DETAILED ACTION
This action is in response to papers filed on 01/29/2026. Claims 1-9, 14-20, and 22-31 of J. Hagel et al., 17/941,531 (09/09/2022) are pending: no claim amendment, and claims 14-17, 20, 23-26, and 30 remain withdrawn. Claims 1-9, 18-19, 22, 27-29, and 31 are pending examination on the merits. Claims 1-9, 18-19, 22, 27-29, and 31 are rejected.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a CON of PCT/CA2021/051214 (09/02/2021) which claims benefit of 63/073,534 (09/02/2020).
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 01/29/2026 has been entered.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 01/29/2026 and 09/17/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Election/Restrictions
In the reply of 4/4/2023, Applicant affirmed the election without traverse of Group I, and the elected species of compound XXIX (
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, R4=OCH3; R7=NO2), determined to read on the amended claims 1-9, 18, 19, 22, 27-29, 31. Claim 30, drawn to a non-elected invention is also withdrawn.
As detailed in the following rejections, the generic claim encompassing the elected species was not found patentable. Therefore, the provisional election of species is given effect, the examination is restricted to the elected species only, and claims not reading on the elected species are held withdrawn. MPEP 803.02; Ex parte Ohsaka, 2 USPQ2d 1460, 1461 (Bd. Pat. App. lnt. 1987). Accordingly, claims 14-17, 20, 23-26 are hereby withdrawn.
Should applicant, in response to this rejection of the Markush-type claim, overcome the rejection through amendment, the amended Markush-type claim will be reexamined to the extent necessary to determine patentability of the Markush-type claim. See MPEP 803.02.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-9, 18-19, 22, and 27-29 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al., (2002), WO 2002/078693 A2 (“Chen”), in view of Rosenblum et al. (US PG-PUB 2017/0081669) (“Rosenblum”), and R. Letra-Vilela et al., Molecular and Cellular Endocrinology 434 (2016) 238e249 (“Letra-Vilela”).
Regarding claims 1 and 28-29, Chen teaches the following compound in Example 894 (see, for e.g., p. 174, Example 894):
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corresponding to claim 1, formula (I), option (ii) wherein: R2, R4, R5 and R6 = H; R7 = NO2; R3a = H; and R3b = H; and regarding claims 28-29, Chen teaches compounds of the invention in pharmaceutical formulations (see, for e.g., claims 21 and 28) for use in the treatment of cognitive disorders (p.5, ll. 25).
The difference between the prior art and the claimed genus recited in romanettes (ii) is the proviso “when each R2, R5, R4, and R6 is a hydrogen atom, R3a and R3b are hydrogen atom and an acyl group respectively.” In the instant case, Chen teaches R3b = a hydrogen, and not an acyl group as required by claim 1.
However, Rosenblum teaches a similar compound on page 7:
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and claim 38, corresponding to claim 1, formula (I), where R2, R4, R6=H; R5=OCH3; R7=NO2; R3a=H; R3b=acyl. Rosenblum also claims the compound in a pharmaceutical formulation (claims 38, 48) for use in the “improvement of cognition in a subject” (Abstract).
An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that it would have similar (useful) properties to a prior art compound. MPEP § 2144.09 (discussing the close structural relationship between homologs and that between position isomers). Obviousness of a claimed compound can also be supported where there is motivation to substitute particular chemical moieties in a prior art compound for others so as to arrive at a claimed compound. MPEP § 2143(I)(B). For example, in the pharmaceutical arts, the rational is stated as motivation to select a known compound and also motivation to structurally modify the selected compound in a particular way to achieve a claimed compound. MPEP § 2143(I)(B) (see for example, MPEP § 2143(I)(B) Example 9, citing Eisai Co. Ltd. v. Dr. Reddy’s Labs., Ltd., 533 F.3d 1353, 87 USPQ2d 1452 (Fed. Cir. 2008). 1 Moreover, "[I]n considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom." In re Lamberti, 545 F.2d 747, 750, 192 USPQ 278, 280 (CCPA 1976). MPEP § 2144.01.
In the instant case, both Chen and Rosenblum teach nitrated psilocybin derivatives, as identified above, for use in the treatment of cognitive disorders as disclosed above. The “lead” compound in this analysis, disclosed by Chen, differs from the instant invention as it relates to the variable R3b. The instant invention requires the variable R3b = acyl group, while Chen teaches said variable as R3b =H. Rosenblum teaches a similar derivative, wherein said R3b = acyl group.
Considering both Chen and Rosenblum’s teachings, one of ordinary skill in the art would be motivated to explore the following:
1. Structural and pharmacophoric continuity
Both Chen and Rosenblum teach an essential nitro-substituted indole pharmacophore known for treating cognitive disorders (Chen: p. 174, Example 894, Rosenblum: p. 7). Chen in view of Rosenblum teaches a chemical compound wherein R3a and R3b are hydrogen atom, provided that when each R2, R5, R4, and R6 is a hydrogen atom, R3a and R3b are a hydrogen atom and an acyl group, respectively as shown below and as presented in instant claims 22 and 27. The nitro-substituted indole pharmacophore remains unchanged and the alternative formed as a result of substituting the hydrogen for an acyl group would be an obvious to try substitution when routinely optimizing Chen's compound, based on Rosenblum's teachings of a similar compound for the same use.
2. Retention of mechanism-of-action at the target receptor
Because both compounds remain full nitro-substituted indole-based compounds, the downstream biology that drives Chen's clinical effects is expected to still be triggered even with a singular substitution of a hydrogen to an acyl.
Letra-Vilela et al., underscores the above point of structural and pharmacophoric continuity. Letra-Vilela et al., teaches in the caption of Fig. 7. That, "The tryptamine core (green) is mostly responsible for the antioxidant and neuroprotective effects of melatonin". The additional side groups can be structurally modified to optimize the core functionality. In one instance, Letra-Vilela teaches that "The N-acetyl group (pink) seems to make melatonin safer (i.e. prevents autophagy) ... ". Fig. 7., caption. Melatonin was compared to 5-Methoxytryptamine, wherein the compounds differed by a singular substitution of a hydrogen to an N-acyl to obtain melatonin. Letra-Vilela teaches in the Abstract that “The N-acetyl group prevents methamphetamine-like autophagy and toxicity…”.
Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to first select the 2-(7-Nitro-1 H-indol-3-yl)ethylamine compound, taught by Chen, as part of a genus of compounds used to treat cognitive disorders, and modify the R3b position wherein R3b=H, for R3b=acyl group, in view of Rosenblum's teachings of a structurally similar psilocybin derivative also used in treating cognitive disorders, and Letra-Vilela teachings that “The N-acetyl group prevents methamphetamine-like autophagy and toxicity…”, and thus suggest an improvement in the safety of the compound when administered. Thus, arrive at the claimed invention successfully.
An ordinary skilled artisan would have had the reasonable expectation that such structurally analogous compounds would have the same activity and the same use, i.e., as pharmaceutical therapeutic agents. In re Finley, 81 USPQ 383 (CCPA 1949); In re Norris, 84 USPQ 458 (CCPA 1950); In re Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (Fed. Cir. 1990). Moreover, one would have been motivated to do so, with reasonable expectation of success because 2-(7-Nitro-1 H-indol-3-yl)ethylamine compound is part of a genus of compounds used to treat cognitive disorder as disclosed above, the similarity between the chemical structures and properties is sufficiently close that one of ordinary skill in the art would have been motivated to make the claimed compounds in searching for new psilocybin derivatives, for use in treating cognitive disorders with minimal adverse effects, for example.
Accordingly, the instantly claimed compound(s) is a structural analog of the reference claimed compound, and is obvious. Note also In re Jones, 21 USPQ2d 1942, which states at 1943 "Particular types or categories of structural similarity without more, have, in past cases, given rise to prima facie obviousness". Similar is In re Schechter and Laforge, 98 USPQ 144, 150, which states "a novel useful chemical compound which is homologous or isomeric with compounds of the prior art is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compounds." Note also In re Deuel 34 USPQ2d 1210, 1214 which states, "Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds ... a known compound may suggest its analogs or isomers, either geometric isomers (cis v. trans) or position isomers (e.g., ortho v. para)." See also MPEP 2144.09, second paragraph.
Additionally, obviousness does not require absolute predictability, but a reasonable expectation of success. See MPEP 2143.02.
In searching for new psilocybin derivatives with less adverse effects, one such compound, for example, based on the teachings of Chen in view of Rosenblum and Letra-Vilela, results in the following compound:
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wherein: R2, R4, R5 and R6 = H; R7 = NO2; R3a = H; and R3b = an acyl group. This compound corresponds to compound III of the instant invention (i.e., see instant, claim 27). Claims 1, and 28-29 are therefore obvious over Chen in view of Rosenblum and Letra-Vilela.
Regarding claims 22 and 27, and as disclosed above and applied to claim 1, Chen in view of Rosenblum and Letra-Vilela’s teachings is discussed.
Chen in view of Rosenblum and Letra-Vilela teach a chemical compound wherein R3a and R3b are hydrogen atom, provided that when each R2, R5, R4, and R6 is a hydrogen atom, R3a and R3b are a hydrogen atom and an acyl group, respectively:
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.
Claims 22 and 27 are therefore also obvious over Chen in view of Rosenblum and Letra-Vilela.
Regarding claim 2, and as disclosed above, Chen in view of Rosenblum and Letra-Vilela teach a compound of claim 1 wherein the compound is of the following formula:
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Moreover, as discussed above, Rosenblum teaches the following compound on page 7:
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and claim 38, corresponding to claim 1, formula (I), where R2, R4, R6=H; R5=OCH3; R7=NO2; R3a=H; R3b=acyl.
The difference between instant claim 2, and prior art teachings is that Rosenblum teaches a methoxy group in the R5 position (i.e., R5=OCH3), while the instant claim requires that “one of R2, R4, or R6 is an O-alkyl group”.
However, it would have been prima facie obvious to one having ordinary skill in the art at the time of the invention, to further modify the “lead” compound, as applied above, and prepare other structural analogs thereof, for example, by interchanging the positions of the methoxy group on the phenyl ring from the R5 position to the R4 position, because the skilled artisan would have had the reasonable expectation that such structurally analogous compounds would have the same activity, and the same use, i.e., as pharmaceutical therapeutic agents. In re Finley, 81 USPQ 383 (CCPA 1949); In re Norris, 84 USPQ 458 (CCPA 1950); In re Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (Fed. Cir. 1990). Both Chen and Rosenblum disclose structurally similar psilocybin derivatives, as identified above, for use in the treatment of cognitive disorders, as discussed above, with various modifications. A skilled artisan would have been motivated to further modify the compound as applied above in claim 1, and do so with reasonable expectation of success because the similarity between the chemical structures and properties is sufficiently close, so that one of ordinary skill in the art would have been motivated to make the claimed compounds in searching for new psilocybin derivatives, for use in treating cognitive disorders with minimal adverse effects, for example.
In addition to that, it is well established that positional isomers are prima facie structurally obvious even in the absence of a teaching to modify. The isomer is expected to be made by the same method and to have generally the same properties. This expectation is then deemed the motivation for preparing the position isomers. This circumstance has arisen many times. See: Ex parte Englehardt, 208 USPQ 343, 349; In re Mehta, 146 USPQ 284, 287; In re Surrey, 138 USPQ 67; Ex Parte Ullyot, 103 USPQ 185; In re Norris, 84 USPQ 459; Ex Parte Naito, 168 USPQ 437, 439; Ex parte Allais, 152 USPQ 66; In re Wilder, 166 USPQ 545, 548; Ex parte Henkel, 130 USPQ 474; Ex parte Biel, 124 USPQ 109; In re Petrzilka, 165 USPQ 327; In re Crownse, 150 USPQ 554; In re Fouche, 169 USPQ 431; Ex parte Ruddy, 121 USPQ 427; In re Wiechert, 152 USPQ 247, In re Shetty, 195 USPQ 753; In re Jones, 74 USPQ 152, 154; and In re Mayne, 41 USPQ2d 1451 (in which the Court took notice of the extreme similarity between the amino acids Leucine and isoleucine: “In fact, Leu is an isomer of Ile -- an identical chemical formula with differences only in the chemical bonding of the atoms. The side chains…of Leu and Ile have the same number of hydrogen and carbon atoms…The structure of Leu and Ile alone suggest their functional equivalency” (at 1454-1455)).
Moreover, for example, “Position isomerism has been used as a tool to obtain new and useful drugs” (Englehardt) and “Position isomerism is a fact of close structural similarity” (Mehta, emphasis in the original). Note also In re Jones, 21 USPQ2d 1942, which states at 1943 “Particular types or categories of structural similarity without more, have, in past cases, given rise to prima facie obviousness”; one of those listed is “adjacent homologues and structural isomers”. Position isomers are the basic form of close “structural isomers.” Similar is In re Schechter and LaForge, 98 USPQ 144, 150, which states “a novel useful chemical compound which is homologous or isomeric with compounds of the prior art is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compounds.” Note also In re Deuel 34 USPQ2d 1210, 1214 which states, “Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds … a known compound may suggest its analogs or isomers, either geometric isomers (cis v. trans) or position isomers (e.g., ortho v. para).” See also MPEP 2144.09, second paragraph.
Accordingly, the instantly claimed compound is a structural analog of the reference claimed compound, and is obvious. Claim 2, as is claim 1, is also obvious.
Regarding claims 3-9 and 18-19, Chen in view of Rosenblum and Letra-Vilela teach a chemical compound according to claim 1. Chen in view of Rosenblum and Letra-Vilela also teach wherein, R4, is a methoxy group (i.e., a C1-O-alkyl group). Claims 3-9 and 18-19, as is claim 1, are obvious.
Regarding claim 31, drawn to a pharmaceutical composition comprising the same product of claim 27, one of ordinary skill in the art would have readily considered a pharmaceutical composition as taught by Chen (see, for e.g., claims 21 and 28) and Rosenblum (see, for e.g., claims 38, and 48) using the optimized drug lead of obvious claim 1. Claim 31, as is claims 1 and 27, is therefore also obvious.
Applicant’s Arguments
Applicant argues that the claimed compounds are not obvious over the prior art, and argues the secondary reference “Rosenblum” as the lead compound. Applicant’s Remarks at page 3. Applicant argues the differences between Rosenblum’s compound and the claimed compounds, contending that Rosenblum teaches R5 as a methoxy group, while the claimed compounds teach R5 as H. Applicant then argues that the Office tries to fill the gap with Chen’s compound “by asserting that a person of ordinary skill in the art, being aware of the Chen compound, would replace the C5-methoxy group up of the Rosenblum compound with a hydrogen atom…” Applicant’s Remarks at page 4. Applicant then discusses and cites references to support their assertion (c.f., Blough et al.), and a Declaration of Dr. Jillian Hagel.
Applicant argues that the evidence shows that tryptamine derivative compounds which are substituted at the 5-position and tryptamine derivative compounds which are not substituted at the 5-position are not functionally comparable. Applicant Remarks at page 6. Applicant also contends that Rosenblum in view of Chen does not teach the claimed invention.
Response to Applicant’s Arguments
Applicant’s arguments are acknowledged, but are not found to be persuasive in view of the rejection above. The Declaration by Dr. Jillian Hagel is also acknowledged.
The Examiner respectfully submits that Applicant’s arguments address the secondary reference “Rosenblum” first, and leads with an analysis of Rosenblum and then address the primary reference, Chen. However, the claims are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al., (2002), WO2002078693A2 (“Chen”), the primary reference, in view of Rosenblum et al. (US 20170081669) (“Rosenblum”), and in further view of R. Letra-Vilela et al., Molecular and Cellular Endocrinology 434 (2016) 238e249 (“Letra-Viela”).
An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that it would have similar (useful) properties to a prior art compound. MPEP § 2144.09 (discussing the close structural relationship between homologs and that between position isomers). Obviousness of a claimed compound can also be supported where there is motivation to substitute particular chemical moieties in a prior art compound for others so as to arrive at a claimed compound. MPEP § 2143(I)(B). For example, in the pharmaceutical arts, the rational is stated as motivation to select a known compound and also motivation to structurally modify the selected compound in a particular way to achieve a claimed compound. MPEP § 2143(I)(B) (see for example, MPEP § 2143(I)(B) Example 9, citing Eisai Co. Ltd. v. Dr. Reddy’s Labs., Ltd., 533 F.3d 1353, 87 USPQ2d 1452 (Fed. Cir. 2008). 2 Moreover, "[I]n considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom." In re Lamberti, 545 F.2d 747, 750, 192 USPQ 278, 280 (CCPA 1976). MPEP § 2144.01.
The “lead” compound, as applied to the chemical analysis of claim 1, disclosed by Chen, differs from the instant invention as it relates to the variable R3b. That is, the instant invention requires the variable R3b = acyl group, while Chen teaches said variable as R3b =H. Rosenblum teaches a similar derivative, wherein said the said R3b = acyl group.
Considering both Chen and Rosenblum’s teachings, one of ordinary skill in the art would be motivated to explore the following:
1. Structural and pharmacophoric continuity
Both Chen and Rosenblum teach an essential nitro-substituted indole pharmacophore known for treating cognitive disorders (Chen: p. 174, Example 894, Rosenblum: p. 7). Chen in view of Rosenblum teaches a chemical compound wherein R3a and R3b are hydrogen atom, provided that when each R2, R5, R4, and R6 is a hydrogen atom, R3a and R3b are a hydrogen atom and an acyl group, respectively as shown below and as presented in instant claims 22 and 27. The nitro-substituted indole pharmacophore remains unchanged and the alternative formed as a result of substituting the hydrogen for an acyl group would be an obvious to try substitution when routinely optimizing Chen's compound, based on Rosenblum's teachings of a similar compound for the same use.
2. Retention of mechanism-of-action at the target receptor
Because both compounds remain full nitro-substituted indole-based compounds, the downstream biology that drives Chen's clinical effects is expected to still be triggered even with a singular substitution of a hydrogen to an acyl.
The lead compound from Chen is:
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Chen: p. 174, Example 894
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In view of Rosenblum: p. 7
To obtain:
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wherein: R2, R4, R5 and R6 = H; R7 = NO2; R3a = H; and R3b = an acyl group. This compound corresponds to compound III of the instant invention (i.e., see instant, claim 27).
The difference between Chen’s compound and the claimed compound is a singular hydrogen modification in the primary amine to an N-acyl group wherein said modification is structurally supported by Rosenblum’s compound comprising an N-acyl group.
While Applicant’s Declaration showed results where other tryptamine compounds, particularly N-acetyl-4-hydroxytryptamine and N-acetyl-4-hydroxy-5-methoxy-tryptamine exhibit different binding features on certain receptors, and attributes that difference to be mediated by the methoxy group at the C5 position since the two compounds are identical but for the methoxy group at the C5 position, this is not the case here. The modification is to Chen’s compound, at the position of the primary amine, and in view of Rosenblum, wherein said modification is structurally supported by Rosenblum’s compound comprising an N-acyl group.
Nonetheless to address Applicant’s arguments, the receptors studied in the Declaration are not the only relevant ones for activity of the tryptamine compounds that are being considered. For example, Rosenblum focuses on quinone reductase 2 expression, and Chen focuses on 5-HT6 receptors, which are none of the receptors discussed by Declarant. To one of ordinary skill in the art, the receptors, as discussed in Declaration (point 5 of Declaration), also plays a critical role in cardiovascular function, while the receptor studied by Chen, 5-HT6 is primarily associated with cognitive function and is located almost exclusively in the central nervous system (CNS). Because Chen compounds remain full nitro-substituted indole-based compounds, the downstream biology that drives Chen's clinical effects is expected to still be triggered even with a singular substitution of a hydrogen to an N-acyl. Furthermore Chen states that, the compounds of the invention provide a valuable treatment for 5-HT6 receptor mediated disorders. Thus, Chen’s compound is expected to retain its affinity for the 5-HT6 receptor, primarily associated with cognitive function and is located almost exclusively in the central nervous system (CNS), even with a modification from H in NH2 to an N-acyl group.
Letra-Vilela et al., underscores the above point of structural and pharmacophoric continuity. Letra-Vilela et al., teaches in the caption of Fig. 7. That, "The tryptamine core (green) is mostly responsible for the antioxidant and neuroprotective effects of melatonin". The additional side groups can be structurally modified to optimize the core functionality. In one instance, Letra-Vilela teaches that "The N-acetyl group (pink) seems to make melatonin safer (i.e. prevents autophagy) ... ". Fig. 7., caption. Melatonin was compared to 5-Methoxytryptamine, wherein the compounds differed by a singular substitution of a hydrogen to an N-acyl to obtain melatonin. Letra-Vilela teaches in the Abstract that “The N-acetyl group prevents methamphetamine-like autophagy and toxicity…”.
Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to first select the 2-(7-Nitro-1 H-indol-3-yl)ethylamine compound, taught by Chen, as part of a genus of compounds used to treat cognitive disorders, and modify the R3b position wherein R3b=H, for R3b=acyl group, in view of Rosenblum's teachings of a structurally similar psilocybin derivative also used in treating cognitive disorders, and Letra-Vilela teachings that “The N-acetyl group prevents methamphetamine-like autophagy and toxicity…”, and thus suggest an improvement in the safety of the compound when administered. Thus, arrive at the claimed invention successfully.
A skilled artisan would have had the reasonable expectation that such structurally analogous compounds would have the same activity and the same use, i.e., as pharmaceutical therapeutic agents. In re Finley, 81 USPQ 383 (CCPA 1949); In re Norris, 84 USPQ 458 (CCPA 1950); In re Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (Fed. Cir. 1990). Moreover, one would have been motivated to do so, with reasonable expectation of success because 2-(7-Nitro-1 H-indol-3-yl)ethylamine compound is part of a genus of compounds used to treat cognitive disorder as disclosed above, the similarity between the chemical structures and properties is sufficiently close that one of ordinary skill in the art would have been motivated to make the claimed compounds in searching for new psilocybin derivatives, for use in treating cognitive disorders with minimal adverse effects, for example.
Accordingly, the instantly claimed compound(s) is a structural analog of the reference claimed compound, and is obvious. Note also In re Jones, 21 USPQ2d 1942, which states at 1943 "Particular types or categories of structural similarity without more, have, in past cases, given rise to prima facie obviousness". Similar is In re Schechter and Laforge, 98 USPQ 144, 150, which states "a novel useful chemical compound which is homologous or isomeric with compounds of the prior art is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compounds." Note also In re Deuel 34 USPQ2d 1210, 1214 which states, "Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds ... a known compound may suggest its analogs or isomers, either geometric isomers (cis v. trans) or position isomers (e.g., ortho v. para)." See also MPEP 2144.09, second paragraph.
Additionally, obviousness does not require absolute predictability, but a reasonable expectation of success. See MPEP 2143.02. In searching for new psilocybin derivatives with less adverse effects, one such compound, for example, based on the teachings of Chen in view of Rosenblum and Letra-Vilela, results in the following compound:
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wherein: R2, R4, R5 and R6 = H; R7 = NO2; R3a = H; and R3b = an acyl group. This compound corresponds to compound III of the instant invention (i.e., see instant, claim 27).
As in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007) (“When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product is not of innovation but of ordinary skill and common sense. Here, the need lies clearly in searching for new psilocybin derivatives (i.e., nature-based medicine), for use in treating cognitive disorders with minimal adverse effects, such as hallucination, for example. Chen, Rosenblum and Letra-Vilela teach nitrated psilocybin derivatives, as identified above, for use in the treatment of cognitive disorders.
In summary, both Chen and Rosenblum teach an essential nitro-substituted indole pharmacophore known for treating cognitive disorders:
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Chen: p. 174, Example 894
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Rosenblum: p. 7
Chen in view of Rosenblum teach an alternative chemical compound of the claimed invention wherein R3a and R3b are hydrogen atom, provided that when each R2, R5, R4, and R6 is a hydrogen atom, R3a and R3b are a hydrogen atom and an acyl group, respectively as shown below and as presented in instant claims 22 and 27:
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The nitro-substituted indole pharmacophore remains unchanged and the alternative formed as a result of substituting the hydrogen for an acyl group would be an obvious to try substitution when routinely optimizing Chen’s compound, based on Rosenblum’s teachings of a similar compound for the same use, and underscored by Letra-Vilela teachings discussed above that the acetylated versions of tryptamine compounds (i.e., melatonin) reduced side effects like autophagy and toxicity: “The N-acetyl group prevents methamphetamine-like autophagy and toxicity.” (Abstract). The claims are obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANTAL ADLAM whose telephone number is (571)270-0923. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm.
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/C A/Examiner, Art Unit 1622
February 5, 2026
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
1 In the chemical arts, a "lead compound" obviousness analysis is often applied; the “lead compound” analysis requiring initial motivation to select a prior art compound and thereafter still further motivation to make the specific structural modifications thereto so as to arrive at a claimed compound. See MPEP § 2143(B) (discussing “lead compound cases” in Examples 9-11 with respect to pharmaceutical applications). However, the MPEP warns against applying the lead compound analysis rigidly in view of the flexible approach stated in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) see also, MPEP § 2143(B), Example 11 (citing Altana Pharma AG v. Teva Pharm. USA, Inc., 566 F.3d 999, 91 USPQ2d 1018 (Fed. Cir. 2009) a ‘restrictive view of the lead compound test would present a rigid test similar to the teaching-suggestion-motivation test that the Supreme Court explicitly rejected in KSR’).
2 In the chemical arts, a "lead compound" obviousness analysis is often applied; the “lead compound” analysis requiring initial motivation to select a prior art compound and thereafter still further motivation to make the specific structural modifications thereto so as to arrive at a claimed compound. See MPEP § 2143(B) (discussing “lead compound cases” in Examples 9-11 with respect to pharmaceutical applications). However, the MPEP warns against applying the lead compound analysis rigidly in view of the flexible approach stated in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) see also, MPEP § 2143(B), Example 11 (citing Altana Pharma AG v. Teva Pharm. USA, Inc., 566 F.3d 999, 91 USPQ2d 1018 (Fed. Cir. 2009) a ‘restrictive view of the lead compound test would present a rigid test similar to the teaching-suggestion-motivation test that the Supreme Court explicitly rejected in KSR’).