Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
This Office Action is in response to Applicant’s Arguments and Amendment filed, 01/14/2026, wherein the Amendment amended claims 1-2, 10, 19, cancelled claims 7-8, 15, and added claims 29-31.
Claims 1-2, 10-11, 13, 16-31 are pending.
Priority
This application claims the following priority:
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Election/Restrictions
Applicant elected Group I, the composition, and further elected the species 3,7-dimethyl-1-n-propyl-xanthine as the caffeine analogue and the species eicosanoyl-5-hydroxytryptamide as the fatty acyl tryptamide, in the reply filed on 04/27/2024.
It is noted that the 01/14/2026 Amendment to the claims deleted “caffeine analogue.” As such, the election of species requirement for caffeine analogue is moot.
Claims 13, and 16-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-2, 10-11, and 29-31 are examined on the merits herein.
REJECTIONS WITHDRAWN
The status for each rejection and/or objection in the previous Office Action is set out below.
Claim Objections
Applicant’s deletion of claims 7-8 are sufficient to overcome these objections.
35 USC 103 rejection that apply Babish as a secondary reference
Applicant’s deletion of “caffeine analog” is sufficient to overcome these rejections since these rejection were applied to address the election of 3,7-dimethyl 1-prpyl xanthine as the caffeine analog, as required by the 01/08/2024 Election of Species requirement.
REJECTIONS MAINTAINED
Applicant’s amendment to independent claim 1 that adds the limitation, “wherein eicosanoyl-5-hydroxytryptamide is the only tryptamide present in the neuroprotective composition,” and the addition of claims 29-31, have resulted in the below new and modified rejections.
The same references continue to be relied upon in the prior art rejections.
Claim Rejections - 35 USC § 112(a)-New Matter
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
(New) Claims 1-2, 10-11 and 29-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a new matter rejection.
In claim 1, last two lines, the phrase “wherein eicosanoyl-5-hydroxytryptamide is the only tryptamide present in the neuroprotective composition,” is new matter.
While Applicant states on pg. 6, Remarks, that support for the claims can be found in previously presented claims 1, and 7-8, a careful review of these claims does not provide support for this limitation. Previous claim 1 recites eicosanoyl-5-hydroxytryptamide, but it does not teach this compound as the only tryptamide present in the composition. And previous claims 7-8 are directed toward pharmaceutically acceptable carriers and excipients.
A careful review of the original disclosure additionally does not provide support for this limitation. While the instant specification teaches eicosanoyl-5-hydroxytryptamide as a tryptamide and teaches administering to mice water containing caffeine and chow containing eicosanoyl-5-hydroxytryptamide, it does not teach eicosanoyl-5-hydroxytryptamide as the only tryptamide present in a composition comprising caffeine and eicosanoly-5-hydroxytryptamide.
As such, the phrase “wherein eicosanoyl-5-hydroxytryptamide is the only tryptamide present in the neuroprotective composition,” is new matter.
All other claims not specifically recited are rejected for depending from an indefinite claim and failing to cure the deficiency.
Claim Interpretation
In claim 1, the transitional phrase “comprising” is recited in line 1. As such, though line 2 recites “a synergistic neuroprotective combination consisting of. . .caffeine and. . .eicosanoyl-5-hydroxytrypamide,” the composition is interpreted as inclusive or open-ended and as not excluding additional, unrecited elements. See MPEP 2111.03.
In claim 29 the transitional phrase “consisting essentially of” is interpreted as referring back to the transitional phrase “comprising” in line 1 of claim 1.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
(Modified) Claims 1-2, 29 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over US PG-PUB 2017/0231955 to Stock (published 2017, IDS of 05/03/2021).
Stock teaches a composition comprising eicosanoyl-5-hydroxytryptamide (EHT) and caffeine (pg. 9, claims 1, 13, 18).
Stock additionally teaches a method of treating traumatic brain injury by administering an effective amount of eicosanoyl 5-hydroxytryptamide (claims 57-58).
Stock teaches the caffeine as comprising less than 10 mg or less than 2mg per serving/unit dosage of its compositions (pgs. 9-10, Claims 19-20, 33; [0037]).
Stock teaches its compositions in unit dosage forms comprising from about 1 mg to about 100 mg of an EHT extract or about 10 to about 60 mg of an EHT extract (pg. 10, claims 50, 51). Stock further teaches that an effective amount of EHT extract is an amount of EHT that provides 0.1 mg-100 mg/day ([0062]).
Regarding the EHT extract, Stock teaches that for purposes of brevity, an EHT extract refers to any component that includes eicosanoyl-5-hydroxytryptamide, such as an extract derived from coffee bean or coffee that contains eicosanoyl-5-hydroxytryptamide, or eicosanoyl-5-hydroxytryptamide itself, whether isolated from an organic starting material or prepared synthetically ([0033]).
Thus, “EHT extract” of Stock meets the limitation “wherein eicosanoyl-5-hydroxytrampamide is the only tryptamide present in the neuroprotective composition,” since Stock teaches “EHT extract” as referring to extracts comprising eicosanoyl-5-hydroxytryptamide or as referring solely to eicosanoyl-5-typtamide.
Stock teaches that the amount of eicosanoyl 5-hydroxytryptamide in coffee ranges from 0.6mg-0.8mg ([0005]).
Thus, Stock teaches compositions comprising a weight ratio of EHT to caffeine as ~1:100 to ~50:1, i.e. 0.1mg EHT:2 mg caffeine to 100 mg EHT:2 mg caffeine
Stock teaches its composition as comprising one or more vitamin or health supplement (pg. 9, claims 27-31, 34-49).
Regarding claims 1-2, while Stock teaches a composition comprising 0.1-100 mg EHT and up to 2 mg to 10 mg caffeine, it differs from that of instant claim 1 in that it does not specifically teaches a ratio of EHT to caffeine of from 1:4.2 to 1:1.
Stock further teaches that the term “effective amount” is interchangeable with “therapeutically effective amount” and means an amount or dose of a compound or composition effective in treating the particular disease, condition, or disorder disclosed herein, and thus “treating” includes producing a desired preventative, inhibitory, relieving, or ameliorative effect. In methods of treatment according to the invention, “an effective amount” of at least one compound is administered to a subject. As understood by the person of ordinary skill in this art, “effective amount” will vary, depending on the compound or composition, the disease (and its severity), the treatment desired, age and weight of the subject, etc. ([0036]).
It would have been prima facie obvious to one ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the ratio of EHT to caffeine, in the composition of Stock, to arrive at the instantly claimed ratios. One of ordinary skill in the art would have been motivated to make such modifications, with a reasonable expectation of success, because:
-Stock teaches that a person of ordinary skill in this art knows that an “effective amount” will vary depending on the compound or composition, the disease (and its severity), the treatment desired, and the age and weight of the subject, etc.,
-in the case where the claimed ranges “overlap or lie inside ranges disclosed in the prior art” a prima facie case of obviousness exists (MPEP 2144.05), and
-"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation" (MPEP 2144.05(II)).
As such, an ordinary skilled artisan would have been motivated to make such modifications to predictably arrive at an optimized ratio of EHT to caffeine to effectively treat diseases, such as traumatic brain injury or chronic traumatic encephalopathy ([0010], [0034]-[0035]; [0060]; pg. 10, claims 55-58).
The optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05.
Regarding claims 29 and 31, Stock teaches administering the EHT extract together with pharmaceutically acceptable excipients, such as magnesium stearate ([0041]; pgs. 9-10, claims 30, 42-43).
Regarding the transition phrase “consisting essentially of,” in claim 29, this phrase is interpreted no differently than "comprising,” since the instant specification provides no discussion or teaching of what limitations "materially affect the basic and novel characteristic(s)" of the claimed composition, see MPEP 2111.03.
(Slightly Modified) Claims 10-11 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over US PG-PUB 2017/0231955 to Stock (published 2017, IDS of 05/03/2021) as applied to claims 1-2, 29 and 31 above, and further in view of US PG-PUB 2009/0028948 to Payne (published 2009, IDS of 05/03/2021).
Stock is applied as discussed above and incorporated herein.
Regarding claims 10 and 30, while Stock teaches a composition comprising EHT as the only tryptamide present, and caffeine in the instantly claimed mg amounts and ratios, it differs from that of instant claims 10 and 30 in that it does not teach nanoparticles.
Payne teaches therapeutically active nanocomposite microstructure compositions including nanoparticle compositions and nanoparticle preparations that comprise therapeutically active agents dispersed in a carrier matrix (abstract). Payne teaches these composition for therapeutic administration ([0136]-[0146]).
Payne teaches that its invention is directed to the surprising and unexpected discovery that improved nanocomposite microstructure compositions can be produced by mechanochemically synthesizing therapeutically active nanoparticles in a carrier matrix using a solid state chemical reaction, which controls the size of the resultant nano particles in the composition leading to improved bioavailability ([012]-[013]).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select the nanoparticles of Payne as the pharmaceutically acceptable carrier in the compositions of Stock, to arrive at instant claims 11 and 30. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Stock and Payne are both directed toward pharmaceutical formulations for therapeutic use, and
-Payne teaches its nanoparticle compositions as having surprising and unexpected properties, such as improved bioavailability.
As such, an ordinary skilled artisan would have been motivated make such a selection to predictably arrive at a composition with improved bioavailability for the treatment of traumatic brain injury or encephalopathy, or other diseases.
Regarding claim 11, Payne teaches the nanoparticles as ranging in size from 40-200 nm ( [0022], [0026], [0069], pgs. 16-17-claims 2, 29, and 67). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP 2144.05).
(Slightly Modified) Claims 1, 29 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Arendash et al. (Jn. of Alzh.’s Disease, published 2010, PTO-892 of 06/10/2024) and Asam et al. (PLOS One, published 2017, PTO-892 of 06/10/2024), and further in view of US PG-PUB 2009/0264496 to Vafai (published 2009, PTO-892 of 06/10/2024).
Arendash teaches caffeine and coffee as therapeutics against Alzheimer’s Disease (AD) (title).
Caffeine protects AD mice against memory loss, reverses memory loss, and reverses AD pathology in aged AD mice (pg. S125, Col. 2, last paragraph).
Arendash teaches administering the caffeine in drinking water in an amount of 1.5mg/ day, which is the human equivalent of 500 mg/day (pg. S118, “Results”).
Regarding instant claim 1, while Arendash teaches caffeine for the treatment of Alzheimer’s Disease, it differs from that of the instantly claimed composition in that it does not teach EHT.
Asam teaches that eicosanoyl-5-hydroxxytryptamide (EHT) prevents Alzheimer’s disease-related cognitive and electrophysiological impairments in mice exposed to elevated concentrations of oligomeric beta-amyloid (title, pgs. 11-12, “Discussion”).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to add the EHT, taught by Asam, to the composition comprising caffeine and water of Arendash, to arrive at the instantly claimed composition. One of ordinary skill in the art would have been motivated to make such an combination, with a reasonable expectation of success, because caffeine and EHT are both taught for the treatment/prevention of Alzheimer’s and "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, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). MPEP 2144.06.
While the combination of Arendash and Asam teaches a composition consisting of EHT caffeine, and water, it differs from that of the instantly claimed composition in that it does not teach the instantly claimed mg amounts or preferred ratios recited in instant claim 1.
Vafai teaches method of treating Alzheimer’s disease with compounds, wherein, EHT is taught as a preferred compound (pg. 25, Compound I-1; see also paragraph 43 of the instant specification that teaches the structure of EHT; paragraph 352; pg. 80, claims 106 and 111).
At least about 0.1-100 mg dosage amounts of the compound are taught (paragraph 386, 488, 406, 415, 416, 418).
Regarding the ratios and mg amounts in instant claims 1, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the mg amounts and hence ratios, of EHT and caffeine in the combined composition of Arendash and Aram, to arrive at the instantly claimed mg amounts and ratios. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Arendash and Aram are directed toward formulations that treat Alzheimer’s Disease (AD)
- Arendash teaches the administration of 500mg caffeine per day to treat AD,
-Aram is directed toward treating AD with EHT and Vafai teaches the administration of 0.1, 8, 12, 20, 50 and 100 mg doses of EHT for the treatment of AD, and
- "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." MPEP 2144.05(II).
As such, one of ordinary skill in the art would have been motivated to optimize the mg amounts and hence ratios of the EHT and caffeine in the combined composition of Arendash and Aram, to predictably arrive at a therapeutically effective composition for the treatment of AD.
The optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05.
Regarding claims 29 and 31, Arendash teaches water.
Regarding the transition phrase “consisting essentially of,” in claim 29, this phrase is interpreted no differently than "comprising,” since the instant specification provides no discussion or teaching of what limitations "materially affect the basic and novel characteristic(s)" of the claimed method, see MPEP 2111.03.
(Slightly Modified) Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Arendash et al. (Jn. of Alzh.’s Disease, published 2010, PTO-892 of 06/10/2024), Asam et al. (PLOS One, published 2017, PTO-892 of 06/10/2024), and US 2009/0264496 to Vafai (published 2009, PTO-892 of 06/10/2024), as applied to claims 1, 29 and 31 above, and further in view of US 2017/0231955 to Stock (published 2017, IDS of 05/03/2021).
The teachings of Arendash, Aram, and Vafai are applied as discussed above, and incorporated herein.
While the combined composition of Arendash, Aram and Vafai teaches a composition comprising a combination consisting of caffeine, EHT, and further comprising water, it differs from that of instant claim 2 in that it does not teach 5-20 mg caffeine.
Stock is applied as discussed above and incorporated herein.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select the mg amounts of caffeine/caffeine analogue, taught by Stock, for the caffeine in the combined composition of Arendash, Aram and Vafai, to arrive at the instantly claimed mg amounts and ratios. One of ordinary skill in the art would have been motivated to make such selections, with a reasonable expectation of success, because:
-Stock and the combination of Arendash, Aram and Vafai are both directed toward compositions of EHT and caffeine that are administered to provide neuroprotection ([0034] of Stock).
-Stock teaches its compositions as comprising mg amounts of EHT and caffeine within the instantly claimed ranges,
-Stock teaches that amounts and ratios can be modified,
-Stock teaches that an effective amount of EHT extract can be determined by one of ordinary skill in the art, and
-"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." MPEP 2144.05(II).
As such, one of ordinary skill in the art would have been motivated to make such a selection, to optimize the mg amount of caffeine, and to predictably arrive at a composition that is therapeutically effective for neuroprotection in PD.
(Slightly Modified) Claims 10-11 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Arendash et al. (Jn. of Alzh.’s Disease, published 2010, PTO-892 of 06/10/2024), Asam et al. (PLOS One, published 2017, PTO-892 of 06/10/2024), and US PG-PUB 2009/0264496 to Vafai (published 2009, PTO-892 of 06/10/2024), as applied to claims 1, 29 and 31 above, and further in view of US PG-PUB 2017/0231955 to US PG-PUB 2009/0028948 to Payne (published 2009, IDS of 05/03/2021).
The teachings of Arendash, Aram, and Vafai are applied as discussed above, and incorporated herein.
While the combined composition of Arendash, Aram and Vafai teaches a composition comprising caffeine, EHT, and water, in the instantly claimed mg amounts and ratios, it differs from that of the instantly claimed invention in that it does not teach nanostructures as recited in instant claim 30 or nanoparticles as recited in instant claims 10-11.
Payne is applied as discussed above and incorporated herein.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select the nanoparticles of Payne as a carrier for the combined composition of Arendash, Aram and Vafai, to arrive at instant claims 10 and 30. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
- Payne and the combination of Arendash, Aram, Vafai are both directed toward pharmaceutical formulations for therapeutic use, and
-Payne teaches its nanoparticle compositions as having surprising and unexpected properties, such as improved bioavailability.
As such, an ordinary skilled artisan would have been motivated make such a selection to predictably arrive at a composition with improved bioavailability for the treatment of Alzheimer’s disease.
Regarding claim 11, Payne teaches the nanoparticles as ranging in size from 40-200nm (, [0022], [0026]). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP 2144.05).
Response to Arguments
On pg. 7, Remarks, Applicant argues that Stock fails to disclose or suggest a composition wherein the ratio of EHT to caffeine is from about 1:4.2 to about 1:1, let alone wherein EHT is the only tryptamide present in the neuroprotective composition.
This argument has been fully considered, but is not found persuasive.
Regarding the ratios, as discussed above:
It would have been prima facie obvious to one ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the ratio of EHT to caffeine, in the composition of Stock, to arrive at 1:4.2 to 1:1. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Stock teaches that a person of ordinary skill in this art knows that an “effective amount” will vary, depending on the compound or composition, the disease (and its severity), the treatment desired, age and weight of the subject, etc.,
-in the case where the claimed ranges “overlap or lie inside ranges disclosed in the prior art” a prima facie case of obviousness exists (MPEP 2144.05), and
-"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation" (MPEP 2144.05(II)).
As such, an ordinary skilled artisan would have been motivated to make such modifications to predictably arrive at an optimized method of treating disease, such as traumatic brain injury or chronic traumatic encephalopathy ([0010], [0034]-[0035]; [0060]; pg. 10, claims 55-58).
The optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05.
Regarding the EHT, Stock teaches that for purposes of brevity, an EHT extract refers to any component that includes eicosanoyl-5-hydroxytryptamide, such as an extract derived from coffee bean or coffee that contains eicosanoyl-5-hydroxytryptamide or eicosanoyl-5-hydroxytryptamide itself, whether isolated from an organic starting material or prepared synthetically ([0033]). Thus, “EHT extract” of Stock meets the limitation “wherein eicosanoyl-5-hydroxytrampamide is the only tryptamide present in the neuroprotective composition,” since Stock teaches “EHT extract” as referring to extracts comprising eicosanoyl-5-hydroxytryptamide or eicosanoyl-5-typtamide itself.
As such, the teachings of Stock meet these limitations.
On pgs. 7-8, Remarks, Applicant argues that instant claim 1 exhibits unexpected results and that the Final Office Action of 03/06/2025 “asserts that the data in Example 2 are not commensurate in scope with the instant claims, Applicant respectfully submits that this assertion is based on an overly narrow reading of both the claims and the experimental disclosure.”
On pg. 8, Remarks, Applicant further argues that in the 03/06/2025 Office Action, the examiner points out that “ ‘Example 2 is directed toward administration of 12mg/kg/day in chow and 50mg/kg/day of caffeine in drinking water. Thus it is not known how many mg in total the mice were administered.’ ” In response, Applicant argues that “the total milligram amount administered over time is not a fixed value, as body weight and intake vary among animals over the course of the study. A person of ordinary skill in the art would readily understand how to reproduce the disclosed dosing regimen and how it relates to the claimed compositions.”
These arguments have been fully considered, but are not found persuasive. Example 2 is limited to administration of 12mg/kg/day in chow containing eicosanoyl-5-hydroxytryptamide and 50mg/kg/day of caffeine in drinking water. The dosage amounts are taught as mg/kg, but the kg weights of the mice are not taught or provided. Thus, it is not known how many mg in total the mice were administered, as required by the instant claims, and it is further not known if the mice were administered a ratio of eicosanoly-5-hydroxytryptamide to caffeine of about 1:4.2 to about 1:1.
As evidenced by Harvard Apparatus (Animal Information Chart Mice-NHPs, PTO-892), a female mouse weights about 18-35grams, which is 0.018-0.035kg, and a male mouse weight 20-40 grams, which is 0.02kg-0.04kg. Thus, a mouse weighing 0.025kg would be administered 0.3mg eicosanoyl-5-hydroxytryptamide and 1.25mg caffeine, which is outside of the scope of the instantly claimed mg amounts, and which is a ratio of about 1:4.2 of eicosanoly-5-hydroxytryptamide to caffeine. A mouse weighting 0.018kg would be administered 0.2mg eicosanoyl-5-hydroxytryptamide and 0.9mg caffeine, which is a ratio of less than 1:4.2 of eicosanoly-5-hydroxytryptamide to caffeine.
As such, these arguments are not persuasive.
As discussed on pg. 8, instant Remarks, in the 03/06/2025 Office Action the examiner points out that instant Example 2 administers the caffeine and EHT separately, while the instant claims recite a composition comprising both the caffeine and EHT, which would be administered together. On pg. 9 of the instant Remarks, Applicant argues that Example 2 co-administers the caffeine and EHT concurrently, rather than separately, “EHT and caffeine were co-administered over the same treatment window via different vehicles.”
This argument has been fully considered, but is not found persuasive. The instant claims are directed toward a single composition comprising both caffeine and EHT in specific mg amounts and ratios. However, the instant Examples do not exemplify a single composition comprising both caffeine and EHT administered in a specific ratio. Moreover, as discussed above, the mg amounts, are outside the scope of the instantly claimed mg amounts, and the example teaches mice placed on a diet of water containing 50mg/kg/day of caffeine and chow delivering 12mg/kg/day EHT. However, the example does not teach the water and chow as administered together, but as a diet that is available to the mice throughout the day. As such, it is not known if the caffeine and EHT are administered together at the instantly claimed ratios since the caffeine and EHT are available for consumption throughout the day. For example, if a mouse ate all of its chow at hour one of the day and did not drink until hour five of the day, and only drank one fourth of the caffeinated water, it does not appear that such administration would reflect a composition comprising the instantly claimed ratios of EHT to caffeine.
As such, the instant example is not commensurate in scope with the instantly claimed composition, which recites a composition comprising both EHT and caffeine in claimed mg amounts and a claimed ratio.
Applicant points to Figures 2A-2G as showing unexpected results. However, as discussed on pg. 20 of the Office Action of 03/06/2025, these Figures are not persuasive to show unexpected results.
Figs. 2A and 2C are related to synuclein levels in the cortex. While the combination of caffeine and EHT do appear to have a synergistic effect on p-synuclein in the cortex, as exhibited by Figures 2A and 2C, Figure 2B, which measures levels of p-synuclein in the hippocampus, shows that the combination of caffeine and EHT exhibit only an additive effect and not a synergistic effect.
While the combination of CAF (abbreviation for caffeine in the instant Figures) and EHT show a synergistic effect on the c-fos in the hippocampus in Fig. 2E, wherein c-fos is a marker used measure neuronal activity, Fig. 2D, which is directed toward the integrity of neuronal structure and activity of the cytoskeletal microtubule associated protein 2 (MAP2) in the cortex, shows only an additive effect of CAF and EHT. Figures 2F and 2G, which show the levels of iba-1 OD and GFAP OD, which are markers of PD, also show an additive effect of CAF and EHT.
As discussed above, this data is based on the mg amounts of caffeine and EHT that are outside the scope of the instantly claimed mg amounts and ratios, as discussed above. Moreover, the instant data only provides results for a single ratio of EHT to caffeine, as discussed above. Applicant is respectfully reminded that to 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), see MPEP 716.02(d). Instant Figures 2A-2G only provide a single mg amount for caffeine, EHT, and a single ratio of EHT to caffeine. Instant Figures 2A-2G do not demonstrate how the composition is affected when amounts/ranges exceed or fall short of the instantly claimed mg and ratio amounts. As such, Figures 2A-2G are not sufficient to show unexpected results.
On pg. 14, Remarks, Applicants states that “the previously filed response dated September 8, 2025, Exhibit A demonstrated in vitro synergy of the neuroprotective composition at a ratio of 1:1.
See pgs. 21-22 of the 10/30/2025 Office Action:
In “10” and “11” Declaration, Exhibit A is referenced. Human neuroblastoma SH-SY5Y cells are pre-treated with caffeine (1uM) and/or EHT (1uM) and challenged with alpha-synuclein preformed fibrils (PFF). Cell toxicity and viability are measured. Exhibit A demonstrates that PFF was not prevented by EHT alone and was only mitigated by 6.5% by caffeine alone. However, the combination of EHT and caffeine protected against PFF toxicity with a high degree of statistical significance, and Exhibit A shows that neither caffeine nor EHT alone protected against the toxicity of PFF, but that the combination of caffeine and EHT robustly and completely protected against PFF with cell viability equal to that of control PBS treated cells.
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While the examiner agrees that Exhibit A shows a synergistic effect in decreasing cell toxicity and increasing cell viability, these results are not commensurate in scope with the instantly claimed invention, which recites caffeine and recites a ratio of EHT to caffeine of 1:4.2 to 1:1. Exhibit A only shows results for a 1:1 ratio of EHT to caffeine.
On pg. 16, Remarks, Applicant argues that “Arendash repeatedly emphasizes that caffeine alone accounts for the therapeutic effects observed, thereby providing no motivation and no reasonable expectation of success for modifying caffeine monotherapy to arrive at the specific synergistic combination of claim 11. On pg. 17, Remarks, Applicant argues that Asam focuses exclusively on EHT monotherapy and its PP2A mediated mechanism and provides no basis from which a person of ordinary skill in the art would be motivated to combine EHT and caffeine, nor any reasonable expectation that co-administration would produce a synergistic neuroprotective effect.
These arguments have been fully considered, but are not found persuasive. Neither Arendash nor Asam are relied on to anticipate the instant claims. It is the combination of these references which teaches the limitations of the instant claims.
As discussed in the above rejection:
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to add the EHT, taught by Asam, to the composition comprising caffeine and water of Arendash, to arrive at the instantly claimed composition. One of ordinary skill in the art would have been motivated to make such an combination, with a reasonable expectation of success, because caffeine and EHT are both taught for the treatment/prevention of Alzheimer’s and "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, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). MPEP 2144.06.
On pg. 17, Remarks, Applicant argues that Vafai does not rectify the deficiencies of Asam or Arendash and that Vafai repeatedly emphasizes that caffeine is a less desirable compound in compositions containing compounds of Formula I, including EHT. Applicant argues that Vafai teaches compositions substantially free of caffeine or containing 10% or less than about 0.01% caffeine and that Vafai teaches that adding a compound of formula I to a decaffeinated coffee, tea or other decaffeinated products is especially appealing.
These arguments have been fully considered, but are not found persuasive. Vafai is a secondary reference that is relied upon to teach mg amounts of EHT that are useful in the treatment of Alzheimer’s diseases. While Vafai teaches embodiments substantially free of caffeine, it also teaches embodiments comprising caffeine.
Regarding [0577] pointed to by Applicant, this is a single example of a “Hexane-ethyl Acetate Extraction of Compounds from Coffee Wax,” wherein caffeine is removed. Regarding [0374], pointed to by Applicant, this paragraph teaches that compounds, such as caffeine can be separated out of botanical sources. Regarding [0442], pointed to by Applicant, this paragraph teaches an embodiment wherein decaffeinated products are preferred.
Regarding these arguments and reference to these specific paragraphs, Applicant is respectfully reminded that patents are relevant as prior art for all they contain and “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994),” see MPEP 2123.
It is further respectfully pointed out that [0382] of Vafai teaches embodiments of its compositions comprising up to 10% caffeine. Moreover, Vafai is relied upon, solely, for its teachings of mg amounts of EHT that are useful for treating Alzheimer’s disease. Vafai is not relied upon as motivation to combine EHT and caffeine.
On pg. 18, Remarks, Applicant argues that routine optimization presupposes that a person of ordinary skill in the art would have had a reasonable expectation of success in formulating the claimed range and argues that because Vafai teaches minimizing or eliminating caffeine, there is no reasonable expectation of success.
This argument has been fully considered, but is not found persuasive. As stated above, Vafai is relied upon solely for its teaching of known effective amounts of EHT in the prior art, that are useful to treat Alzheimer’s disease.
As discussed in the above rejection:
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the mg amounts and hence ratios, of EHT and caffeine in the combined composition of Arendash and Aram, to arrive at the instantly claimed mg amounts and ratios. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Arendash and Aram are directed toward formulations that treat Alzheimer’s Disease (AD)
- Arendash teaches the administration of 500mg caffeine per day to treat AD
-Aram is directed toward treating AD with EHT and Vafai teaches the administration of 0.1, 8, 12, 20, 50 and 100 mg doses of EHT for the treatment of AD, and
- "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." MPEP 2144.05(II).
As such, one of ordinary skill in the art would have been motivated to optimize the mg amounts and hence ratios of the combined composition of Arendash and Aram, to predictably arrive at a therapeutically effective composition for the treatment of AD.
The optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05.
On pg. 18, Remarks, Applicant argues that although Arendash and Asam each relate to neurodegenerative disease, each presents its respective active agent as independently sufficient to achieve therapeutic benefit.
This argument has been fully considered, but is not found persuasive for the reasons stated above. Moreover, it is respectfully pointed out that Arendash and Asam are not directed toward neurodegenerative diseases, in general, but are both directed to the treatment of a single neurodegenerative disease, Alzheimer’s disease.
On pgs. 18-19, Remarks, Applicant argues that the Federal Circuit has explained that statements that express preferences in prior art references are relevant in determining whether a skilled artisan would have been motivated to combine or modify prior art references and that Vafai does not leave an open problem to be solved by combination but instead teaches a contrary solution that negates the rationale asserted by the Office Action.
This argument has been fully considered, but is not found persuasive. With respect to the Polaris case, it is noted that this case is not in the MPEP. It is not clear that the facts of the Polaris case align with those of the instant application. Applicant has only provided his own summary of the case, but has not addressed the fact patterns within the case or the opinion of the Court.
On pg. 19, Remarks, Applicant argues that the reliance on routine optimization is misplaced given the unexpected results.
This argument has been fully considered, but is not found persuasive. For the reasons discussed above, the data provided by Applicant in the Specification and the Declaration of 09/08/2025, is not sufficient to demonstrate unexpected results.
On pg. 19, Remarks, Applicant argues that the Office Action does not allege or evidence that a range of caffeine and EHT amounts encompassing the claimed compositions are disclosed in any of the references, but that the Office Action merely alleges that it is routine optimization to optimize the mg amounts and hence ratios of the combined composition of Arendash and Aram.
This argument has been fully considered, but is not found persuasive. As discussed in the above rejection and paragraphs, the prior art references themselves provide motivation to arrive at the instantly claimed mg amounts and ratios.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the mg amounts and hence ratios, of EHT and caffeine in the combined composition of Arendash and Aram, to arrive at the instantly claimed mg amounts and ratios. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Arendash and Aram are directed toward formulations that treat Alzheimer’s Disease (AD)
- Arendash teaches the administration of 500mg caffeine per day to treat AD
-Aram is directed toward treating AD with EHT and Vafai teaches the administration of 0.1, 8, 12, 20, 50 and 100 mg doses of EHT for the treatment of AD, and
- "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." MPEP 2144.05(II).
As such, one of ordinary skill in the art would have been motivated to optimize the mg amounts and hence ratios of the combined composition of Arendash and Aram, to predictably arrive at a therapeutically effective composition for the treatment of AD.
The optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05.
Regarding the reference to Pfizer v. Apotex on pg. 19, Remarks, it is respectfully pointed out that MPEP 2143.03 teaches that obviousness does not require absolute predictability, but a reasonable expectation of success. As demonstrated in the above italicized paragraphs, there is a reasonable expectation of success.
On pg. 19, Remarks, Applicant argues that the Board reversed obviousness rejections that were based on a similar rationale to vary parameters until reaching the claimed invention.
This argument has been fully considered, but has not been found persuasive. As discussed similarly above, this case is not in the MPEP. As such, it is not clear that the facts of this case (In re Marom, Appeal 2024-001947) align with those of the instant application. The Applicant has only provided a single sentence from the case, but has not addressed the fact patterns within the case. And it is further not clear if the cited portion is the opinion of the Board.
The remaining arguments on pgs. 20-22 have been fully addressed above.
For these reasons, Applicant’s arguments are not persuasive to overcome the instant rejections.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/LAUREN WELLS/Examiner, Art Unit 1622