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
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Status of Claims
Claims 30 - 59 are currently pending. Claim 30 and 46 have been amended in Applicant’s amendment filed September 9, 2024. No claims have been added, or canceled by the Applicant’s amendment filed September 9, 2024.
Priority
The present application filed July 9, 2020 claims the benefit of a CON of Application Number 16/696,158, filed November 26, 2019, which claims the benefit of a CON of Application Number 16/201,142, filed November 27, 2018, which claims the benefit of a PRO of Application Number 62/659,911, filed April 19, 2018, which claims the benefit of a PRO of Application Number 62/590,911, filed November 27, 2017.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on November 14, 2024, September 16, 2024, August 7, 2024, and June 18, 2024 have been considered. An initialed copy of the IDSs accompanies this Office Action.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed September 9, 2024 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or
objection not specifically addressed below are herein withdrawn.
Claim Rejections - 35 USC § 102
The rejection of claims 30 – 55 and 57 – 59 is withdrawn under 35 U.S.C. 102 (a)(1)/(a)(2) as being anticipated by Sternson et al. (hereinafter referred to as Sternson) (US Patent Application Publication US 2010/0130420 A1, Published May 27, 2010).
Sternson does not teach the amino acids 166 – 180 of Seq ID No. 2 (amended claim 30).
In view of the withdrawn rejection, Applicant’s arguments are moot.
Claim Rejection - 35 USC § 103
The rejection of claims 30 - 59 is withdrawn under 35 U.S.C. 103 as being unpatentable over Sternson et al. as applied to claims 30 – 55, and 57 - 59 above, and further in view of Yang et al. (hereinafter referred to as “Yang”) (Yang T. et al. The current agonists and positive allosteric modulators of α7 nAChR for CNS indications in clinical trials. Acta Pharm Sin B. 2017 Nov;7(6):611-622. doi: 10.1016/j.apsb.2017.09.001. Epub 2017 Oct 16. PMID: 29159020; PMCID: PMC5687317.).
Sternson does not teach the amino acids 166 – 180 of Seq ID No. 2 (amended claim 30).
In view of the withdrawn rejection, Applicant’s arguments are moot.
Maintained Objections/Rejections
Claim Rejection - 35 USC § 112(b)
The rejection of claims 30 – 41 and 58 is maintained 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 30 is indefinite for the recitation of “the Cys-loop domain” in line 10. There is a lack of antecedent basis for the term “the Cys-loop domain.”
Claim 30 is indefinite for the recitation of “Cys-loop domain of the human nAChR-derived ligand binding domain” in line 10. It is unclear what is the difference between a Cys-loop receptor and a cys-loop domain, and whether the Cys-loop receptor recited in line 8 comprises a Cys-loop domain recited in line 10. Thus, the metes and bounds of the claim cannot be determined.
Claim 30 is indefinite for the recitation of “amino acids 150-157 or amino acids 150 – 164 of Seq ID No. 4 is replaced by a Cys-loop domain from the second LGIC receptor corresponding to amino acids 166 – 172 or amino acids 166 – 180 of Seq ID No. 2” in line 11-13. It is unclear whether the amino acids 150 – 157 will be replaced by amino acids 166 – 172 or 166 – 182, i.e. whether the same number of amino acids will be replaced by the new sequence. Thus, the metes and bounds of the claim cannot be determined.
Claim 30 is indefinite for the recitation of the term “amino acids 150 – 164” in line 11; and the term “amino acids 150 – 157” because a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. In the present instant, claim 30, line 11 broadly recites “amino acids 150 – 164”; and the term “amino acids 150 – 157,” which is the narrower statement of the range/limitation because it is unclear what amino acids will be replaced by the amino acids of Seq ID No. 2. Accordingly, the metes and bounds of the claim are not clear.
Claims 34, 35, 37, 38, 40 and 41 are indefinite for the recitation of the terms “one or more amino acid substitutions at a residue” and “the amino acid substitution” such as recited in claim 33, line 2. There is insufficient antecedent basis for the terms “one or more amino acid substitutions” and “the amino acid substitution” in the claim because claim 30 has been amended to delete the term “a substitution”, as well as, to add the term “amino acids…is replaced by” in claim 30, line 11. Moreover, it is unclear whether the ‘one or more amino acid substitutions’ recited in claim 33 are referring to the “amino acids…replaced by” as recited in claim 30. Thus, the metes and bounds of the claim cannot be determined.
The rejection of claim 58 is maintained as being indefinite for the recitation of “a movement disorder” in line 2 and “spasticity disorder” in line 3. It is unclear what disorders are encompassed by the term a “movement disorder” and “a spasticity disorder” such that is the movement or spasticity is impaired, halted, and to what degree. Thus, the metes and bounds of the claim cannot be determined. (Please See Response to Arguments below).
Claims 31 – 32, 36, and 39 are indefinite insofar as they ultimately depend from claim 30.
Response to Arguments (Regarding claim 58)
Applicant’s arguments filed September 9, 2024 have been fully considered but they are not persuasive. Regarding claim 58, Applicant essentially asserts that (a) atypical or involuntary movements can result from aberrantly acting neurons and that these symptoms can be observed in subjects diagnosed with movement disorders or spasticity disorders (Applicant Remarks, pg. 11, third full paragraph); (b) Paragraph [0192] provides specific examples of movement and spasticity disorders, such that these disorders can be treated by compositions and methods of the invention wherein several movement disorders and spasticity disorders can be treated by compositions and methods of the invention (Applicant Remarks, pg. 11, fourth full paragraph).
Regarding (a), Applicant’s assertion that the atypical or involuntary movements can result from aberrantly acting neurons is not found persuasive. There are numerous sources for movement disorders as taught by MedLine (Medline Plus, Movement Disorders, Feb. 9, 2024, https://medlineplus.gov/movementdisorders.html). Medline teaches that movement disorders can be caused by genetics, infection, medicines, damage to the brain, spinal cord, or peripheral nerves, metabolic disorders, strokes, or toxins (Causes of Movement Disorders). There are many different causes of movements disorders, and thus claim and specification is not clear as to which movement disorders it is referring to.
Regarding (b), Applicant’s recites in Paragraph [0192] specific examples of movement and spasticity disorders, such that these disorders can be treated by compositions and methods of the invention. However, as noted above, there are many types of movement disorders, and it is not known if all of them will be treated by such a composition and method. Further, Medline teaches that the treatment varies by disorder, wherein sometimes medicine can help to cure the disorder, but other times, there is no treatment (Paragraph after Causes of Movement Disorders). Thus, it is unclear to one of ordinary skill in the art which movement and/or spasticity disorders will be treated.
The Examiner suggests amending claim 56 to include the specific movement and spasticity disorders that are being treated by the instantly claimed invention.
New Objections/Rejections
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 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.
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 30 – 55, and 57 - 59 are rejected under 35 U.S.C. 103 as being unpatentable over
Sternson et al. (hereinafter referred to as Sternson) (US Patent Application Publication US 2010/0130420 A1, Published May 27, 2010), and further in view of Xu et al. (hereinafter referred to as “Xu”) (US 2015/0307582 A1, published October 29, 2015). This is a new rejection necessitated by amendment of the claims in the response filed September 9, 2024.
Regarding claims 30 (in part) and 31 – 41, Sternson teaches a genetic construct encoding a chimeric receptor, wherein the chimeric receptor comprises a ligand binding domain from an α7 nicotinic acetylcholine receptor (α7-nAChR) fused to a transmembrane domain from a ligand-gated ion channel protein (interpreted as an engineered receptor, comprising a ligand from α7-nAChR and an ion pore domain derived from second LGIC receptor, instant claim 30). Sternson teaches that the transmembrane domain is from a ligand- gated ion channel of the Cys-loop family, including glycine receptors and Gaba receptors (Paragraph [0033]) (interpreted as comprising a Cys-loop from a second LGIC receptor, wherein the second LGIC receptor is a Cys-loop receptor, and not an α7-nAChR receptor, instant claim 30, and the second receptor is a glycine receptor or GABA receptor, instant claim 32). Sternson teaches that the receptors have mutations in the transmembrane domain, specifically the M2 regions and regions flanking the M2 region of the Cys-loop ion channels, which affect conductance and desensitization properties (Paragraph [0036]). Further, Sternson teaches that the sequence of the receptors can be replaced other Cys-loop receptors (Paragraph [0037]) (interpreted as a substitution of the ligand binding domain’s endogenous Cys-loop domain with a Cys-loop domain from a second LGIC receptor, instant claim 30) (Please note: The as-Filed Specification teaches that the substitution of the endogenous β1-2 loop sequence with a heterologous β1-2 loop sequence may increase the conductivity of the Cys-loop LGIC, Paragraph [0108]). Sternson teaches that the ligand binding domain of the α7-nAChR sequence (termed Seq ID No: 1) can have a point mutation at position W77 (Paragraph [0034] and Figure 10) (interpreted as at least a 85% sequence identity to Seq ID NO: 4, instant claim 31, and the ligand binding domain comprises a substitution of W77, instant claim 33). (Note: Seq ID NO:4 has a 99% sequence alignment score to Seq ID No: 1 (as taught by Sternson)). Sternson also teaches that the receptors of the invention can also contain mutation that reduce binding to acetylcholine, including Y115F (Paragraph [0035]) (interpreted as the ligand binding domain comprises amino acid substitutions corresponding to Y115, instant claim 34, 35, 37, 38, 40, and 41). (Note: The as-filed Specification teaches that the amino acid substitutions of the ligand binding domain decreases the potency of acetylcholine on the receptor, Paragraph [0022]. Even though the substitution Y115D is not explicitly taught by Sternson, one of ordinary skill would know that appropriate mutations to decrease binding to acetylcholine (referring to instant claim 35)). Sternson teaches the amino acid sequence of the α7-GlyR, (termed Seq ID No. 6), which is a transmembrane domain from the glycine receptor (Paragraph [0042]) and Figure 11) (interpreted as the second LGIC receptor is a GlyR, and has a sequence identity of at least 85% to SEQ ID No: 33, instant claim 36, and the ligand binding domain further comprise a β1-2 loop domain from the second LGIC receptor, instant claim 39). (Note: Note: Seq ID NO: 33 has a 95% sequence alignment score to Seq ID No: 6 (as taught by Sternson). Furthermore, the as-Filed Specification teaches that the β1-2 loop domain is incorporated into SEQ ID No:41, and the engineered receptor has a sequence alignment of at least 85% to SEQ ID No: 41 (Paragraph [0021]). Seq ID No: 41 has a 95% alignment score to Seq ID No: 6 (as taught by Sternson).
Regarding claims 42 – 45, and 47 – 51, Sternson teaches that the nucleic acids encoding the chimeric receptors may be operably linked to a promoter and incorporated into a genetic construct or vector (Paragraph [0038]) (interpreted as a polynucleotide encoding the engineered receptor, instant claim 42, and a vector comprising the polynucleotide sequence, instant claim 43). Sternson teaches the use of viral vectors, specifically retroviral vectors, for introducing a polynucleotide into a host cell (Paragraph [0048]) (interpreted as the vector is a viral vector, and a retroviral vector, instant claim 44, and polynucleotide is delivered to the subject in a viral vector, instant claim 47 - 48). Sternson further teaches that adeno-associated viruses can also be used to deliver the polynucleotide to the host (Paragraph [0048]) (interpreted as the AAV vector, instant claim 49). (Note: Sternson does not specifically exemplify AAV5, AAV6, AAV9 or variants thereof. However, one of ordinary skill in the art would know the appropriate AAV vector to use to deliver a polypeptide, referring to instant claim 49). Sternson teaches other physical, chemical, and biological means to introduce the genetic construct to the host, such as lipofection, and cell sonication (Paragraph [0047]) (interpreted as a non-viral administration method, instant claims 50 and 51). Sternson teaches a pharmaceutical composition of the vector encoding the chimeric receptors and the use of pharmaceutical acceptable carriers (Paragraph [0080] and [0082]) (referring to claim 45).
Regarding claim 46, Sternson teaches a method of treating a disease associated with the nervous system, wherein the chimeric receptor, which comprises a ligand binding domain from an α7 nicotinic acetylcholine receptor fused to a transmembrane domain from a ligand-gated ion channel protein, and a compound, which binds to receptor, is delivered to the patient (Paragraph [0014]) (interpreted as administering to the subject engineered receptor and the binding agent (i.e. compound), instant claim 46). The compounds, referred to as formula I, II, or III, preferentially bind and activate the chimeric receptor (Paragraph [0009]) (interpreted as the binding agent acts as an agonist of the engineered receptor, instant claim 46). (Note: the As-filed Specification teaches that an agonist is a binding agent that induces a signaling response, Paragraph [0136]).
Regarding claims 52 – 55, and 57 - 59, Sternson teaches that the nucleotide encoding the chimeric receptor is operably linked to a neuron specific promoter, for example, TRPV1 promoter can be used to target sensory neurons (Paragraph [0038]) (interpreted as the polynucleotide encoding the receptor is operably linked to a promoter that is in an active cell, instant claim 52, the excitable cell is a sensory neuron, instant claims 53 – 54). Sternson teaches that the administration of the chimeric receptor composition can be subcutaneous (Paragraph ([0083]) (referring to instant claim 55 and 57). (Note: The composition taught by Sternson includes the compound (i.e. binding agent)). Sternson teaches that invention can be applied to epilepsy, which is a disorder of excessive neuronal activity in the brain ultimately leading to seizures (Paragraph [0094]) (interpreted as the subject suffers from a seizure disorder, instant claim 58). Sternson teaches the pharmaceutical compositions that are safe for humans (Paragraph [0081]) (interpreted as the subject is human, instant claim 59).
Sternson does not specifically exemplify that the Cys-loop domain corresponding to amino acids 150 – 157 of Seq ID No:4 is replaced by amino acids 166 – 172 of Seq ID No. 2 (instant claim 30, in part) and a binding agent as recited in claim 56 (referring to instant claim 56).
Regarding claim 30 (in part), Xu teaches a receptor comprising a transmembrane domain an extracellular domain of pLGIC and interfacial sequences between the extracellular and transmembrane domain (Paragraph [0007]). Xu teaches that the pLGIC are homologues of Cys-loop receptors with structural similarity (Paragraph [0074]). Xu teaches that pLGICs are major pharmaceutical targets (Paragraph [0107]). Xu teaches that the interface between the transmembrane domain and the extracellular domain can be optimized using specific loops in the interface, wherein the interface controls the kinetics and efficacy and activation of the receptors (Paragraph [0133]). Xu teaches Seq ID No. 35 as the sequence for loop 2 (Paragraph [0133]). Xu teaches that the sequences for loop 2 is from human glycine receptors, wherein the loops are used to alter the strength of the interface and the efficacy of the response (Paragraph [0145]). Please Note: Seq ID No. 35 has 100% alignment match with amino acids 160 – 180 of instantly claimed Seq ID No. 2. Xu teaches engineered receptors for the use of therapeutics, such as for pain management and for the treatment of asthma or cystic fibrosis (Paragraph [0003]).
Sternson does not specifically exemplify a binding agent as recited in claim 56 (referring to instant claim 56).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of developing engineered receptors for the use of therapeutics as taught by Xu, it would have been prima facia obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the sequence of the chimeric receptor comprising a ligand binding domain from an α7 nicotinic acetylcholine receptor (α7-nAChR) fused to a transmembrane domain from a ligand-gated ion channel protein as taught by Sternson (specifically Sternson Seq ID No. 1) with the Cys-loop of the glycine receptor sequence (Xu Seq ID No. 35) as taught by Xu, with a reasonable expectation of success in improving the interface of the transmembrane domain and the extracellular domain to enhance the efficacy of the receptor. It would be prima facia obvious to combine the cited references because Sternson teaches that the Cys-loops affect conductance and desensitization properties of the receptor, and that the sequence of the receptors can be replaced other Cys-loop receptors, and Xu teaches the advantages of Seq ID No. 35, which is the Cys loop from the GlyR receptor, including enhancing the activation and efficacy of the receptor.
Claims 30 - 59 are rejected under 35 U.S.C. 103 as being unpatentable over Sternson and Xu, as
applied to claims 30 – 55 and 57 – 59 above, and further in view of Yang et al. (hereinafter referred to as “Yang”) (Yang T. et al. The current agonists and positive allosteric modulators of α7 nAChR for CNS indications in clinical trials. Acta Pharm Sin B. 2017 Nov;7(6):611-622. doi: 10.1016/j.apsb.2017.09.001. Epub 2017 Oct 16. PMID: 29159020; PMCID: PMC5687317.). This is a new rejection necessitated by amendment of the claims in the response filed September 9, 2024. This is a new rejection necessitated by amendment of the claims in the response filed September 9, 2024.
The teachings of Sternson with regard to claims 30 – 55 and 57 - 59 are described supra.
Sternson and Xu do not specifically exemplify the binding agents (claim 56).
Regarding claim 56, Yang teaches α7 nAChR agonists, specifically AZD0328, wherein AZD0328 acts as a partial α7 nAChR agonist exhibiting (α7 nAChR agonists, Paragraph 3 and Table 1).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of stability and favorable pharmacokinetic properties of AZD0328, compared to other agonists, as exemplified by Yang, it would have been prima facia obvious to obvious for one of skill in the art before the effective filing date of the claimed invention to modify the method of treating a disease with a chimeric receptor comprising a ligand binding domain from an α7 nicotinic acetylcholine receptor fused to a transmembrane domain from a ligand-gated ion channel protein and a compound as taught by Sternson and Xu, to include AZD0328 as the binding agent and compound as taught by Yang, with a reasonable expectation of success of increasing the binding between the compound and the α7 nicotinic acetylcholine receptor. It would have been prima facia obvious to combine the references because Sternson and Xu teach modifications formula I, II, and III, and many variations of compounds that can be used in the method, while Yang teaches that AZD0328 as the strongest agonist in relation to the α7 nicotinic acetylcholine receptor.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103 as obvious over the art.
Conclusion
Claims 30 – 59 remain rejected.
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 VYOMA SHUBHAM TIWARI whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 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, Maria Leavitt can be reached on (571) 272-1085. 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.
/VYOMA SHUBHAM TIWARI/Examiner, Art Unit 1634
/AMY M BUNKER/Primary Examiner, Art Unit 1684
