Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application, Amendments and/or Claims
2. The response dated 5/11/2026 is acknowledged and entered into record. Claims 1-3, 8, 12, 17 and 19 have been amended. Claims 1-20 are currently pending.
3. Claims 1-20, drawn to a kit and a vector comprising a first and a second nucleic acid, are under consideration in the instant application.
Priority
4. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
5. The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
6. The disclosure of the prior-filed provisional application, Application No. 62/580,846, filed 11/2/2017, fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The provisional application teaches a vector comprising (a first) nucleic acid encoding the neuropeptide and operably linked to a promoter, a vector comprising a (second) nucleic acid encoding a conditional receptor (hM3DREADD) and operably linked to a promoter (page 62 of 84, Viral constructs; page 66 of 84, last para); and CNO (page 17 of 84, para 2). That is the provisional application supports the limitations of instant claim 1(b), 3, 4(b)-11. The provisional application however, does not disclose a single vector comprising the first and second nucleic acid, and having either one or two promoters as recited in instant claims 1(a), 2, 4(a), 12. Since dependent claims shall be construed to include all the limitations of the independent claims (1 and 12), and because claims 2-11 and 13-20 depend from claims 1 and 12 respectively, none of the elected claims receive benefit of the provisional application 62/580,846. Accordingly, for the purpose of applying prior art, claims 1-20 are accorded the effective filing date of 1 November 2018, the date that the parent non-provisional application 16/178,461, issued as US patent 11376337, was filed. Note that the instant application is a divisional of the ‘461 application.
7. Should applicant disagree with the examiner’s factual determination above, applicant should point to evidence that the previously-filed applications provide written description and enablement of each of the relevant claim limitations above. This could be accomplished by pointing to specific page and line numbers within the applications that describe the limitations now claimed.
Claim Objection/Rejections Withdrawn
8. Upon consideration of amendment of claim 19, the objection is withdrawn.
9. Upon consideration of proper amendment of the relevant claims, the rejection under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn.
10. 103 rejections: Applicant argues that Andero (primary reference) teaches the use of “vectors and CNO within a study using DREADD technology to silence Tac2-expressing neurons”. Applicant alleges that Andero provides no guidance or reason to the skilled artisan “to use a conditional receptor configured to increase activity of the neuron that expresses” the receptor upon binding of an agonist or application of a stimulus to the receptor, because Andero discloses “that the conditional receptor is used to inducibly silence the neuron” (Applicant’s Remarks: para spanning pages 6 and 7). Applicant also argues that since Roth is cited for the hM3DREADD teaching, “which enhances neuronal firing and activates Gq signaling in neuronal and non-neuronal cells”, Roth (for activating neurons) and Andero (for silencing neurons using hM4Di-mCherry) teach the application of DREADD technology “for opposite purposes”. Applicant further argues that the secondary references (Dissen, Shen, Foti, Gascon) fail to cure the deficiencies of Andero. Applicant therefore, requests withdrawal of the rejections.
11. Applicant’s arguments are fully considered and found to be persuasive. All the 103 rejections are therefore, withdrawn.
New Rejections
Claim Rejections - 35 USC § 102
12. 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.
13. Claims 1 and 3-11 are rejected under AIA 35 U.S.C. 102(a)(1) as being anticipated by Zelikowsky et al (Cell 173: 1265-1279, 5/17/2018).
14. The claims are directed to a kit comprising a first nucleic acid encoding a neuropeptide, and a second nucleic acid encoding a conditional receptor configured to increase the activity of the neuron upon binding of an agonist or application of a stimulus to the receptor, wherein each of the nucleic acids are operably linked to a promoter configured to drive expression in a neuron in two different vectors (claims 1(b), 3) and both promoters are neuropeptide promoters (claim 7); wherein: the first and second vectors comprises an AAV (claim 4(b); the neuropeptide is neurokinin or neurokinin B (claims 5, 6); the kit further comprises the agonist or stimulus source (claim 8); and the neuron is a neuropeptidergic neuron (claim 9) of one or more types as listed in claim 10; and the conditional receptor is hM3DREADD, the agonist is clozapine-N-oxide (CNO) (claim 11).
15. Zelikowsky et al teach the generation of Tac2-overexpression AAV vector linked to hSyn promoter, and use of another AAV vector comprising hSyn promoter and hM3D(Gq) plasmid (page e2; page e4, para 3; Figure 7 legend). It is noted that the instant specification (para 0098) uses CMV and hSyn promoters in viral constructs for expression of the neuropeptide neurokinin, implying that these would necessarily be neuropeptide promoters (instant claim 7). The reference also teaches the use of CNO along with vectors encoding hM3D, a Tac2 cDNA (page 1271, col 2, para 3), for enhancement of Tac2 expression and neuronal activity during behavioral testing. The reference further teaches Tac2 is expressed in dBNSTa, CeA, dorsomedial hypothalamus (DMH) and anterior cingulate cortex (ACC) (neuropeptidergic neurons) (page 1267, col 2, para 3) (instant claims 1(b), 3, 4(b), 5-11). The reference therefore, anticipates the invention.
Claim Rejections - 35 USC § 103
16. 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.
17. Claims 1-14 and 16-20, are rejected under AIA 35 U.S.C. 103 as being unpatentable over Zelikowsky et al (5/2018), in view of Foti et al (Gene Ther 16: 1314-1319 (1-13), 2009).
18. The claims recite a single vector with one or two promoters (claims 1(a), 2, 12). The claims also recite a vector comprising a first nucleic encoding a neuropeptide, and a second nucleic acid encoding a conditional receptor, wherein each of the nucleic acids are operably linked to the single promoter configured to drive expression in a neuropeptidergic neuron (claims 12, 14); wherein the vector is an adeno-associated virus (AAV) (claim 13); the neuropeptide is neurokinin or neurokinin B (claims 16, 17); the neuron is a neuropeptidergic neuron (claim 18) of one or more types as listed in claim 19; the conditional receptor comprises hM3DREADD and the agonist is clozapine-N-oxide (claim 20).
19. The teachings of Zelikowsky et al are set forth above.
20. Zelikowsky et al do not teach that the first and second nucleic acid are in a single vector AAV.
21. Foti et al teach a proteolytic approach for the “expression and secretion of multiple gene products from a single AAV vector”. The reference teaches a recombinant AAV vector having two genes (green fluorescence protein or GFP and galanin) under the control of one promoter, which upon infusion into the piriform cortex, results in the expression of both GFP and galanin in neurons (Abstract; page 3, para 2, 3; page 4, para 5). The reference also teaches that consideration of more than one gene from a single virus vector enhances the benefit of gene therapy from “increasing the absolute number of gene products per virus vector to the delivery of distinct genes”, thereby resulting in better coordination of the “delivery of multiple therapeutic genes” facilitating effective treatment (Introduction, para 1; page 4, para 4).
22. It would have been, therefore, obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to modify the vectors comprising nucleic acids encoding a neuropeptide neurokinin and DREADD in different AAV vectors in view of the teachings of Zelikowsky et al, to having both genes in a single AAV vector in view of the teachings of Foti et al. The person of ordinary skill would have been motivated as different genes in a single vector would ensure that the transduced cell expresses both genes; and further the presence of a single promoter would allow one transcript, hence preventing differential promoter silencing, transcriptional interference and unequal levels of gene expression” thus leading to effective delivery of different genes to neurons (Foti et al, page 2, para 1). The person of ordinary skill would have expected success because development of vector constructs with one or more genes and single or dual promoters for research and clinical applications was an actively ongoing effort, before the effective filing date of the instant invention.
23. Thus, the claimed invention as a whole was prima facie obvious over the combined teachings of the prior art.
24. Claims 1, 12 and 15 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Zelikowsky et al (5/2018) in view of Gascon et al (J Neurosci Meth 168: 104-112, 2008).
25. The claims also recite a single vector with two nucleic acids and two promoters (claims 1(a)(ii), 12), wherein each nucleic acid is operably linked to a promoter configured to drive expression specifically in neuropeptidergic neurons (claim 15).
26. The teachings of Zelikowsky et al are set forth above.
27. Zelikowsky et al do not teach two promoters in a single vector.
28. Gascon et al teach neuron specific and regulated expression by single lentiviral vectors, which provide valuable tools for neuronal function studies (Abstract). The reference teaches the development of a dual promoter viral vector comprising two human synapsin (hSyn) promoters for driving the expression of two cDNAs of two reporter fluorescent proteins (DsRed and EGFP) in a neuron-specific manner (page 105, col 1, para 2; Fig, 1A; Materials and methods, para 1; Results, 3.1). The results show co-expression of the cDNAs in neurites and cell bodies of cultured neurons, which is mediated by a single dual promoter vector (Results – 3.3, page 109; Fig. 3). Teaching the advantages of dual promoter viral vectors, the reference states that the presence of all molecular components in one unique vector “guarantees expression of the two cDNAs in the target cells”, hence could prove “an important tool for the understanding of neuronal function in normal and pathological conditions” (para spanning pages 111 and 112).
29. It would have been, therefore, obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to modify the vectors comprising nucleic acids encoding a neuropeptide neurokinin and DREADD, each operably linked to a different promoter in different vectors as taught by Zelikowsky et al, by having a single vector with two different promoters for driving the expression of two nucleic acids in view of Gascon et al. The person of ordinary skill would have been motivated having two promoters in a single vector as the presence of all molecular components in one unique vector “guarantees expression of the two cDNAs in the target cells”, hence could prove “an important tool for the understanding of neuronal function in normal and pathological conditions” (Gascon et al). The person of ordinary skill would have expected success because development of vector constructs with one or more genes and single or dual promoters for research and clinical applications was an actively ongoing effort, before the effective filing date of the instant invention.
30. Thus, the claimed invention as a whole was prima facie obvious over the combined teachings of the prior art.
NOTE: The above art rejections are based upon consideration of the effective filing date of instant claims as 1 November 2018, for reasons stated in the “Priority” paragraph.
31. Claims 1, 3-4 and 7-11 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Anderson et al (US PGPB 2014/0178305, 6/26/2014) in view of Burnett et al (J Neurosc 39: 9268-9282, 2016).
32. Anderson et al teach compositions for activating stimuli for sensory neurons (MrgprB4+) (Abstract; para 0068), and kits comprising the inventive compositions along with tubes, instructions etc. (para 0124). The reference teaches the use of a viral vector comprising MrgprB4-tdTomato-2A-Cre with AAV8, under the control of a cytomegalovirus or CMV promoter (Example 2; para 0168), resulting in efficient expression of MrgprB4+ neurons (para 0168), wherein Mrgprs (Mas-Related G Protein-Coupled Receptors) are sensory neuronal proteins (para 0067). The reference also teaches a pharmacogenetic strategy for stimulation or activation of the neurons using an AAV encoding hM3-(Gq-coupled) DREADD19 and CNO, for injecting Mrgprb4-cre mice (Example 6; para 0181) (instant claim 11). The reference further teaches the use of different promoters like synapsin, CMV, CAG, etc. (para 0127; Fig 19), but teaches CMV as the preferred embodiment for higher expression (para 0037). It is noted that the instant specification (para 0098) uses CMV and hSyn promoters in viral constructs for expression of the neuropeptide neurokinin, implying that these would necessarily be neuropeptide promoters (instant claim 7). Since the vectors and nucleic acids are used for expression, the promoters would understandably be expected to be operatively linked to the nucleic acid encoding the neuronal protein or the conditional receptor, absent any evidence to the contrary. (instant claims 1(b), 3, 4, 8-9, 11).
33. Anderson et al do not teach a neuropeptide.
34. Burnett et al teach that DREADD molecules are highly effective tools for studying “neural circuits underlying behavioral outputs” (Abstract). The reference teaches that neuropeptide receptors are reasonable targets for manipulating circuit nodes downstream from a signaling molecule origin. The review article provides the example of neuropeptide-Y (NPY) signaling in the bed nucleus of stria terminalis (BNST) (neuropeptidergic neuron) influencing addiction (instant claims 9, 10). The reference states that targeted DREADD expression to NPY receptor expressing cells in the BNST, and manipulation of the activity of these cells, “replicated acute activation studies suppressing binge-drinking” behavior in a rodent model (page 9275, col 1, para 2).
35. It would have been, therefore, obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to modify the vectors comprising nucleic acids encoding a neuronal protein receptor and DREADD in different AAV vectors in view of the teachings of Anderson et al, by substituting MrgprB4 (receptor) with a neuropeptide (NPY), in view of Burnett et al. Since neuropeptide (neuronal protein) receptors are reasonable targets for manipulating circuit nodes downstream from a signaling molecule for influencing behavior, it would be obvious to one of ordinary skill in the art to have a simple substitution of functionally equivalent elements, i.e., the substitution of a neuronal protein receptor (e.g. MrgprB4) for neuropeptide (e.g. NPY) with predictable results (MPEP 2143 (B)). The person of ordinary skill would have been motivated to substitute a neuronal protein receptor with a neuropeptide, as both neuropeptide and their receptors have been investigated with DREADD for studying neural activity, and as targeting DREADD expression to the receptor expressing cells, and manipulating the activity of these cells, replicated the behavior patterns of the neuropeptide (Burnett et al). The person of ordinary skill in the art would have had a reasonable expectation of success, based on the cumulative disclosures of these prior art references, at the time of filing of the instant invention.
36. Thus, the claimed invention as a whole was prima facie obvious over the combined teachings of the prior art.
37. Claims 1 and 3-11 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Anderson et al (2014) and Burnett et al (2016), in view of Duarte et al (Cell Tiss Res 323: 43-51, 2006), Mileusnic et al (Neurobiol Aging 20: 19-35, 1999), and Roth et al (Neuron 89: 983-994 (1-25), 2/2016).
38. The claims also recite that the neuropeptide is neurokinin or neurokinin B (claims 5, 6).
39. The teachings of Anderson et al, and Burnett et al are set forth above.
40. Anderson et al also teach that activation of MrgprB4+ neurons can influence positive-valence behavior like enhance mood, reduce anxiety, relieve stress, etc. (para 0069). The reference teaches the use of AAV8 viruses expressing DREADD for behavioral studies (para 0137).
41. Anderson et al and Burnett et al do not teach that the neuropeptide is a neurokinin B.
42. Duarte et al teach the expression pattern of NkB and the encoding gene Tac2 in rats and mice (Abstract; Introduction, para 1), and points to behavioral aspects of NkB (Abstract). Table 1 of the reference teaches that Tac2 is expressed in central amygdala nucleus and bed nucleus of the stria terminalis (instant claims 5-6, 9-10).
43. Mileusnic et al teach that NkB is concentrated in areas involved in learning and memory. The reference teaches that many morphologically similar neurons express both NkB and its receptor NK-3R (page 28, col 1). The reference also teaches that neuronal presence of NkB is related to survival, and could be acting as a neuroprotective factor (page 27, para 2).
44. Roth teaches Designer Receptors Exclusively Activated by Designer Drugs (DREADD) and their use in chemogenetic methods for identifying neuronal circuitry, cell signaling and behavior in subjects, and understanding brain function (Abstract). The reference teaches that hM3DqDREADD (hM3DREADD) is typically used for enhancing neuronal firing in neurons (activation of neurons), and that hM3DqDREADD can be activated by clozapine-N-oxide or CNO.
45. It would have been, therefore, obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to modify the use of neuropeptide NPY based upon the combined teachings of Anderson et al and Burnett et al, with NkB neurokinin neuropeptide, also associated with behavior in view of Duarte et al, and Mileusnic et al, wherein the behavior can be studied using chemogenetic methods employing DREADD and CNO as taught by Roth. Since both, NPY and NkB are neuropeptides that are associated with behavior, wherein both neuropeptides and their receptors are expressed in morphologically similar neurons, it would be obvious to one of ordinary skill in the art to have a simple substitution of equivalent elements, i.e., the substitution of NPY for NkB with predictable results (MPEP 2143 (B)). The person of ordinary skill in the art would have been motivated to substitute NPY with NkB, as both are neuropeptides playing important roles in behavior, and both of have been used in experiments with DREADD based chemogenetic tools (Anderson et al, Burnett et al, Duarte et al, Mileusnic et al, Roth (Abstract)). The person of ordinary skill in the art would have had a reasonable expectation of success, based on the cumulative disclosures of these prior art references, at the time of filing of the instant invention.
46. Thus, the claimed invention as a whole was prima facie obvious over the combined teachings of the prior art.
47. Claims 1-14 and 16-20 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Anderson et al (2014) and Burnett et al (2016), in view of Duarte et al (2006), Mileusnic et al (1999), and Roth (2016), and further in view of Foti et al (2009).
48. The claims recite a single vector with one or two promoters (claims 1(a), 2, 12). The claims also recite a vector comprising a first nucleic encoding a neuropeptide, and a second nucleic acid encoding a conditional receptor, wherein each of the nucleic acids are operably linked to the single promoter configured to drive expression in a neuropeptidergic neuron (claims 12, 14); wherein the vector is an adeno-associated virus (AAV) (claim 13); the neuron is a neuropeptidergic neuron (claim 18); the neuropeptidergic neuron is a neuron of one or more types listed in claim 19; and the conditional receptor comprises hM3DREADD and the agonist is clozapine-N-oxide (claim 20).
49. The teachings of Anderson et al, Burnett et al, Duarte et al, Mileusnic et al, and Roth are set forth above.
50. Anderson et al, Burnett et al, Duarte et al, Mileusnic et al, or Roth do not teach that the first and second nucleic acid are administered in a single vector AAV.
51. The teachings of Foti et al are set forth above.
52. It would have been, therefore, obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to modify the vectors comprising nucleic acids encoding a neuropeptide and DREADD in different AAV vectors in view of the teachings of Anderson et al, Burnett et al, Duarte et al, Mileusnic et al, and Roth, to having both genes in a single AAV vector in view of the teachings of Foti et al. The person of ordinary skill would have been motivated as different genes in a single vector would ensure that the transduced cell expresses both genes; and further the presence of a single promoter would allow one transcript, hence preventing differential promoter silencing, transcriptional interference and unequal levels of gene expression” thus leading to effective delivery of different genes to neurons (Foti et al, page 2, para 1). The person of ordinary skill would have expected success because development of vector constructs with one or more genes and single or dual promoters for research and clinical applications was an actively ongoing effort, before the effective filing date of the instant invention.
53. Thus, the claimed invention as a whole was prima facie obvious over the combined teachings of the prior art.
54. Claims 1 12 and 15 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Anderson et al (2014) and Burnett et al (2016), in view of Duarte et al (2006), Mileusnic et al (1999), and Roth (2016), in further view of Gascon et al (2008).
55. The claims also recite a single vector with two nucleic acids and two promoters (claims 1(a)(ii), 12), wherein each nucleic acid is operably linked to a promoter configured to drive expression specifically in neuropeptidergic neurons (claim 15).
56. The teachings of Anderson et al, Burnett et al, Duarte et al, Mileusnic et al, and Roth are set forth above.
57. Anderson et al, Burnett et al, Duarte et al, Mileusnic et al, or Roth do not teach two promoters in a single vector.
58. The teachings of Gascon et al are set forth above.
59. It would have been, therefore, obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to modify the vectors comprising nucleic acids encoding a neuropeptide and DREADD, each operably linked to a different promoter in different vectors as taught by Anderson et al, Burnett et al, Duarte et al, Mileusnic et al, and Roth, by having a single vector with two different promoters for driving the expression of two nucleic acids in view of Gascon et al. The person of ordinary skill would have been motivated having two promoters in a single vector as the presence of all molecular components in one unique vector “guarantees expression of the two cDNAs in the target cells”, hence could prove “an important tool for the understanding of neuronal function in normal and pathological conditions” (Gascon et al). The person of ordinary skill would have expected success because development of vector constructs with one or more genes and single or dual promoters for research and clinical applications was an actively ongoing effort, before the effective filing date of the instant invention.
60. Thus, the claimed invention as a whole was prima facie obvious over the combined teachings of the prior art.
61. Claims 1 and 3-11 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Anderson et al (2014), in view of Duarte et al, (2006), Mileusnic et al (1999) and Roth (2016).
62. The teachings of Anderson et al, Duarte et al, Mileusnic et al and Roth are set forth above.
63. Anderson et al, Duarte et al, Mileusnic et al or Roth do not teach a nucleic acid encoding NkB and a second nucleic acid encoding a conditional receptor.
64. It would have been, therefore, obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to modify a kit comprising the first nucleic acid encoding MrgprB4 protein, wherein the activation of MrgprB4+ neurons has a positive impact on behavior, as taught by Anderson et al, with a nucleic acid encoding NkB neurokinin neuropeptide, also associated with neuroprotective behavior in view of Duarte et al and Mileusnic et al, wherein the behavior can be studied using chemogenetic methods employing DREADD and CNO induced neuronal activation as taught by Roth. Since both, MrgprB4 and NkB are associated with positive behavior, it would be obvious to one of ordinary skill in the art to have a simple substitution of equivalent elements, i.e., the substitution of MrgprB4 for NkB with predictable results (MPEP 2143 (B)). The person of ordinary skill would have been motivated to substitute MrgprB4 with NkB, as both are neuronal proteins playing important roles in behavior, which has been shown to be effectively studied using DREADD based chemogenetic tools (Anderson et al, Duarte et al, Roth (Abstract)). Given the existing knowledge about similarities in neuronal localization of neuropeptides and their receptors (Mileusnic et al), and the positive behavioral influences of NkB, the person of ordinary skill would have been motivated to explore multiple complementary approaches for NkB including the established DREADD technology for activation of neurons and manipulation of behavior. The person of ordinary skill in the art would have had a reasonable expectation of success, based on the cumulative disclosures of these prior art references, at the time of filing of the instant invention.
65. Thus, the claimed invention as a whole was prima facie obvious over the combined teachings of the prior art.
66. Claims 1-14 and 16-20 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Anderson et al (2014), in view of Duarte et al, (2006), Mileusnic et al (1999) and Roth (2016), in further view of Foti et al (2009).
67. The teachings of Anderson et al, Duarte et al, Mileusnic et al and Roth are set forth above.
68. Anderson et al, Duarte et al, Mileusnic et al or Roth do not teach that the first and second nucleic acid are administered in a single vector AAV.
69. The teachings of Foti et al are set forth above.
70. It would have been, therefore, obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to modify the vectors comprising nucleic acids encoding a neuropeptide neurokinin and DREADD in different AAV vectors in view of the teachings of Anderson et al, Duarte et al, Mileusnic et al and Roth, to having both genes in a single AAV vector in view of the teachings of Foti et al. The person of ordinary skill would have been motivated as different genes in a single vector would ensure that the transduced cell expresses both genes; and further the presence of a single promoter would allow one transcript, hence preventing differential promoter silencing, transcriptional interference and unequal levels of gene expression” thus leading to effective delivery of different genes to neurons (Foti et al, page 2, para 1). The person of ordinary skill would have expected success because development of vector constructs with one or more genes and single or dual promoters for research and clinical applications was an actively ongoing effort, before the effective filing date of the instant invention.
71. Thus, the claimed invention as a whole was prima facie obvious over the combined teachings of the prior art.
72. Claims 1, 12 and 15 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Anderson et al (2014), in view of Duarte et al, (2006), Mileusnic et al (1999) and Roth (2016), in view of Gascon et al (2008).
73. The teachings of Anderson et al, Duarte et al, Mileusnic et al and Roth are set forth above.
74. Anderson et al, Duarte et al, Mileusnic et al or Roth do not teach two promoters in a single vector.
75. The teachings of Gascon et al are set forth above.
76. It would have been, therefore, obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to modify the vectors comprising nucleic acids encoding a neuropeptide neurokinin and DREADD, each operably linked to a different promoter in different vectors as taught by Anderson et al, Duarte et al, Mileusnic et al and Roth, by having a single vector with two different promoters for driving the expression of two nucleic acids in view of Gascon et al. The person of ordinary skill would have been motivated having two promoters in a single vector as the presence of all molecular components in one unique vector “guarantees expression of the two cDNAs in the target cells”, hence could prove “an important tool for the understanding of neuronal function in normal and pathological conditions” (Gascon et al). The person of ordinary skill would have expected success because development of vector constructs with one or more genes and single or dual promoters for research and clinical applications was an actively ongoing effort, before the effective filing date of the instant invention.
77. Thus, the claimed invention as a whole was prima facie obvious over the combined teachings of the prior art.
Conclusion
78. No claims are allowed.
79. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Aditi Dutt whose telephone number is (571)272-9037. The examiner can normally be reached on M-F 9:00am-5:00pm.
80. 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.
81. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker, can be reached on 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/A. D./
Examiner, Art Unit 1675
2 August 2026
/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675
Prosecution Insights