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
Status of claims
The amendment filed on November 13, 2025 is acknowledged. Claims 1-8 and 10-11 have been canceled. Claims 9 and 12-17 are under examination in the instant office action.
Applicants' arguments, filed on November 13, 2025, have been fully considered but they are not deemed to be persuasive or moot in view of a new ground of rejection necessitated by the newly added limitations. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Responses are limited to Applicants' arguments relevant to either reiterated or newly applied rejections.
The rejection of Claims 9-10, 12, and 17 under 35 U.S.C. 102(a)(1) as being anticipated by Baek et al. (Nutrients, 12, 910, Published: 26 March 2020) is hereby withdrawn in view of Hyun Joon Kim’s declaration under 37 CFR 1.130 filed on 11/13/2025.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 9 and 12-17 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by US 2010/0016207 (hereafter, Wurtman) as evidenced by Dong et al. (Journal of Alzheimer’s Disease, 18: 459–469, 2009).
Wurtman teaches a method for treating a cognitive or memory disturbance (mild cognitive impairment) or an Alzheimer's disease in a subject in need thereof, comprising administering to said subject a composition comprising a glutamine, a salt thereof, or a glutamine-rich peptide, thereby treating a cognitive or memory disturbance or an Alzheimer's disease in a subject in need thereof (abstract, [0048] and claim 19). Wurtman further teaches that Alzheimer's disease is at a mild stage or a moderate stage, which is characterized by decline in cognitive function or memory (mild cognitive impairment). The subject with Alzheimer's disease is a subject having brain damage (neuronal loss) and mild cognitive impairment caused by accumulation of amyloid-beta 42 (Aβ42) as evidenced by Dong et al. (p459, col 1, para 1 and p461, col 1, para 2).
Wurtman further teaches a use of glutamine in the manufacture of a medicament, pharmaceutical composition, or nutritional supplement ([0057]). Wurtman discloses that the pharmaceutical compositions contain an active component and excipients that are pharmaceutically acceptable and compatible with the active ingredient ([0102]).
In addition, Wurtman discloses that the composition is formulated in a form suitable for oral administration, i.e. as a solid or a liquid preparation wherein suitable solid oral formulations include tablets, capsules, pills, granules, and pellets and suitable liquid oral formulations include solutions, suspensions, dispersions, emulsions, and oils ([0088]). The nutritional supplement composition reads on a quasi-drug recited in claim 16 since it is defined as non-prescription products that have therapeutic or preventive effects on the human body, but are not as potent as prescription drugs.
As to the new limitations (i.e., reduction of ROS/RNS level in brain tissue and restoring cognitive function), those are intended results of the active method step and as such are non-limiting since the language does not result in manipulative difference in steps of claims. The prior art teaches the administration of the same compound (i.e., glutamine) to the same patient (AD patient), thus the method of the prior art inherently performs the functions as recited in claims when the composition comprising glutamine is administered to the same subject as taught by the prior art. It should be noted that products of identical chemical composition cannot have mutually exclusive properties and a chemical composition and its properties are inseparable. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir.1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). “[N]ewly discovered results of known processes directed to the same purpose are not patentable." Bristol-Myers Squibb, 246 F.3d at 1376. Also, see In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980) (a case indicating that the burden of proof can be shifted to the applicant to show that the subject matter of the prior art does not possess the characteristic relied on whether the rejection is based on inherency under 35 U.S.C.102 or obviousness under 35 U.S.C. 103).
As such, the instant claims are anticipated by Wurtman.
Response to Applicant’s arguments
Applicants argued that Wurtman lacks any causes recited in the amended claims. Applicant further argued that Wurtman merely refers to general age-related cognitive decline and neurodegeneration without identifying the specific molecular or physiological etiologies that define the present invention and there is no disclosure or evidence that glutamine acts upon reduces or ameliorates Aβ42 accumulation or Aβ42-induced neuronal damage. In addition, Applicant argued that Wurtman fails to disclose or suggest the functional limitations now recited-that glutamine administration reduces ROS/RNS and restores cognitive functions.
In response, the target patient population of clamed method is a subject in need of ameliorating brain damage and mild cognitive impairment caused by Aβ42 accumulation. As evidenced by Dong et al., those with Alzheimer's disease have brain damage (neuronal loss) and mild cognitive impairment caused by accumulation of Aβ42. Thus, the patient with Alzheimer's disease is a species of the target patient population of the claimed method. Wurtman explicitly discloses a method for treating Alzheimer's disease (AD) in a subject in need thereof, comprising administering to the subject a composition comprising glutamine, thereby treating an Alzheimer's disease in a subject in need thereof (see claim 19). Accordingly, the method of the prior art anticipates the claimed method.
As to the functional limitations (i.e., reduction of ROS/RNS level in brain tissue and restoring cognitive function), the administration of the same agent (i.e., glutamine) to the same patient (AD patient) as taught by prior art necessarily have the claimed functional effects, whether expressly recognized by prior art or not.
Though mechanisms of action of chemical entities are not doubt important contributions to scientific and pharmaceutical development, the assessment of patentability under 35 U.S.C. 102 is based upon the therapeutic applications (i.e., target patient population) of the compounds, not the mechanism by which they exert such a therapeutic use. Furthermore, it is generally well settled in the courts that a mechanistic property of a chemical compound, or combination of chemical compounds, when administered under identical conditions, is necessarily present, despite the fact that such a property may not have been readily apparent to, or recognized by, one of ordinary skill in the art. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” See Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Also see In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).
It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter, which there is reason to believe inherently includes functions that are newly cited, or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter to be shown in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) (“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention”). However, Applicants did not provide any evidence that subject matter to be shown in the prior art does not possess the characteristic relied on.
In response to applicants’ argument that the prior art does not provide enabling disclosure since it does not demonstrate in vivo efficacy, efficacy is not a requirement for prior art enablement. A prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." ImpaxLabs. Inc. v. Aventis Pharm . Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006). See also MPEP § 2122. In this case, the prior art explicitly teaches and claim a method of administering the same compound (glutamine) for treatment of the same condition (AD having brain damage and MCI caused by Aβ42 accumulation) as claimed. Thus, the prior art describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention. Finally, when the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to provide facts rebutting the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). However, Applicants did not provide sufficient factual evidence why or how the reference is not enabled.
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 of this title, 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.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 9 and 12-17 are rejected under 35 U.S.C. 103 as being unpatentable over US 2010/0016207 (hereafter, Wurtman) in view of Dong et al. (Journal of Alzheimer’s Disease, 18: 459–469, 2009) and Chen et al. (PloS One, 7(3), e33177, March 2012; cited in IDS filed on 3/3/2023).
Wurtman as applied supra is herein applied for the same teachings in their entirety.
Wurtman does not specifically teach that the brain damage and mild cognitive impairment (MCI) are caused by stress or accumulation of amyloid-beta 42 (Aβ42).
However, it was known in the art that increasing levels of amyloid beta peptide including Aβ42 have been correlated with cognitive impairments in AD patient and higher levels of chronic psychological distress (stress) were associated with an increased incidence of mild cognitive impairment (MCI) as evidenced by Dong et al. (p461, col 1 para 2-col 2, para 2). Dong et al. further teach that stress and stress hormones may increase production of Aβ and its incorporation into Aβ plaques and stress could also enhance Aβ-mediated neuronal toxicity or increase tau accumulation or phosphorylation and tangle formation (p462, col 2, para 3).
Chen et al. teaches that glutamine acts as a neuroprotectant against DNA damage, beta-amyloid and H2O2-induced stress and the neuroprotective effects of glutamine supplementation may prove beneficial in the treatment of AD (Title and abstract). Chen et al. further teach that cells in low glutamine are more sensitive to the effects of a variety of different stressors (p4, col 2, para 1) and glutamine is essential for the stress-response and post damage survival of cells (p5, col 2, para 1). Chen et al. also teach that glutamine supplementation protects neuronal cells against the amyloid peptide (Aβ1–42) (abstract and p2, col 2, para 1) and neurons in AD mouse models in vivo (p9, Fig. 6). Chen et al. further discloses two different mouse models of familial AD responded in positive ways to a relatively short (10-day) nutritional supplement of glutamine in their drinking water (drink) (p10, col 2, para 2). In addition, Chen et al. teaches that glutamine supplementation in vitro enables nerve cells to resist stresses similar to those that affect the human brain during the course of Alzheimer's disease and glutamine supplementation may have a protective effect on AD pathogenesis in vivo (p10, col 2, para 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use glutamine for treating brain damage and MCI caused by stress or accumulation of amyloid-beta 42 (Aβ42) because of the following reasons. Wurtman already teaches the use of a food supplement comprising glutamine for treating a cognitive or memory disturbance or an Alzheimer's disease, which has MCI and brain damage. Also, Dong et al. further teach that stress and stress hormones was taught to be associated with an increased incidence of MCI and Aβ-mediated neuronal toxicity. In addition, Chen et al. teach that glutamine is essential for the stress-response and post damage survival of cells and glutamine supplementation protects neuronal cells against the amyloid peptide (Aβ1–42). Chen et al. further teach that glutamine supplementation in vitro enables nerve cells to resist stresses similar to those that affect the human brain during the course of Alzheimer's disease and glutamine supplementation may have a protective effect on AD pathogenesis in vivo. Thus, one of ordinary skill in the art would have been motivated to use the glutamine formulation of Wurtman for ameliorating brain damage and MCI caused by stress or accumulation of amyloid-beta 42 (Aβ42) with a reasonable expectation of success based on its neuroprotective effects against Aβ-mediated neuronal toxicity and stress responses as evidenced by Chen et al.
Response to Applicants’ argument:
Applicants argued that Wurtman discuss only general cognitive maintenance, not amelioration of stress-or amyloid-induced neuronal injury, thus fail to teach the specific cause or effect required by the claim as amended. Applicant further argued that Dong et al. merely observed a correlation between stress and amyloid pathology, but there is no teaching that glutamine or any compound can reverse the resulting damage or restore cognitive function. Also, Applicant argued that Chen et al. report limited in vitro protection of neuronal cells from oxidative damage but do not demonstrate in vivo reduction of ROS/RNS in brain tissue or behavioral recovery of cognitive performance. In addition, Applicant argued that the specification demonstrates that oral glutamine administration in vivo reduces ROS/RNS level in brain tissue, restore hippocampal neuronal integrity, and reverses memory and learning deficits caused by stress and Aβ42 and these synergistic in vivo effects are not predictable from the prior art, which taught only general nutritional or cell-culture observation.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). It is important to note that in an obvious rejection, it is not necessary that one reference addresses any limitation in a particular claim but that the references, when combined, do so.
In this case, Wurtman already teaches and suggest the use of a food supplement comprising glutamine for treating a subject having cognitive or memory disturbance or Alzheimer's disease, which has MCI and brain damage. Also, Dong et al. is cited for demonstrating that stress and Aβ-mediated neuronal toxicity are well-known causes of MCI and AD. In addition, Chen et al. teach that glutamine is essential for the stress-response and post damage survival of cells and glutamine supplementation protects neuronal cells against the amyloid peptide (Aβ1–42) in AD mouse models in vivo (p9, Fig. 6). Chen et al. further teach that glutamine supplementation in vitro enables nerve cells to resist stresses similar to those that affect the human brain during the course of Alzheimer's disease and glutamine supplementation may have a protective effect on AD pathogenesis in vivo. In addition, Chen et al. disclose that glutamine supplementation protects neuronal cells against the amyloid peptide (Aβ1–42) (abstract and p2, col 2, para 1) and neurons in AD mouse models in vivo (p9, Fig. 6).
“[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. The motivation to combine may be implicit and may be found in the knowledge of one of ordinary skill in the art, or, in some cases, from the nature of the problem to be solved. Id. at 1366, 80 USPQ2d at 1649. “[A]n implicit motivation to combine exists not only when a suggestion may be gleaned from the prior art as a whole, but when the improvement’ is technology-independent and the combination of references results in a product or process that is more desirable, for example because it is stronger, cheaper, cleaner, faster, lighter, smaller, more durable, or more efficient. Because the desire to enhance commercial opportunities by improving a product or process is universal-and even common-sensical-we have held that there exists in these situations a motivation to combine prior art references even absent any hint of suggestion in the references themselves. In such situations, the proper question is whether the ordinary artisan possesses knowledge and skills rendering him capable of combining the prior art references.” Id. at 1368, 80 USPQ2d at 1651.
Consistent with this reasoning, the skilled artisan, who is aware of the teachings of Dong et al. and Chen et al, would have been motivated to use the glutamine formulation of Wurtman, which is useful for treating AD, for ameliorating brain damage and MCI caused by stress or accumulation of amyloid-beta 42 (Aβ42) with a reasonable expectation of success based on its neuroprotective effects against Aβ-mediated neuronal toxicity and stress responses as evidenced by Chen et al.
In response to applicant's argument that the references fail to show certain features of applicant’s invention (i.e., in vivo reduction of ROS/RNS level in brain tissue, restoring hippocampal neuronal integrity, and reversing memory and learning deficits caused by stress and Aβ42), it should be noted that mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) (“The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.”). In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990) discussed in MPEP § 2144 are also pertinent to this issue. In this case, the prior art in combination teach, suggest and motivate administering the same composition comprising glutamine to the same patient (those having brain damage and MCI caused by stress and/or accumulation of Aβ42), the newly recited effects of administration of the same composition (i.e., in vivo reduction of ROS/RNS level in brain tissue, restoring hippocampal neuronal integrity, and reversing memory and learning deficits caused by stress and Aβ42as recited in the amended claim 1) necessarily occurs as such effects are inherent properties of glutamine. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter, which there is reason to believe inherently includes functions that are newly cited, or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter to be shown in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) (“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention”). Furthermore, it is generally well settled in the courts that a mechanistic property of a chemical compound, or combination of chemical compounds, when administered under identical conditions, is necessarily present, despite the fact that such a property may not have been readily apparent to, or recognized by, one of ordinary skill in the art.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See MPEP 2145(X)(A) (citing In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971)). As set forth in the rejection of the claims, the combination of each teaching was properly motivated by a rationale derived independently of applicant’s disclosure.
For the foregoing reasons, Applicant’s arguments have not been found to be persuasive.
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 extension fee 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 date of this final action.
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/BONG-SOOK BAEK/Primary Examiner, Art Unit 1611