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 .
Priority
This application claims priority to U.S. provisional applications 63/322,868, filed on 27
April 2022. The effective filing date is 27 April 2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 31 October 2025, 28 May 2025, 02 January 2025, 31 October 2024, 29 August 2024, 09 July 2024, 07 June 2024, 16 January 2024, and 27 September 2023 are being considered by the examiner.
Status of Application, Amendments, and/or Claims
Claims 1-24 are pending and the subject of this office action.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 9, and 12-15 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by US20190169264 A1 (herein Sternson).
In regard to claim 1, Sternson discloses engineered human chemogenetic cell-surface receptors comprising: a ligand binding domain from human α7-nAChR, and an ion pore domain from either a human glycine receptor (GlyR) or the human serotonin 3 receptor (5HT3) ([0009], [0026], and figure 1). These receptors have been engineered to possess higher specificity/potency towards non-native ligands ([0006], [0008], and figures 3 and 4). One of the disclosed embodiments cites varenicline and its derivatives as examples of a non-native ligand ([0008], [0009], table 11, and figures 3 and 4). As varenicline is associated with cessation of nicotine use and use of nicotine results in reinforcing behavior, the engineered receptor disclosed in this publication meets all of the limitations established in claim 1 of the instant application.
In regard to claim 9, Sternsons discloses that the engineered chemogenetic receptors described are ligand gated ion channel ([0009]).
In regard to claim 12-15, Sternson discloses a chemogenetic cell-surface receptor, as discussed for claims 1 and 9, that is administered to cultured mammalian cells, HEK cells ([0038], figure 6). It is further taught the receptor may be administered to a neuron within a mammal ([0021]).
Claim Rejections - 35 USC § 103
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.
Claims 1, 9-16, and 20, are rejected under 35 U.S.C. 103 as being unpatentable over US20190169264 A1 (herein Sternson) in view of WO2021035179 A1 (herein Lau), and Rössger K, et al. (2013) A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice. Nat Commun. 2013;4:2825 (herein Rössger) with Kern KA, et al. (2020) Distributed amylin receptor signaling and its influence on motivated behavior. Physiol Behav. 2020 Aug 1;222:112958 (herein Kern) providing additional evidentiary value.
In regard to claims 1 and 16, Sternson discloses an engineered human chemogenetic cell-surface receptor comprising: a ligand binding domain from human α7-nAChR, and an ion pore domain from either a human glycine receptor (GlyR) or the human serotonin 3 receptor (5HT3) ([0009], [0026], and figure 1). This receptor has been engineered to possess higher specificity/potency towards non-native ligands ([0006], [0008], and figures 3 and 4).
Sternson does not teach that the engineered receptor, upon ingestion of a substance, either reduces the reward response or increases the aversion response to the ingested substance. Sternson also does not teach the use of the disclosed chemogenetic receptors for the treatment of a disorder associated with the ingestion of a substance. These deficiencies are taught by Lau and Rössger.
Rössger teaches a designer gene circuit utilizing a synthetic transcription factor made of a chimeric receptor comprising the ligand binding domain of human peroxisome proliferator-activated receptor α (PPARα) and the bacterial phloretin-responsive repressor (TtgR) (abstract). In the disclosed system the PPARα binding domain mediates fatty acid binding and modulates transcription of a gene encoding pramlintide, an amylin analog licensed for type 2 diabetes therapy, under the control of a chimeric promoter specific for the TtgR domain (Results: Design of a synthetic mammalian lipid-sensing receptor and figure 1). Using this chimeric receptor, Rössger et al demonstrate that the receptor is capable of acting as a lipid-sensor, tuning the levels of pramlintide to correspond with fatty acid levels in mice with diet-induced obesity, and reducing blood fat levels, food intake, and body weight in treated mice versus control mice (Results: Application of LSR in diet-induced obese mice and figure 4). When considered alongside the many studies associating amylin receptor binding with attenuated dopaminergic signaling (i.e. dopaminergic reward pathway), as summarized by Kern (Section 3: Amylin signaling in the mesolimbic system), this study effectively teaches the use of a chemogenetic receptor as an inhibitor of the reward response following the ingestion of a substance that triggers reinforcing behavior (e.g. fatty acid), which is a fundamental aspect of the instant application. Essentially, Rössger teaches the use of an engineered receptor that acts both as a sensor for a substance that triggers a reward response and an effector molecule (i.e. altered reward/aversion response to the ingested substance). Rössger however, does not teach the use of an extracellular chemogenetic receptor for the treatment of a disorder associated with the use of an ingested substance (i.e. addiction or substance abuse). Lau teaches this deficiency.
Lau teaches the use of chemogenetic receptors, ligand-gated ion channels, for the treatment of disease and disorders of the nervous system, including substance abuse/addiction ([0089], [0207], claim 70). Thus, providing the bridge between the teachings of Rössger and Sternson.
It would have been obvious to one skilled in the art to combine the teachings of Sternson (a human chemogenetic cell-surface receptor comprising: an engineered ligand binding domain and an activation domain) with the chimeric receptor-mediated negative feedback pathway taught by Rössger, and to use the combined teachings as method to treat substance abuse/addiction as taught by Lau. Rössger provides the core-concept upon which the instant application relies, despite the differences in methods. One of ordinary skill in the art at the time of filing would have been motivated to modify the chemogenetic receptors, taught by Sternson, to both specifically bind substances that trigger reinforcing behavior and alter the reward/aversion pathways associated with ingestion of the substrate, due to the recognized benefit associated with linking the sensor and effector function of a chemogenetic treatment into a single therapeutic network, as taught by Rössger (Discussion). Furthermore, by combining these pre-existing elements, the instant application discloses a claimed invention that behaves in a predictable manner, based on the prior art describing each element individually.
In regard to claims 9-11, Sternson, Lau, and Rössger teach a method of treating a disorder associated with the use of an ingested substance comprising: delivering a human chemogenetic receptor engineered to bind the ingested substance and either reduce the reward response or increase the aversion response for the substance, as discussed for claims 1 and 16.
Sternsons discloses engineered chemogenetic receptors that are ligand gated ion channel ([0009]). Lau also teaches an engineered chemogenetic receptors that are ligand-gated ion channels, with a ligand binding domain derived from human Cys-loop receptors, including alpha-7-5HT3 LBD and alpha 7-GlyR LBD ([0089], [0105]-[0108]).
In regard to claims 12-15, Sternson, Lau, and Rössger teach a method of treating a disorder associated with the use of an ingested substance comprising: delivering a human chemogenetic receptor engineered to bind the ingested substance and either reduce the reward response or increase the aversion response for the substance, as discussed for claims 1 and 16.
Sternson discloses a chemogenetic cell-surface receptor, as discussed for claims 1 and 9, that is administered to cultured mammalian cells, HEK cells ([0038], and figure 6). It is further taught the receptor may be administered to a neuron within a mammal ([0021], [0166]-[0168], and figure 7).
In regard to claim 20, Sternson, Lau, and Rössger teach a method of treating a disorder associated with the use of an ingested substance comprising: delivering a human chemogenetic receptor engineered to bind the ingested substance and either reduce the reward response or increase the aversion response for the substance, as discussed for claims 1 and 16.
Sternson teaches that administering the modified chemogenetic receptor may be in vivo administration or an ex vivo administration and may include the administration of a nucleic acid that encodes the receptor ([0021]).
Claims 2-8, 17-19, and 21-24, are rejected under 35 U.S.C. 103 as being unpatentable over US20190169264 A1 (herein Sternson) in view of WO2021035179 A1 (herein Lau), and Rössger K, et al. (2013) A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice. Nat Commun. 2013;4:2825 (herein Rössger) with Kern KA, et al. (2020) Distributed amylin receptor signaling and its influence on motivated behavior. Physiol Behav. 2020 Aug 1;222:112958 (herein Kern), Magnus CJ, et al. (2019) Ultrapotent chemogenetics for research and potential clinical applications. Science. 2019 Apr 12;364(6436) (herein Magnus (2019)), Magnus CJ, et al. (2011) Chemical and genetic engineering of selective ion channel-ligand interactions. Science. 2011 Sep 2;333(6047):1292-6 (herein Magnus (2011)), and Volkow ND, et al. (2019) The Neuroscience of Drug Reward and Addiction. Physiol Rev. 2019 Oct 1;99(4):2115-2140 (herein Volkow) providing additional evidentiary value.
Sternson, Lau, and Rössger teach a method of treating a disorder associated with the use of an ingested substance comprising: delivering a human chemogenetic receptor engineered to bind the ingested substance and either reduce the reward response or increase the aversion response for the substance, as discussed for claims 1 and 16.
Sternson, Lau, and Rössger do not specifically teach the use of chemogenetic receptors for the treatment of a disorder resulting from the use of a controlled substance that is addictive such as: cocaine, cocaine metabolites, methylphenidate, amphetamine (MDMA or methamphetamine), cathinone (bupropion, MDPV, mephedrone, or methylone), opioids (morphine, oxycodone, dihydrocodeine, heroin, methadone, or fentanyl), or certain nutrient substances (i.e. sugar, caffeine, or fatty acid). However, it would have been prima facie obvious to apply the teachings of Sternson, Lau, and Rössger to the treatment of substance addiction, due to a conserved mechanism of reward response as summarized by Volkow (figure 1 and section 2: Drug reward) and Kern (introduction and section 3). In brief, all of the drugs/nutrients listed in the relevant claims either directly or indirectly cause elevated dopamine levels in the shell sub-region of the nucleus accumbens. Thus, a similar mechanism of action could be shared between the inventions described in the relevant claims in regard to reducing the reward response, with the only necessary variation between receptors being differences in ligand specificity of the ligand binding domain, the method of whose design is taught by Sternson, Magnus (2011), and Magnus (2019).
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 1-24 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1, 130-138, 161, and 164-172 of U.S. Patent No. 10961296 in view of in view of WO2021035179 A1 (herein Lau), and Rössger K, et al. (2013) A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice. Nat Commun. 2013;4:2825 (herein Rössger) with Kern KA, et al. (2020) Distributed amylin receptor signaling and its influence on motivated behavior. Physiol Behav. 2020 Aug 1;222:112958 (herein Kern) providing additional evidentiary value.
‘296, claims 1, 130-138, 161, and 164-172, describes a modified LGIC comprised of a modified human α7-nAChRL131G, Q139L, Y217F LBD, and an IPD from one of the following receptors: 5HT3, GlyR, GABA, or α7-nAChR. This is relevant to the receptor of claims 1 and 9 of the instant application, because the mutations described allow the receptor to bind varenicline, a ligand associated with an ingested substance whose ingestion results in reinforcing behavior.
U.S. Patent No. 10961296 does not teach that the engineered receptor, upon ingestion of a substance, either reduces the reward response or increases the aversion response to the ingested substance. ‘296 also does not teach the use of the chemogenetic receptor in the treatment of a disorder associated with the ingestion of a substance. As described above in the 103 section (claims 1-24) Lau and Rössger teach these deficiencies.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Lau and Rössger with the receptor described in claims 1 of U.S. Patent No. 10961296. An ordinarily skilled artisan would have been motivated to combine the use of chemogenetic receptors for the treatment of disorders of the nervous system, as taught by Lau ([0089], [0207], claim 70), with a receptor capable of acting as an inhibitor of the reward response, as taught by Rössger (Results: Application of LSR in diet-induced obese mice and figure 4), which effectively links the sensor and effector function of a chemogenetic treatment into a single therapeutic network. Furthermore, by combining these pre-existing elements, the instant application discloses a claimed invention that behaves in a predictable manner, based on the prior art describing each element individually.
Claims 1-24 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-17 of co-pending Application No. 18/834135 in view of in view of WO2021035179 A1 (herein Lau), and Rössger K, et al. (2013) A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice. Nat Commun. 2013;4:2825 (herein Rössger) with Kern KA, et al. (2020) Distributed amylin receptor signaling and its influence on motivated behavior. Physiol Behav. 2020 Aug 1;222:112958 (herein Kern) providing additional evidentiary value.
‘135, claims 1-17, describe modified LGICs comprised of a modified human α7-nAChR LBD, and an IPD. This is relevant to the receptor of claims 1 and 9 of the instant application, because the mutations described in the claims allow the receptor to bind varenicline, a ligand associated with an ingested substance whose ingestion results in reinforcing behavior.
‘135 does not teach that the engineered receptor, upon ingestion of a substance, either reduces the reward response or increases the aversion response to the ingested substance. ‘135 also does not teach the use of the chemogenetic receptor in the treatment of a disorder associated with the ingestion of a substance. As described above in the 103 section (claims 1-24) Lau and Rössger teach these deficiencies.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Lau and Rössger with the receptor described in claims 1 of Application No. 18/834135. An ordinarily skilled artisan would have been motivated to combine the use of chemogenetic receptors for the treatment of disorders of the nervous system, as taught by Lau ([0089], [0207], claim 70), with a receptor capable of acting as an inhibitor of the reward response, as taught by Rössger (Results: Application of LSR in diet-induced obese mice and figure 4), which effectively links the sensor and effector function of a chemogenetic treatment into a single therapeutic network. Furthermore, by combining these pre-existing elements, the instant application discloses a claimed invention that behaves in a predictable manner, based on the prior art describing each element individually.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW CURRAN METCALF whose telephone number is (571)272-5520. The examiner can normally be reached 7:30AM-5:00PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at (571)272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MATTHEW CURRAN METCALF/ Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647