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
Claims 1-2,5-6,8-13,15-16,19,21-22,24-41,43-46, 67 – 70, 85, and 100 are currently pending in the instant application.
Restriction/Election
Applicant's election , without traverse, in the reply filed 14 August, 2025 of Group I, claims 1-2,5-6,8-13,15-16,19,21-22,24-41,and 43-45, directed to a method of increasing GBA1 expression in the cell; and the following election of Species, without traverse, is acknowledged:
Species (A): a class II transposase (Claim 5),
Species (B): a UBC promoter(claim 9),
Species (C): electrotransfer (claim 11),
Species (D): introduced into the cell at the same time (claim 19),
Species (E): rs76763715 (claim 28);
Species (F): SNP encodes a serine, rather than an asparagine, at position 370 (N370S) (claim 30).
Claims 46, 67 – 70, 85, and 100 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 6,8,10, 25,26,32,34,36,38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
Please Note: claim 33 refers to back to withdrawn claim 32 and, therefore, claim 33 has not been examined on the merits.
Please Note: claim 35 refers to back to withdrawn claim 34 and, therefore, claim 35 has not been examined on the merits.
Please Note: claim 37 refers to back to withdrawn claim 36 and, therefore, claim 37 has not been examined on the merits.
Please Note: claim 39 refers to back to withdrawn claim 38 and, therefore, claim 39 has not been examined on the merits.
The restriction requirement is still deemed proper and is therefore made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1,2,5,9,11,12,13, 15, 16,19,21, 22,24,27-31,40-41, and 43-45 are under consideration to which the following grounds of rejection are applicable.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 21 March, 2024 has been considered. An initialed copy of the IDS accompanies this Office Action.
Priority
The present application filed 20 July, 2022 claims the benefit of Provisional Application 63/224,395, filed 21 July, 2021, and Provisional Application 63/272,675, Filed 27 October, 2021.
Therefore, the earliest priority date is 21 July, 2021.
Claim objection
Claim 1 is objected to because of the following informalities: Abbreviations such as GBA1 should be spelled out at the first encounter in the claims. Appropriate correction is required.
Claim Rejection - 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 1,2,5,9,11,12,13, 15, 16,19,21, 22,24,27-31,40-41, and 43-45 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.
Claim 1 is indefinite for the recitation of “the DNA sequence is positioned between inverted terminal repeats” in line 5 – 6. It is unclear how the DNA is positioned between inverted terminal repeats if the only a DNA sequence operably linked to a promoter is being introduced into the cell. It is unclear whether the DNA sequence alone is being introduced, or whether the DNA sequence part of a expression vector that is being introduced. Thus, the metes and bounds of the claim cannot be determined.
Claim 1 is indefinite for the recitation of “ introducing in (i) and (ii) results in integration of the DNA sequence” in lines 7 – 8. Claim 1 recites “a)” and “b),” and therefore, it is unclear what the “ (i) and (ii)” is referring to.
Claims 1, 11, 19, 22, and 40 are indefinite for the recitation of “the cell” such as recited in claim 1, line, 7. There is a lack of antecedent basis for the term “the cell,” because claim 1, line 3 recites “a pluripotent stem cell.”
Claim 2 is indefinite for the recitation of “the cell comprises a variant of GBA1” in lines 1 -2. It is unclear whether the cell inherently comprises a variant of GBA1 or the DNA sequence encoding GBA that is introduced is a variant of GBA1. Thus, the metes and bounds of the claim cannot be determined.
Claim 11 is indefinite for the recitation of “the nucleic acid encoding a transposase and/or the DNA sequence encoding GBA1 are introduced into the cell by electrotransfer” such as recited in claim 11, lines 1-3. It is unclear what the metes and bounds of the term “and/or”, could interpreted in claim 1. Specifically, it is unclear both the sequence encoding the transposase and the DNA sequence or one of the sequences are introduced by electro transfer. Thus, the metes and bounds of the claim cannot be determined.
Claim 13 is indefinite for the recitation of “and/or” in line 2. It is unclear what the metes and bounds of the term “and/or” could be interpreted in claim 13. Specifically, it is unclear nucleic acid encoding a transposase is part of a plasmid, and the DNA sequence encoding GBA1 is part of a plasmid, or just the transposase or GBA1 is part of a plasmid. Claim 16 is indefinite for the recitation of “the plasmid” in lines 1 and 2. There is a lack of antecedent basis for the terms “the plasmid,” as claim 1 does not teach “a plasmid.”
Claim 22 is indefinite for the recitation of “the cell exhibits reduced activity of the GCase enzyme” in lines 6 – 7. There is a lack of antecedent basis for the term “the GCase enzyme,” as claim 1 does not teach the “GCase enzyme.”
Claim 31 is indefinite for the recitation of “the wild-type form of GBA1” in lines 1 – 2. There is a lack of antecedent basis for the term “the wild-type form of GBA1.” Further, it is unclear whether this form is different from the variant of GBA1 that is taught in claim 2. Thus, the metes and bounds of the claim cannot be determined.
Claim 9, 15, 21, 27 – 30, 41, and 43 - 45 are indefinite insofar as it ultimately depends from claim 1.
Claim Rejection - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 16 is rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 16 recites “the plasmid containing the DNA sequence and the plasmid containing the nucleic acid sequence encoding the transposase” in lines 1 – 2. Claim 16 depends from claim 1, which recites “introducing a DNA sequence” in line 3 and “introducing a transposase or a nucleic acid sequence encoding a transposase” in line 7, does not teach introducing a plasmid. Thus, claim 16 is an improper dependent claims for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejection - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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, 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.
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.
Claim 1,2,5,9,11,12,13, 15, 16,19,21, 22,24,27-31,40-41, and 43-45 are rejected under 35 U.S.C. 103 as being unpatentable over Mason et al. (hereinafter referred to as “Mason”) (US20210000929 A1, published 7 January, 2021), and further in view of Largaespada et al. (hereinafter referred to as “Largaespada”) (WO 2018112415 A1, published 21 June, 2018).
Regarding claim 1 and 2, Mason teaches a method of treating Parkinson's disease in a subject, the method comprising administering to the subject a composition comprising a population of pluripotent cells that express a transgene encoding glucocerebrosidase (GBA) (claim 1) (interpreted as introducing into a pluripotent stem cell DNA encoding GBA1 and GBA1 is associated with Parkinson’s disease, instant claim 1 and 2). Mason teaches that the expression of the GBA in the pluripotent cell is driven using a ubiquitous promoter, phosphoglycerate kinase 1 (PGK) (claims 171 and 172) (interpreted as the GBA is linked to a promoter, instant claim 1). Mason teaches transposon-mediated gene transfer, wherein the transposon, containing the gene of interest, is excised, and the gene of interest can be integrated into the genome of a mammalian cell (Paragraph [0207]).
Mason does not specifically exemplify introducing a transposase, resulting in integration of the DNA sequence encoding GBA1 into the genome of the cell, and that the DNA sequence is positioned between inverted terminal repeats (instant claim 1), the transposase is a Class II transposase (instant claim 5), the DNA sequence encoding GBA1 is introduced as an intron (instant claim 21)
Regarding claim 1, 5, 12, 19, 21 Largaespada teaches that the hAT family transposon components, such as TcBuster, enhance gene transfer into human hematopoietic and immune system cells using hAT family transposon components (Paragraph [0050]). Largaespada teaches that this system is used for inserting an exogenous gene into the host genome (Paragraph [00113]) (interpreted as introducing a transposase for the integration of DNA sequence into the genome of the cell, instant claim 1 and 12). Largaespada teaches the use of a mutant TcBuster transposase, wherein the mutant transposase has increased transposition efficiency compared to wild-type TcBuster transposase (Paragraph [0004]) (interpreted as TcBuster is a class II transposase, instant claim 5). Largaespada teaches that transposon comprises a cargo cassette positioned between two inverted repeats (claim 73). Largaespada teaches that the cargo cassette comprises the PGK promoter (claim 82). Largaespada teaches that the cargo cassette comprises a transgene (claim 101). Largaespada teaches that cell can be an iPSC (Paragraph [0024]). Largaespada teaches a method of treatment, comprising administering the genetically modified cells, comprising the TcBuster transposase, a patient in need of treatment (Claim 104). Largaespada teaches that a transgene can be derived from, or a variant of, a gene in nature, or can be artificially designed, and comprise introns (Paragraph [00108]) (interpreted as the DNA sequence encoding GBA1 is an intron, instant claim 21).
Therefore, in view of the benefits of enhancing gene transfer into cells using the hAT family transposon components as taught by Mason, it would have been prima facia obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of comprising a population of pluripotent cells that express a transgene encoding GBA, as taught by Mason, to include the use of the mutant TcBuster transposase, comprising a cargo cassette positioned between two inverted repeats and comprises a transgene, as taught by Largaespada, with a reasonable expectation of success in enhancing the delivery of GBA to the target cells, and thus improving the treatment of Parkinson’s disease. It would have been prima facia obvious to combine the cited sources because Mason teaches a method of treating Parkinson’s disease, comprising administering a population of pluripotent cells that express a transgene encoding glucocerebrosidase (GBA), and are attached via PGK promoter. Mason also discusses the method of transposon mediated gene transfer, but does not specifically teach how to do this. Largaespada teaches hAT family transposon components, comprising a TcBuster transposon linked to a cargo cassette, comprising a transgene, via a PKG promoter, and the advantage of this system in enhancing gene transfer into the pluripotent stem cells for the treatment of various diseases.
Regarding claim 9, the combined teachings of Mason and Largaespada render obvious the teachings of claim 1. Moreover, Mason teaches that the expression of the GBA in the pluripotent cell is driven using a ubiquitous promoter, phosphoglycerate kinase 1 (PGK) (claims 171 and 172).
Regarding claim 11, the combined teachings of Mason and Largaespada render obvious the teachings of claim 1. Moreover, Mason teaches that pluripotent cells are transfected using electroporation (claim 163). (Please Note: The as-Filed Specification teaches that the the electrotransfer is by electroporation or nucleofection (Paragraph [0013]).
Regarding claims 13 and 15, the combined teachings of Mason and Largaespada render obvious the teachings of claim 1. Moreover, Mason teaches that stable expression of GBA in a mammalian cell can be achieved by integration of the polynucleotide using a variety of vectors (Paragraph [0174]) (interpreted as the DNA sequence encoding a GBA1 is part of a plasmid, instant claim 13). Further, Mason teaches that the transposons are polynucleotides that encode transposase enzymes, and once the transposons are delivered into a cell, expression of the transposase gene commences (Paragraph [0207]) (interpreted as the nucleic acid encoding the transposase is DNA, instant claim 15).
Regarding claim 16, the combined teachings of Mason and Largaespada render obvious the teachings of claim 1. Moreover, Mason teaches that pluripotent cells described herein can be transfected with multiple plasmids (Paragraph [0175]) (interpreted as the plasmid containing the DNA sequence and the plasmid containing the transposase are different, instant claim 16).
Regarding claim 19, the combined teachings of Mason and Largaespada render obvious the teachings of claim 1. Moreover, Mason teaches transposon-mediated gene transfer (Paragraph [0207]) (interpreted as the DNA sequence encoding GBA1 and the transposase are introduced into the cell at the same time, instant claim 19).
Regarding claim 22, the combined teachings of Mason and Largaespada render obvious the teachings of claim 1. Moreover, Mason teaches that there is reduced GBA activity has been reported in the substantia nigra, cerebellum, and caudate of Parkinson’s disease patients (Paragraph [0121]).
Regarding claim 24, the combined teachings of Mason and Largaespada render obvious the teachings of claim 1. Moreover, Mason teaches the transgene encoding GBA contains a polynucleotide encoding wild-type human GBA (Paragraph [0006]).
Regarding claims 27 – 31, the combined teachings of Mason and Largaespada render obvious the teachings of claim 1. Moreover, Mason teaches that the GBA-encoding include transgenes comprising polynucleotides that encode wild-type GBA or a variant thereof (Paragraph [0123]). Mason teaches that the mild GBA mutations N370S (also known as rs76763715) associated with Parkinson’s disease (Paragraph [0088]) (interpreted as the variant of GBA1 comprising a SNP encodes a serine, rather than an asparagine, at amino acid position 370 (N370S), instant claims 27 – 31).
Regarding claim 40 – 41, the combined teachings of Mason and Largaespada render obvious the teachings of claim 1. Moreover, Mason teaches administering to the subject a composition comprising a population of pluripotent cells that express a transgene encoding glucocerebrosidase (claim 1). Mason teaches that the iPS cells can be generated by introducing specific sets of reprogramming factors into a non-pluripotent cell (Paragraph [0093]) (interpreted as the iPSC is artificially derived from a non-pluripotent cell from a subject, instant claim 41).
Regarding claim 43 – 44, the combined teachings of Mason and Largaespada render obvious the teachings of claim 1. Moreover, Mason teaches a method of treating Parkinson's disease in a subject (claim 1).
Regarding claim 45, the combined teachings of Mason and Largaespada render obvious the teachings of claim 1. Moreover, Mason teaches the gene of interest can be integrated into the genome of a mammalian cell by transposase-catalyzed cleavage, allowing allows the gene of interest to be inserted into the cleaved nuclear DNA at the complementary excision sites (Paragraph [0207]) (interpreted as determining the location of integrated DNA sequence in the genome of the cell, instant claim 45).
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103 as obvious over the art.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VYOMA SHUBHAM TIWARI whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 EST.
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/VYOMA SHUBHAM TIWARI/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634