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 . Claims 17-37 filed May 16, 2025 are currently pending.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/16/2025 has been entered.
Status of Claims
As indicated in the Office Action of 04/08/2024, claims 23-26 were withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/28/2024.
Response to Amendment
Applicant's arguments, filed 05/16/2025 have been fully considered. Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and objections presently being applied to the instant application.
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.
Claim(s) 17-20, 27-32, 34, 36-37 remain rejected under 35 U.S.C. 103 as being unpatentable over the combination of Zhang (WO2002/002190 published 01/10/2002), Kumar (European Journal of Pharmacology Vol. 615 pages 91-101 published 2009) and Pathak (Bioscience Rep. Vol. 28 pages 73-81 published 2008).
Zhang teaches the method of treating Alzheimer’s disease and inhibiting neuronal cell death in neuronal cells in a subject in need comprising administering a therapeutically effective amount of a small molecule compound that elevates the intracellular levels of at least one Phase II detoxification enzyme including catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase (abstract, page 7 lines 1-5, page 10 lines 25-30, claims 1, 6-8, 13).
Oral administration of said compound is embraced within the teachings of Zhang, wherein said compound is formulated with pharmaceutically acceptable carriers (page 22 lines 1-25, page 24 lines 20 to page 25 line 15). Regarding claims 36-37, the specification does not comprise any structural limitations for the phrase “dietary supplement” and as such, the administration of said composition further comprising an antioxidant reads on the disclosed claims. In the present case, Zhang teaches that said composition is formulated with antioxidant preservative parabens (page 20 line 29 to page 21 line 10).
Zhang teaches administration of said compounds in doses of 0.01-7.5 mg/kg per day, which overlaps with the therapeutically effective amounts embraced within the claims (page 25 lines 16-26). Applicant is reminded of MPEP 2144.05 in where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Kumar (European Journal of Pharmacology Vol. 615 pages 91-101 published 2009) teaches that neurodegenerative diseases attenuate the activity of catalase activity and superoxide dismutase activity in the afflicted patient (abstract, page 95 right col., page 99 right col.). Kumar additionally teaches that the art-recognized Alzheimer’s disease therapeutic rivastigmine is efficacious at upregulating superoxide dismutase and catalase activity in the brain of patients with neurodegenerative diseases (abstract). As shown in Table 1, compounds that are efficacious at stimulating superoxide dismutase and catalase levels in the brain are efficacious at treating Alzheimer’s disease in a subject (Table 1, page 95 right col., page 99 right col.,).
However, neither Zhang nor Kumar specifically teach the administration of queuine to treat Alzheimer’s disease in a subject in need.
Pathak teaches that queuine is a nutrient that is efficacious at promoting the cellular antioxidant defense system and inhibiting reactive oxygen species, thereby reducing oxidative stress in a subject in need (abstract, page 73 right col.). Pathak teaches that increase in oxidative stress leads to various pathological conditions including metabolic dysfunction and neurodegenerative disorders (page 73, right col.). Pathak teaches administration of 0.4-1.6 mg/kg queuine, wherein said 0.4-1.6 mg/kg queuine is efficacious at increasing the activities of enzymatic antioxidants of catalase, superoxide dismutase and glutathione peroxidase compared to control (page 76 right col. through page 77 right col., Figures 3-5).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to administer the antioxidant defense system promoter queuine to treat Alzheimer’s disease in a subject in need in view of the combined teaching of Zhang, Kumar and Pathak.
MPEP 2143 provides rationale for a conclusion of obviousness including (A): Combining prior art elements according to known methods to obtain predictable results;
In the present case, it was known in the prior art that compounds that elevate the intracellular levels of at least one Phase II detoxification enzyme including catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase are therapeutically effective for the treatment of Alzheimer’s disease in a subject in need. Considering Pathak teaches that queuine is art-recognized as efficacious at increasing the activities of enzymatic antioxidants of catalase, superoxide dismutase and glutathione peroxidase compared to control, said artisan would have applied the teachings of Pathak to the method of Zhang above, arriving at the instantly claimed methodology with a reasonable expectation of success.
Regarding the capacity of the administered queuine to yield a neuroprotective effect in the individual with Alzheimer’s, properties that accrue from the process step of administering an overlapping therapeutically effective amount of queuine to an Alzheimer’s diseased patient are considered characteristic features of the claimed methodology.
It is noted that MPEP 2112 discusses the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product or method instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the present case the burden is shifted to Applicant to prove that the administered therapeutically effective amount of queuine administered to a patient with Alzheimer’s disease embraced in the combined teachings of Zhang, Kumar and Pathak above will not yield a neuroprotective effect in the afflicted patient.
Claim(s) 21-22, 33 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Zhang (WO2002/002190 published 01/10/2002), Kumar (European Journal of Pharmacology Vol. 615 pages 91-101 published 2009) and Pathak (Bioscience Rep. Vol. 28 pages 73-81 published 2008) as applied to claim(s) 17-20, 27-32, 34, 36-37 above, in view of Becker (J. Alzheimer’s Disease Vol. 15 pages 303-325 published 2008).
As disclosed above, the combination of Zhang, Kumar and Pathak render obvious the administration of a therapeutically effective amount of queuine to treat Alzheimer’s disease in a subject in need, as queuine is art-recognized as efficacious at increasing the activities of enzymatic antioxidants of catalase, superoxide dismutase and glutathione peroxidase, coupled with the knowledge small molecule compounds that elevate the intracellular levels of at least one Phase II detoxification enzymes including catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase are efficacious at treating Alzheimer’s disease in a subject in need.
However, the combination of Zhang, Kumar and Pathak do not specifically teach administering donepezil, memantine or rivastigmine to the Alzheimer’s diseased patient treated with queuine.
Becker teaches that donepezil, memantine, rivastigmine and galantamine are all FDA approved for the treatment of Alzheimer’s disease in a subject in need (page 1, page 7).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to administer the Alzheimer’s disease treating queuine of Zhang, Kumar and Pathak above, with donepezil, memantine, rivastigmine or galantamine in view of Becker in order to arrive at the presently claimed.
Motivation to administer donepezil, memantine, rivastigmine or galantamine together with queuine flows logically from the very fact each agent or combination of agents was known in the prior art to have the same therapeutic utility of treating Alzheimer’s disease in a subject in need and, in turn, raises the reasonable expectation of success, that when combined, a composition comprising donepezil, memantine, rivastigmine or galantamine together with queuine would be efficacious at treating Alzheimer’s disease in an afflicted subject. The instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose (MPEP 2144.06).
Applicant traverses. Applicant argues that the surprising experimental findings of queuine on enhancing neuron survival and neuroprotective and restorative effect on cortical neurons intoxicated with ABeta 1-42 peptide within the present specification are sufficient to overcome a prima facie case.
Response to Arguments
Applicant’s arguments, filed 05/16/2025 are acknowledged and have been carefully considered.
Regarding Applicant’s contention that the unexpected enhancement of neuron survival and neuroprotective and restorative effect on cortical neurons intoxicated with amyloid peptides afforded by in-vitro administration of queuine is sufficient to overcome a prima facie case of obviousness, the examiner is unconvinced. As recited in the combination of Zhang and Pathak, queuine is art-recognized as efficacious at increasing the activities of enzymatic antioxidants of catalase, superoxide dismutase and glutathione peroxidase compared to control. Considering it was known in the prior art of Zhang that administering compounds that elevate the intracellular levels of at least one Phase II detoxification enzyme including catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase are efficacious at inhibiting neuronal cell death in neuronal cells in a Alzheimer’s diseased subject in need, said artisan would have readily predicted that administration of the therapeutically effective amount of queuine of Pathak to increase the activities of enzymatic antioxidants of catalase, superoxide dismutase and glutathione peroxidase in the subject would have inhibited neuron cell death and thereby enhanced neuron survival (Pathak: page 76 right col. through page 77 right col., Figures 3-5; Zhang: abstract, page 7 lines 1-5, page 10 lines 25-30, claims 1, 6-8, 13).
Secondly, as shown in MPEP 716.02 (E); An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). "A comparison of the claimed invention with the disclosure of each cited reference to determine the number of claim limitations in common with each reference, bearing in mind the relative importance of particular limitations, will usually yield the closest single prior art reference." In re Merchant, 575 F.2d 865, 868, 197 USPQ 785, 787 (CCPA 1978) (emphasis in original). Where the comparison is not identical with the reference disclosure, deviations therefrom should be explained, In re Finley, 174 F.2d 130, 81 USPQ 383 (CCPA 1949), and if not explained should be noted and evaluated, and if significant, explanation should be required. In re Armstrong, 280 F.2d 132, 126 USPQ 281 (CCPA 1960).
In the instant case, the closest prior art is Zhang teaches the method of treating Alzheimer’s disease and inhibiting neuronal cell death in neuronal cells in a subject in need comprising administering a therapeutically effective amount of a small molecule compound that elevates the intracellular levels of at least one Phase II detoxification enzyme including catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase, in doses of 0.01-7.5 mg/kg per day, which overlaps with the therapeutically effective amounts embraced within the claims (abstract, page 7 lines 1-5, page 10 lines 25-30, page 25 lines 16-26, claims 1, 6-8, 13).
Applicants have provided no comparative data to the closest prior art of record to show that 1) the claimed queuine results in improved efficacy at treating Alzheimer’s disease or providing a neuroprotective effect in an individual having Alzheimer’s disease compared to the small molecule compounds that elevate intracellular levels of catalase, superoxide dismutase and glutathione peroxidase taught by Zhang, or that administration of the therapeutically effective amount of queuine embodied within Pathak will not be efficacious. In essence, there is no positive control experiment between the methodology of the present claims and the methodology embraced within Zhang. Data must be provided that demonstrates that the instantly claimed queuine methodology performs better than the small molecule compounds that elevate intracellular levels of catalase, superoxide dismutase and glutathione peroxidase taught by Zhang in order to demonstrate that the claimed combination possesses a property not shared with the closest prior art. Applicant must also show that the different results of the between the instantly claimed and those of the prior art are in fact unexpected and unobvious and of both statistical and practical significance. See MPEP 716.02(B) and Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). Because Applicant has not shown any comparative data, the results lack both statistical and practical significance.
MPEP 716.02(d) addresses the subject of unexpected results commensurate in scope with the claimed invention: "[W]hether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the objective evidence of non-obviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. See In re Peterson, 315 F. 3d 1325, 1329-31 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003). As also cited in MPEP 716.02(D) “[T]o establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960). ). As shown in independent claims 17 and 26, the claims embrace the administration of any amount of queuine is efficacious at treating Alzheimer’s disease in a subject in need or provide neuroprotection to an Alzheimer’s diseased patient. However, as shown in Figures 2-3 above, this is not the case.
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As shown in Figures 2, the 30 nM dose of queuine is no different that the control patient being dosed with the amyloid plaques found within Alzheimer’s diseased patients (ABeta 1-42). Nor is there any statistical difference between the control patient with AB1-42 until a dose of at least 300 nM.
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Further, as shown in Figure 3, there is no difference between the Tau/neurite ratio of the 30 nM dose of queuine compared to the control patient being dosed with the amyloid plaques found within Alzheimer’s diseased patients. Lastly, on page 26 of the present specification discusses in-vivo administration of 1, 5 or 10 mg/kg queuine to ABeta 1-42 patients but no results are provided. It remains unclear if doses of queuine that lie within the therapeutically effective amount of claims 19 and 28, but lie outside the therapeutically effective range of claims 31 are truly efficacious at treating Alzheimer’s disease in a subject in need, or provide neuroprotection in-vivo.
In the instant case, just as a single point in space fails to define a line, one of ordinary skill in the art cannot ascertain a trend that would allow him/her to reasonably extend the probative value to any concentrations of the art-recognized catalase, superoxide dismutase and glutathione peroxidase activator queuine to yield an unexpected or striking efficacy at treating Alzheimer’s disease in a subject over the prior art of record, absent any concrete evidence or scientifically sound reasoning as to why all concentrations would have been reasonably expected to demonstrate the same unexpected efficacy in treating Alzheimer’s disease in a subject in comparison to that disclosed in Zhang and Figures 2-3 above. In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Double Patenting-Rejection(s) Maintained
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 17-20, 27-32, 34, 36-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-7, 9, 11-12 of U.S. Patent No. 10,857,135 in view of Zhang (WO2002/002190 published 01/10/2002) and Pathak (Bioscience Rep. Vol. 28 pages 73-81 published 2008).
Claims 2-7, 9, 11-12 of U.S. Patent 10,857,935 are directed to the treatment of Parkinson’s disease in a subject in need comprising administering a therapeutically effective amount of queuine. Oral administration and formulation of queuine as a dietary supplement with antioxidants embraced within claims 9, 11-12 overlap with the subject matter of 20, 32, 36-37, while the therapeutically effective amounts of queuine embraced within claims 3-6 overlap with the amounts embraced within claims 18-19 an 28-31.
However, claims 2-7, 9, 11-12 of U.S. Patent 10,857,135 do not specifically teach treating Alzheimer’s disease in a subject in need comprising administering a therapeutically effective amount of queuine.
Zhang teaches the method of treating Alzheimer’s disease and Parkinson’s disease and inhibiting neuronal cell death in neuronal cells in a subject in need comprising administering a therapeutically effective amount of a small molecule compound that elevates the intracellular levels of at least one Phase II detoxification enzyme including catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase (abstract, page 7 lines 1-5, page 10 lines 25-30, claims 1, 6-8, 13).
Oral administration of said compound is embraced within the teachings of Zhang, wherein said compound is formulated with pharmaceutically acceptable carriers (page 22 lines 1-25, page 24 lines 20 to page 25 line 15)., Zhang teaches that said composition is formulated with antioxidant preservatives such as parabens (page 20 line 29 to page 21 line 10). Zhang teaches administration of said compounds in doses of 0.01-7.5 mg/kg per day, which overlaps with the therapeutically effective amounts embraced within the claims (page 25 lines 16-26). Applicant is reminded of MPEP 2144.05 in where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)
And while Zhang does not specifically teach the administration of queuine to treat Alzheimer’s disease nor Parkinson’s disease in said subject, Pathak teaches that queuine is a nutrient that is efficacious at promoting the cellular antioxidant defense system and inhibiting reactive oxygen species, thereby reducing oxidative stress in a subject in need (abstract, page 73 right col.). Pathak teaches administration of 0.4-1.6 mg/kg queuine, wherein said 0.4-1.6 mg/kg queuine is efficacious at increasing the activities of enzymatic antioxidants of catalase, superoxide dismutase and glutathione peroxidase compared to control (page 76 right col. through page 77 right col., Figures 3-5).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to administer the Parkinson’s disease treating queuine of claims 2-7, 9, 11-12 of U.S. Patent 10,857,135 to treat Alzheimer’s disease in a subject in need in view of the combined teaching of Zhang and Pathak.
MPEP 2143 provides rationale for a conclusion of obviousness including (A): Combining prior art elements according to known methods to obtain predictable results;
In the present case, it was known in the prior art that compounds that elevate the intracellular levels of at least one Phase II detoxification enzyme including catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase are therapeutically effective for the treatment both Alzheimer’s disease and Parkinson’s disease in a subject in need. Considering Pathak teaches that the Parkinson’s disease treating queuine of U.S. Patent 10,857,135 is also art-recognized as efficacious at increasing the activities of enzymatic antioxidants of catalase, superoxide dismutase and glutathione peroxidase compared to control said artisan would have applied the teachings of Pathak and U.S. Patent 10,857,135 to the method of Zhang above, arriving at the instantly claimed methodology with a reasonable expectation of success.
Claims 17-20, 27-32, 34, 36-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8, 10-11 of U.S. Patent No. 11,684,611 in view of Zhang (WO2002/002190 published 01/10/2002) and Pathak (Bioscience Rep. Vol. 28 pages 73-81 published 2008).
Claims 1-6, 8, 10-11 of U.S. Patent 11,684,611 are directed to the treatment of Parkinson’s disease in a subject in need comprising administering a therapeutically effective amount of queuine. Oral administration and formulation of queuine as a dietary supplement with antioxidants embraced within claims 8, 10-11 overlap with the subject matter of 20, 32, 36-37, while the therapeutically effective amounts of queuine embraced within claims 2-5 overlap with the amounts embraced within claims 18-19 an 28-31.
However, claims 1-6, 8, 10-11 of U.S. Patent 11,684,611 do not specifically teach treating Alzheimer’s disease in a subject in need comprising administering a therapeutically effective amount of queuine.
Zhang teaches the method of treating Alzheimer’s disease and Parkinson’s disease and inhibiting neuronal cell death in neuronal cells in a subject in need comprising administering a therapeutically effective amount of a small molecule compound that elevates the intracellular levels of at least one Phase II detoxification enzyme including catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase (abstract, page 7 lines 1-5, page 10 lines 25-30, claims 1, 6-8, 13). Oral administration of said compound is embraced within the teachings of Zhang, wherein said compound is formulated with pharmaceutically acceptable carriers (page 22 lines 1-25, page 24 lines 20 to page 25 line 15)., Zhang teaches that said composition is formulated with antioxidant preservatives such as parabens (page 20 line 29 to page 21 line 10). Zhang teaches administration of said compounds in doses of 0.01-7.5 mg/kg per day, which overlaps with the therapeutically effective amounts embraced within the claims (page 25 lines 16-26). Applicant is reminded of MPEP 2144.05 in where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)
And while Zhang does not specifically teach the administration of queuine to treat Alzheimer’s disease nor Parkinson’s disease in said subject, Pathak teaches that queuine is a nutrient that is efficacious at promoting the cellular antioxidant defense system and inhibiting reactive oxygen species, thereby reducing oxidative stress in a subject in need (abstract, page 73 right col.). Pathak teaches administration of 0.4-1.6 mg/kg queuine, wherein said 0.4-1.6 mg/kg queuine is efficacious at increasing the activities of enzymatic antioxidants of catalase, superoxide dismutase and glutathione peroxidase compared to control (page 76 right col. through page 77 right col., Figures 3-5).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to administer the Parkinson’s disease treating queuine of claims 1-6, 8, 10-11 of U.S. Patent 11,684,611 to treat Alzheimer’s disease in a subject in need in view of the combined teaching of Zhang and Pathak.
MPEP 2143 provides rationale for a conclusion of obviousness including (A): Combining prior art elements according to known methods to obtain predictable results;
In the present case, it was known in the prior art that compounds that elevate the intracellular levels of at least one Phase II detoxification enzyme including catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase are therapeutically effective for the treatment both Alzheimer’s disease and Parkinson’s disease in a subject in need. Considering Pathak teaches that the Parkinson’s disease treating queuine of U.S. Patent 11,684,611 is also art-recognized as efficacious at increasing the activities of enzymatic antioxidants of catalase, superoxide dismutase and glutathione peroxidase compared to control said artisan would have applied the teachings of Pathak and U.S. Patent 11,684,611 to the method of Zhang above, arriving at the instantly claimed methodology with a reasonable expectation of success.
Applicant traverses with the same rationale as found in the Arguments of 08/22/2024. In said arguments, Applicant asserts that the claims in the ‘135 patent are for treating Parkinson’s disease, not Alzheimer’s disease as claimed. Applicant argues that no skilled artisan would have readily expected that an anti-Parkinson’s disease therapeutic would act as an anti-Alzheimer’s disease therapeutic absent unexpected experimental discovery such as those made by the inventors, and the examiner has not presented evidence showing otherwise. Applicant contends that the combination of Zhang and Pathak above fail to provide a reasonable expectation of success. Applicant further traverses the double patenting rejection with U.S. Patent ‘611 in view of Zhang and Pathak for the same reasons as applied to the ‘135 patent.
Response to Arguments
Applicant’s arguments, filed 08/11/2024 are acknowledged and have been carefully considered but remain unpersuasive. Arguments directed to the combined teachings of Zhang and Pathak are cited above. Regarding Applicant’s contention that no skilled artisan would have readily expected that an anti-Parkinson’s disease therapeutic would act as an anti-Alzheimer’s disease therapeutic with a reasonable expectation of success, this argument remains unavailing. A reasonable expectation of success logically flows from the fact that administration of a small molecule compound that elevates the intracellular levels of at least one Phase II detoxification enzyme including catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase is art-recognized at treating both Alzheimer’s disease and Parkinson’s disease, as taught by Zhang above (abstract, page 7 lines 1-5, page 10 lines 25-30, claims 1, 6-8, 13). Applicant has not provided objective evidence on the record that the methodology embraced within Zhang will neither treat Alzheimer’s disease nor Parkinson’s disease. As Pathak teaches that the Parkinson’s disease treating queuine of U.S. Patent 10,857,135 is also art-recognized as efficacious at increasing the activities of enzymatic antioxidants of catalase, superoxide dismutase and glutathione peroxidase, the same mechanistic pathway taught by Zhang above to treat both Alzheimer’s and Parkinson’s diseases, said skilled artisan would have applied the teachings of Pathak and U.S. Patent 10,857,135 to the method of Zhang above, arriving at the instantly claimed methodology with a reasonable expectation of success.
Secondly, in view of Applicant’s arguments pertaining to the double patenting rejection of record with U.S. Patent 11,684,611 in view of Zhang and Pathak, the pending double patenting rejection of record with U.S. Patent 11,684,611 is maintained for the same reasons as applied to the 10,867,135 patent.
Conclusion
In view of the rejection set forth above, no claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE W KOSTURKO whose telephone number is (571)270-5903. The examiner can normally be reached M-F 9:00-5:30.
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/GEORGE W KOSTURKO/Examiner, Art Unit 1621