DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicants’ reply to the June 4, 2025 Office Action, filed October 3, 2025, is acknowledged.
Applicants previously canceled claims 1-38, and now cancel claims 51 and 53-58. Applicants amend claim 39. Claims 39-50 and 52 are pending in this application, and are under examination. In addition, due to the cancellation of claims 51 and 58, claims 39-50 and 52 are deemed to have a priority filing date of June 17, 2013, the filing date of U.S. Provisional Patent Application No. 61/836,123.
Any objection or rejection of record in the previous Office Action, mailed June 4, 2025, which is not addressed in this action has been withdrawn in light of Applicants’ amendments and/or arguments. This action is FINAL.
Information Disclosure Statement
The Information Disclosure Statement filed October 3, 2025 has been considered.
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 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.
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 39-50 are rejected under 35 U.S.C. 103 as being unpatentable over Doudna et al. (U.S. Patent Application Publication No. 2014/0068797, published March 6, 2014, claiming priority to U.S. Provisional Patent Application No. 61/757,640, filed January 28, 2013, and cited in the Information Disclosure Statement filed March 17, 2021). This is a new rejection necessitated by Applicants’ amendments.
Regarding claim 39, Doudna discloses vectors comprising heterologous nucleic acids encoding CRISPR-Cas9 systems, including one or more guides, tracr mate sequences, and tracr sequences (paragraph [0137]). Doudna discloses that the vectors can be adeno-associated (AAV) virus vectors (paragraph [0302]). Doudna discloses that the CRISPR-Cas9 nucleic acids can be heterologous to the viral vector (paragraph [0117]). Doudna discloses that expression of the CRISPR-Cas9 nucleic acids can be driven by the T7 promoter and expression of T7 polymerase (paragraph [00106]). Doudna discloses cells, organisms and tissues, where the organism is a eukaryotic organism, such as a mammal, which is interpreted as delivering the system to an organism in vivo (paragraph [0017]). Doudna discloses targeting brain cells in genetically modified organisms, using a Cas9 molecule, which can be naturally-occurring or modified/chimeric (paragraph [0361]). Doudna discloses that the DNA of the targeted cells can be modified (paragraph [0361]). Douda discloses that neurons (neuronal cells) can be targeted (paragraph [0362]). Doudna discloses that Cas9 can be used to modulate transcription and/or modify DNA and/or modify polypeptides associated with DNA, and that the properties of any gene of choice, expression product of choice or genomic locus of choice can be studied (paragraph [0790]).
Regarding claim 40, Doudna discloses that the system guides can be chimeric RNA (paragraph [0015]).
Regarding claim 41, Doudna discloses that multiple DNA-targeting RNAs can be used to simultaneously modify different locations on a target DNA (paragraph [0271]).
Regarding claim 42, Doudna further discloses that the heterologous molecule encodes a homologous recombination template for homology-directed repair (paragraph [0150]).
Regarding claims 43-44, Doudna discloses that the Cas9 can be from a variety of bacterial sources, including Streptococcus pyogenes, Staphylococcus, and Campylobacter (paragraphs [0013], [0596], and [0719]).
Regarding claim 45, Doudna discloses that the Cas9 can direct cleavage of both strands at the target sequence (paragraphs [0014], [0085], and [0127]).
Regarding claim 46, Doudna discloses that the Cas9 can contain mutations that provide for the Cas9 being a nickase or a double nickase (paragraphs [0014], [0085], and [0127]). Doudna further discloses that the mutations can be in the RuvC domain of Cas9, and/or one or more of D10A and H840A (paragraphs [0014] and [0085]).
Regarding claims 47-48, Doudna discloses that the vector can comprise a nuclear localization signal (NLSs), and because Doudna discloses that “a” can be plural, this encompasses two or more NLSs (paragraphs [0160] [0241]).
Regarding claim 49, Doudna discloses that the vector can further comprise additional functional domains (paragraph [0418]).
Regarding claim 50, Doudna discloses that the function domain can be a transcriptional activation domain, such as VP64 (paragraph [0418]).
Regarding claim 52, Doudna discloses use of a promoter that drives expression in neurons (paragraph [0478]).
While Doudna does not explicitly disclose that expression of an altered gene product results in a phenotypic change, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the method of Doudna could be used to produce a phenotypic change in the organism because, as disclosed by Doudna, the Cas9 system can be used to target brain/neuronal cells and can be used to study the modulation of transcription and/or modification of DNA and/or modification of polypeptides associated with DNA. Thus, Doudna’s disclosure that the properties of any gene of choice, expression product of choice or genomic locus of choice can be studied provides one of ordinary skill in the art the motivation to target neuronal cells in order to alter a phenotype in a mammalian organism. This would also be useful for the treatment of diseases by altering a phenotype associated with a specific disease, which is desirable in treating mammalian organisms for genetically associated diseases and conditions, such as those associated with a neurological/neuronal disease or disorder.
Claim 52 is rejected under 35 U.S.C. 103 as being obvious over Doudna, as applied to claims 39-50 above, and in view of Asuri et al. (20(2) Molecular Therapy 329-338 (November 22, 2011), and cited in the Information Disclosure Statement filed March 17, 2021) and Damian et al. (21(4) Molecular Therapy 720-722 (April, 2013), and cited in the Information Disclosure Statement filed March 17, 2021). This rejection is modified as necessitated by Applicants’ amendments.
Doudna discloses a method of modifying brain/neuronal cells in a mammalian organism, as discussed above.
Regarding claim 52, Doudna discloses use of a promoter that drives expression in neurons (paragraph [0478])
Doudna fails to explicitly disclose or suggest that the AAV vector is AAV1, AAV2, AAV4, AAV5, or AAV8.
Asuri discloses several adeno-associated virus vectors that can be used to deliver genetic material to a cell (abstract). Specifically, Asuri discloses AAV1.9, AAV2 and AAV6 vectors carrying zinc finger nucleases (page 334, paragraph bridging columns 1 and 2).
Damian discloses that AAV vectors could be used to deliver CRISPR-Cas9 systems to cells instead of TALENs and ZFNs because the CRISPR-Cas9 system is smaller, and thus could more easily be packaged into AAV vectors (page 720, paragraph bridging columns 2 and 3 and column 3, first full paragraph and page 721, column 3, second full paragraph).
Thus, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to use any known AAV serotype vector according to Asuri to deliver the Doudna’s CRISPR-Cas9 systems using AAV systems according to Asuri and Damian, because Doudna’s CRISPR-Cas9 system will fit better inside any of the AAV vector systems according to Asuri and Damian, and thus have a predictable and reasonable expectation of success. Further, it would be well within the purview of one with ordinary skill in the art before the effective filing date of the claimed invention to optimize the level of Doudna’s indel formation to 20% or more, or any desirable level of indel formation. It would also have been obvious to one with ordinary skill in the art that Doudna’s viral vector could be used to treat any particular disease or condition that is genetically based because, as taught by Doudna, the viral vector system can be tailored by altering the sequences of the guides. Thus, one of ordinary skill in the art would have a predictable and reasonable expectation of success in targeting any particular gene in a eukaryotic system, where it was desirable to make a modification of the genetic material.
It would also have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to target neurological/neuronal diseases with the CRISPR/Cas system of Doudna, Asuri, and Damian because, as disclosed by Doudna, these diseases relate to specific organs of the organism, and one of ordinary skill in the art would have known that such cells and promoters of Doudna, which are able to target brain and neuronal cells, along with the vectors disclosed by Doudna, Asuri, and Damian would target those specific organs for treatment of diseases associated with those organs.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 39-50 and 52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-41 of U.S. Patent No. 9,840,713 in view of Doudna et al. (U.S. Patent Application Publication No. 2014/0068797, published March 6, 2014, claiming priority to U.S. Provisional Patent Application No. 61/757,640, filed January 28, 2013, and cited in the Information Disclosure Statement filed March 17, 2021), Asuri et al. (20(2) Molecular Therapy 329-338 (November 22, 2011), and cited in the Information Disclosure Statement filed March 17, 2021) and Damian et al. (21(4) Molecular Therapy 720-722 (April, 2013), and cited in the Information Disclosure Statement filed March 17, 2021).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘713 patent and the instant application claim methods of modifying a eukaryotic organism by administering a CRISPR/Cas9 system to the organism.
While the ‘713 patent does claim that the vector can be an adeno-associated viral (AAV) vector, the ‘713 patent does not claim the specific AAV serotypes, nor specific conditions that can be targeted.
Regarding claim 39, Doudna discloses vectors comprising heterologous nucleic acids encoding CRISPR-Cas9 systems, including one or more guides, tracr mate sequences, and tracr sequences (paragraph [0137]). Doudna discloses that the vectors can be adeno-associated (AAV) virus vectors (paragraph [0302]). Doudna discloses that the CRISPR-Cas9 nucleic acids can be heterologous to the viral vector (paragraph [0117]). Doudna discloses that expression of the CRISPR-Cas9 nucleic acids can be driven by the T7 promoter and expression of T7 polymerase (paragraph [00106]). Doudna discloses cells, organisms and tissues, where the organism is a eukaryotic organism, such as a mammal, which is interpreted as delivering the system to an organism in vivo (paragraph [0017]). Doudna discloses targeting brain cells in genetically modified organisms, using a Cas9 molecule, which can be naturally-occurring or modified/chimeric (paragraph [0361]). Doudna discloses that the DNA of the targeted cells can be modified (paragraph [0361]). Douda discloses that neurons (neuronal cells) can be targeted (paragraph [0362]). Doudna discloses that Cas9 can be used to modulate transcription and/or modify DNA and/or modify polypeptides associated with DNA, and that the properties of any gene of choice, expression product of choice or genomic locus of choice can be studied (paragraph [0790]).
Regarding claim 40, Doudna discloses that the system guides can be chimeric RNA (paragraph [0015]).
Regarding claim 41, Doudna discloses that multiple DNA-targeting RNAs can be used to simultaneously modify different locations on a target DNA (paragraph [0271]).
Regarding claim 42, Doudna further discloses that the heterologous molecule encodes a homologous recombination template for homology-directed repair (paragraph [0150]).
Regarding claims 43-44, Doudna discloses that the Cas9 can be from a variety of bacterial sources, including Streptococcus pyogenes, Staphylococcus, and Campylobacter (paragraphs [0013], [0596], and [0719]).
Regarding claim 45, Doudna discloses that the Cas9 can direct cleavage of both strands at the target sequence (paragraphs [0014], [0085], and [0127]).
Regarding claim 46, Doudna discloses that the Cas9 can contain mutations that provide for the Cas9 being a nickase or a double nickase (paragraphs [0014], [0085], and [0127]). Doudna further discloses that the mutations can be in the RuvC domain of Cas9, and/or one or more of D10A and H840A (paragraphs [0014] and [0085]).
Regarding claims 47-48, Doudna discloses that the vector can comprise a nuclear localization signal (NLSs), and because Doudna discloses that “a” can be plural, this encompasses two or more NLSs (paragraphs [0160] [0241]).
Regarding claim 49, Doudna discloses that the vector can further comprise additional functional domains (paragraph [0418]).
Regarding claim 50, Doudna discloses that the function domain can be a transcriptional activation domain, such as VP64 (paragraph [0418]).
Regarding claim 52, Doudna discloses use of a promoter that drives expression in neurons (paragraph [0478])
Doudna fails to explicitly disclose or suggest that the AAV vector is AAV1, AAV2, AAV4, AAV5, or AAV8.
Asuri discloses several adeno-associated virus vectors that can be used to deliver genetic material to a cell (abstract). Specifically, Asuri discloses AAV1.9, AAV2 and AAV6 vectors carrying zinc finger nucleases (page 334, paragraph bridging columns 1 and 2).
Damian discloses that AAV vectors could be used to deliver CRISPR-Cas9 systems to cells instead of TALENs and ZFNs because the CRISPR-Cas9 system is smaller, and thus could more easily be packaged into AAV vectors (page 720, paragraph bridging columns 2 and 3 and column 3, first full paragraph and page 721, column 3, second full paragraph).
Thus, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to use any known AAV serotype vector according to Asuri to deliver the Doudna’s CRISPR-Cas9 systems using AAV systems according to Asuri and Damian for use in the ‘713 patent, because Doudna’s CRISPR-Cas9 system will fit better inside any of the AAV vector systems according to Asuri and Damian, and thus have a predictable and reasonable expectation of success. It would also have been obvious to one with ordinary skill in the art that the ‘713 patent’s method could be practiced with Doudna’s viral vector could be used to treat any particular disease or condition that is genetically based because, as taught by Doudna, the viral vector system can be tailored by altering the sequences of the guides. Thus, one of ordinary skill in the art would have a predictable and reasonable expectation of success in targeting any particular gene in a eukaryotic system, where it was desirable to make a modification of the genetic material.
It would also have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to target neurological/neuronal diseases with the CRISPR/Cas system of Doudna, Asuri, and Damian because, as disclosed by Doudna, these diseases relate to specific organs of the organism, and one of ordinary skill in the art would have known that such cells and promoters of Doudna, which are able to target brain and neuronal cells, along with the vectors disclosed by Doudna, Asuri, and Damian would target those specific organs for treatment of diseases associated with those organs.
Claims 39-50 and 52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,407,985 in view of Doudna et al. (U.S. Patent Application Publication No. 2014/0068797, published March 6, 2014, claiming priority to U.S. Provisional Patent Application No. 61/757,640, filed January 28, 2013, and cited in the Information Disclosure Statement filed March 17, 2021). This rejection is modified as necessitated by Applicants’ amendments.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘985 patent and the instant application claim methods of modifying a eukaryotic organism by administering a CRISPR/Cas9 system to the organism in vivo using an AAV vector having the same serotypes. Both the ‘985 patent and the instant application claim methods of targeting specific organs/tissues in order to target an ocular disease or condition.
The ‘985 patent fails to claim targeting brain/neuronal cells or treating an associated disease.
Regarding claim 39, Doudna discloses vectors comprising heterologous nucleic acids encoding CRISPR-Cas9 systems, including one or more guides, tracr mate sequences, and tracr sequences (paragraph [0137]). Doudna discloses that the vectors can be adeno-associated (AAV) virus vectors (paragraph [0302]). Doudna discloses that the CRISPR-Cas9 nucleic acids can be heterologous to the viral vector (paragraph [0117]). Doudna discloses that expression of the CRISPR-Cas9 nucleic acids can be driven by the T7 promoter and expression of T7 polymerase (paragraph [00106]). Doudna discloses cells, organisms and tissues, where the organism is a eukaryotic organism, such as a mammal, which is interpreted as delivering the system to an organism in vivo (paragraph [0017]). Doudna discloses targeting brain cells in genetically modified organisms, using a Cas9 molecule, which can be naturally-occurring or modified/chimeric (paragraph [0361]). Doudna discloses that the DNA of the targeted cells can be modified (paragraph [0361]). Douda discloses that neurons (neuronal cells) can be targeted (paragraph [0362]). Doudna discloses that Cas9 can be used to modulate transcription and/or modify DNA and/or modify polypeptides associated with DNA, and that the properties of any gene of choice, expression product of choice or genomic locus of choice can be studied (paragraph [0790]).
Regarding claim 40, Doudna discloses that the system guides can be chimeric RNA (paragraph [0015]).
Regarding claim 41, Doudna discloses that multiple DNA-targeting RNAs can be used to simultaneously modify different locations on a target DNA (paragraph [0271]).
Regarding claim 42, Doudna further discloses that the heterologous molecule encodes a homologous recombination template for homology-directed repair (paragraph [0150]).
Regarding claims 43-44, Doudna discloses that the Cas9 can be from a variety of bacterial sources, including Streptococcus pyogenes, Staphylococcus, and Campylobacter (paragraphs [0013], [0596], and [0719]).
Regarding claim 45, Doudna discloses that the Cas9 can direct cleavage of both strands at the target sequence (paragraphs [0014], [0085], and [0127]).
Regarding claim 46, Doudna discloses that the Cas9 can contain mutations that provide for the Cas9 being a nickase or a double nickase (paragraphs [0014], [0085], and [0127]). Doudna further discloses that the mutations can be in the RuvC domain of Cas9, and/or one or more of D10A and H840A (paragraphs [0014] and [0085]).
Regarding claims 47-48, Doudna discloses that the vector can comprise a nuclear localization signal (NLSs), and because Doudna discloses that “a” can be plural, this encompasses two or more NLSs (paragraphs [0160] [0241]).
Regarding claim 49, Doudna discloses that the vector can further comprise additional functional domains (paragraph [0418]).
Regarding claim 50, Doudna discloses that the function domain can be a transcriptional activation domain, such as VP64 (paragraph [0418]).
Regarding claim 52, Doudna discloses use of a promoter that drives expression in neurons (paragraph [0478])
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to target neurological/neuronal diseases with the CRISPR/Cas system of Doudna because, as disclosed by Doudna, these diseases relate to specific organs of the organism, and one of ordinary skill in the art would have known that such cells and promoters of Doudna, which are able to target brain and neuronal cells, along with the vectors disclosed by Doudna, would target those specific organs for treatment of diseases associated with those organs instead of the ocular disorders of the ’985 patent.
Claims 39-50 and 52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12,018,275 in view of Doudna et al. (U.S. Patent Application Publication No. 2014/0068797, published March 6, 2014, claiming priority to U.S. Provisional Patent Application No. 61/757,640, filed January 28, 2013, and cited in the Information Disclosure Statement filed March 17, 2021), Asuri et al. (20(2) Molecular Therapy 329-338 (November 22, 2011), and cited in the Information Disclosure Statement filed March 17, 2021) and Damian et al. (21(4) Molecular Therapy 720-722 (April, 2013), and cited in the Information Disclosure Statement filed March 17, 2021). This rejection is modified as necessitated by Applicants’ amendments.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘275 patent and the instant application claim methods of modifying a eukaryotic organism by administering a CRISPR/Cas9 system to the organism in vivo using an AAV vector having the same serotypes. Both the ‘275 patent and the instant application claim methods of targeting specific organs/tissues in order to target a disease or condition relating to those organs, which include liver disorders.
The ’275 patent does not claim an AAV vector, nor the AAV serotypes.
Regarding claim 39, Doudna discloses vectors comprising heterologous nucleic acids encoding CRISPR-Cas9 systems, including one or more guides, tracr mate sequences, and tracr sequences (paragraph [0137]). Doudna discloses that the vectors can be adeno-associated (AAV) virus vectors (paragraph [0302]). Doudna discloses that the CRISPR-Cas9 nucleic acids can be heterologous to the viral vector (paragraph [0117]). Doudna discloses that expression of the CRISPR-Cas9 nucleic acids can be driven by the T7 promoter and expression of T7 polymerase (paragraph [00106]). Doudna discloses cells, organisms and tissues, where the organism is a eukaryotic organism, such as a mammal, which is interpreted as delivering the system to an organism in vivo (paragraph [0017]). Doudna discloses targeting brain cells in genetically modified organisms, using a Cas9 molecule, which can be naturally-occurring or modified/chimeric (paragraph [0361]). Doudna discloses that the DNA of the targeted cells can be modified (paragraph [0361]). Douda discloses that neurons (neuronal cells) can be targeted (paragraph [0362]). Doudna discloses that Cas9 can be used to modulate transcription and/or modify DNA and/or modify polypeptides associated with DNA, and that the properties of any gene of choice, expression product of choice or genomic locus of choice can be studied (paragraph [0790]).
Regarding claim 40, Doudna discloses that the system guides can be chimeric RNA (paragraph [0015]).
Regarding claim 41, Doudna discloses that multiple DNA-targeting RNAs can be used to simultaneously modify different locations on a target DNA (paragraph [0271]).
Regarding claim 42, Doudna further discloses that the heterologous molecule encodes a homologous recombination template for homology-directed repair (paragraph [0150]).
Regarding claims 43-44, Doudna discloses that the Cas9 can be from a variety of bacterial sources, including Streptococcus pyogenes, Staphylococcus, and Campylobacter (paragraphs [0013], [0596], and [0719]).
Regarding claim 45, Doudna discloses that the Cas9 can direct cleavage of both strands at the target sequence (paragraphs [0014], [0085], and [0127]).
Regarding claim 46, Doudna discloses that the Cas9 can contain mutations that provide for the Cas9 being a nickase or a double nickase (paragraphs [0014], [0085], and [0127]). Doudna further discloses that the mutations can be in the RuvC domain of Cas9, and/or one or more of D10A and H840A (paragraphs [0014] and [0085]).
Regarding claims 47-48, Doudna discloses that the vector can comprise a nuclear localization signal (NLSs), and because Doudna discloses that “a” can be plural, this encompasses two or more NLSs (paragraphs [0160] [0241]).
Regarding claim 49, Doudna discloses that the vector can further comprise additional functional domains (paragraph [0418]).
Regarding claim 50, Doudna discloses that the function domain can be a transcriptional activation domain, such as VP64 (paragraph [0418]).
Regarding claim 52, Doudna discloses use of a promoter that drives expression in neurons (paragraph [0478])
Asuri discloses several adeno-associated virus vectors that can be used to deliver genetic material to a cell (abstract). Specifically, Asuri discloses AAV1.9, AAV2 and AAV6 vectors carrying zinc finger nucleases (page 334, paragraph bridging columns 1 and 2).
Damian discloses that AAV vectors could be used to deliver CRISPR-Cas9 systems to cells instead of TALENs and ZFNs because the CRISPR-Cas9 system is smaller, and thus could more easily be packaged into AAV vectors (page 720, paragraph bridging columns 2 and 3 and column 3, first full paragraph and page 721, column 3, second full paragraph).
Thus, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to use any known AAV serotype vector according to Asuri to deliver the ‘275 patent’s CRISPR-Cas9 systems using AAV systems according to Asuri and Damian because the ‘275 patent’s CRISPR-Cas9 system will fit better inside any of the AAV vector systems according to Asuri and Damian, and thus have a predictable and reasonable expectation of success.
It would also have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to target neurological/neuronal diseases with the CRISPR/Cas system of Doudna because, as disclosed by Doudna, these diseases relate to specific organs of the organism, and one of ordinary skill in the art would have known that such cells and promoters of Doudna, which are able to target brain and neuronal cells, along with the vectors disclosed by Doudna, would target those specific organs for treatment of diseases associated with those organs instead of the ocular disorders of the ’275 patent.
Claims 39-50 and 52 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-5, 7, 10-13, 32-35, 37-38, 40, 45, and 54-58 of copending Application No. 14/971,169 (reference application). This rejection is modified as necessitated by Applicants’ amendments.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘169 application and the instant application claim methods of modifying a eukaryotic organism by administering a CRISPR/Cas9 system to the organism in vivo using an AAV vector having the same serotypes. Both the ‘169 application and the instant application claim methods of targeting specific organs/tissues in order to target a disease or condition relating to those organs, which include neuronal and ocular disorders. Therefore, the claims are not deemed to be patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 39-50 and 52 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6,8-10, 15-17, 32-40, and 45-60 of copending Application No. 14/971,356 (reference application) in view of Doudna et al. (U.S. Patent Application Publication No. 2014/0068797, published March 6, 2014, claiming priority to U.S. Provisional Patent Application No. 61/757,640, filed January 28, 2013, and cited in the Information Disclosure Statement filed March 17, 2021). This rejection is modified as necessitated by Applicants’ amendments.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘356 application and the instant application claim methods of modifying a eukaryotic organism by administering a CRISPR/Cas9 system to the organism in vivo using an AAV vector having the same serotypes. Both the ‘356 application and the instant application claim methods of targeting specific organs/tissues in order to target a disease or condition relating to those organs, which include liver disorders.
Regarding claim 39, Doudna discloses vectors comprising heterologous nucleic acids encoding CRISPR-Cas9 systems, including one or more guides, tracr mate sequences, and tracr sequences (paragraph [0137]). Doudna discloses that the vectors can be adeno-associated (AAV) virus vectors (paragraph [0302]). Doudna discloses that the CRISPR-Cas9 nucleic acids can be heterologous to the viral vector (paragraph [0117]). Doudna discloses that expression of the CRISPR-Cas9 nucleic acids can be driven by the T7 promoter and expression of T7 polymerase (paragraph [00106]). Doudna discloses cells, organisms and tissues, where the organism is a eukaryotic organism, such as a mammal, which is interpreted as delivering the system to an organism in vivo (paragraph [0017]). Doudna discloses targeting brain cells in genetically modified organisms, using a Cas9 molecule, which can be naturally-occurring or modified/chimeric (paragraph [0361]). Doudna discloses that the DNA of the targeted cells can be modified (paragraph [0361]). Douda discloses that neurons (neuronal cells) can be targeted (paragraph [0362]). Doudna discloses that Cas9 can be used to modulate transcription and/or modify DNA and/or modify polypeptides associated with DNA, and that the properties of any gene of choice, expression product of choice or genomic locus of choice can be studied (paragraph [0790]).
Regarding claim 40, Doudna discloses that the system guides can be chimeric RNA (paragraph [0015]).
Regarding claim 41, Doudna discloses that multiple DNA-targeting RNAs can be used to simultaneously modify different locations on a target DNA (paragraph [0271]).
Regarding claim 42, Doudna further discloses that the heterologous molecule encodes a homologous recombination template for homology-directed repair (paragraph [0150]).
Regarding claims 43-44, Doudna discloses that the Cas9 can be from a variety of bacterial sources, including Streptococcus pyogenes, Staphylococcus, and Campylobacter (paragraphs [0013], [0596], and [0719]).
Regarding claim 45, Doudna discloses that the Cas9 can direct cleavage of both strands at the target sequence (paragraphs [0014], [0085], and [0127]).
Regarding claim 46, Doudna discloses that the Cas9 can contain mutations that provide for the Cas9 being a nickase or a double nickase (paragraphs [0014], [0085], and [0127]). Doudna further discloses that the mutations can be in the RuvC domain of Cas9, and/or one or more of D10A and H840A (paragraphs [0014] and [0085]).
Regarding claims 47-48, Doudna discloses that the vector can comprise a nuclear localization signal (NLSs), and because Doudna discloses that “a” can be plural, this encompasses two or more NLSs (paragraphs [0160] [0241]).
Regarding claim 49, Doudna discloses that the vector can further comprise additional functional domains (paragraph [0418]).
Regarding claim 50, Doudna discloses that the function domain can be a transcriptional activation domain, such as VP64 (paragraph [0418]).
Regarding claim 52, Doudna discloses use of a promoter that drives expression in neurons (paragraph [0478])
It would also have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to target neurological/neuronal diseases with the CRISPR/Cas system of Doudna because, as disclosed by Doudna, these diseases relate to specific organs of the organism, and one of ordinary skill in the art would have known that such cells and promoters of Doudna, which are able to target brain and neuronal cells, along with the vectors disclosed by Doudna, would target those specific organs for treatment of diseases associated with those organs instead of the ocular disorders of the ‘356 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 39-50 and 52 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20-21 of copending Application No. 15/230,161 (reference application) Doudna et al. (U.S. Patent Application Publication No. 2014/0068797, published March 6, 2014, claiming priority to U.S. Provisional Patent Application No. 61/757,640, filed January 28, 2013, and cited in the Information Disclosure Statement filed March 17, 2021). This rejection is modified as necessitated by Applicants’ amendments.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application claims a method of modifying a eukaryotic organism by administration of a CRISPR/Cas9 system in vivo and the ‘161 application claims an animal/organism comprising a cell transformed with a vector comprising a CRISPR/Cas9 system. Absent evidence to the contrary, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that any eukaryotic organism produced by the instant method would result in a eukaryotic organism that is the same as that claimed by the ‘161 application.
The ‘161 application fails to claim modification of a brain/neuronal cell in the organism.
Regarding claim 39, Doudna discloses vectors comprising heterologous nucleic acids encoding CRISPR-Cas9 systems, including one or more guides, tracr mate sequences, and tracr sequences (paragraph [0137]). Doudna discloses that the vectors can be adeno-associated (AAV) virus vectors (paragraph [0302]). Doudna discloses that the CRISPR-Cas9 nucleic acids can be heterologous to the viral vector (paragraph [0117]). Doudna discloses that expression of the CRISPR-Cas9 nucleic acids can be driven by the T7 promoter and expression of T7 polymerase (paragraph [00106]). Doudna discloses cells, organisms and tissues, where the organism is a eukaryotic organism, such as a mammal, which is interpreted as delivering the system to an organism in vivo (paragraph [0017]). Doudna discloses targeting brain cells in genetically modified organisms, using a Cas9 molecule, which can be naturally-occurring or modified/chimeric (paragraph [0361]). Doudna discloses that the DNA of the targeted cells can be modified (paragraph [0361]). Douda discloses that neurons (neuronal cells) can be targeted (paragraph [0362]). Doudna discloses that Cas9 can be used to modulate transcription and/or modify DNA and/or modify polypeptides associated with DNA, and that the properties of any gene of choice, expression product of choice or genomic locus of choice can be studied (paragraph [0790]).
Regarding claim 40, Doudna discloses that the system guides can be chimeric RNA (paragraph [0015]).
Regarding claim 41, Doudna discloses that multiple DNA-targeting RNAs can be used to simultaneously modify different locations on a target DNA (paragraph [0271]).
Regarding claim 42, Doudna further discloses that the heterologous molecule encodes a homologous recombination template for homology-directed repair (paragraph [0150]).
Regarding claims 43-44, Doudna discloses that the Cas9 can be from a variety of bacterial sources, including Streptococcus pyogenes, Staphylococcus, and Campylobacter (paragraphs [0013], [0596], and [0719]).
Regarding claim 45, Doudna discloses that the Cas9 can direct cleavage of both strands at the target sequence (paragraphs [0014], [0085], and [0127]).
Regarding claim 46, Doudna discloses that the Cas9 can contain mutations that provide for the Cas9 being a nickase or a double nickase (paragraphs [0014], [0085], and [0127]). Doudna further discloses that the mutations can be in the RuvC domain of Cas9, and/or one or more of D10A and H840A (paragraphs [0014] and [0085]).
Regarding claims 47-48, Doudna discloses that the vector can comprise a nuclear localization signal (NLSs), and because Doudna discloses that “a” can be plural, this encompasses two or more NLSs (paragraphs [0160] [0241]).
Regarding claim 49, Doudna discloses that the vector can further comprise additional functional domains (paragraph [0418]).
Regarding claim 50, Doudna discloses that the function domain can be a transcriptional activation domain, such as VP64 (paragraph [0418]).
Regarding claim 52, Doudna discloses use of a promoter that drives expression in neurons (paragraph [0478])
It would also have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to target neurological/neuronal diseases with the CRISPR/Cas system of Doudna because, as disclosed by Doudna, these diseases relate to specific organs of the organism, and one of ordinary skill in the art would have known that such cells and promoters of Doudna, which are able to target brain and neuronal cells, along with the vectors disclosed by Doudna, would target those specific organs for treatment of diseases associated with those organs instead of the ocular disorders of the ‘161 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 39-50 and 52 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 22 of copending Application No. 17/034,754 (reference application) in view of Doudna et al. (U.S. Patent Application Publication No. 2014/0068797, published March 6, 2014, claiming priority to U.S. Provisional Patent Application No. 61/757,640, filed January 28, 2013, and cited in the Information Disclosure Statement filed March 17, 2021). This rejection is modified as necessitated by Applicants’ amendments.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application claims a method of modifying a eukaryotic organism by administration of a CRISPR/Cas9 system in vivo and the ‘754 application claims an animal/organism comprising a cell transformed with a vector comprising a CRISPR/Cas9 system. Absent evidence to the contrary, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that any eukaryotic organism produced by the instant method would result in a eukaryotic organism that is the same as that claimed by the ‘754 application.
Regarding claim 39, Doudna discloses vectors comprising heterologous nucleic acids encoding CRISPR-Cas9 systems, including one or more guides, tracr mate sequences, and tracr sequences (paragraph [0137]). Doudna discloses that the vectors can be adeno-associated (AAV) virus vectors (paragraph [0302]). Doudna discloses that the CRISPR-Cas9 nucleic acids can be heterologous to the viral vector (paragraph [0117]). Doudna discloses that expression of the CRISPR-Cas9 nucleic acids can be driven by the T7 promoter and expression of T7 polymerase (paragraph [00106]). Doudna discloses cells, organisms and tissues, where the organism is a eukaryotic organism, such as a mammal, which is interpreted as delivering the system to an organism in vivo (paragraph [0017]). Doudna discloses targeting brain cells in genetically modified organisms, using a Cas9 molecule, which can be naturally-occurring or modified/chimeric (paragraph [0361]). Doudna discloses that the DNA of the targeted cells can be modified (paragraph [0361]). Douda discloses that neurons (neuronal cells) can be targeted (paragraph [0362]). Doudna discloses that Cas9 can be used to modulate transcription and/or modify DNA and/or modify polypeptides associated with DNA, and that the properties of any gene of choice, expression product of choice or genomic locus of choice can be studied (paragraph [0790]).
Regarding claim 40, Doudna discloses that the system guides can be chimeric RNA (paragraph [0015]).
Regarding claim 41, Doudna discloses that multiple DNA-targeting RNAs can be used to simultaneously modify different locations on a target DNA (paragraph [0271]).
Regarding claim 42, Doudna further discloses that the heterologous molecule encodes a homologous recombination template for homology-directed repair (paragraph [0150]).
Regarding claims 43-44, Doudna discloses that the Cas9 can be from a variety of bacterial sources, including Streptococcus pyogenes, Staphylococcus, and Campylobacter (paragraphs [0013], [0596], and [0719]).
Regarding claim 45, Doudna discloses that the Cas9 can direct cleavage of both strands at the target sequence (paragraphs [0014], [0085], and [0127]).
Regarding claim 46, Doudna discloses that the Cas9 can contain mutations that provide for the Cas9 being a nickase or a double nickase (paragraphs [0014], [0085], and [0127]). Doudna further discloses that the mutations can be in the RuvC domain of Cas9, and/or one or more of D10A and H840A (paragraphs [0014] and [0085]).
Regarding claims 47-48, Doudna discloses that the vector can comprise a nuclear localization signal (NLSs), and because Doudna discloses that “a” can be plural, this encompasses two or more NLSs (paragraphs [0160] [0241]).
Regarding claim 49, Doudna discloses that the vector can further comprise additional functional domains (paragraph [0418]).
Regarding claim 50, Doudna discloses that the function domain can be a transcriptional activation domain, such as VP64 (paragraph [0418]).
Regarding claim 52, Doudna discloses use of a promoter that drives expression in neurons (paragraph [0478])
It would also have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to target neurological/neuronal diseases with the CRISPR/Cas system of Doudna because, as disclosed by Doudna, these diseases relate to specific organs of the organism, and one of ordinary skill in the art would have known that such cells and promoters of Doudna, which are able to target brain and neuronal cells, along with the vectors disclosed by Doudna, would target those specific organs for treatment of diseases associated with those organs instead of the ocular disorders of the ‘754 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 39-50 and 52 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 4 of copending Application No. 17/245,952 (reference application) in view of Doudna et al. (U.S. Patent Application Publication No. 2014/0068797, published March 6, 2014, claiming priority to U.S. Provisional Patent Application No. 61/757,640, filed January 28, 2013, and cited in the Information Disclosure Statement filed March 17, 2021), Asuri et al. (20(2) Molecular Therapy 329-338 (November 22, 2011), and cited in the Information Disclosure Statement filed March 17, 2021) and Damian et al. (21(4) Molecular Therapy 720-722 (April, 2013), and cited in the Information Disclosure Statement filed March 17, 2021). This rejection is modified as necessitated by Applicants’ amendments.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application claims a method of modifying a eukaryotic organism by administration of a CRISPR/Cas9 system in vivo and the ‘952 application claims an animal/organism comprising a cell transformed with a vector comprising a CRISPR/Cas9 system. Both the instant application and the ‘952 application claim an S. pyogenes Cas 9 and the use of two nuclear localization signals. Absent evidence to the contrary, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that any eukaryotic organism produced by the insta