DETAILED ACTION
Notice of Pre-AIA or 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 .
Election/Restrictions
Applicant’s election with traverse of Group I (i.e., claims 1-11 and 43-47) in the reply filed on 03/04/2026 is acknowledged. The traversal is on the ground(s) that Group I and Group II include the same special technical feature of the patient having an a-galactosidase A mutation selected from the group consisting of: A29D, R38S, N53Y, Y88C, V124G, 1133F, A143V, Y152N, F159C, A160D, D165N, F1691, L180V, D182G, R196T, W209R, A257T, P259S, G271A, S276T, M290V, A291 S, 1303T, 1303V, L310V, G360A, G360R, G375A, L394P, G411 S, and N419D and that this special technical feature is not disclosed in Benjamin (WO 2009/102895). This is not found persuasive because the claims of group I and group II are distinct inventions and they lack unity of invention and the technical feature. In addition to the rationale outlined in the restriction requirement, the examiner notes that group I is clearly directed towards a method for the treatment of Fabry disease. Group II on the other hand is directed towards a method for enhancing a-galactosidase A. Although the groups may share some common features, the examiner maintains that the inventions lack unity. The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons: the use of 1-deoxygalactonojirimycin (aka Migalastat) for the treatment of Fabry disease is known in the art as taught by Benjamin (WO 2009/102895) (abstract; page 11, lines 11-14; claims 9 and 29). The requirement is still deemed proper and is therefore made FINAL.
Applicant’s cancellation of claims 45-47 is acknowledged. There are new claims (i.e., claims 94-96).
Since, the applicant elected Group I and cancelled claims 45-47, therefore, based on that election, claims 48-51 are being withdrawn from consideration as being drawn to a non-elected group.
Claims 1-11, 43-44, and 94-96 are under consideration in this office action and will be examined on the merits.
Status of Claims
Claims 1-11, 43-44, and 94-96 are pending. Applicant added new claims 94-96, and canceled claims 45-47. Claims 48-51 are withdrawn from consideration.
Claims 1-11, 43-44, and 94-96 are under consideration in the instant office action.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 43 and 44 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 43 and 44 have limitations with reference to a “pharmacological reference table”. Claims must, under modern claim practice, stand alone to define an invention, and incorporation into claims by express reference to the specification is not permitted. See Ex parte Fressola, 27 USPQ 2d 1608 (1993). It is suggested that Applicant incorporate the table into the claim to overcome this rejection, assuming such incorporation does not introduce new matter.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Applicant Claims
2. Determining the scope and contents of the prior art.
3. Ascertaining the differences between the prior art and the claims at issue, and resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-11 and 94-96 are rejected under 35 U.S.C. 103(a) as being unpatentable over Germain et al. (“Safety and pharmacodynamic effects of a pharmacological chaperone on α-galactosidase A activity and globotriaosylceramide clearance in Fabry disease: report from two phase 2 clinical studies” Orphanet Journal of Rare Diseases 2012, 7:91. (2012)) in view of US20140219986A1 to Greene et al. (“Dosing regimens for the treatment of Fabry disease” herein after ‘Greene’ filed March 08, 2012), further in view of US11034946B2 to Calhoun et al. (“Glycosylation independent proteins” herein after ‘Calhoun’ filed Oct. 5, 2018) and Altarescu et al. (“Identification of fifteen novel mutations and genotype–phenotype relationship in Fabry disease”. Clinical Genetics, 60: 46-51. (Published: 20 December 2001)).
Regarding claims 1-7, 9-11, and 94-96, Germain teaches methods for the treatment of Fabry disease in a human patient. Germain teaches Fabry disease (FD) is a genetic disorder resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A), which leads to globotriaosylceramide (GL-3) accumulation in multiple tissues. Germain reports on the safety and pharmacodynamics of migalastat hydrochloride, an investigational pharmacological chaperone given orally at 150 mg every-other-day. (Abstract; Background: lines 1-4). Germain further teaches Migalastat HCl is a candidate pharmacological chaperone that provides a novel genotype-specific treatment for FD. It enhanced α-Gal A activity and resulted in GL-3 substrate decrease in patients with responsive GLA mutations (Abstract; Conclusions: lines 1-3). Germain teaches that migalastat HCl is a candidate pharmacological chaperone that provides a genotype-specific treatment for FD. When administered at an oral dose of 150 mg on an every-other-day regimen, it was well tolerated, increased α-Gal A activity in patients with responsive GLA mutations, and resulted in GL-3 substrate reduction. (Pg. 10, Para. 2, lines 1-7). Germain discloses patient population that include both males and females. With regards to that, Germain teaches the safety and pharmacodynamics of migalastat HCl in 9 male FD patients given 150 mg orally every other day. (Pg. 8, Discussion, Para. 3, lines 2, 3). Germain teaches that in females, an increase in activity with migalastat HCl might reflect the chaperoning of the wild-type enzyme. It has been increasingly recognized that females with FD can have significant clinical manifestations (Pg. 10, Para. 1, lines 11-15), thus arriving at instant claims 1-3, 6, 7 and 9-11.
However, Germain does not explicitly teach administration by injection, free base form and a specific dosage amount of 123 mg of migalastat.
Greene teaches 1-deoxygalactonojirimycin can be administered as the free base or as a pharmacologically acceptable salt form, including 1-deoxygalactonojirimycin hydrochloride (a.k.a., migalastat hydrochloride). It can be administered in a form suitable for any route of administration, including e.g., orally in the form tablets, capsules, or liquid, or in sterile aqueous solution for injection (Detailed description, [0046], lines 1-6).
It would have been obvious to a person having ordinary skill in the art at the time the invention was filed to formulate the therapeutic composition of Germain as a free base as well as an injectable formulation; thus, arriving at the claimed invention of claim 5 and 8. One skilled in the art would be motivated to do so, with a reasonable expectation of success, because formulating the composition as free base, and as an injectable formulation provides the benefits of good dissolution rate as well as optimize and enhance therapeutic effects, as taught by Greene
Regarding dosage amount of about 123 mg of migalastat in claims 4 and 5, it is noted that, while Germain and Greene do not specifically teach the exact instantly claimed dosage of about 123 mg. The Examiner also notes that Applicant defines “about” in paragraph [0048] on page 15 of the instant specification field on September 6, 2022 to mean, “…an acceptable degree of error for the quantity measured given the nature or precision of the measurements.” Applicant also indicates that “Typical, exemplary degrees of error are within 20 percent (%)…of a given value or range of values.” (Id.) Twenty percent ± of a dosage of about 123 mg, leads to a dosage ranging from 98.4 mg to 147.6 mg. A dosage of 147.6 mg would be expected to exhibit the same or substantially similar effects as the prior art dosage of 150 mg, because it is very close in magnitude to the prior art dosage. Additionally, the Examiner notes that the optimum amounts of the presently claimed active agents and excipients would have been a matter well within the insight of one of ordinary skill in the art. Such a determination would have been made in accordance with a variety of factors, such as the route of administration, pharmacological considerations, such as the activity, efficacy, pharmacokinetics and toxicology profiles of the combination regimen, as well as the age, weight, sex, diet and medical condition of the patient, and the severity of the condition. Thus, the determination of the optimum or workable amounts given the guidance of the prior art would have been generally prima facie obvious to the ordinary skilled artisan. Please see MPEP 2144.05 [R-2] (II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (“[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation."). Accordingly, the particular amounts claimed do not impart patentability to the claims, absent a showing of the criticality of the particular amounts claimed.
Regarding claims 1 and 94-96, Germain teaches the method of claim 1, as detailed above.
However, Germain does not explicitly teach a laundry list of a-galactosidase A mutation selected from the group consisting of: A29D, R38S, N53Y, Y88C, V124G, 1133F, A143V, Y152N, F159C, A160D, D165N, F1691, L180V, D182G, R196T, W209R, A257T, P259S, G271A, S276T, M290V, A291S, 1303T, 1303V, L310V, G360A, G360R, G375A, L394P, G411S, and N419D.
Altarescu teaches novel missense mutations of the instant claims 1, 94-96 that encompass 1303T, 1303V, and G375A (Abstract; para. 3, lines 1-5), and Calhoun teaches a-galactosidase A polypeptide mutation W209R (claim 3).
It would have been obvious to a person having ordinary skill in the art at the time the invention was filed to combine the teachings of Germain and Greene with the teachings of Altarescu and Calhoun; thus, arriving at the claimed invention. One skilled in the art would have been motivated to do so, with a reasonable expectation of success, because it is known in the art that many missense mutations are the underlying causes of lysosomal storage diseases that make an individual prone to Fabry disease. Fabry disease is an X-linked recessive disorder caused by a deficiency in the lysosomal enzyme α-galactosidase A, which results in a progressive multisystem disease(s) as taught by Altarescu.
Conclusion
Claims 1-11, 43-44, and 94-96 are rejected. No claims are allowed.
Pertinent prior art included but not relied upon:
Eng, C M et al. “Fabry disease: thirty-five mutations in the alpha-galactosidase A gene in patients with classic and variant phenotypes.” Molecular medicine (Cambridge, Mass.) vol. 3, 3 (1997): 174-82.
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/SAHAR INAM/
Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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