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 .
Election/Restrictions
Applicant’s election without traverse of Inventive Group 1 in the reply filed on 07/01/2025 is acknowledged.
Claims 5-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventive group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/01/2025.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Pickering et al. (Viral Vector Delivery of DREADDs for CNS therapy, 2021) in view of Ginty et al. (US 2021/0356455 A1), Engel et al. (US 2022/0378941 A1), and Nathanson et al. (Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of AAV and lentiviral vectors, 2009)
Regarding Claim 1: Pickering et al. teaches that designer receptors activated exclusively by designer drugs (DREADDs) are genetically engineered GPCRs which have altered ligand binding profiles. (Pg 191, Introduction) Pickering further teaches that viral vectors, specifically AAV vectors, are used frequently for the delivery of DREADDs to the central nervous system as
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illustrated in the following diagram (pg 194, Introduction and Fig 3):
Lastly, Pickering teaches that AAVs are useful as vehicles for DREADD delivery due to their capability to infect multiple tissue types, combinatory use of cell-type specific promotors, and suitable capsids as this allows for targeted delivery to only relevant cells. (Pg 196, AAVs As DREADD Delivery Vectors) Pickering fails to teach use of GPR173 specifically as a target for delivery.
Ginty teaches use of a therapeutically effective agent that activates G-protein coupled receptors (GPCR) in neuron subtypes of the somatosensory neurons. (57) Ginty further discloses the manufacture of an adeno-associated virus (AAV) (0208) and details that in certain embodiments of the invention, the GPCR is selected from a group consisting of GPR173. (0186) Both Pickering and Ginty fail to teach use of PHP.eB.
Engel et al. teaches a recombinant vector for expression of a target gene in a host cell. (0003) Engel further teaches an example of the invention in which expression cassettes were packaged into AAV-PhP.eB capsids. (0091) Importantly, Engel teaches that specifically, PhP.eB serotypes show enhanced capacity to cross the blood brain barrier (0107) and show widespread transduction of gray matter (0113) in addition to predominantly transducing neurons. (0119) Pickering, Ginty, and Engel fail to teach use of CamkII as a gene enhancer sequence.
Nathanson et al. teaches the characterization of the transduction of mouse somatosensory cortical neuron types by way of recombinant AAVs pseudotyped with serotype capsid 1 and VSV glycoprotein, respectively. (Pg 1, Abstract) In addition to the AAV used, CamKII (hereafter mCAMK) promoters were incorporated into the plasmid. (Pg 2, Experimental procedures) Nathanson found that the mCAMK promoter was able to generate a more clear bias towards gene expression in excitatory cortical neurons (pg 8, Discussion) and consistently drove gene expression in both inhibitory and excitatory neurons (pg 7, Results) which is further illustrated in Fig. 6 shown below:
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It would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Pickering of use of an AAV vector as a DREADD delivery tool with the teachings of Ginty which specify use of GPR173 as the GPCR of interest, Engel of the use of PhP.eB, and Nathanson of use of CamkII as a gene enhancer sequence to create a recombinant AAV vector comprising a sequence encoding GPR173 to introduce GPR173 in the neurons of the brain comprising PHP.eB. and use of CamkII as a gene enhancer sequence. One would have had motivation to do so and a reasonable expectation of success due to the teachings of Pickering, who detail use of DREADDs (a type of GPCR) in AAVs to target neurons, Ginty who specifies GPR173 as a therapeutic GPCR of interest, and Engel who discloses that PhP.eB serotypes show widespread transduction of gray matter, predominately transduce neurons, and have enhanced capacity to cross the blood brain barrier.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Pickering et al. (Viral Vector Delivery of DREADDs for CNS therapy, 2021) in view of Ginty et al. (US 2021/0356455 A1), Matsumoto et al. (US 6555344 B1), Engel et al. (US 2022/0378941 A1), and Nathanson et al. (Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of AAV and lentiviral vectors, 2009)
The teachings of Pickering, Ginty, Engel, and Nathanson are disclosed above. All fail to teach use of an amino acid sequence which matches SEQ ID NOs 1 or 2 by at least 80%.
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Regarding Claim 4: Matsumoto teaches a method for creating a novel G protein coupled receptor protein for use as a way to therapeutically treat diseases of the central nervous system which includes delivery of a target amino acid sequence matching SEQ ID NOs. 2, 4, 5, 22, or 26, which are all proteins expressed in the central nervous system. (col 3, ln 30-61) SEQ ID NO. 26 as claimed by Matsumoto matches the claimed SEQ ID NO. 1 as disclosed in claim 4, as shown by the alignment chart below:
Matsumoto further teaches that g protein-coupled receptors are widely present in the central nervous system and therefore are useful as therapeutic targets for diseases of the central nervous system, such as use of dopamine to treat schizophrenia. (Col 3, ln 3-8)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use SEQ ID NO. 26 as taught by Matsumoto with the teachings of Pickering of use of an AAV vector as a DREADD delivery tool, the teachings of Engel of use of a PhP.eB, the teachings of Nathanson of use of CamkII, and the teachings of Ginty which specify use of GPR173 as the GPCR of interest to create an AAV comprising an amino acid sequence matching the claimed SEQ ID NO. 1, which is 100% identical to SEQ ID NO. 26 as claimed by Matsumoto. One would have had motivation to do so and a reasonable expectation of success due to the teachings of Matsumoto who details that the use of isolated genes matching the claimed SEQ ID NO. 1 paired with g protein-coupled receptors are useful in treating diseases of the central nervous system.
Response to Arguments
Applicant's arguments filed 11/11/2025 have been fully considered but they are not persuasive. Applicant argues that the DREADDS as taught by Pickering act on the central nervous system and are functionally different than GPCRs, making them unpredictable when introducing GPCRs into AAV vectors. This is unpersuasive. Pickering discloses that DREADDs are genetically engineered GPCRs which, when expressed in target cells, facilitate the initiation of G-protein mediated signaling cascades. (Pg 191, Introduction) Furthermore, Pickering teaches packaging of said DREADDs into AAVs to facilitate the delivery of transgenes to the CNS, of which the brain is a part of. Furthermore, Pickering teaches that the major application of DREADD use is in the brain itself, and therefore any potential delivery mechanism must be able to safely and efficiently transduce neuronal or glial cells in a targeted manner. (Pg 194, Introduction)
Applicant further argues that Ginty targets peripheral neurons, not the CNS. However, this is unpersuasive because the primary argument presented by the Examiner relies on the teachings of Pickering, who specifically details use of DREADDs coupled with AAVs to facilitate delivery to the brain and CNS. The teachings of Ginty are supplementary to Pickering, and are intended to facilitate the incorporation of GPR173 into the AAV comprising the DREADD as taught by Pickering, which is directed to the brain and CNS.
Applicant further argues that the GPR173 referenced by Ginty is associated with peripheral neurons and not the CNS and that GPR173 is one of many GPRs suggested in the invention. This is unpersuasive because the rejection relies on the combination of teachings of use of DREADDs with AAVs targeting the CNS and brain as taught by Pickering combined with the teachings of Ginty regarding selection of the specific GPCR. Furthermore, per MPEP2141.II.C "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR, 550 U.S. at 421, 82 USPQ2d at 1397. "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418, 82 USPQ2d at 1396.
Examiner further recognizes Applicant’s argument that as claim 1 has been amended to incorporate use of CamkII as a gene enhancer sequence, further narrowing the original claim regarding use of CMV, CamkII, mDlx, GAD65, and/or GAD6/7, the original rejection regarding now withdrawn claim 3 is irrelevant to now amended claim 1. However, as necessitated by amendment, claim 1 now incorporates the teachings of Nathanson, who detail use of a CamkII promoter.
Based on the above discussion, the arguments surrounding claim 1 are unpersuasive. As Applicant’s arguments regarding claim 4 rely on the argument presented for independent claim 1, the arguments surrounding claim 4 are also found unpersuasive.
Conclusion
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 extension fee 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNA M THUESON whose telephone number is (571) 272-3680. The examiner can normally be reached M-F 7:30-5 EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Tracy Vivlemore, can be reached on (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/HANNA MARIE THUESON/ Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638