DETAILED ACTION
Notice of AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application
Claims 251-270 are pending and subject to examination on the merits.
Priority
The instant application is a CON of US application 16987884 (now US Patent 11833164) which claims benefit of US provisional applications 62986297 and 62883759, filed 06 March 2020 and 07 August 2019, respectively.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 270 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 270 recites an increased stability of the alpha-galactosidase A protein bound to migalastat as compared to a naturally occurring alpha-galactosidase A protein. However, it is well known that many alpha-galactosidase A exist across many prokaryotic and eukaryotic species such as S. cerevisiae, A. niger, Homo sapiens, etc. which may have differing degrees of stability if or when bound to migalastat. As such, any increased stability should be in a direct comparison with a naturally occurring alpha-galactosidase A from the same species, having the same mutation(s).
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 251-255 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to migalastat (Galafold®/AT1001/1-deoxygalactonojirimycin) bound to an alpha-galactosidase A protein, wherein said alpha-galactosidase A comprises a mutation selected from 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 and D25H, wherein the residues are numbered relative to SEQ ID NO:2 (human). Thus, the claims are drawn to migalastat bound to any alpha-galactosidase A protein from any species having the requisite substitutions, because the substitutions only have to be relative to SEQ ID NO: 2 but the starting alpha-galactosidase A is not required to be SEQ ID NO: 2. In addition, the claim is open and comprising and thus the mutations/substitutions of the alpha-galactosidase A protein are not only limited to those recited in the claim. Rather, said alpha-galactosidase A can any an unlimited number of additional substitutions/mutations. Thus, the genus of alpha-galactosidase A mutant enzymes, having a mutation of an amino acid 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 and D25H in addition to/unlimited in any other mutations is enormous. The specification, admittedly discloses numerous single or double mutations of human wild-type alpha-galactosidase A comprising SEQ ID NO: 2, which have single or double mutations which are identified as amendable or non-amenable substitutions (e.g. which mutations will be amenable to being helped/stabilized by the binding of migalastat or not). However, the specification is (a) drawn solely to mutations/substitutions in human alpha-galactosidase A comprising SEQ ID NO: 2, wherein not a single other alpha-galactosidase A protein from any other species is contemplated or disclosed; and (b) each of the substitutions of the human alpha-galactosidase A comprising SEQ ID NO: 2 are single, at most double, substitutions. Not an unlimited number of substitutions/mutations as currently claimed. Thus, these are not a representative number of the alpha-galactosidase A proteins having substitutions/mutations, minimally of amino acids 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 and D25H.
As a suggestion to overcome these issues the claim could be amended to something like: A molecule comprising migalastat bound to a human alpha-galactosidase A protein, wherein said human alpha-galactosidase A protein possesses a mutation selected from the group consisting 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 and D25H, and wherein said amino acid numbering corresponds to SEQ ID NO: 2.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 251-270 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11833164. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘164 patent will necessarily render obvious the instant claims.
The claims in their broadest are drawn to a molecule comprising migalastat bound to an α-galactosidase A protein comprising a HEK assay amenable mutation selected from the group consisting 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 and D25H, wherein the residues are numbered relative to SEQ ID NO:2.
The claims of the ‘164 patent in their broadest are drawn to a method of treating Fabry disease in a subject comprising: accessing mutation information corresponding to the subject, the mutation information identifying one or more α-galactosidase A mutations; determining, based on the mutation information, that the subject has at least one mutation selected from a first group consisting 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, F181, F18L, A20G, L21H, V22A, V22F, V22I, V22L, S23P, S23T, W24S, D25H, I26N, P27A, P27L, P27S, P27T, G28E, G28R, G28W, A29G, A29P, A29V, R30G, L32M, …………………, Q422P, M423I, M423K, M423L, M423T, S424L, L425F, D427N and L429R; and
administering migalastat or a salt thereof to the subject determined to have at least one mutation selected from the first group.
With dependent claim 2, reciting wherein the at least one mutation includes a mutation: at amino acid residue 5 that comprises N5D or N5K; at amino acid residue 6 that comprises P6L, P6Q, P6R, P6S, or P6T; at amino acid residue 7 that comprises E7D, E7K, E7V; at amino acid residue 8 that comprises, L8I, L8P, L8Q; at amino acid residue 9 that comprises H9L, H9Q, H9R, or H9Y; at amino acid residue 10 that comprises, L10M, L10P, L10QL10R, or L10V; at amino acid residue 11 that comprises G11C, G11D, G11R, G11S, or G11V; at amino acid residue 12 that comprises C12G, C12R, C125, or C12Y; at amino acid residue 13 that comprises A13E or A13G; at amino acid residue 14 that comprises L14F, L14H, or L14V at amino acid residue 17 that comprises R17C, R17G, R17H, R17P, or R175; at amino acid residue 18 that comprises, F18I or F18L; at amino acid residue 20 that comprises A20G; at amino acid residue 21 that comprises L21H; at amino acid residue 22 that comprises V22A, V22F, V22I, or V22L; at amino acid residue 23 that comprises S23P orS23T; at amino acid residue 24 that comprises W24S; at amino acid residue 25 that comprises D25H; at amino acid residue 184 that comprises Y184S; at amino acid residue 228 that comprises N228H; or at amino acid residue 412 that comprises T412I; wherein the residues are numbered relative to SEQ ID NO:2
Thus, the difference between the two sets of claims is that the methods of the ‘164 patent do not specifically recite that when migalastat is administered to a patient having an alpha-galactosidase A protein with the noted mutations, which directly overlap and correspond to the same mutations in the instant claims, that upon administration said migalastat will inherently bind the mutated alpha-galactosidase A in the patient, resulting in the instant claimed molecules.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUZANNE M NOAKES whose telephone number is (571)272-2924. The examiner can normally be reached M-F (7-4).
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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 24 March 2026