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
Applicant's preliminary amendment filed on May 4, 2026 is acknowledged. Claims 2, 6-8, 11, 14, 19-22, 25, 27, 28, 32, and 34-81 have been canceled. Claim 1 was amended. Claims 1, 3-5, 9, 10, 12, 13, 15-18, 23, 24, 26, 29-31, and 33 are pending and are examined on the merits herein.
Election/Restrictions
Applicant's election with traverse of SOD1 as the endogenous gene in the reply filed on May 4, 2026 is acknowledged. The traversal is on the ground(s) that the claimed method differs from Farrar’s in at least two steps.
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This is not found persuasive because the technical feature of the method of claim 1 is taught by Farrar et al. (US 2006/0128648; reference cited by Applicant) in view of Carlo et al. (US 2020/0040362).
Farrar et al. teaches use of suppression strategies to target either the disease or normal alleles alone or to target both disease and normal alleles. The replacement gene will have nucleotide changes from the endogenous wild type gene but will code for identical amino acids as the wild type gene. Farrar et al. also teaches use of the wobble hypothesis to enable continued expression of a replacement normal or beneficial gene (a gene modified from the wild type such that it provides an additional beneficial effect) [0010]. Further, suppression effectors such as nucleic acids--antisense or sense, ribozymes, peptide nucleic acids (PNAs), triple helix forming oligonucleotides, peptides and/or antibodies directed to sequences in a gene, in transcripts or in protein, can be employed in the invention to achieve gene suppression [0013]. Farrar et al. also teaches that the suppressing nucleic acids are unable to bind to equivalent regions in the genomic DNA or cDNA to prevent expression of the replacement gene [abstract].
However, Farrar et al. does not teach wherein the first coding sequence is operably linked to a first splice acceptor sequence.
Carlo et al. teaches that the donor polynucleotide comprises a coding sequence, wherein the first strand comprises a first coding sequence, wherein the second strand comprises a second coding sequence, wherein the first nucleotide sequence that corrects the mutation in the gDNA comprises the first coding sequence, wherein the second nucleotide sequence that corrects the mutation in the gDNA comprises the second coding sequence, wherein the first coding sequence is located downstream of the first 3′ splice site, and wherein the second coding sequence is located downstream of the second 3′ splice site [0046].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of modifying expression of an endogenous gene in a cell wherein the first coding sequence is linked to a splice acceptor sequence because Farrar et al. taught the use of suppression strategies to target either the disease or normal alleles alone or to target both disease and normal alleles. The replacement gene will have nucleotide changes from the endogenous wild type gene but will code for identical amino acids as the wild type gene. Farrar et al. also taught the use of the wobble hypothesis to enable continued expression of a replacement normal or beneficial gene (a gene modified from the wild type such that it provides an additional beneficial effect) and Carlo et al. taught that the donor polynucleotide comprises a coding sequence, wherein the first strand comprises a first coding sequence, wherein the second strand comprises a second coding sequence, wherein the first nucleotide sequence that corrects the mutation in the gDNA comprises the first coding sequence, wherein the second nucleotide sequence that corrects the mutation in the gDNA comprises the second coding sequence, wherein the first coding sequence is located downstream of the first 3′ splice site, and wherein the second coding sequence is located downstream of the second 3′ splice site [0046]. One of ordinary skill in the art would have made such a modification because it would have amounted to combining known prior art elements to yield predictable results.
The requirement is still deemed proper and is therefore made FINAL.
Priority
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Information Disclosure Statement
The information disclosure statement (IDS) submitted on August 26, 2022 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
Drawings
The drawings were received on August 26, 2022. These drawings are found acceptable by the examiner.
Specification
The substitute specification filed on September 17, 2025 has been entered.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because the abstract is less than 50 words in length. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because of the following informalities:
In the description of drawings section for FIG. 7, “SA” and “SD” that is referred to in the figure is not defined.
Page 37, line 8 reads “SEPINA” and should read “SERPINA” (emphasis added).
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informality:
Claim 1 has periods within the claim at the bullet points. See MPEP 608.01(m).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 3 and 31 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 3 is indefinite because the claim depends from a canceled claim and is therefore incomplete. Claim 3 recites in part “The method of claim 2”; however, claim 2 is canceled. In the interest of compact prosecution, the Examiner is interpreting claim 3 to depend from claim 1.
The term “about” in claim 31 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, the phrase “about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99%” and “about 5-10%, 10-20%, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90%, 90-95%, or 95-99%” has been rendered indefinite by the use of the term “about”. One of skill cannot know the metes and bounds of the limitation in the claim because the term “about” is an undefined relative term.
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Written Description
Claims 1, 3-5, 9, 10, 12, 13, 15-18, 23, 24, 26, 29-31, and 33 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 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 3-5, 9, 10, 12, 13, 15-18, 23, 24, 26, 29-31, and 33 are drawn to the provision of a genus of silencing agents defined solely by function. The specification discloses that the term “silencing agent” refers to a nucleic acid that reduces the levels of RNA or protein from an endogenous gene [page 18, second full paragraph]. Thus, the claims encompass a large genus of silencing agents defined solely by function to reduce expression of the second allele of the endogenous gene.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
The specification envisions administering a silencing agent that reduces expression of an endogenous gene at the same time or following integration of the corrective coding sequence resistant to silencing. The agent can include antisense oligonucleotides, shRNA, siRNA, miRNA, or any other RNA suitable for reducing gene expression. The use of the silencing agent further reduces the expression of the gain-of-function allele particularly in cells that do not have an integration event or have a single integration event but within a wild-type allele [page 4, last paragraph bridging to page 5]. The specification envisions that the silencing agent can be RNA or DNA or a combination of RNA and DNA. Further, the silencing agent may be shRNA, siRNA, miRNA or an antisense oligonucleotide [page 18, second full paragraph].
The specification discloses the following:
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[page 49, last paragraph]. Further, the specification discloses that an siRNA is designed to silence endogenous ATXN3 alleles and targets SEQ ID NO: 22 [page 87, last paragraph]. In addition, shRNA is designed to silence unmodified endogenous SOD1 alleles and targets SEQ ID NO: 23 [page 88, second paragraph] and shRNA is designed to silence unmodified endogenous CACNA1A alleles and targets sequence within the mRNA encoded by exon 47 of the CACNA1A gene [page 89, first paragraph]. No description is provided of any other silencing agents.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of a small group of silencing agents. The results are not necessarily predictive of other silencing agents falling within the broadly claimed genus of any silencing agent not limited to any particular structure. Thus, it is impossible for one to extrapolate from the limited examples described herein those silencing agents that would necessarily meet the structural/functional characteristics of the rejected claims.
Pusch et al. (Nucleic Acids Research 2003) discloses that the number and location of nucleotide mismatches affect the activity of si/shRNA [abstract]. Pusch et al. demonstrated that maximally effective HIV-1-specific RNAi requires perfect homology between shRNA and the chosen target. Variable degrees of gene silencing occur when target and shRNA differ in a single nucleotide, depending on the position of the nucleotide mismatch within the shRNA [page 6447, right column].
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of silencing agents that could result in reducing expression of the second allele of the endogenous gene.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1, 3-5, 9, 10, 12, 13, 15-18, 23, 24, 26, 29-31, and 33.
Claim Rejections - 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 (i.e., changing from AIA to pre-AIA ) 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.
The factual inquiries 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.
Claims 1, 3, 4, 5, 9, 10, 12, 13, 15, 16, 17, 18, 24, 26, 29, 30, 31, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Farrar et al. (US 2006/0128648; reference cited by Applicant) in view of Carlo et al. (US 2020/0040362) and Premsrirut (WO 2019/108644; reference cited by Applicant).
Regarding claims 1, 3, 5, 13, 15, 16, 17, and 18, Farrar et al. teaches use of suppression strategies to target either the disease or normal alleles alone or to target both disease and normal alleles. The replacement gene will have nucleotide changes from the endogenous wild type gene but will code for identical amino acids as the wild type gene. Farrar et al. also teaches use of the wobble hypothesis to enable continued expression of a replacement normal or beneficial gene (a gene modified from the wild type such that it provides an additional beneficial effect) [0010]. Further, suppression effectors such as nucleic acids--antisense or sense, ribozymes, peptide nucleic acids (PNAs), triple helix forming oligonucleotides, peptides and/or antibodies directed to sequences in a gene, in transcripts or in protein, can be employed in the invention to achieve gene suppression [0013]. Farrar et al. also teaches that the suppressing nucleic acids are unable to bind to equivalent regions in the genomic DNA or cDNA to prevent expression of the replacement gene [abstract].
Regarding claims 4, 9, 10, and 12, Farrar et al. teaches providing genomic DNA or cDNA (complete or partial) encoding a replacement gene wherein the nucleic acids are unable to bind to equivalent regions in the genomic DNA or cDNA to prevent expression of the replacement gene. The replacement nucleic acids will not be recognized by suppression nucleic acids or will be recognized less effectively than the endogenous gene. The coding sequence of replacement nucleic acids can be altered to prevent or reduce efficiency of suppression. Replacement nucleic acids have modifications in one or more third base (wobble) positions such that replacement nucleic acids still code for the wild type or equivalent amino acids [0026].
Regarding claims 24 and 26, Farrar et al. teaches that suppression effectors means nucleic acids, peptide nucleic acids (PNAs), peptides, antibodies or modified forms of these used to silence or reduce gene expression in a sequence specific manner [0018]. Further, suppression effectors, such as antisense nucleic acids can be DNA or RNA and can be directed to coding sequences [0019].
Regarding claim 29, Farrar et al. teaches that the replacement gene will have nucleotide changes from the endogenous wild type gene but will code for identical amino acids as the wild type gene [0010].
Regarding claim 30, Farrar et al. teaches that the nucleic acid for gene suppression can be administered before, after or at the same time as the replacement gene is administered [0035].
Regarding claim 31, Farrar et al. teaches a strategy for suppressing expression of an endogenous gene with a deleterious mutation, wherein said strategy comprises providing suppression effectors such as antisense nucleic acids able to bind to sequences of a gene to be suppressed, to prevent the functional expression thereof [0017]. Further, it may be necessary to block expression of a disease allele completely to prevent disease symptoms whereas for others low levels of mutant protein may be tolerated [0016].
Regarding claim 33, Farrar et al. teaches that effective gene therapies for dominant or polygenic diseases may be targeted to the primary defect and in this case may require suppression of the disease allele while in many cases still maintaining the function of the normal allele. This is particularly relevant where disease pathology is due to a gain of function mutation [0005]. Farrar et al. also teaches that one allele of the gene in question will be mutated and possess alterations in its nucleotide sequence that affects the function or level of the gene product [0012].
However, Farrar et al. does not teach a splice acceptor sequence or a second splice acceptor sequence. Farrar et al. does not teach a first or second terminator (claims 3 and 5). Farrar et al. also does not teach that the first and second coding sequences are positioned in a tail-to-tail orientation (claim 5). Farrar et al. also does not teach administering a viral vector comprising the transgene (claim 13) or administering a non-viral vector comprising the transgene (claim 16). Farrar et al. also does not teach that the transgene is equal to or less than 4.7 kb (claim 15). Farrar et al. does not teach administering a CRISPR nuclease wherein the CRISPR nuclease creates a double-stranded break within an intron (claims 17 and 18).
Carlo et al. teaches that the donor polynucleotide comprises a coding sequence, wherein the first strand comprises a first coding sequence, wherein the second strand comprises a second coding sequence, wherein the first nucleotide sequence that corrects the mutation in the gDNA comprises the first coding sequence, wherein the second nucleotide sequence that corrects the mutation in the gDNA comprises the second coding sequence, wherein the first coding sequence is located downstream of the first 3′ splice site, and wherein the second coding sequence is located downstream of the second 3′ splice site [0046].
Premsrirut teaches that a regulatory region (e.g., splice acceptor) may be used to regulate expression of the shRNA strand for transcription from a transgene in vivo [085]. Further, the term “regulatory element” includes transcription termination signals, such as polyadenylation signals and poly-U sequences [038]. Premsrirut also teaches gene editing and expressing DNA molecules encoding the one or more gene products an engineered, non-naturally occurring vector system comprising one or more vectors comprising: a) a first regulatory element operably linked to one or more Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated (Cas) system guide RNAs that hybridize with target sequences in genomic loci of the DNA molecules encoding the one or more gene products [062]. Further, Premsrirut teaches a system for creating genetically defined RNAi using Cre- mediated recombination to stably invert an integrated a single RNAi expression cassette into the desired orientation at a defined locus [076].
Regarding claim 13, Premsrirut teaches a vector system for introducing shRNA constructs into cells are retroviral vector systems, such as lentiviral vector systems [093].
Regarding claim 15, Premsrirut teaches that vectors containing as little as 300 base pairs of AAV can be packaged and can integrate, but space for exogenous DNA is limited to about 4.5 kb [096].
Regarding claim 16, Premsrirut teaches that a vector can be introduced into host cells to thereby produce transcripts, proteins, or peptides, including fusion proteins or peptides [038].
Regarding claim 17, Premsrirut teaches a Cas9 protein comprises at least two nuclease domains (e.g., a RuvC-like nuclease domain and a HNH-like nuclease domain). The RuvC and HNH domains work together to cut single strands to make a double-stranded break in DNA [068].
Regarding claim 18, Premsrirut teaches that "homologous recombination (HR)” refers to the specialized form of an exchange of genetic information between two polynucleotides that takes place during repair of double- strand breaks in cells wherein HR results in an alteration of the sequence of the target molecule such that part or all of the sequence of the donor polynucleotide is incorporated into the target polynucleotide [035]. Premsrirut also teaches that non-limiting examples of polynucleotides include coding or non-coding regions of a gene or gene fragment and introns [019].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of modifying expression of an endogenous gene in a cell wherein the first coding sequence is linked to a splice acceptor sequence and a terminator and wherein the transgene further comprises a second coding sequence, a second splice acceptor sequence, and a second terminator because Farrar et al. taught the use of suppression strategies to target either the disease or normal alleles alone or to target both disease and normal alleles. The replacement gene will have nucleotide changes from the endogenous wild type gene but will code for identical amino acids as the wild type gene. Farrar et al. also taught the use of the wobble hypothesis to enable continued expression of a replacement normal or beneficial gene (a gene modified from the wild type such that it provides an additional beneficial effect), Carlo et al. taught that the donor polynucleotide comprises a coding sequence, wherein the first strand comprises a first coding sequence, wherein the second strand comprises a second coding sequence, wherein the first coding sequence is located downstream of the first 3′ splice site, and wherein the second coding sequence is located downstream of the second 3′ splice site, and Premsrirut taught that a regulatory region (e.g., splice acceptor) may be used to regulate expression of the shRNA strand for transcription from a transgene in vivo [085] and also taught that the term “regulatory element” includes transcription termination signals, such as polyadenylation signals and poly-U sequences. One of ordinary skill in the art would have made such a modification because it would have amounted to combining known prior art elements to yield predictable results. Furthermore, although Premsrirut does not explicitly disclose incorporating a second terminator, it would have been obvious to try because Farrar et al. taught that a strategy for gene suppression and gene replacement is described to circumvent the difficulties associated with specifically targeting a disease mutation and with the genetic heterogeneity present in inherited disorders [0008]. One of ordinary skill in the art would have been motivated to test the effect of a second terminator because Premsrirut taught that a regulatory region may be used to regulate expression for transcription from a transgene.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of modifying expression of an endogenous gene in a cell wherein a viral or non-viral vector comprising the transgene is administered and wherein the transgene is equal to or less than 4.7 kb because Farrar et al. taught the use of suppression strategies to target either the disease or normal alleles alone or to target both disease and normal alleles. The replacement gene will have nucleotide changes from the endogenous wild type gene but will code for identical amino acids as the wild type gene. Farrar et al. also taught the use of the wobble hypothesis to enable continued expression of a replacement normal or beneficial gene (a gene modified from the wild type such that it provides an additional beneficial effect), Carlo et al. taught that the donor polynucleotide comprises a coding sequence, wherein the first strand comprises a first coding sequence, wherein the second strand comprises a second coding sequence, wherein the first coding sequence is located downstream of the first 3′ splice site, and wherein the second coding sequence is located downstream of the second 3′ splice site, and Premsrirut taught a vector system for introducing shRNA constructs into cells are retroviral vector systems, such as lentiviral vector systems and taught vectors containing as little as 300 base pairs of AAV can be packaged and can integrate, but space for exogenous DNA is limited to about 4.5 kb. Premsrirut also taught that a vector can be introduced into host cells to thereby produce transcripts, proteins, or peptides, including fusion proteins or peptides. One of ordinary skill in the art would have made such a modification because it would have amounted to combining known prior art elements to yield predictable results.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of modifying expression of an endogenous gene in a cell wherein the method further comprises administering a CRISPR nuclease wherein the CRISPR nuclease creates a double-stranded break within an intron because Farrar et al. taught the use of suppression strategies to target either the disease or normal alleles alone or to target both disease and normal alleles. The replacement gene will have nucleotide changes from the endogenous wild type gene but will code for identical amino acids as the wild type gene. Farrar et al. also taught the use of the wobble hypothesis to enable continued expression of a replacement normal or beneficial gene (a gene modified from the wild type such that it provides an additional beneficial effect), Carlo et al. taught that the donor polynucleotide comprises a coding sequence, wherein the first strand comprises a first coding sequence, wherein the second strand comprises a second coding sequence, wherein the first coding sequence is located downstream of the first 3′ splice site, and wherein the second coding sequence is located downstream of the second 3′ splice site, and Premsrirut taught that a Cas9 protein comprises at least two nuclease domains (e.g., a RuvC-like nuclease domain and a HNH-like nuclease domain). The RuvC and HNH domains work together to cut single strands to make a double-stranded break in DNA. Premsrirut also taught that "homologous recombination (HR)” refers to the specialized form of an exchange of genetic information between two polynucleotides that takes place during repair of double- strand breaks in cells wherein HR results in an alteration of the sequence of the target molecule such that part or all of the sequence of the donor polynucleotide is incorporated into the target polynucleotide and non-limiting examples of polynucleotides include coding or non-coding regions of a gene or gene fragment and introns. One of ordinary skill in the art would have made such a modification because it would have amounted to combining known prior art elements to yield predictable results.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Farrar et al. (US 2006/0128648; reference cited by Applicant) in view of Carlo et al. (US 2020/0040362) and Premsrirut (WO 2019/108644; reference cited by Applicant) as applied to claims 1, 3, 4, 5, 9, 10, 12, 13, 15, 16, 17, 18, 24, 26, 29, 30, 31, and 33 above, and further in view of Jaskula-Ranga et al. (WO 2018/009534).
Regarding claim 23, the teachings of Farrar et al., Carlo et al., and Premsrirut are discussed above.
However, Farrar et al., Carlo et al., and Premsrirut do not teach wherein the endogenous gene is SOD1.
Jaskula-Ranga et al. teaches a method of altering expression of one or more gene products in a eukaryotic or non-eukaryotic cell wherein the cell comprises a DNA molecule encoding one or more gene products [page 57, second full paragraph]. Jaskula-Ranga et al. teaches that examples of proteins associated with Amyotrophic Lateral Sclerosis include SOD1 (superoxide dismutase 1) [page 71, lines 10-11].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Farrar et al., Carlo et al., and Premsrirut wherein the endogenous gene is SOD1 because Farrar et al., Carlo et al., and Premsrirut taught a method of modifying expression of an endogenous gene in a cell and Jaskula-Ranga et al. taught a method of altering expression of one or more gene products in a eukaryotic or non-eukaryotic cell wherein the cell comprises a DNA molecule encoding one or more gene products and also taught that examples of proteins associated with Amyotrophic Lateral Sclerosis include SOD1. One of ordinary skill in the art would have made such a modification because it would have amounted to a simple substitution of one known element for another to obtain predictable results.
Conclusion
No claims are allowed.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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