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 .
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Status
Claims 1-8, 11, 14-16, 18, 20-24, 26, and 35 were previously pending.
Receipt is acknowledged of applicant's Amendments filed 07 November, 2025. Claims 1, 2, 5, 7, 8, 11, 14, 16, and 26 are amended. Claims 3-4 are cancelled.
Applicant previously elected the invention of group I (claims 1-8, 11, 14-16, 18, 20-24, and 26) without traverse. Applicant also previously elected without traverse the species of lysosomal storage disease, the species of AAV, the species of albumin, the species of beta galactosidase, the species of spCas9, and the species of rs1291543917.
Claim 35 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The species elections filed on 03 April, 2025 are being applied to all pending claims.
Therefore, claims 1-2, 5-8, 11, 14-16, 18, 20-24, and 26 are pending and are the subject of the present Official Action.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2020/054835, filed 08 October, 2020, which claims priority to United States Provisional Application No. 62912329, filed 08 October, 2019. Acknowledgment is made of applicant’s claim for priority under 35 U.S.C. 119 (e).
Therefore, the earliest possible priority for the instant application is 08 October, 2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07 November, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings filed on 07 November, 2025 are accepted by the Examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Because no sequence listing has been provided, a complete search of SEQ ID NO: 15 could not be completed. Applicant is advised that amended claim 26 has not been further treated on the merits because a complete search could not be completed.
To advance prosecution, the examiner has been able to interpret the breadth of independent claim 1 and issue a Final Office Action though SEQ ID NO:15 has not been provided by Applicant. See claim rejections below.
Drawings
Applicant’s amendment of 7 November 2025 to the drawings (Figure 12) has been received. This corrects the deficiencies noted in the previous Office action.
Withdrawn Rejections/Objections in view of Applicant’s Amendments/Arguments
Claim Objections
The objection to claims 1, 7-8, 11, 14, 16, 20, and 26 because of the following informalities: abbreviations/acronyms need to be spelled out upon their first encounter in the claims (e.g. “Cas”, “gRNA”, “rAAV”, “Rosa26”, “BCR”, “AAVS1”, “CCR5”, “HPRT”, “hexM”, “eSpCas9”, “SpCas9-HF1”, “HypaCas9”, “Fokl”) is withdrawn in view of Applicant’s amendments to the claims. Applicant has amended the claims to spell out all abbreviations/acronyms.
Claim Rejections - 35 USC § 102
The rejection of claim 26 under 35 U.S.C. 102(a)(2) as being anticipated by US 2023/0201373 (effectively filed: 15 December, 2017) (hereinafter “Ou”) is withdrawn in view of Applicant’s amendments to the claims. Applicant has amended claim 26 to require SEQ ID NO: 15 which Ou does not disclose.
The rejection to claim 26 under 35 U.S.C. 102(a)(2) as being anticipated by US Patent No. 11,028,411 (hereinafter “Friedland”) is withdrawn in view of Applicant’s amendments to the claims. Applicant has amended claim 26 to require SEQ ID NO: 15 which Friedland does not disclose.
Double Patenting
The provisional rejection of claims 1-2 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-8, 11-13, 16-20, and 22-27 of copending Application No. 16/954,171 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims render obvious the instant claims in view of McCurdy, Diss. Auburn University, 2014., page 35, hereinafter “McCurdy” is withdrawn in view of Applicant’s amendments to the claims. Amended claim 1 now requires the specific SEQ ID NO: 15 which is not claimed or taught by the reference application.
Maintained Rejections/Objections in view of Applicant’s Amendments/Arguments
Claim Rejections - 35 USC § 112
Claims 1-2, 5-8, 11, 14-16, 18, 20-24, and 26 remain 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. This rejection has been modified as necessitated by Applicant’s amendments to the claims.
Amended claim 1 recites “the human albumin gene intron” in the tenth, fourteenth, and eighteenth lines of the claim. This language is indefinite because it is unclear which intron of the human albumin gene the claim is referring to. The way it is currently written, it appears to suggest that there is a single intron in the human albumin gene when, in fact, there are 14 different introns in the human albumin gene. Further, if the claim is intended to be targeted to a single intron of the human albumin gene, it is unclear which intron is intended to be the target to fall within the scope of amended claim 1. Claims 2, 5-8, 11, 14-16, 18, and 20-24 are further rejected for their dependency on a rejected base claim.
Claims 5 and 15 are dependent on a canceled claim (i.e., claim 32) and are therefore “incomplete.” See MPEP § 608.01(n)(V).
Amended claim 5 recites “the first intron of the gene” in the first and second lines of the claim. There is insufficient antecedent basis for this limitation in the claim. In addition, amended claim 5 depends from claim 3 which is a cancelled claim. Accordingly, the scope of claim 5 cannot be determined. With regard to the antecedent basis issues, no antecedent can be present when the claim depends from a cancelled claim. See MPEP § 2173.05(e). Even were amended claim 5 to depend instead from claim 1, there would be insufficient antecedent basis for “the first intron of the gene” because claim 1 does not recite “a gene”. Claim 1 instead recites “the human albumin gene”.
Claims 1-2, 5-8, 11, 14-16, 18, and 20-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. This rejection has been modified as necessitated by Applicant’s amendments to the claims.
Applicant has amended claim 1 to specify that one of the gRNAs comprises SEQ ID NO: 15. However, the claim encompasses one or more gRNAs and only specifies that one comprises SEQ ID NO: 15. Therefore, amended claim 1 continues to read on gRNAs comprising any sequence which targets the human albumin gene intron (see 112(b) rejection above for discussion of indefiniteness regarding this recitation).
Amended claim 1 as elected still broadly encompasses an in vivo method of inhibiting, or treating any lysosomal storage disease (elected species) in a human comprising: administering to the human via any route of administration an effective amount of i) SpCas9 or an isolated nucleic acid encoding SpCas9, and ii) an isolated nucleic acid for one or more gRNAs comprising any sequence which targets an albumin locus and nucleic acid comprising a beta galactosidase coding sequence flanked by any homology arms that bind to an albumin locus, or an effective amount of iii) isolated nucleic acid encoding SpCas9 and nucleic acid for one or more gRNAs comprising any sequence which targets an albumin locus, and iv) isolated nucleic acid comprising a beta galactosidase coding sequence (elected species) flanked by any homology arms that bind to an albumin locus, wherein the expression of the beta galactosidase coding sequence in the human, inhibits, or treats the lysosomal storage disease. Claim 6 requires at least one of i) or ii) or at least one of iii) or iv) to be delivered via any AAV as elected. Claims 22-23 require at least one homology arm to be targeted to a rs1291543917 polymorphism as elected and no further structure is claimed for the homology arms. Thus, the claims broadly encompass homology arms of any length and of any sequence wherein at least one homology arm targets a rs1291543917 polymorphism as elected.
For ease of reference, specific citations to the instant specification will be made by referencing the published US patent No. 2023/0416776. The specification does not provide sufficient guidance to a skilled artisan in the field of CRISPR-Cas gene therapies to use the invention commensurate in scope with these claims.
The instant specification lists exemplary AAV viral vectors (AAV2, AAV5, AAV6, AAV8, AAV9) and prophetically teaches treating diseases generally and specifies that it can be, for example, an in vivo method ([0004]). The specification also teaches that any sequence for gRNA and homology arms may be employed so long as adequate expression of the introduced gene is achieved ([0004]). The albumin locus is listed as one potential insertion site among a list of others and systemic administration is taught as one suitable route of administration ([0004]). The specification also teaches beta galactosidase as one potential gene for introduction and lists a wide spectrum of lysosomal storage disorders ([0005], [0103]). The specification teaches that deficiency in beta galactosidase or galactosamine-6-sulfate sulfatase is associated with Morquio syndrome and is also known as mucopolysaccharidosis type IV and that deficiency in beta galactosidase alone is associated with GM1-gangliosidosis ([0010]). The specification does not teach that a gene therapy to provide beta-galactosidase can be used to treat Morquio syndrome in which the underlying cause is a deficiency in galactosamine-6-sulfate sulfatase nor whether such a therapy can be used to treat any other lysosomal storage disorders besides GM1-gangliosidosis and some cases of Morquio syndrome in which beta-galactosidase deficiency is the causative factor. The specification teaches that any route of administration may be employed and lists a wide array of potential routes ([0080]-[0081]). The specification prophetically teaches that such a method can be used in a phase I/II clinical trial in humans ([0123]). However, no such administration to humans to treat a lysosomal storage disease is taught. The specification also teaches the targeted insertion of IDUA into intron 1 of the albumin locus of a mouse model of mucopolysaccharidosis type I via AAV2/8 vectors and SaCas9 ([0128]-[0130], and [0132]-[0136]). The specification also teaches that were this to be done in humans SpCas9, different homology arms, dual vector Cas system, AAV2/6 vectors, and introduction of 9 mutations in the homology arms would be employed (Table 3). The specification does not teach the homology arms to be used in humans, nor which specific gRNAs would be needed to effectuate a treatment for any lysosomal storage disorder in humans. The working examples teach the testing of 12 different gRNAs targeting intron 1 of the human albumin locus alongside SaCas9 in vitro by transfecting human hepatocytes ([0198]) and teach that none of the 12 gRNAs tested produced detectable cleavage at the albumin intron 1 locus ([0199]). The working examples also teach 3 different gRNAs tested under the same conditions with SpCas9 instead and teach that only one of the gRNAs tested (SEQ ID NO: 15) mediated cleavage at the target locus ([0201]). The working examples also teach that intron 1 of the albumin locus has 164 polymorphisms and that the gRNA and/or homology arm sequence may be tailored to the genotype of the recipient and teach two specific homology arms (SEQ ID Nos. 16 and 19) ([0208]-[0210]). But out of 15 different gRNAs tested only one provided cleavage for applicants. Therefore, directing a skilled artisan to account for polymorphisms in intron 1 of the human albumin locus amounts to a direction to engage in trial and error on an individualized basis to find a gRNA suitable to effectuate cleavage of the target site and effectuate a treatment for any lysosomal storage disease. The working examples also teach that there are 70 genetically distinct lysosomal storage diseases and teach that mucopolysaccharidosis type I model mice treated with the CRISPR-Cas system had lower Chito levels ([0211]-[0214]). The working examples provide no teaching of any vector encoding beta galactosidase nor any use of said vector to treat anything let alone an in vivo application of a CRISPR-Cas system to insert beta galactosidase into intron 1 of the albumin locus of any organism at all. Only one specific gRNA is provided that facilitates cleavage of intron 1 of the human albumin locus in in vitro testing and only two specific homology arms are taught. Further, applicants teach that 164 polymorphisms exist in intron 1 of the human albumin locus and merely teach to engage in trial and error to find gRNAs/homology arms that work on an individualized basis.
At the time of filing, it was known that while CRISPR systems have been extensively studied for in vitro and ex vivo applications, significant challenges still exist in the transition of CRISPR systems to in vivo applications (Luther et al. (Expert opinion on drug delivery 15.9 (Published online: 12 September, 2018): 905-913., hereinafter “Luther”, Luther, page 906, only full paragraph)). Luther teaches that adenoviral vectors elicit host-immune responses that hamper its efficacy as an in vivo CRISPR-Cas delivery system (Luther, page 908, first partial paragraph), and lentiviral vectors nonspecifically integrate into host-genome and cause insertional mutagenesis or even tumorigenesis which hampers their efficacy as in vivo CRISPR-Cas delivery systems (Luther, page 908, first full paragraph). Luther also teaches that immunogenicity, off-target effects, and potential mutagenesis of various delivery vectors are important considerations and that, while AAV vectors avoid random integration, they still may simply be too dangerous for clinical application because of immunogenicity of the viral components and of Cas protein itself (Luther, page 910, last full paragraph). Thus, a skilled artisan at the time of filing knew from the teachings of Luther that different viral vectors have different drawbacks for clinical application of CRISPR-Cas systems and that, although AAV vectors avoid insertional mutagenesis concerns, they still may simply be too dangerous for clinical applications. At the time of filing, it was also known that there are still hurdles that need to be overcome to achieve in vivo genome editing in a therapeutic context with CRISPR-Cas systems (Mout et al. (Bioconjugate chemistry 28.4 (2017): 880-884., hereinafter “Mout”, Mout, Abstract)). Mout specifically discusses the challenges associated with translation of CRISPR-Cas systems to in vivo therapeutic contexts and teaches that off-target effects and immunogenicity are two of the major hurdles to achieving such a translation (Mout, page 882, “CHALLENGES” subheading; page 883, first partial and first and second full paragraphs). Mout teaches that even though the gRNA is designed to target a specific gene of interest, often a significant number of nonspecific genes are targeted by the same Cas9/gRNA and that off-target effects of CRISPR systems in vivo have not been explored (Mout, page 882, last partial paragraph; page 883, first partial paragraph). Mout also teaches that gene-based delivery of CRISPR elements can permanently integrate Cas9 gene into host cells leading to immunogenicity and elimination of Cas9 expressing cells, and that AAV-based CRISPR systems delivered in vivo can suffer and has in fact suffered this fate (Mout, page 883, first full paragraph). Thus, a skilled artisan at the time of filing knew from the teachings of Mout that off-target effects of CRISPR-Cas systems have yet to be fully explored in vivo and that immunogenicity and off-target effects remain significant hurdles to applying CRISPR-Cas systems in an in vivo therapeutic context. At the time of filing, it was also known that different AAV serotypes display different tissue-specific tropism, that different lysosomal storage diseases require different routes of administration when AAVs are used to effectuate gene therapy, and that for lysosomal storage diseases effecting the CNS ex vivo HSC-directed gene therapy may be necessary to treat them (Nagree et al. (Expert opinion on biological therapy 19.7 (2019): 655-670., hereinafter “Nagree”, page 660, first full paragraph; Table 1; page 657, first paragraph)). Nagree also teaches that currently no gene therapy has been executed in humans to treat GM1-gangliosidosis and only one pre-clinical study was known at the time of filing for treating GM1-gangliosidosis in felines which required intracerebral administration (Nagree, Table 2). Nagree also teaches that treating lysosomal storage diseases that effect the brain with systemically delivered viral vectors face particular challenged and that exemplary AAV vectors that cross the blood-brain-barrier are AAV9 and AAVrh10 (Nagree, page 661, fourth paragraph). For the pre-clinical feline study, beta-galactosidase was provided to a feline model of GM1-gangliosidosis via AAVrh8 or AAV1 vector (McCurdy, Diss. Auburn University, 2014., page 35, last paragraph). Thus, a skilled artisan at the time of filing knew from the teachings of Nagree and McCurdy that to-date beta-galactosidase has only been administered intracerebrally to a feline model of GM1-gangliosidosis, that different AAV serotypes display different tissue-specific tropism that impacts potential therapeutic strategies for different lysosomal storage diseases, that administration route differs depending on the disease, and that no treatment of humans with lysosomal storage diseases via CRISPR-Cas system had been carried out at the time of filing.
Therefore, in view of the breadth of the claims, the lack of sufficient guidance in the specification for any vector encoding beta galactosidase nor any use of said vector to treat ex vivo any lysosomal storage disease let alone an in vivo application of a CRISPR-Cas system to insert beta galactosidase into intron 1 of the albumin locus to inhibit or treat any lysosomal storage disease, the unpredictability evidenced by the art at the time of filing with respect to in vivo CRISPR-Cas gene therapy methods, different AAV serotypes, different lysosomal storage disease treatment requirements, and the lack of a teaching in the art at the time of filing of any CRISPR-Cas-based therapy for any lysosomal storage disease in humans, it would require undue experimentation to use the invention commensurate in scope with the claims.
Response to Arguments
Applicant Argues that the claims are fully enabled. Applicant engaged in their own Wands factor analysis and concluded their argument with the position that the cited references do not teach inoperability or unpredictability that would preclude enablement. These arguments have been fully considered but have not been found persuasive for the following reasons.
Applicant argues “The cited references acknowledge known challenges (immunogenicity, off-target assessment, delivery tropism) but do not teach inoperability or unpredictability that would preclude enablement, especially given Applicant's experimental data showing long-term efficacy, specificity, and absence of adverse events in vivo (Table 5). Rather, the art corroborates that practitioners possessed the tools and knowledge to execute genome-editing therapies with reasonable effort. Considering the specification's extensive disclosure, working examples, sequences, and routine nature of any optimization, the claims are fully enabled” (Remarks, pages 4-5). For conciseness, Applicant’s Wands factor analysis is not replicated here but will be addressed below.
Applicant supports their argument against lack of enablement by referring to “robust in vivo studies in…mice” (Remarks, page 3), describing CRISPR/Cas genome editing principles as “well-characterized” (Remarks, page 3), and stating that application of those CRISPR principles to AAV delivery is “an approach within routine skill of molecular-gene-therapy practitioners” (Remarks, page 3). Applicant asserts that POSA had access to “extensive literature and commercial toolkits” for AAV vector construction, CRISPR/Cas expression cassettes, gRNA design, and HDR donor assembly (Remarks, page 3). With regard to predictability, Applicant asserts that using designer nucleases to add genes to the albumin locus and AAV8/9 mediated delivery of genome editors was “commonplace” and therefore predictable (Remarks, page 4). Applicant also argues that POSA “would need only routine, empirical verification” given the guidance in the disclosure and not undue experimentation (Remarks, page 4). Respectfully, Applicant is missing the point of the enablement rejection and the fundamental issue that is posed by the methods instantly claimed. The existence of AAV methods of treatment isn’t at issue any more than the “well-characterized” CRISPR system is. The problem lies in their application to treat humans in vivo based upon a supporting disclosure whose working examples provide no teaching of any vector encoding beta galactosidase nor any use of said vector to treat anything let alone an in vivo application of a CRISPR-Cas system to insert beta galactosidase into intron 1 of the albumin locus of any organism at all. With regard to unpredictability, Mout specifically discusses the challenges associated with translation of CRISPR-Cas systems to in vivo therapeutic contexts and teaches that off-target effects and immunogenicity are two of the major hurdles to achieving such a translation (Mout, page 882, “CHALLENGES” subheading; page 883, first partial and first and second full paragraphs). Mout teaches that even though the gRNA is designed to target a specific gene of interest, often a significant number of nonspecific genes are targeted by the same Cas9/gRNA and that off-target effects of CRISPR systems in vivo have not been explored (Mout, page 882, last partial paragraph; page 883, first partial paragraph). Mout also teaches that gene-based delivery of CRISPR elements can permanently integrate Cas9 gene into host cells leading to immunogenicity and elimination of Cas9 expressing cells, and that AAV-based CRISPR systems delivered in vivo can suffer and has in fact suffered this fate (Mout, page 883, first full paragraph). Applicant’s assertion that these teachings do not preclude enablement are accurate insofar as the teachings alone do not do so. However, when combined with the lack of guidance in the specification, the teachings of Mout provide a glaring and insurmountable hurdle to any skilled artisan contemplating the treatment of a human disease with an in vivo CRISPR therapy. As Applicant has implicitly acknowledged with their arguments, the Wands factors inform the analysis but no one factor is conclusive. The specification’s disclosure was not “extensive” but was rather limited especially for the context. The working examples taught no treatment of any disease using CRISPR administered in vivo. The art exemplifies just how not routine the design and implementation of in vivo CRISPR treatment methods are and rather evidences significant unpredictability with respect to treating diseases in humans in vivo with a CRISPR system. Accordingly, the claims are not enabled because a skilled artisan would be required to undertake undue experimentation to use the invention claimed and Applicant’s arguments are, respectfully, not found to be persuasive.
Provisional Double Patenting
Claims 1-2, 5-8, 11, 14-16, 18, and 20-24 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-8, 11-14, 16-17, 21-22, 25-28, and 31-32 of copending Application No. 18/832,877 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims render obvious the instant claims in view of McCurdy, Diss. Auburn University, 2014., page 35, hereinafter “McCurdy”.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 of copending application is directed to:
A method to prevent, inhibit or treat one or more symptoms so GM1-gangliosidosis in a
mammal, comprising:
administering to the mammal an effective amount of i) Cas or an isolated nucleic encoding Cas, and ii) isolated nucleic acid for one or more gRNAs comprising a targeting sequence for a mammalian genomic target and nucleic acid comprising a coding sequence for beta- galactosidase flanked by homology arms that bind to the mammalian genomic target, or an effective amount of iii) isolated nucleic encoding Cas and nucleic acid for one or more gRNAs comprising a targeting sequence for a mammalian genomic target, and iv) isolated nucleic acid comprising a coding sequence for a beta galactosidase flanked by homology arms that bind to the mammal genomic target, wherein the expression of the coding sequence in the mammal prevents, inhibits or treats the disease.
Claim 1 of the invention is directed to:
A method to prevent, inhibit or treat a lysosomal storage disease in a 1. human, comprising: administering to the human an effective amount of
i) CRISPR-associated nuclease (Cas) or an isolated nucleic sequence encoding the Cas, and
ii) an isolated nucleic acid sequence that (a) codes for one or more CRISPR guide RNAs (gRNAs), each gRNA comprising a targeting sequence for a human genomic target locus, wherein one gRNA comprises SEQ ID NO: 15; and b) a nucleic acid sequence comprising a coding sequence for a prophylactic or therapeutic gene product flanked by first and second homology arms that bind to the human genomic target, wherein the targeting sequence and homology arms are targeted to the human albumin gene intron, or
an effective amount of
iii) an isolated nucleic sequence encoding Cas and a nucleic acid sequence for one or more gRNAs comprising a targeting sequence for a human genomic target locus, wherein the targeting sequence is targeted to the human albumin gene intron and wherein one gRNA comprises SEQ ID NO: 15, and
iv) isolated nucleic acid sequence comprising a coding sequence for a prophylactic or therapeutic gene product flanked by first and second homology arms that bind to the human genomic target, wherein the homology arms are targeted to the human albumin gene intron, wherein the expression of the coding sequence for the therapeutic gene product in the human prevents, inhibits or treats the disease.
Copending claim 1 is both broader and narrower than instant claim 1. Copending claim 1 is narrower than instant claim 1 in that it is directed to a method of treating GM1-gangliosidosis whereas instant claim 1 is directed to a method of treating a disease (lysosomal storage disease as elected). Copending claim 1 is broader than instant claim 1 in that it is directed to a method of treating a mammal whereas instant claim 1 is directed to a method of treating a human and in that copending claim 1 is directed to a gRNA targeting a mammalian genomic locus whereas amended claim 1 requires SEQ ID NO: 15 more specifically.
McCurdy teaches a method of treating a cat which is a mammal with GM1-gangliosidosis by administering beta-galactosidase via AAVrh8 or AAV1 vector (MeCurdy, last paragraph). Therefore, it would have been obvious from the teachings of McCurdy to apply the therapy to a mammal more generally.
Note that MPEP 804(II)(2)(a) sets forth instances where it is acceptable to utilize the disclosure of a U.S. patent document in conjunction with its claims for ODP rejections.
In particular, the MPEP notes that the portion of the specification that supports the patent claims may be considered. The court in AbbVie Inc. v. Kennedy Institute of Rheumatology Trust pointed out that “this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined.” In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014). The court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
In this case, the copending specification discloses a sequence identical to SEQ ID NO: 15 (Copending specification, page 64, line 22). Therefore, the instantly claimed sgRNA having SEQ ID NO: 15 is an obvious variant of the more general sgRNA targeting a mammalian genomic locus as taught by the copending application.
Dependent claim limitations recited in the instant claims 2-8, 11, 14-16, 18, 20-24 are all recited in the dependent claims of the copending application.
Applicants offer to provide a terminal disclaimer upon indication by the Examiner of allowable claims. However, Applicant’s request is not a proper response to the rejections of record as it neither traverses the grounds of rejection by providing specific arguments, nor indicates that a terminal disclaimer has been filed to overcome the rejection. As such, the rejections of record stand.
New Grounds of rejection
35 U.S.C. 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 11 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, 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. This is a new rejection necessitated by Applicant’s amendments to the claims. Claim 11 depends from claim 1 which recites “the targeting sequence…targeted to the human albumin gene intron”. Claim 11 expands the scope of claim 1 by reciting other targets for the one or more gRNAs. Claim 11 broadens the scope of the claimed e human albumin gene intron, permitting that it may be any of the targets recited in amended claim 11.
Applicant may cancel the claim, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Additional Comments
Amended claim 26 appears free of the prior art of record. Because a full search could not be completed, claim 26 was not further treated on the merits.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/BRENDAN THOMAS TINSLEY/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634