 / 04 / 2026, pages 235 / 370 225 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase S201 T 21522 ± 1510 43648 ± 2695 0.000 1 60.5 ± 3.4 122.5 ± 4.4 62.0 2.0 E203 A 2061 ± 101 4400 ± 185 0.000 1 8.2 ± 0.5 17.3 ± 0.8 9.1 2.1 E203 G 12576 ± 575 21197± 865 0.000 1 48.9 ± 1.9 83.7 ± 4.4 34.8 1.7 E203 Q 612 ± 36 2639 ± 161 0.000 1 1.9 ± 0.1 8.2 ± 0.7 6.3 4.3 W20 4S 355 ± 31 7926 ± 612 0.000 1 1.4 ± 0.1 30.8 ± 2.2 29.4 22.3 W ± 3.5 34.2 ± 1.8 7.4 1.3 L206 I 7337 ± 1182 18864± 2437 0.000 2 25 ± 3.2 66.7 ± 7.2 41.7 2.6 L206 R 3629 ± 311 4495 ± 188 0.010 4 12.7 ± 1.1 15.8 ± 0.8 3.1 1.2 Petition 870260032676, dated 08 / 04 / 2026, pp. 236 / 370 226 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase L206 V 16753± 1106 30218± 1706 0.000 1 61.1 ± 2.7 113.7 ± 7.9 52.6 1.8 Y207 F 1499±68 3459 ± 412 0.000 1 4.8 ± 0.2 10.2 ± 0.9 5.4 2.3 M20 8K 1899±80 14453± 1319 0.000 1 6.6 ± 0.3 48.4 ± 3.1 41.9 7.6 W20 9C 11982 ± 1623 18442 ± 991 0.000 1 33.3 ± 4.1 52.8 ± 4.1 19.5 1.5 W20 9G 27639 ± 2262 35592 ± 1340 0.000 5 77.9 ± 6.3 101.9 ± 6.7 24.0 1.3 P210 H 20611 ± 1077 32983 ± 1037 0.000 1 63.4 ± 2.6 102.9 ± 4 39.5 1.6 P210 T 17748 ± 2301 21988± 829 0.007 7 53.5 ± 6 69.5 ± 3.7 16.0 1.2 F211 C 15289 ± 1161 22737 ± 1182 0.000 1 44.4 ± 3.3 65.9 ± 3.1 21.4 1.5 F211 L 27936 ± 2981 44713 ± 1823 0.000 1 65 ± 5.8 106.5 ± 3.4 41.5 1.6 Petition 870260032676, dated 08 / 04 / 2026, pages 237 / 370 227 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute amount (% WT) Relative amount F211 S 22923 ± 1035 34359 ± 1783 0.000 1 68 ± 4.4 100.9 ± 5.9 32.9 1.5 F211 V 2484 ± 2353 ± 2353 1742 0.000 3 72.7 ± 5.9 103.8 ± 5.7 31.1 1.4 F211 Y 28160 ± 2206 35233 ± 1670 0.004 9 83.4 ± 7.5 104.3 60 ± 2.23 H 32993 ± 2051 40381 ± 2380 0.004 9 87.6 ± 4.3 108.6 ± 6 21.0 1.2 Q21 2P 14401 ± 1189 19918± 903 0.000 3 .71 3.5 ± 3.5 ± 3.3 15.9 1.4 K213 E 16620 ± 1446 20792 ± 1647 0.009 6 37.7 ± 1.9 48.1 ± 2.8 10.4 1.3 K213 Q 20448 ± 1811 26374 2044 ± 3073 2.8 60.8 ± 4 13.7 1.3 P214 A 18022 ± 1147 36961 ± 1888 0.000 1 54.1 ± 4.3 110.2 ± 6.9 56.1 2.1 P214 H 1652 ± 1618 ± 1618 0.000 1 4.8 ± 0.4 46.9 ± 4 42.1 9.8 Petition 870260032676, dated 08 / 04 / 2026, pages 238 / 370 228 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase P214 R 25368 ± 1515 46719 ± 2717 0.000 1 74.9 ± 4.7 137.3 ± 7.8 62.4 1.8 P214 T 14899 ± 1328 36244 ± 2498 0.000 1 43.4 ± 4.5 103.9 ± 8.4 60.5 2.4 N21 5H 7453 ± 631 18621 ± 1170 0.000 1 22.2 ± 2.2 55.6 ± 4.2 33.3 2.5 N21 5K 10660± 1166 20220 ± 1700 0.000 1 31.6 ± 2.4 61.4 ± 3.3 29.7 1.9 N21 5T 5392 ± 425 13007± 910 0.000 1 16.6 ± 1 40 ± 1.7 23.4 2.4 N21 5Y 2599 ± 259 12737± 1218 0.000 1 7.4 ± 0.6 36.2 ± 2.8 28.8 4.9 Y216 F 30024 ± 2106 37273 ± 1708 0.002 6 94.3 ± 6.3 118.9 ± 6.6 24.6 1.2 Y216 H 17014 ± 764 27689 ± 1530 0.000 1 53.3 ± 1.9 86.7 ± 4.1 33.4 1.6 Y216 N 2280 ± 162 19311 ± 1513 0.000 1 7 ± 0.6 56.2 ± 3 49.2 8.5 Petition 870260032676, dated 08 / 04 / 2026, pp. 239 / 370 229 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase T217 A 18943 ± 1372 26939 ± 2043 0.002 6 57.8 ± 3.9 81.4 ± 5.2 23.7 1.4 T217 I 16049 ± 1284 23470 ± 1933 0.002 6 48.1 ± 3.2 70.4 ± 4.8 22.3 1.5 T217 K 23428 ± 1823 33844 ± 2556 0.002 4 71 ± 4.9 101.9 ± 6.3 30.9 1.4 T217 P 16181 ± 1175 22379 ± 1763 0.012 0 49.2 ± 3.4 67.2 ± 4.1 18.0 1.4 T217 R 17019 ± 1476 25272 ± 1907 0.001 3 51 ± 3.8 75.7 ± 4.5 24.8 1.5 T217 S 22763 ± 1515 30767 ± 1213 0.000 1 71.8 ± 4.6 98.3 ± 5.3 26.5 1.4 E218 A 25638 ± 2941 39175± 3493 0.002 2 76 ± 7.5 116.7 ± 8.1 40.7 1.5 E218 D 33776 ± 2840 43841 ± 3581 0.007 2 93.6 ± 8.3 122.7 ± 11.5 29.1 1.3 E218 G 7563 ± 677 26769 ± 3204 0.000 1 19.9 ± 1.3 68 ± 4.3 48.2 3.5 Petition 870260032676, dated 08 / 04 / 2026, pages 240 / 370 230 / 305 Table 7 Mutant form of α- Gal 10 pM (% WT) Absol ute increase (% WT) Relative increase E218 K 12974 ± 1017 27016± 2228 0.000 1 39.3 ± 2.8 82.1 ± 6 42.8 2.1 E218 Q 30758 ± 2592 42487 ± 3621 0.016 9 92.7 ± 7 128 ± 9.5 35.3 1.4 E218 V 26041 ± 1888 36278 ± 2419 0.001 3 71.4 ± 5.3 101.7 ± 8.6 30.3 1.4 I219 F 5506 ± 561 29184± 2616 0.000 1 14.9 ± 1.5 80.6 ± 7.3 65.6 5.3 I219 M 8627 ± 769 26166± 1736 0.000 1 23.6 ± 2.1 71.5 ± 4.3 47.9 3.0 I219 S 154 ± 20 3592 ± 274 0.000 1 0.4 ± 0.1 10.3 ± 1.1 9.8 23.3 R22 0L 18399± 1213 27014± 1455 0.000 1 49.7 ± 2.9 73.7 ± 3.6 24.0 1.5 Q22 1E 30425 ± 2264 37571 ± 2598 0.036 0 86.7 ± 6.1 109.5 ± 8.8 22.8 1.2 Q22 1H 31494 ± 2714 40085 ± 3310 0.011 1 87.8 ± 6.6 113.5 ± 8.3 25.7 1.3 Petition 870260032676, dated 08 / 04 / 2026, pp. 241 / 370 231 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase Q22 1K 33217 ± 2944 42352 ± 3561 0.031 9 93.5 ± 7.4 122.5 ± 10.4 29.0 1.3 Q22 1L 31279 ± 2821 39379 ± 3245 0.015 8 87.6 ± 7 112.4 ± 8.8 24.9 1.3 Q22 1R 29462 ± 2455 38738 ± 3284 0.028 3 82.1 ± 5.8 110.5 ± 8.7 28.4 1.3 Y222 C 21231 ± 1470 32597 ± 1888 0.000 1 52.6 ± 2.9 83.5 ± 6.1 30.9 1.5 Y222 D 1393±93 12177± 1005 0.000 1 3.9 ± 0.2 34.5 ± 2.5 30.6 8.7 Y222 H 31229 ± 1985 41680± 2577 0.002 0 87.2 ± 4.4 118.6 ± 6.8 31.4 1.3 Y222 N 25948 ± 1953 37634 ± 2615 0.000 7 72.1 ± 4.4 107.8 ± 7.2 35.6 1.5 Y222 S 22757 ± 1745 35534 ± 2237 0.000 1 63.4 ± 4.1 101.2 ± 6.1 37.9 1.6 N22 4H 26013 ± 2235 42176± 3315 0.000 6 64.6 ± 5.1 109.2 ± 10.4 44.6 1.6 Petition 870260032676, dated 08 / 04 / 2026, pages 242 / 370 232 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase R22 7G 1392 ±71 5084 ± 651 0.000 1 3.4 ± 0.1 11.9 ± 1.3 8.5 3.7 N22 8H 23110 ± 1663 37026 ± 2206 0.000 1 56.1 ± 3.7 90.8 ± 5.2 34.7 1.6 N22 8I 42680 ± 3934 65879 ± 4049 0.000 2 102 ± 7.8 158.6 ± 6.1 56.6 1.5 N22 8T 47321 ± 3640 57308 ± 3851 0.040 5 122.7 ± 8.2 149.8 ± 8.1 27.1 1.2 F229 I 26139 ± 2203 31786± 1919 0.030 1 63.2 ± 4.6 77.3 ± 3.6 14.1 1.2 F229 S 55992 ± 4881 67601 ± 4129 0.036 0 134 ± 9.1 163.4 ± 7.6 29.4 1.2 F229 Y 45676 ± 3431 56301 ± 4108 0.031 9 110.8 ± 6.6 135.1 ± 7.9 24.3 1.2 A230 D 19022 ± 1950 25008 ± 2188 0.028 3 62.5 ± 4.5 84 ± 4.8 21.5 1.3 A230 G 34550 ± 3372 51722 ± 3294 0.000 8 123.1 ± 9.6 189 ± 9.5 65.9 1.5 Petition 870260032676, dated 08 / 04 / 2026, pp. 243 / 370 233 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration A230 P 18686± 1606 27571 ± 2579 0.007 2 63.2 ± 4.9 92.7 ± 7.3 29.5 1.5 A2302 V 3070 ± 2070 40168± 2422 0.003 9 81.3 ± 4.2 106.6 ± 3.6 25.3 1.3 I232 L 1031 ±81 7224 ± 945 0.000 1 2.7 ± 0.2 17.5 1.6 ± 1.20 M 15493 ± 1384 41190± 2297 0.000 1 38.6 ± 2.2 109.4 ± 8.9 70.8 2.7 I232 V 44901 ± 3412 63373 ± 3592 0.0003 3.17.87 ± 12.6 7.7 48.9 1.4 D23 3A 23075 ± 1494 33219± 2019 0.000 2 59.1 ± 3.1 86.1 ± 5.7 27.0 1.4 D23 3E 17676 ± 758 23493 .9040 ± 2019 51 ± 2.4 67.3 ± 2.5 16.4 1.3 D23 3G 15091 ± 776 21651 ± 773 0.000 1 41.5 ± 1.9 60 ± 2.4 18.6 1.4 D23 3V 145 53 494 ± 494 0.000 1 42.1 ± 2.3 64.1 ± 2.5 22.0 1.5 Petition 870260032676, dated 08 / 04 / 2026, pp. 244 / 370 234 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration S235 A 1594±58 10500± 653 0.000 1 4.4 ± 0.1 28.1 ± 1.1 23.7 6.6 S235 T 1 1.8 ± 0.1 13.4 ± 0.7 11.6 7.5 K237 I 27059 ± 1342 40071 ± 1794 0.000 1 79.4 ± 2.6 119 ± 5 39.6 1.5 S238 C 439 ± 39.6 ± 381 ± 677 0.000 1 12.6 ± 0.9 39 ± 1.3 26.4 3.2 S238 I 1456±58 11704± 556 0.000 1 4.3 ± 0.3 33.8 ± 1.9 29.5 8.08 S256 ± 257 T 32589 ± 1426 0.000 1 64.7 ± 4 93.7 ± 4.6 29.0 1.4 I239 L 15008± 905 26331 ± 1039 0.000 1 42.7 ± 2.5 75.43 3.3 .28 K 34180 ± 2424 41878± 3056 0.045 5 105.2 ± 5.1 130.6 ± 7.9 25.4 1.2 K240 M 20450 ± 2148 32367 ± 2715 0.001 49.62 ± 69.5 6.2 37.2 1.6 Petition 870260032676, of 08 / 04 / 2026, p. 245 / 370 235 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration K240 R 15131 ± 1420 22482 ± 1791 0.003 0 46.8 ± 3.7 70.8 ± 5.5 23.9 1.5 C ± 1839 0.028 3 60.5 ± 4.1 75.9 ± 4 15.5 1.3 S241 I 18643 ± 1223 39204 ± 2588 0.000 1 53.8 ± 2.4 113.8 5.7 ± 0.0, 2.2 S2.2 T 29172 ± 2586 38406 ± 3223 0.005 7 82.6 ± 4.4 108.9 ± 5.2 26.2 1.3 I242 L 5.7 37.7 1.7 I242 M 2184 ± 180 4826 ± 337 0.000 1 6.4 ± 0.5 13.9 ± 0.9 7.5 2.2 I242 S 1533±62 15351 ± 937 ± 0.000 ± 0.48 44.9 ± 2.5 40.1 10.0 L243 M 24772 ± 1493 36055 ± 2526 0.000 4 72.7 ± 3.7 104.7 ± 5.3 31.9 1.5 L243 S 7839 ± 138 0.000 1 23.6 ± 1.8 61.7 ± 2.9 38.1 2.7 Petition 870260032676, dated 08 / 04 / 2026, pages 246 / 370 236 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase L243 V 23758 ± 1553 32500 ± 2227 0.002 0 68.4 ± 2.7 94.1 ± 4.9 25.7 1.4 D24 4A 10530 ± 850 20925 ± 1168 0.000 1 28.3 ± 1.6 57.5 ± 2.6 29.2 2.0 D24 4E 16889± 1765 31657± 1775 0.000 1 45.1 ± 3.7 86.8 ± 3.7 41.7 1.9 D24 4G 9983 ± 848 23926 ± 1422 0.000 1 26.8 ± 1.6 64.6 ± 2.2 37.8 2.4 D24 4V 983 ± 99 7446 ± 537 0.000 1 2.8 ± 0.3 20.2 ± 1 17.4 7.6 D24 4Y 5983 ± 586 15554± 1191 0.000 1 15.7 ± 1.2 42 ± 2.3 26.3 2.6 W24 5C 23353 ± 1993 33826 ± 2561 0.001 5 63.8 ± 4.2 93.4 ± 6.6 29.7 1.5 T246 A 20184 ± 1516 26581 ± 909 0.000 1 67.4 ± 5.2 89.3 ± 5.1 21.9 1.3 T246 I 18702 ± 1095 29303 ± 1319 0.000 1 61.2 ± 3.1 98.8 ± 6.8 37.6 1.6 Petition 870260032676, dated 08 / 04 / 2026, pp. 247 / 370 237 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration T246 K BLD 4118 ± 265 0.000 1 N / A 14 ± 1.2 14.0 NC T246 R BLD 1009 ± 64 0.000 1 N / A BLD 1009 ± 64 0.000 1 N / A A 24276 ± 1509 29111 ± 1498 0.004 5 80 ± 4.9 97.9 ± 7.1 18.0 1.2 S247 F 7957 ± 848 18686± 1093 0.000 1 25.3, 26.6 ± 26.6 37.3 2.4 S247 T 16039± 1152 22511 ± 1461 0.000 3 53.2 ± 3.9 74.8 ± 5.2 21.6 1.4 S247 Y 7433 ± 798 18101 1419 ± 20.05 ± 2035 60.3 ± 4.9 36.8 2.4 F248 C 20087 ± 2973 27351 ± 4250 0.028 3 57.9 ± 3.3 77.1 ± 5 19.2 1.4 F248 L 2 59.8 ± 4.4 79.5 ± 5.2 19.8 1.3 F248 V 20424 ± 2940 27075 ± 4121 0.042 9 58.6 ± 3.1 76.7 ± 5 18.1 1.3 Petition 870260032676, dated 08 / 04 / 2026, pages 248 / 370 238 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase F248 Y 25850 ± 2314 31204 ± 1758 0.001 8 86.6 ± 4.9 107.8 ± 6.1 21.2 1.2 N24 9D 9050 ± 1262 19080± 2665 0.000 1 26.6 ± 1.7 55.7 ± 2.8 29.0 2.1 N24 9H 25157 ± 2681 32119± 3556 0.002 8 76.1 ± 2.2 96.2 ± 2.9 20.1 1.3 N24 9I 1864±80 3353 ± 340 0.001 4 7.1 ± 0.4 13.1 ± 1.8 6.0 1.8 N24 9S 7395 ± 926 12077± 977 0.001 8 26.2 ± 2.9 45.1 ± 4.6 18.9 1.6 N24 9T 13923 ± 1557 21314± 2561 0.002 2 42.4 ± 2.8 64.4 ± 3.7 21.9 1.5 N24 9Y 16445 ± 2008 22166± 2504 0.001 8 49.4 ± 3.1 66.8 ± 2.5 17.3 1.4 Q25 0E 8159 ± 688 14252 ± 1068 0.000 1 30.2 ± 1.6 52.9 ± 2.4 22.8 1.8 Q25 0L 2088 ± 234 7820 ± 877 0.000 1 7.6 ± 0.6 28.9 ± 3 21.4 3.8 Petition 870260032676, dated 08 / 04 / 2026, pp. 249 / 370 239 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration E251 G 11980 ± 1124 16458± 1113 0.006 4 46.1 ± 3.6 64.1 ± 3.3 18.0 1.4 K 21714± 2048 0.033 9 58.7 ± 6 80.8 ± 6.4 22.0 1.4 E251 Q 11708 ± 1222 16261 ± 1537 0.014 7 43.2 ± 3.6 60.8 .41 V.25.7 18585± 562 24051 ± 593 0.000 1 61.6 ± 2.2 81.1 ± 3.9 19.5 1.3 R25 2G 18020 ± 692 23372 ± 803 0.000 1 60.5 3.7.7 ± 3.49 17.4 1.3 I253 F 21127 ± 1055 26426 ± 1084 0.001 8 71.2 ± 3 89 ± 2.7 17.8 1.3 I253 N 1319 ±62 8202 ± 357 0.00 0.010.30. 1.3 25.7 6.2 I253 V 28837 ± 2142 37575 ± 3353 0.005 3 83.9 ± 5.7 105.4 ± 4.3 21.5 1.3 V254 A 23186 ± 1352 30783 3076 86.2 ± 4.9 114.5 ± 5 28.3 1.3 Petition 870260032676, dated 08 / 04 / 2026, pages 250 / 370 240 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase V254 D 9616 ± 701 17536 ± 1256 0.000 1 36.2 ± 2.9 65.7 ± 4.9 29.5 1.8 V254 F 17887 ± 792 25725 ± 1079 0.000 1 67 ± 3.5 96.5 ± 4.9 29.5 1.4 V254 G 16438 ± 761 23014± 1190 0.000 1 63.8 ± 3.3 88.3 ± 4 24.5 1.4 D25 5A 25626 ± 616 30916± 1369 0.002 0 83.5 ± 2.1 100.1 ± 3.7 16.6 1.2 D25 5E 23441 ± 971 28215± 1532 0.007 7 75.6 ± 2.1 90 ±3 14.4 1.2 D25 5H 28982 ± 1416 35899 ± 1244 0.000 5 93.8 ± 3.8 117 ± 4.2 23.1 1.2 D25 5N 17034 ± 769 22522 ± 1285 0.001 66.2 ± 3.3 86.9 ± 4.8 20.7 1.3 D25 5V 12495 ± 504 17974± 1031 0.000 2 40.2 ± 0.9 57.4 ± 2.2 17.2 1.4 D25 5Y 20319 ± 836 25724 ± 1133 0.000 4 65.8 ± 2 83.2 ± 2.9 17.5 1.3 Petition 870260032676, dated 08 / 04 / 2026, pages 251 / 370 241 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase V256 D 22272 ± 1410 31742 ± 1047 0.000 1 77.2 ± 4.4 110.7 ± 3.2 33.5 1.4 V256 G 21683 ± 942 30389 ± 884 0.000 1 75.2 ± 2.4 106.6 ± 3.8 31.4 1.4 V256 L 24022 ± 935 31507± 1624 0.002 8 77.3 ± 1.7 100.9 ± 3.2 23.6 1.3 A257 S 23677 ± 1041 30608 ± 983 0.000 1 82.7 ± 3.4 107.4 ± 4 24.7 1.3 G25 8E 17926 ± 1400 26780 ± 1366 0.000 1 62.6 ± 4.8 93.7 ± 4.9 31.1 1.5 P259 A 19721 ± 1213 32585 ± 3063 0.000 1 57 ± 2.4 91.7 ± 4.4 34.7 1.7 P259 T 10040 ± 780 20286 ± 925 0.000 1 34.6 ± 2.3 71.2 ± 3.4 36.6 2.0 G26 0W 155 ± 55 1188 ± 98 0.000 1 0.4 ± 0.1 3.4 ± 0.2 3.0 7.7 G26 1A 27318 ± 2249 34233 ± 3145 0.038 2 79.5 ± 5.9 96.4 ± 4.5 16.9 1.3 Petition 870260032676, dated 08 / 04 / 2026, pages 252 / 370 242 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase N26 3H 7205 ± 590 22283 ± 1252 0.000 1 25.4 ± 2 78.9 ± 4.7 53.6 3.1 N26 3T 527 ± 54 4649 ± 207 0.000 1 1.8 ± 0.2 17.2 ± 1.5 15.4 8.8 D26 4H 407 ± 21 4188 ± 439 0.000 1 1.5 ± 0.1 15.4 ± 2.2 14.0 10.3 D26 4N 18857± 1196 31010± 1310 0.000 1 66 ± 4.1 110.4 ± 5.7 44.4 1.6 P265 A 35589 ± 1537 47153± 2302 0.000 1 86.9 ± 7.1 114 ± 8.6 27.1 1.3 P265 Q 8975 ± 521 31993± 1540 0.000 1 21 ± 1.1 76.8 ± 5.2 55.8 3.6 M26 7L 2982 ± 411 9684 ± 760 0.000 1 8.4 ± 1.1 26.8 ± 1.3 18.4 3.3 M26 7V 13852 ± 1513 17656± 1363 0.021 9 39 ± 3.8 50.2 ± 3.5 11.2 1.3 L268 F BLD 3139 ± 435 0.000 1 N / A 8 ± 1.1 8.0 NC Petition 870260032676, dated 08 / 04 / 2026, pp. 253 / 370 243 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute amount (% WT) Relative amount L268 I 30462 ± 1925 36529 ± 2102 0.041 1 74 ± 4.1 90.1 ± 5.3 16.1 1.2 V2694 L 0.000 1 1 ± 0.1 11.7 ± 1.3 10.6 10.9 I270 L 36361 ± 2544 46689 ± 3106 0.010 4 87.4 ± 3.4 113.7 ± 5.2 26.27 170 ± 239 S 7634 ± 573 0.000 1 0.7 ± 0.1 21.3 ± 1.8 20.6 27.9 I270 V 30682 ± 2319 37467 ± 2651 0.030 1 73.6 ± 3.5 90.3 3.6 ± 1.26 N 2D 28459 ± 2692 39327 ± 2685 0.002 4 68.5 ± 4.5 95.9 ± 4.5 27.4 1.4 F273 Y 35815± 3175 45321 ± 3511 0.031 ± 51.38 ± 5.5 6.6 23.5 1.3 L275 I 5669 ± 420 22341 ± 1943 0.000 1 13.1 ± 0.6 52.8 ± 3.9 39.6 3.9 W27 7L 28295 ± 2855 371900 ± 3020.634 ± 5.8 86.8 ± 10.3 24.9 1.3 Petition 870260032676, dated 08 / 04 / 2026, pages 254 / 370 244 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration N27 8I 471 ± 67 7024 ± 774 0.000 1 1.1 ± 0.1 16.7 ± 1.7 15.6 14.9 Q28 0L 44 444 ± 1494 0.000 1 1 ± 0.1 19.2 ± 2.2 18.1 17.7 Q28 0R 1165 ± 139 10482 ± 1406 0.000 1 2.7 ± 0.2 24.8 ± 3.3 22.2 9.0 V2813 A 45870 ± 2186 0.000 1 58.6 ± 3.1 97.1 ± 5.7 38.4 1.7 V281 E 23351 ± 783 37701 ± 1194 0.000 1 53.1 ± 1.3 85.8 12.6 ± 1.26 G 8729 ± 380 17662 ± 959 0.000 1 18.3 ± 0.9 37.4 ± 2.4 19.2 2.0 V281 L 30655 ± 1494 38560 ± 1647 0.000 7 4.1 6.1 ± 3.4 ± 3.4 16.9 1.3 T282 S 16612 ± 753 25105± 1005 0.000 1 37.7 ± 1.3 57 ± 1.5 19.3 1.5 Q28 3E 366 ± 31 6195 ± 4195 ± 0.000 .001 ± 1.83 ± 1.2 12.6 16.9 Petition 870260032676, of 08 / 04 / 2026, p. 255 / 370 245 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase Q28 3H 32420 ± 1104 44815 ± 1903 0.000 1 74.1 ± 2.4 101.7 ± 3.1 27.6 1.4 Q28 3L 160 ± 25 7906 ± 977 0.000 1 0.4 ± 0.1 21.3 ± 1.9 20.9 49.5 M28 4I 24698 ± 1943 35578 ± 2125 0.001 1 58.6 ± 3.7 85.3 ± 3.7 26.7 1.4 M28 4L 28797 ± 1915 36282 ± 1676 0.000 8 65.4 ± 3.7 83.8 ± 4.1 18.4 1.3 A285 G 21580 ± 1326 29210± 1510 0.000 6 51.9 ± 2.5 70.1 ± 2.4 18.2 1.4 A285 T 20186 ± 1322 32504 ± 2023 0.000 1 45.5 ± 2.4 73.5 ± 3.7 28.0 1.6 A285 V 23407 ± 861 32500 ± 1568 0.000 1 55.1 ± 2.1 76.5 ± 3.6 21.4 1.4 L286 F 29390 ± 1225 39732 ± 2859 0.000 4 64.5 ± 2.8 87.7 ± 7.3 23.2 1.4 L286 H 359 ± 52 7960 ± 1511 0.000 1 0.8 ± 0.1 16.2 ± 2.5 15.4 22.2 Petition 870260032676, dated 08 / 04 / 2026, pages 256 / 370 246 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase L286 V 28713 ± 3734 41335 ± 3422 0.003 0 66 ± 5.1 98.9 ± 4.3 32.9 1.4 A288 G 22208 ± 1755 30458 ± 2381 0.005 7 56.8 ± 6.3 76.7 ± 7.4 19.9 1.4 A288 S 45790 ± 3395 55988 ± 2609 0.020 6 114.6 ± 10.6 140.4 ± 10.5 25.8 1.2 A288 V 32777 ± 3168 45501 ± 4634 0.019 3 82.5 ± 9 114.2 ± 12.4 31.7 1.4 I289 L 37941 ± 3208 49640 ± 3368 0.007 7 96.9 ± 10.5 124.4 ± 11.3 27.5 1.3 I289 T 15033± 1450 29673 ± 2480 0.000 1 38.6 ± 4.8 75.3 ± 7.9 36.7 2.0 I289 V 25845 ± 1706 31489± 1397 0.003 9 61.2 ± 3.2 74.8 ± 2.7 13.6 1.2 A291 G 6953 ± 474 16073± 954 0.000 1 26.6 ± 1.5 61.5 ± 2.6 34.9 2.3 A292 G 12091 ± 652 19406± 1361 0.000 1 41.1 ± 2.2 65.3 ± 4 24.3 1.6 Petition 870260032676, dated 08 / 04 / 2026, pages 257 / 370 247 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase A292 S 18002 ± 1127 23779 ± 1584 0.007 7 68.6 ± 2.9 89.9 ± 3.4 21.3 1.3 L294 F 10147 ± 971 23486 ± 2100 0.000 1 29.6 ± 3 68.4 ± 6.5 38.8 2.3 L294 I 8345 ± 717 26761 ± 1915 0.000 1 24.8 ± 2.4 78.4 ± 6 53.6 3.2 L294 V 1452 ±71 13038± 880 0.000 1 4.4 ± 0.3 38.2 ± 2.7 33.8 9.0 F295 I 26687 ± 1470 35634 ± 2203 0.001 3 78.3 ± 4.5 104.1 ± 6.6 25.7 1.3 F295 S 230 ± 45 3847 ± 309 0.000 1 0.6 ± 0.1 11.1 ± 0.9 10.5 16.8 F295 V 24973 ± 1752 41782 ± 2877 0.000 1 73.4 ± 5.7 121.5 ± 7.7 48.0 1.7 F295 Y 21452 ± 1929 34502 ± 2504 0.000 3 62.9 ± 6.1 99.2 ± 6.5 36.3 1.6 S297 T BLD 3178 ± 327 0.000 1 N / A 9.7 ± 0.8 9.7 NC Petition 870260032676, dated 08 / 04 / 2026, pp. 258 / 370 248 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration N29 8D 795 ± 56 7645 ± 388 0.000 1 2.5 ± 0.2 24.2 ± 1.2 21.7 9.6 N29 8I 294 294 235 ± 135 0.000 1 9.2 ± 0.7 44.1 ± 1.8 34.9 4.7 N29 8T 20581 ± 1736 25249 ± 1705 0.003 3 61.2 ± 4.7 75.4 ± 4.3 14.291 .293 H 8424 ± 875 0.000 1 1 ± 0.1 23.1 ± 2.4 22.1 23.5 D29 9N 11973 ± 1961 14668± 809 0.000 5 29.2 ± 4.7 37.1 0.000 L 7328 ± 448 19317± 757 0.000 1 20.7 ± 0.9 55.1 ± 2 34.4 2.6 L300 V 406 ± 48 5354 ± 203 0.000 1 1.3 0.2 ± 13.60 H30 2D 32677 ± 1437 41716± 1847 0.000 8 95.1 ± 5.8 120.8 ± 6.6 25.8 1.3 H30 2L 24188 ± 1797 34251 1760 ± 0.000.67 ± 60.6 85.3 ± 4.7 24.6 1.4 Petition 870260032676, dated 08 / 04 / 2026, pages 259 / 370 249 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase H3O 2N 31958 ± 1777 42296 ± 2028 0.000 3 91.2 ± 4.3 121.4 ± 6.2 30.2 1.3 H3O 2Y 22554 ± 1372 31688± 1241 0.000 1 59 ± 3.5 84.2 ± 5.2 25.3 1.4 I303 S BLD 1496 ± 117 0.000 1 N / A 3.8 ± 0.3 3.8 NC S304 I 11675 ± 939 17257± 1837 0.007 2 30.6 ± 1.4 44.6 ± 2.4 13.9 1.5 Q30 6E 31745 ± 2212 39019± 2405 0.016 9 82 ± 2.8 101.7 ± 4.2 19.7 1.2 Q30 6L 19792 ± 1899 26515± 1960 0.014 7 56.9 ± 4 76.4 ± 3.4 19.6 1.3 Q30 6P 19933± 1648 29495 ± 1671 0.000 4 57.4 ± 2.8 87.5 ± 4.8 30.0 1.5 A307 D 42522 ± 2430 54502 ± 3031 0.002 6 126 ± 5.7 161.9 ± 8.6 35.9 1.3 A307 G 17871 ± 1029 26053 ± 1631 0.000 6 52.9 ± 2.5 76.3 ± 3.1 23.4 1.5 Petition 870260032676, dated 08 / 04 / 2026, pp. 260 / 370 250 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration A307 P 11388 ± 905 15572 ± 1124 0.007 2 32.8 ± 1.7 45.2 ± 2.1 12.3 1.4 A3037 S 2938 ± 2857 ± 2274 0.002 6 85.9 ± 4.5 113.6 ± 5.2 27.7 1.3 A307 V 11478 ± 1200 25989 ± 2015 0.000 1 27.5 ± 2 62.2 ± 3.33 3.398 I ± 1555 29251 ± 2026 0.000 5 48.6 ± 3.9 72.7 ± 3.6 24.2 1.5 K308 Q 24208 ± 1996 35663 ± 2680 0.002 2 59.18 ± 3.00.35. 1.5 K308 R 27103 ± 1767 35824 ± 2438 0.005 7 68.9 ± 4.3 89.1 ± 4.5 20.3 1.3 A309 D 31696± 3036 38325 2376 ± 0.78.78 95.8 ± 3.7 17.6 1.2 A309 T 29214 ± 1907 36228 ± 1841 0.006 7 74.1 ± 4.6 92.7 ± 4.8 18.6 1.2 L310 I 31871 ± 2599 ± 3315 0.026 6 72.8 ± 3.6 92.4 ± 5.1 19.6 1.3 Petition 870260032676, dated 08 / 04 / 2026, pages 261 / 370 251 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase L311 I 4020 ± 235 11558 ± 781 0.000 1 12.1 ± 0.8 35.3 ± 3.1 23.2 2.9 Q31 2E 1365 ± 57 6331 ± 466 0.000 1 4.1 ± 0.2 19.2 ± 1.7 15.1 4.6 Q31 2K 6733 ± 510 11934± 624 0.000 1 19.7 ± 1.4 35.2 ± 1.8 15.5 1.8 Q31 2L 16986± 1428 23967 ± 1400 0.001 1 50.1 ± 4.1 71.5 ± 4.6 21.3 1.4 D31 3E 14321 ± 1579 18273± 1330 0.001 4 42.5 ± 2.3 55.7 ± 1.9 13.2 1.3 D31 3V 894 ± 33 3480 ± 580 0.000 1 2.9 ± 0.2 9.6 ± 0.9 6.7 3.9 K314 E 13026 ± 1767 16765± 2098 0.003 3 37.7 ± 2.5 48.7 ± 2.8 11.0 1.3 K314 M 18231 ± 2878 23043 ± 2838 0.001 4 50.9 ± 3.8 66.8 ± 3.8 15.9 1.3 K314 N 14205 ± 2418 17364± 2225 0.002 2 39.1 ± 3.4 49.9 ± 2.6 10.8 1.2 Petition 870260032676, dated 08 / 04 / 2026, pp. 262 / 370 252 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute amount (% WT) Relative amount K314 T 25162 ± 2701 30501 ± 2332 0.003 6 75.9 ± 4.4 93.8 ± 4.5 17.9 1.2 D31 A 24758 ± 1512 0.003 6 68.3 ± 4.8 93.4 ± 7 25.1 1.3 D31 5G 13326 ± 859 19115± 1697 0.004 2 49.7 ± 3.7 73.3 83 .23 H 9791 ± 1077 14136± 1573 0.003 0 35.7 ± 2.8 53.2 ± 5.5 17.4 1.4 D31 5N 8553 ± 425 13037± 869 0.000 1 34.1 1.7 ± 3.7 ± 5.7 17.9 1.5 D31 5V 8191 ± 717 14580± 1235 0.000 1 31.2 ± 3.6 56 ± 6 24.8 1.8 D31 5Y 9198 ± 1179 12674 ± 1008 30.35.35. 48.7 ± 2.4 14.2 1.4 V316 A 13166± 1029 18908± 1577 0.003 3 48.8 ± 4.1 71.5 ± 7.1 22.7 1.4 V316 L 0.000 1 47.4 ± 3.9 81.3 ± 6.3 33.9 1.7 Petition 870260032676, dated 08 / 04 / 2026, pages 263 / 370 253 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase I317 L 14780 ± 1222 18770 ± 1141 0.019 9 54.4 ± 4.9 70.9 ± 5.6 16.5 1.3 I317 M 340 ± 29 3988 ± 177 0.000 1 1 ± 0.1 11.2 ± 0.8 10.2 11.7 I317 V 14885 ± 1495 19927± 1565 0.014 7 55 ± 6.1 73.6 ± 5.5 18.6 1.3 A318 D 15357 ± 1499 20838 ± 1817 0.001 2 42.5 ± 3.6 59.4 ± 5.3 16.9 1.4 A318 P 526 ± 42 2799 ± 174 0.000 1 1.5 ± 0.2 8 ± 0.8 6.5 5.3 A318 T 16954 ± 1483 22296 ± 1232 0.000 9 45.2 ± 2.8 62.9 ± 4.6 17.7 1.3 A318 V 14603 ± 1377 19658± 1108 0.002 2 37.9 ± 2.1 54.4 ± 3.5 16.5 1.4 I319 M 12191 ± 433 14802 ± 727 0.004 7 47.4 ± 2.2 56.8 ± 2.3 9.4 1.2 N32 0S 21562 ± 1285 28097 ± 1522 0.002 2 82.9 ± 4.5 106.7 ± 3.9 23.9 1.3 Petition 870260032676, dated 08 / 04 / 2026, pp. 264 / 370 254 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with 10 μM Migalastate (nmol / mg / hr) Mann-Whitney U Value Baseline α-Gal A Activity (% WT) α-Gal A Activity with 10 pM Migalastate (% WT) Absolute Increase (% WT) Relative Increase N32 0T 5597 ± 442 11276 ± 658 0.000 1 21.6 ± 1.5 43.3 ± 1.9 21.8 2.0 Q32 1K 7590 ± 520 16046± 870 0.000 1 29.2 ± 2 61.2 ± 2.4 32.0 2.1 D32 2A 1908 ± 139 6170 ± 310 0.000 1 6.8 ± 0.4 22.2 ± 1 15.3 3.2 D32 2V 714 ± 53 3989 ± 217 0.000 1 2.6 ± 0.2 14.3 ± 0.6 11.7 5.6 L324 V 17027 ± 1167 20866 ± 1331 0.009 0 57.2 ± 2.1 70.2 ±2 13.0 1.2 L324W 20623±721 25772±1045 0.000 4 73.5±1.8 93.3±4.5 19.8 1.3 G32 5A 18183±1254 27523±1456 0.000 1 64.9 ± 3.8 99.2 ± 5.4 34.4 1.5 G32 5C 14482 ± 695 23873 ± 1021 0.000 1 51.4 ± 1.7 85.9 ± 4 34.5 1.7 G32 5V 572 ± 30 5333 ± 294 0.000 1 2.2 ± 0.2 19.3 ± 1.1 17.1 9.3 Petition 870260032676, dated 08 / 04 / 2026, pages 265 / 370 255 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline α-Gal A Activity (% WT) α-Gal A Activity with migalast at 10 pM (% WT) Absolute Increase (% WT) Relative Increase K326 E 15541 ± 832 22340 ± 828 0.000 1 55.6 ± 2.6 80.9 ± 3.9 25.3 1.4 K326 M 8482 ± 500 31204± 1979 0.000 1 24.4 ± 1.6 87.6 ± 3.5 63.2 3.7 K326 Q 22075 ± 1209 29168± 1869 0.001 0 78 ± 3 104.1 ± 5.7 26.1 1.3 K326 R 17744 ± 923 31690± 1112 0.000 1 61.7 ± 3.4 109.7 ± 2.9 48.0 1.8 K326 T 19442 ± 739 26653 ± 877 0.000 1 69.6 ± 2.4 96 ± 3.7 26.4 1.4 Q32 7H BLD 2197 ± 226 0.000 1 N / A 7.4 ± 0.7 7.4 NC Q32 7P 7775 ± 561 18612 ± 1075 0.000 1 26.2 ± 1.8 62.6 ± 3.1 36.4 2.4 Y329 C 9148 ± 414 11442 ± 480 0.001 1 31.2 ± 1.5 38.9 ± 1.6 7.8 1.3 Y329 D 1249 ±66 4917 ± 181 0.000 1 4.2 ± 0.2 16.7 ± 0.6 12.5 3.9 Petition 870260032676, dated 08 / 04 / 2026, pp. 266 / 370 256 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration Y329 F 10368± 646 15566± 603 0.000 1 30.6 ± 1.5 47.1 ± 2.8 16.6 1.5 Y329 ± 1373 ± 1867 772 0.000 2 47.2 ± 3.8 63.4 ± 2.6 16.2 1.4 Y329 N 6448 ± 436 11035± 429 0.000 1 21.8 ± 1.5 37.4 ± 1.2 1.65 ± E 730 ± E 345 13086± 589 0.000 1 26.4 ± 1.5 46.4 ± 2.6 19.9 1.7 Q33 0H 9296 ± 649 20752 ± 592 0.000 1 33.1 ± 2.8 ± 3.94 ± 2.60 Q33 0K 20289 ± 720 26149± 1074 0.000 1 71 ± 2.7 92.1 ± 4.2 21.1 1.3 L331 H 11743 ± 634 19003± 791 0.000 1 .43.26 ± 3.3 25.9 1.6 L331 P 157 ± 20 1029 ± 32 0.000 1 0.6 ± 0.1 3.7 ± 0.2 3.1 6.5 L331 R 9725 ± 634 15841 ± 639 0.000 1.33.25 ± 5.5 3.2 23.3 1.6 Petition 870260032676, dated 08 / 04 / 2026, pages 267 / 370 257 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) Activity of α-Gal A with migalast up to 10 μM (nmol / mg / hr) MannWhitn Value and U Baseline α-Gal A Activity (% of WT Gal A Activity) at 10 pM (% WT) Absolute concentration (% WT) Relative concentration L331 V 25163± 801 33050 ± 967 0.000 1 89.4 ± 4.5 117.4 ± 5.6 28.0 1.3 R33 2343 743 ± 1959 0.000 2 78.8 ± 2.7 102.3 ± 4.6 23.4 1.3 R33 2I 24614 ± 1678 41550± 2461 0.000 1 63.3 ± 4.5 106.64 2.33 R 33936 ± 2528 41700± 2778 0.019 3 87.6 ± 6.6 108.1 ± 8.4 20.5 1.2 R33 2T 26141 ± 1254 39363 ± 2176 0.030 ± 193.39. 4.7 36.2 1.5 Q33 3E 30291 ± 2094 38709 ± 2428 0.006 7 77.8 ± 5.3 101.3 ± 7.6 23.5 1.3 Q33 3L 25450 ± 20450 ± 3727 ± 1094 2 68.6 ± 2.9 93.3 ± 4.1 24.7 1.3 Q33 3P 11819 ± 1039 22746 ± 1255 0.000 1 30.3 ± 1.7 61.3 ± 3.9 31.0 1.33 R 2587 31174 ± 2016 0.042 9 58.9 ± 4.6 76.4 ± 2.7 17.5 1.2 Petition 870260032676, dated 08 / 04 / 2026, pages 268 / 370 258 / 305 Table 7 Mutant form of α- Gal 10 pM (% WT) Absol ute increase (% WT) Relative increase G33 4V 31991 ± 2390 38301 ± 2744 0.021 9 68.4 ± 3.2 82.1 ± 3.8 13.7 1.2 D33 5A 21055± 1662 33829 ± 4641 0.012 0 57.9 ± 3 85.6 ± 6.9 27.7 1.6 D33 5E 30532 ± 1962 39124± 2722 0.005 3 68.7 ± 4.8 86.5 ± 4.5 17.7 1.3 D33 5G 22766 ± 1355 30341 ± 3325 0.023 4 51.3 ± 2.8 67 ± 5.6 15.7 1.3 D33 5V 7938 ± 336 16557± 929 0.000 1 18.1 ± 0.6 37.5 ± 1.6 19.4 2.1 D33 5Y 19469 ± 982 24732 ± 2214 0.014 7 43 ± 1.7 54.1 ± 3.5 11.0 1.3 N33 6D 23869 ± 1072 39534 ± 2519 0.000 1 53.7 ± 2.8 88.1 ± 4.9 34.3 1.7 N33 6I 8544 ± 1083 18303± 1404 0.000 1 20.7 ± 2.7 43.8 ± 1.6 23.0 2.1 N33 6S 32974 ± 2396 40651 ± 2487 0.016 9 79.7 ± 3.8 98.4 ± 3.1 18.7 1.2 Petition 870260032676, dated 08 / 04 / 2026, pages 269 / 370 259 / 305 Table 7 Mutant Form of α-Gal A Baseline α-Gal A Activity (nmol / mg / hr) α-Gal A Activity with migalast at 10 μM (nmol / mg / hr) Mann-Whitney U p-value Baseline ...

Claims

CLAIMS 1. A computer-implemented method characterized in that it comprises: receiving an electronic communication corresponding to an identification of a particular mutation; querying a data storage medium using the identification of the particular mutation, wherein the data storage medium includes an identification of each of a set of susceptible mutations, and wherein each of the set of susceptible mutations corresponds to a mutation listed in Table 2; detecting a result of the query, wherein the result is indicative of whether the particular mutation is represented in the set of susceptible mutations; generating, based on the response, an output that is indicative of the suitability of treating an individual with the particular mutation with migalastat or a migalastat salt; and transmitting the output.

2. A system characterized by the fact that it comprises: one or more data processors; and a non-transient, computer-readable storage medium containing instructions that, when executed on one or more data processors, cause one or more data processors to perform actions including: Petition 870260032676, dated 08 / 04 / 2026, page 1.317 / 370 2 / 8 receive an electronic communication corresponding to an identification of a particular mutation; query a data storage medium using the identification of the particular mutation, wherein the data storage medium includes an identification of each of a set of susceptible mutations, and wherein each of the set of susceptible mutations corresponds to a mutation listed in Table 2; detect a query result, wherein the result is indicative of whether the particular mutation is represented in the set of susceptible mutations; generate, based on the response, an output that is indicative of the suitability of treating an individual with the particular mutation with migalastat or a migalastat salt; and transmit the output.

3. A computer program product tangibly embedded in a non-transient, machine-readable storage medium, characterized in that it includes instructions configured to cause one or more data processors to perform actions including: receiving an electronic communication that corresponds to an identification of a particular mutation; querying a data storage medium using the identification of the particular mutation, wherein the data storage medium includes an identification of each mutation. Petition 870260032676, dated 08 / 04 / 2026, p.318 / 370 3 / 8 of a set of susceptible mutations, where each mutation in the set of susceptible mutations corresponds to a mutation listed in Table 2; detect a query result, where the result is indicative of whether the particular mutation is represented in the set of susceptible mutations; generate, based on the response, an output that is indicative of the suitability of treating an individual with the particular mutation with migalastat or a migalastat salt; and transmit the output.

4. A computer-implemented method characterized in that it comprises: accessing a data storage medium storing a dataset that identifies, for each mutation in a set of mutations, a degree to which α-Gal A activity responds to migalastate or a migalastate salt when the mutation is present, wherein the set of mutations includes one or more mutations listed in Table 2; receiving a communication that identifies one or more particular mutations; querying the data storage medium using a representation of the one or more particular mutations; detecting a query result that indicates, for each particular mutation in the set of mutations, the Petition 870260032676, dated 08 / 04 / 2026, p.319 / 370 4 / 8 degree to which α-Gal A activity responds to migalastat or a migalastat salt when the particular mutation is present; determine a metric corresponding to a predicted efficacy of treating an individual having one or more particular mutations with migalastat or a migalastat salt; and issue the metric.

5. A system characterized in that it comprises: one or more data processors; and a non-transient, computer-readable storage medium containing instructions that, when executed on the one or more data processors, cause the one or more data processors to perform actions including: accessing a data set unit storing a data set that identifies, for each mutation in a set of mutations, a degree to which the activity of αGal A responds to migalastate or a salt of migalastate when the mutation is present, wherein the set of mutations includes one or more mutations listed in Table 2; receiving a communication that identifies one or more particular mutations; querying the data set unit using a representation of the one or more particular mutations; detecting a query result that indicates, for each particular mutation in the one or more particular mutations, the Petition 870260032676, dated 08 / 04 / 2026, p.320 / 370 5 / 8 degree to which α-Gal A activity responds to migalastat or a migalastat salt when the particular mutation is present; determine a metric corresponding to a predicted efficacy of treating an individual having one or more particular mutations with migalastat or a migalastat salt; and issue the metric.

6. A computer program product tangibly embedded in a non-transient, machine-readable storage medium, characterized in that it includes instructions configured to cause one or more data processors to perform actions including: accessing a data set unit storing a data set that identifies, for each mutation in a set of mutations, a degree to which the activity of αGal A responds to migalastate or a salt of migalastate when the mutation is present, wherein the set of mutations includes one or more mutations listed in Table 2; receiving a communication that identifies one or more particular mutations; querying the data set unit using a representation of one or more particular mutations; detecting a query result that indicates, for each particular mutation in one or more particular mutations, the degree to which the activity of αGal A responds to Petition 870260032676, dated 08 / 04 / 2026, p.321 / 370 6 / 8 migalastat or a migalastat salt when the particular mutation is present; determine a metric corresponding to a predicted efficacy of treating a subject having one or more particular mutations with migalastat or a migalastat salt; and issue the metric.

7. A method characterized in that it comprises: accessing mutation information corresponding to an individual, the mutation information identifying one or more α-galactosidase A mutations; determining, based on the mutation information, that the individual has a mutation for which the α-Gal A activity in lysates prepared from HEK-293 cells transiently transfected with a mutant form of αGal A and incubated for 5 days in the presence of migalastat at 10 μM is greater than a reference α-Gal A activity in other lysates prepared from other HEK293 cells transiently transfected with the mutant form of αGal A and incubated for 5 days in the absence of migalastat at 10 μM, the mutant form of α-Gal A corresponding to the mutation; and in response to the determination, issue an indication that the mutation is susceptible to treatment with migalastat or a salt thereof.

8. System characterized by the fact that it comprises: Petition 870260032676, dated 08 / 04 / 2026, page 322 / 370 7 / 8 one or more data processors; and a non-transient, computer-readable storage medium containing instructions that, when executed on one or more data processors, cause one or more data processors to perform actions including: accessing mutation information corresponding to an individual, mutation information identifying one or more α-galactosidase A mutations;To determine, based on mutation information, that the individual has a mutation for which the α-Gal A activity in lysates prepared from HEK-293 cells transiently transfected with a mutant form of αGal A and incubated for 5 days in the presence of 10 μM migalastat is greater than a reference α-Gal A activity in other lysates prepared from other HEK293 cells transiently transfected with the mutant form of αGal A and incubated for 5 days in the absence of 10 μM migalastat, the mutant form of α-Gal A corresponding to the mutation; and in response to the determination, to issue an indication that the mutation is amenable to treatment with migalastat or an alt thereof.

9. Computer program product tangibly embedded in a non-transient machine-readable storage medium, characterized by the fact that it includes Petition 870260032676, dated 08 / 04 / 2026, page.323 / 370 8 / 8 instructions configured to cause one or more data processors to perform actions including: accessing mutation information corresponding to an individual, the mutation information identifying one or more α-galactosidase A mutations; determining, based on the mutation information, that the individual has a mutation for which the α-Gal A activity in lysates prepared from HEK-293 cells transiently transfected with a mutant form of αGal A and incubated for 5 days in the presence of migalastat at 10 μM is greater than a reference α-Gal A activity in other lysates prepared from other HEK293 cells transiently transfected with the mutant form of αGal A and incubated for 5 days in the absence of migalastat at 10 μM, the mutant form of α-Gal A corresponding to the mutation; and in response to the determination, issue an indication that the mutation is susceptible to treatment with migalastat or a salt thereof.

Images