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
Claims 1-18, 20, and 24-35 are cancelled. Claim 38 is newly added. Claims 19, 21, 23, and 36-38 are pending and under examination.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09/ has been entered.
Response to Arguments
Applicant's arguments filed 09/15/2025 have been fully considered but they are not persuasive. Applicant argues that the claims are not obvious because the cited references do not teach the concentrations claimed or the specific use claimed.
However, MPEP§ 2144.05 II states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382. ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.") Moreover, modified Beecham teaches the oral administration of the food product as claimed, which would inherently result in augmentation of bioavailable spermidine.
Applicant argues that Beecham teaches that the food product is split into 5 daily doses, therefore, at best, teaches a food product comprising 812 micrograms of spermidine.
Nonetheless, the entire food product of Beecham is still administered, regardless of whether or not it is split into doses, therefore, a spermidine concentration of approximately 4 mg is administered.
Applicant argues that there is no apparent reason to combine the cited references and points to sections of Clarkson that were not relied on for the rejection presented below.
As Examiner stated in the rejection, Clarkson teaches that spermine has neuroprotective effects, while Beecham teaches administration of a food product containing spermidine to prevent deterioration during aging of human cognitive function. Moreover, Beecham teaches that spermine is a polyamine (para. [0051]) and that polyamine decline with age is associated with various pathologies. Therefore, one of ordinary skill in the art would have been motivated to incorporate spermine into the food product of Beecham to further improve brain health in a user.
Declaration Under 37 C.F.R. 1.132
The declaration by inventor Natella under 37 CFR 1.132 filed 9/15/2025 is insufficient to overcome the rejection of claims 19, 21, 23, and 36-38 based upon obviousness over Beecham et al., (US 2020/0101029 A1, found in the IDS and previously cited) in view of Clarkson et al., 2004 (Neuroprotective effects of spermine following hypoxia-ischemia-induced brain damage, previously cited) and Kibe et al., 2014 (Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice, previously cited), as set forth in the last Office action, because: contrary to Applicant’s allegation of unexpected results, the prior art teaches or suggests that the claimed subject matter functions as it was intended to function.
Applicant again argues against the spermine concentration of Clarkson and points to sections of Beecham and Clarkson that were not relied on for the rejection presented below. Applicant argues that administration of the claimed composition yields unexpected results because it unexpectedly increased Beclin-1 levels, which is a marker for autophagy. However, these results are not unexpected as Beecham teaches that a key pathway by which nature enables partial autophagy in the brain is via spermidine (para. [007]), as stated in the rejection below.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
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.
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.
Claims 19, 21, 23, and 36-38 are rejected under 35 U.S.C. 103 as being unpatentable over Beecham et al., (US 2020/0101029 A1, found in the IDS and previously cited) in view of Clarkson et al., 2004 (Neuroprotective effects of spermine following hypoxia-ischemia-induced brain damage, previously cited) and Kibe et al., 2014 (Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice, previously cited), as evidenced by Brito et al., 2017 (Bioactive amines and phenolic compounds in cocoa beans are affected by fermentation, found in the IDS and previously cited) and Jadhav et al., 2023 (Triglycerides of medium-chain fatty acids, previously cited)
Regarding claim 19, Beecham teaches methods for improving brain health in a user during aging comprising administering a food product comprising cocoa and spermidine at a concentration of approximately 4 mg (Examples 1 and 2). Beecham teaches that the method is for preventing deterioration during aging of human cognitive function (para. [0002]). Beecham teaches that the formulation of their invention can be configured as beverages, ice creams, or smoothies (Paragraph 0139), i.e., edible and therefore orally administered.
Although cocoa is used as an nrf2 activator in the invention of Beecham, cocoa is also a spermidine-containing fruit, as evidenced by Brito (Abstract). Beecham also teaches that spermidine-rich foods comprise wheat germ, mushrooms, green peas, shellfish, chicken liver, potatoes, pears, and aged cheese (para. [0078]). Therefore, it would have been obvious to one of ordinary skill in the art that any of the spermidine-rich foods mentioned, which encompass spermidine-containing fruits, vegetables, legumes, and grains, may be used in the invention of Beecham. Beecham teaches that, in addition to cocoa and spermidine, the subject is also provided probiotics comprising Bifidobacterium, as it is a known spermidine-producing microbe (para. [0077]).
Beecham does not teach the concentration of the spermidine-producing bacteria, the administration of spermine, or administration of the spermidine precursor, arginine.
However, Clarkson teaches the administration of spermine as a neuroprotective agent (Abstract) at 10 mg/kg (Page 3, Paragraph 2). Although the concentration differs from that of the instant claim, section 2144.05 II of the MPEP states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.")” The selection of specific spermine concentrations would have been a routine matter of optimization on the part of the artisan of ordinary skill, said artisan recognizing that spermine concentrations would affect the neuroprotective effects in subjects.
The combination of Beecham and Clarkson does not teach the administration of arginine, or the concentration of the spermidine-producing bacteria.
However, Kibe teaches the administration of the spermidine precursor, arginine at concentrations ranging from 0-0.8 mg/g (Figure 2A) in combination with Bifidobacterium animalis (Abstract) at 108 CFU (Page 10, Column 1, Paragraph 3). Although the concentration of the probiotic differs from that of the instant claim, generally differences in concentration will not affect patentability as it is not inventive to discover the optimum or workable ranges by routine experimentation, as stated above.
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have included spermine and arginine, as taught by Clarkson and Kibe, respectively, in the food product/probiotic combination taught by Beecham. One of ordinary skill in the art would have been motivated to do so because Clarkson teaches that spermine is a neuroprotective agent (Abstract), while Kibe teaches that administration of arginine in combination with Bifidobacterium increased longevity in mice and protected mice from age-induced memory impairment by increasing polyamine concentrations (Abstract). Therefore, one of ordinary skill would be reasonably expected to understand that adding arginine and spermine to the invention of Beecham would further increase polyamine content in the subject, which would protect said subject from neurocognitive pathologies associated with declining polyamine levels (para. [0051], para. [0075], para. [0077]).
Regarding claim 21, Beecham teaches the use of Bifodobacterium but does not teach strain LKM12. However, Kibe teaches that administration of the probiotic Bifidobacterium animalis subsp. lactis LKM512 in combination with the spermidine precursor, arginine, results in increased longevity in mice (Introduction, Paragraph 1). Therefore, one of ordinary skill in the art would have been reasonably expected to understand that the B. animalis subsp. lactic LKM12 strain taught by Kibe may be used as the Bifidobacterium probiotic taught by Beecham.
Regarding claim 23, Beecham teaches the use of aged cheddar cheese as a spermidine source (Example 2). Cheese is made from milk fat, and milk fat contains medium chain triglycerides, as evidenced by Jadav (Page 2145, Sources of medium chain triglycerides). Therefore, Beecham’s spermidine-containing food, cheese, inherently contains at least one medium chain triglyceride.
Regarding claim 36, Beecham teaches that the formulation of their invention can be configured as beverages, ice creams, or smoothies (Paragraph 0139).
Regarding claim 37, Beecham teaches that a key pathway by which nature enables partial autophagy in the brain is via spermidine (para. [007]). Therefore, increasing autophagy would be an inherent result of the method of Beecham.
Regarding claim 38, Beecham teaches that the food product comprises approximately 4g of spermidine (Examples 1 and 2), Clarkson teaches a spermine concentration of 10 mg/kg (Page 3, Paragraph 2), and Kibe teaches an arginine concentration of 0-0.8 mg/g (Figure 2A). Although the concentration of the probiotic differs from that of the instant claim, generally differences in concentration will not affect patentability as it is not inventive to discover the optimum or workable ranges by routine experimentation, as stated above. The selection of spermidine, spermine, and arginine concentrations would have been a routine matter of optimization on the part of the artisan of ordinary skill, said artisan recognizing that concentration would affect neuroprotective effects.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 EST.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/RACHEL EMILY MARTIN/Examiner, Art Unit 1657