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 .
DETAILED ACTION
Claim status
Claims 1, 2, 4-6, 11-16, 19-20, 33-34, 37-38, 41, 47, and 52 are pending
Claims 12-16, 19-20, 33-34, 37-38, 41, 47, and 52 are withdrawn
Claims 1, 2, 4-6, and 11 are under examination
Election/Restrictions
Applicant’s election of the following invention without traverse in the reply filed on 8/18/2025 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Group I, claims 1, 2, 4-6, and 11, drawn to a method of treatment comprising an AAV vector encoding human beta-galactosidase.
Claims 12-16, 19-20, 33-34, 37-38, 41, 47, and 52 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 8/21/2023 and 8/18/2025 in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claim 1 is objected to because of the following informalities: instant claim recites the phrase “in target cell”, which is not grammatically correct.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated 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 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. 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, 2, 4 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Sena-Esteves (US2021/0228739, filed 5/15/2019) in view of Taghian (Mol Therapy, 2020, 28(2):411-421, ePub 11/16/2019, see IDS filed 8/21/2023) and Latour et al. (Mol Gen Met Rep, 2019, 100513, pgs. 1-8)
In regard to claim 1, Sena-Esteves teaches a therapeutic regimen for treating GM1 gangliosidosis in a human patient comprising administering an AAV vector encoding beta-galactosidase under control of regulatory sequences that direct expression in a human target cell ([0003, 0007, 0091], Fig. 8, see Claims 1, 7, 11 and 23 of Sena-Esteves)
In regard to the route of administration, Sena-Esteves teaches the AAV is delivered by cisterna magna injection [0101].
In regard to the dose of the AAV vector, Sena-Esteves teaches the AAV is delivered at a concentration of about 10^13 GC/mL or more [0109]
However, Sena-Esteves is silent with respect to a preferred embodiment of a dosing regimen for treating a human subject with GM1 gangliosidosis by cisterna magna injection, wherein the AAV is delivered to the cisterns at a dose between 3 x 10^13 GC to 3 x 10^14 GC.
Nevertheless, in regard to dose of AAV in a human as per claim 1, the prior art of Taghian et al. (2019), which includes the inventor Sena-Esteves as an author, teaches dosing regimens for treating a human subject with GM2 gangliosidosis, wherein the AAV is delivered to the cisterns by injection at a a dose between 3 x 10^13 GC to 3 x 10^14 GC.
Specifically, Taghian teaches that for a human patient of 30 months in age, a total dose of 1 x 10^14 vg was administered, wherein 9 mL was administered to the premedullary cistern and 3 mL at the L2 level of the spinal cord. Thus, for the single dose of 9 mL to the cistern that was about 3/4ths the volume of the total dose, the amount of AAV delivered was about 0.75 x 10^14 vg.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice the treatment regimen for treating GM1 gangliosidosis comprising intra-cisterna magna injection of a AAV beta-galactosidase vector as taught by Sena-Esteves, and choose a single dose of about 0.75 x 10^14 vg as taught by Taghian with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so for several reasons. First, in regard to turning to related non-patent literature of Taghian by the same inventor of Sena-Esteves, is standard practice to analyze the scientific publications of patent inventors who are also registered as authors of scientific publications, as these boundary crossing between the science and technology spheres reflect a degree of cooperation between representatives of the technological and scientific activity spheres. Second, arriving at a particular dose of AAV vector would have been obvious since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233. In instant case, Taghian discloses a dose of an AAV vector to treat a related childhood disease of GM2 gangliosidase by a similar manner of cisternal delivery, thus the disclosed dose would have been an obvious starting point for a workable range. In regard to the reasonable expectation of success of treating a human at least 12 months old with the AAV-beta-galactosidase gene therapy to treat GM1, the prior art of Latour et al. (2019), which includes the inventor Sena-Esteves as an author, teaches a human GLB1 knock-out organoid model that demonstrates AAV-beta-galactosidase gene therapy successfully reduces GM1 gangliosidosis (Abstract, Figs. 1-4). Latour concludes that this demonstration was the final step in the pre-clinical development of the AAV-GLB1 vector for a clinical trial for children with type II GM1 gangliosidosis (p. 4, Discussion, last para.).
In regard to claim 2, Sena-Esteves teaches the 2034 nt nucleic acid sequence for human beta-galactosidase of SEQ ID NO:1 [0039], which is 100% identical to instant claim’s SEQ ID NO:5 (see SCORE search 10/16/2025, rnpbm.file, result #1).
In regard to claim 4, Sena-Esteves teaches the AAV vector genome comprises 5’ and 3’ ITR sequences, a chimeric intron, and an SV40 polyA signal ([0032], see Fig 8).
In regard to claim 5, as stated supra, Latour makes obvious treating type II GM1 gangliosidosis in a human. Furthermore, since Latour evidences that there only two types of type II GM1 (i.e., type IIa that is late-infantile and type IIb that is juvenile) (Introduction, 1st para.), one of ordinary skill in the art would have immediately envisioned the type IIa option from such a small genus. Furthermore, the 30 month AAV dose taught by Taghian was within the well-known window for the onset of symptoms in type IIa GM1 gangliosidosis (i.e., 4-36 months), thereby providing a reasonable expectation of success for treating this subtype of disease.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Sena-Esteves (US2021/0228739, filed 5/15/2019, see IDS filed 8/21/2023) in view of Taghian (Mol Therapy, 2020, 28(2):411-421, ePub 11/16/2019, see IDS filed 8/21/2023) and Latour et al. (Mol Gen Met Rep, 2019, 100513, pgs. 1-8), as applied to claim 1, in further view of Hordeaux et al. (Mol Therapy, 2018, 10:68-78, see IDS filed 8/21/2023)
As stated supra, Sena-Esteves in view of Taghian and Latour suggest a therapeutic regimen for treating the lysosomal storage disease of GM1 gangliosidosis in a human patient at least 12 months old comprising intra-cisterna magna administration of about 7.5 x 10^13 GC AAV vectors encoding beta-galactosidase under control of regulatory sequences that direct expression in a target cell.
However, Sena-Esteves is silent to further administering immunosuppressive agents as co-therapy to the patient at least one day prior to the day of delivery of the rAAV. Nevertheless, Taghian cites the prior art of Hordeaux (2018).
Hordeaux teaches a therapeutic regimen for treating a lysosomal storage disease in non-human primate patients comprising a single intra-cisterna magna administration of 1.7 or 5 x 10^13 GC rAAV vectors and further administering immunosuppressive agent co-therapy to the patient at least one day prior to the day of delivery of the rAAV (p. 69, Study Design).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice the treatment regimen for treating lysosomal storage disease of GM1 gangliosidosis comprising intra-cisterna magna injection of a rAAV beta-galactosidase vector as suggested by Sena-Esteves, and combine administering immunosuppressive agents as co-therapy to the patient at least one day prior to the day of delivery of the rAAV as taught by Hordeaux with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so because Hordeaux teaches the immunosuppressive co-therapy reduces the amount of neutralizing antibodies (p. 70, 2nd para., Fig. 2B).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Sena-Esteves (US2021/0228739, filed 5/15/2019, see IDS filed 8/21/2023) in view of Taghian (Mol Therapy, 2020, 28(2):411-421, ePub 11/16/2019, see IDS filed 8/21/2023) and Latour et al. (Mol Gen Met Rep, 2019, 100513, pgs. 1-8), as applied to claim 1, in further view of Nestrasil et al. (Mol Genet Metab, 2018, 123:97-104, see IDS filed 8/21/2023)
As stated supra, Sena-Esteves in view of Taghian and Latour suggest a therapeutic regimen for treating GM1 gangliosidosis in a human patient at least 12 months old comprising intra-cisterna magna administration of about 7.5 x 10^13 GC AAV vectors encoding beta-galactosidase under control of regulatory sequences that direct expression in a human target cell.
However, Sena-Esteves is silent to assessing the efficacy of treatment in the human subject by volumetric MRI analysis.
Nestrasil discloses a longitudinal study to describe disease progression in childhood gangliosidoses such as GM1 gagnliosidosis by volumetric MRI analysis.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice the treatment regimen for treating GM1 gangliosidosis in a human as suggested by Sena-Esteves et al., and combine volumetric analysis by MRI imaging as taught by Nestrasil with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Nestrasil because quantitative brain MRI volumetry (qMRI) is a non-invasive marker of disease progression for clinical treatment trials (Abstract, p. 4, Objectives).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
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/ARTHUR S LEONARD/ Examiner, Art Unit 1631