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 .
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.
This office action is a response to applicant’s communication submitted April 25, 2024, wherein claims 2, 5, 6, and 12-14 were preliminarily amended, claim 11 was cancelled, and claim 18 was added. This application is a 371 of PCT/CN2022/127414 filed 10/25/2022 and claims benefit to US provisional application 63/271,411 filed 10/25/2021.
Claims 1-10 and 12-18 are pending in this application.
Drawings
The drawings are objected to because:In figure 4A the titles are illegible.
In figure 4B, the figure labels are illegible, particularly the X axis in the graph and the Y axis on the image.
In figure 5, the axis labels are illegible.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
The use of the term L-Selectride® (BenchChem, 2026, cited on PTO-892, abstract), which is a trade name or a mark used in commerce, has been noted in this application (See instant specification, pg. 10, top of page, pg. 11, middle of page, pg. 12, para. 0017, pg. 13, para. 0018, pg. 16, top of page). The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The Scheme on page 30 is blurry, particularly the R superscripts and atom subscripts, rendering them illegible.
Appropriate correction is required.
Claim Objections
Claims 1-4, 7-9, 14-15, 18 are objected to because of the following informalities:
In claim 1 the phrase “can is” should read “is”.
In claims 1-3 the phrase “Methyl” should read “methyl”.
In claim 4, the structural formulas are blurry, rendering them illegible, particularly the R groups and sugar hydroxyls.
In claim 7 the phrase “compounds of Formulas (16)” should be amended for consistency to read “compound of Formula (16)”.
In claim 8 the phrase “compounds of Formulas (12)” should be amended for consistency to read “compound of Formula (12)”.
In claim 9 the phrases “regio-“ and “region-” should read “regio-selective”.
In claim 14 the phrase “hippocampal nerves” should read “hippocampal neurons” (based on instant specification experimental examples, see pg. 22, para. 0069).
In claim 15 the phrases “umber“ should read “number”.
In claim 18 the phrases “derivatives“ should read “derivative”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-10 and 12-18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 1-3 and 12-18: Claim 1 recites the phrase “substituted or nonsubstituted Formula (2) or Formula (3)”, “substituted or nonsubstituted Formula (4 or Formula (5)”. The phrase substituted or nonsubstituted” renders the claim indefinite because it is unclear whether nonsusbtituted refers to wherein the defined R groups are hydrogen and substituted refers to R groups that are non-hydrogen, or refers to further substitution in the molecule in any position or of non-hydrogen R groups. The instant specification does not define these terms. Thus a person of ordinary skill in the art would be unable to ascertain the metes and bounds of the invention. Dependent claims 2-3 also recite ”substituted or nonsubstituted” are similarly rejected. Claims 12-18 which depend from claim 1 are similarly rejected as they do not clarify this issue.
Regarding claims 1-3 and 12-18: Claims 1-3 recite the structural formulas (4) and (5) which appear to show a methyl group at the bottom of the structure:
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. However, it is believed based upon the instant specification this meant to describe a point of attachment to formulas (2) and (3) (See instant specification pg. 30, scheme). However, based on the claim, it is not clear this is the case. Thus the scope of the claims encompassed by the formula is unclear, thereby rendering the claims indefinite. Claims 12-18 which depend from claim 1 are similarly rejected as they do not clarify this issue. The Examiner suggests using complete formulas to clearly show structural connectivity’s, such as those recited in instant claim 4.
Regarding claim 4: Claim 4 recites “The Isopropyl-D-glucopyranoside derivative of claim 1, wherein the Isopropyl-D-glucopyranoside derivative comprises following compounds:” and then recites individual formulas of the compounds of claim 1. The phrase “comprising” renders the claim indefinite because it is unclear what other alternatives are intended to be encompassed by the claim (See MPEP 2173.05(h)).
Regarding claim 4: Claim 4 recites R4 twice, but does not define R3. Thus the metes and bounds of the claim cannot be determined, thereby rendering the claim indefinite.
Regarding claim 5:
In the beginning of claim 5, claim 5 recites R1-R2 are limited to Me, Et, Pr, H, or OH, and R3-4 are limited to Me, Et, Pr, or H, but at the end of the claim, these variables are expanded to include deuterium, and tritium. It is unclear from the method steps how these would be incorporated or expanded in this manner. The scope of the claims is thus unclear, rendering the claim indefinite.
Claim 5 recites an “acylation” but does not depict an acylation reaction (incorporation of an acyl) occurring. According to the specification, the reaction incorporates this group:
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(pg. 30, top of page), as shown in formula 8 in claim 5. The instant specification does not redefine acylation to mean anything other than a person of ordinary skill in the art would interpret the phrase to mean. The contradiction with the phrase “acylation” and the eventual product results in a lack of clarity, rendering the claim indefinite.
In claim 5, the phrase “this intermediate” renders the claim indefinite as there is insufficient antecedent basis for this limitation in the claim. In claim 5, the phrase “the deprotection reagent 1” renders the claim indefinite as there is insufficient antecedent basis for this limitation in the claim
In claim 5, the phrase “can be”, which occurs throughout the claim renders the claim indefinite because it is unclear whether the limitations following the phrase are exemplary or are mean to be limitations. The phrase “base 1, which includes” also renders the claim indefinite because it is unclear whether the limitations following the phrase are exemplary or are mean to be limitations.
In claim 5, the phrases “electrophilic reagent 1”, “base 1”, “electrophilic reagent 2”, “base 2”, “reducing agent 1”, “desilylation reagent 1”, “glycosylation reagent 1”, “reagent 1”. The phrases are not clearly defined within the claim, or within the instant specification. While a person of ordinary skill in the art would know what constitutes a reducing agent generally for example, the recitation of “reducing agent 1” implies a specific class of reagents that is not defined by the instant specification and would not be recognized by a person of ordinary skill in the art. The instant specification merely describes what “can be” these agents, but does not clearly defines them. Thus these phrases render the claim indefinite because the phrases are not clearly defined. The examiner notes that “deprotection reagent 1” is explicitly defined within the claim, but lacks antecedent basis as described above.
In claim 5, R groups are defined at the end, but R4 is defined twice, while R3 is undefined. A person of ordinary skill in the art would be unable to ascertain the metes and bounds of the invention without R3 being defined. It is also unclear whether the R groups are meant to be for formula (6) which structure was not incorporated into the claim. The Examiner suggests incorporation of Formula (6) into the claim for purposes of clarity.
Claim 5 contains the trademark/trade name L-selectride® (BenchChem, 2026, cited on PTO-892, abstract). Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a chemical reagent and, accordingly, the identification/description is indefinite.
Claims 6-7, which depend from claim 5 are similarly rejected.
Regarding claim 6: Claim 6 recites further limiting step (B) by converting the formula (11) into formula (15). However, claim 5, of which claim 6 depends recites arriving at formula (11) following step C. Thus the metes and bounds of the present invention cannot be determined, rendering claim 6 indefinite. Claim 7 carries this error forward and is thus similarly rejected.
In claim 6, the phrase “can” in the first line renders the claim indefinite because it is unclear whether the limitation is merely a description of what can be tolerated and is an optional step, or is meant to further limit step (b).
In claim 6, the phrase “can be”, which occurs throughout the claim renders the claim indefinite because it is unclear whether the limitations following the phrase are exemplary or are mean to be limitations.
In claim 6, R groups are defined at the end, but R4 is defined twice, while R3 is undefined. A person of ordinary skill in the art would be unable to ascertain the metes and bounds of the invention without R3 being defined.
Claim 7 which depends from claim 6 is similarly rejected.
Regarding claim 7:
In claim 7, the phrase “can” in the first line renders the claim indefinite because it is unclear whether the limitation is merely a description of what can be tolerated and is an optional step, or is meant to further limit after the step (B1).
In claim 7, the phrase “can be”, which occurs throughout the claim renders the claim indefinite because it is unclear whether the limitations following the phrase are exemplary or are mean to be limitations.
Claim 7 contains the trademark/trade name L-selectride® (BenchChem, 2026, cited on PTO-892, abstract). Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a chemical reagent and, accordingly, the identification/description is indefinite.
In claim 7, R groups are defined at the end, but R4 is defined twice, while R3 is undefined. A person of ordinary skill in the art would be unable to ascertain the metes and bounds of the invention without R3 being defined.
Regarding claims 6-7: It is unclear whether the claims are intended to limit the specific deprotection of acetal, an isomerization, and removal of benzoyl group (claim 6) and selective reduction (claim 7) steps as recited by instant claim 5 by including structural formulas, or is meant to describe the synthesis of compounds separate from formula 6 as recited by instant claim 5. See image below:
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The lack of clarity presented by the new structural formulas renders claims 6-7 indefinite.
Regarding claims 8-10:
In claims 8-10, the phrase “can be”, which occurs throughout the claims renders the claim indefinite because it is unclear whether the limitations following the phrase are exemplary or are mean to be limitations.
In claims 9-10, the phrase “can” in the first line renders the claim indefinite because it is unclear whether the limitation is merely a description of what can be tolerated and is an optional step, or is meant to further limit after the step (A) or (B).
In claim 8, the phrases “reducing agent 2”, “deprotection reagent 2”. Claim 9 recites “reducing agent 3”. Claim 10 recites the phrase “reducing reagent 4”. The phrases are not clearly defined within the claim, or within the instant specification. While a person of ordinary skill in the art would know what constitutes a reducing agent generally for example, the recitation of “reducing agent 2” implies a specific class of reagents that is not defined by the instant specification and would not be recognized by a person of ordinary skill in the art. The instant specification merely describes what “can be” these agents, but does not clearly defines them. Thus these phrases render the claim indefinite because the phrases are not clearly defined.
Claims 8-10 contains the trademark/trade name L-selectride® (BenchChem, 2026, cited on PTO-892, abstract). Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a chemical reagent and, accordingly, the identification/description is indefinite.
Claim 10 recites the limitation "the reduced temperature". There is insufficient antecedent basis for this limitation in the claim.
Regarding claims 13-14: Claims 13-14 recite the limitation "the nerve injury" There is insufficient antecedent basis for these limitation in the claims.
Regarding claims 15-17: Claims 15-17 recite “The method of claim 1”, however, claim 1 is directed to a compound. Thus, the metes and bounds of the claim are thereby rendered indefinite. Claim 15 recites the limitation "the treating". Claim 16 recites the limitation "when administered". Claim 17 recites the limitation "the effective dose range" There is insufficient antecedent basis for these limitation in the claims. The claims will be interpreted as if dependent from claim 18. The Examiner suggests in claim 16, the phrase “when administered nasally” be rephrased because it is unclear whether the phrase is a describing a property of the compounds, or an active step of the method.
Claim Rejections - 35 USC § 112 (d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 6-7 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claims 6-7: It is unclear whether the claims are intended to limit the specific deprotection of acetal, an isomerization, and removal of benzoyl group (claim 6) and selective reduction (claim 7) steps as recited by instant claim 5 by including structural formulas, or is meant to describe the synthesis of compounds separate from formula 6 as recited by instant claim 5. See image below:
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In either case, the claims either expand, or fail to limit instant claim 5.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-4 and 15-17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more.
Miyase (Chem. Pharm. Bull., 1988, cited on PTO-892) teaches compound 7 (icariside B5) has the following structure
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wherein R1 is Glc and R2 is OH, which is isolated from epimedium grandiflorum Morr. Var. thunberganum and is thus a natural product (pg. 2475, para. 1, pg. 2476, chart 1, compound 7). Compound 7 meets the structural limitations of claims 1 and 3-4.
So (Bioorganic Chemistry, 2019, cited on PTO-892) teaches the compound 6 which has the following structure
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, which is a natural product isolated from U. davidiana (pg. 5, figure 1, compound 6). So teaches this compound is (+)-cis-roseoside (pg. 5, col. 1, para. 2). According to the instant specification, roseoside promotes ex vivo retinal neuronal tissue repair at concentrations of 13 uM or 130 uM (pg. 29, paras. 0115-0116).
Kim (Heterocycles, 2014, cited on PTO-892) teaches compound 3, byzantionoside B, which has the following structure:
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(pg. 1914, figure 1, pg. 1916-1917, bridging para.). Kim teaches the compound is isolated from phyteuma japnoicum, and is thus a natural product (abstract).
This judicial exception is not integrated into a practical application because the compounds described above which are encompassed by the instant claims are not different from the compounds found in nature (See MPEP 2106 (b)). Without the inclusion of the treatment step as recited by instant claim 18, claims 1-4 and 15-17 do not integrate these elements into a practical application. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is directed to a natural product. Although claims 15-17 recite the phrase “method” as best understood in view of the 112(b) rejections above, these claims are directed towards properties of the compounds themselves. Since the claims are product claims, they do not transform the nature of the claim to claim more than the judicial exception.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2 and 15-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by So (Bioorganic Chemistry, 2019, cited on PTO-892).
Regarding claims 1-2, 15-17: So teaches the compound 6 which has the following structure
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, which is a natural product isolated from U. davidiana (pg. 5, figure 1, compound 6). This compound meets the structural limitations of claims 1-2. So teaches this compound is (+)-cis-roseoside (pg. 5, col. 1, para. 2). According to the instant specification, roseoside promotes ex vivo retinal neuronal tissue repair at concentrations of 13 uM or 130 uM (pg. 29, paras. 0115-0116). Although So does not disclose its ability to increase number of neurons, ability to penetrate the blood-brain barrier to enter the brain when administered nasally, or the effective dose range between 9.674 nM to 1342 uM as recited by instant claims 15-17, a compounds properties cannot be separated from the compound itself and thus are inherent properties of the compound. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference (See MPEP 2112 (II)).
Claims 1, 3-4, and 15-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim (Heterocycles, 2014, cited on PTO-892).
Regarding claims 1, 3-4, 15-17: Kim teaches compound 3, byzantionoside B, which has the following structure:
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(pg. 1914, figure 1, pg. 1916-1917, bridging para.). Kim teaches the compound is isolated from phyteuma japnoicum, and is thus a natural product (abstract). Kim teaches compound 3 increases NGF secretion in glioma cells and inhibits LPS-stimulated NO production in microglial cells with an effective concentration of ~20 uM (pg. 1917, table 2, pg. 1918, table 3). According to the instant specification, byazntionoside B promotes neurite outgrowth in cortical neurons (pgs. 122-23, para. 0073-0074). The instant specification discloses that byazntionoside B promotes retinal neuronal repair at concentrations of 13.5 uM or 135 uM (pg. 28, paras. 0111-0112). Although So does not disclose its ability to increase number of neurons, ability to penetrate the blood-brain barrier to enter the brain when administered nasally, or the effective dose range between 9.674 nM to 1342 uM as recited by instant claims 15-17, a compounds properties cannot be separated from the compound itself and thus are inherent properties of the compound. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference (See MPEP 2112 (II)).
Claims 1 and 3-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ma (Phytochemistry, 2001, cited on PTO-892).
Regarding claims 1 and 3-4: Ma teaches the following compound 5a
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(pg. 821, col. 1, fig. 1, compound 5a).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 12-13 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (Heterocycles, 2014, cited on PTO-892) as applied to claims 1, 3-4, and 15-17 above in view of So (Bioorganic Chemistry, 2019, cited on PTO-892).
Regarding claims 12-13 and 18: As discussed above, Kim teaches Kim teaches compound 3, byzantionoside B, which has the following structure:
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(pg. 1914, figure 1, pg. 1916-1917, bridging para.). Kim teaches the compound is isolated from phyteuma japonicum. Kim teaches compound 3 increases NGF secretion in glioma cells and inhibits LPS-stimulated NO production in microglial cells with an effective concentration of ~20 uM (pg. 1917, table 2, pg. 1918, table 3).
Kim does not teach a method of treating neural injury comprising administering the compound to a subject wherein the neural/nerve injury is a central nervous system or neuron injury.
However, So teaches NO is an inflammatory mediator in CNS (central nervous system) and the overproduction of NO can result in neuronal damage (pg. 103145, col. 1, para. 1). It was reported that neurotrophic factors such as NGF, has the potential to regulate the survival, proliferation, migration, and differentiation of cells in the nervous system (pg. 103145, col. 1, para. 1). Phytochemicals that induce the secretion of neurotrophins such as NGF will be able to protect neurons against degeneration caused by uncontrolled neuroinflammation (pg. 103145, col. 1, para. 1). Activated microglia causes the excessive production of inflammatory mediators such as NO, which play a key role in neurodegeneration (pg. 103145, col. 1, para. 2).
Taken together it would have been prima facie obvious to utilize the compound of Kim in order to use the compound of Kim to treat neural injury in the central nervous system as suggested by So. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success in order to protect neurons against degeneration as the compound increases NGF secretion which is a known mechanism for protecting against neuronal damage via inhibition of NO production.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Kim (Heterocycles, 2014, cited on PTO-892) and So (Bioorganic Chemistry, 2019, cited on PTO-892) as applied to claims 1, 3-4, 12-13, and 15-18 above in view of Liao (Biochemical and Biophysical Research Communications, 2005, cited on PTO-892).
Regarding claim 14: As discussed above, Kim and So render obvious the method of claim 18.
They do not state specifically wherein the nerve injury comprises cortical neurons.
However, Liao teaches the formation of nitric oxide (NO) by LPS in rat astrocytes has been suggested to correlate with the neurodegenerative process (abstract). In identifying the effect of neuroprotection, Liao found that garcinol prevented NO accumulation in LPS-treated astrocytes (abstract). Liao found that garcinol displays a neuroprotective effect in regulating NO accumulation in rat cortical astrocytes (i.e. cortical neurons, pg. 1312, col. 1, para.). Liao teaches astrocyte–neuron interaction has been implicated in a variety of signaling pathways essential to normal brain function (pg. 1312, col. 2, para. 2). Astrocytic gap junction channels connect with neighboring cells, including both neurons and glial cells, accompanying the exchange of glucose, inositol trisphosphate, glutamate, and lactate (pg. 1312, col. 2, para. 2). Under pathological conditions, such as hypoxia/reoxygenation, arachidonic acid byproducts decrease gap junctional communication in astrocytes and increase neuronal injury by an oxidative stress (pg. 1312, col. 2, para. 2). These reports suggest that an astrocyte–neuron interaction has a neurotrophic and neuroprotective role (pg. 1312, col. 2, para. 2). However, whereas co-culture of neurons with NO-generating astrocytes initially causes mitochondrial damage, extending the period of exposure results in neuronal death (pg. 1312, col. 2, para. 2). Garcinol displayed an inhibitory effect of NO-generation in LPS- or IL-1b-activated rat astrocytes (pg. 1312, col. 2, para. 2). We have demonstrated that garcinol enhanced neurite-outgrowth and prevented LPS-induced neuronal cell death in astrocyte/neuron co-cultures (pg. 1312, col. 2, para. 2). Thus, Liao establishes the neuroprotective effect on cortical astrocytes, which would reduce cortical neuron cell death.
Thus, wherein Kim and So teach administration of the compound for treating neural injury caused by NO overproduction, and the brain necessarily possesses cortical neurons which are impacted by NO overproduction as taught by Liao, the treatment of cortical neurons necessarily flows as a result of practicing the method, absent evidence to the contrary.
Conclusion
No claims are allowed in this action.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Fu (J. Carbohydrate Chemistry, 2015, cited on PTO-892) teaches the total synthesis of lauroside B (pg. 448, Scheme 1).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL L GALSTER whose telephone number is (571)270-0933. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Y Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAMUEL L GALSTER/Examiner, Art Unit 1693
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