DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
Receipt and consideration of Applicant’s amended claim set and Applicant’s arguments/remarks submitted on May 5, 2025 are acknowledged.
All rejections/objections not explicitly maintained in the instant office action have been withdrawn per Applicant’s claim amendments and/or persuasive arguments.
Status of the Claims
Claims 2-18 are pending and under consideration in this action. Claim 1 is cancelled.
Terminal Disclaimer
The terminal disclaimer filed on May 5, 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of prior patent Nos. 10,117,882; 10,525,068; and 11,400105 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Claim Rejections - 35 USC § 112
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.
Claims 2-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for changes in the bioavailability and bioefficacy of the claimed lipid composition, does not reasonably provide enablement for the improvement in cognitive performance as claimed in the instant claims 2-18. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
An analysis based upon the most relevant Wands factors is set forth below.
To be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In Genentech Inc. v. Novo Nordisk 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997); In re Wright 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993),. See also Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir. 1991); In re Fisher 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Further, in In re Wands 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) the court stated:
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman (230 USPQ 546, 547 (Bd. Pat App Int 1986)). They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art and (8) the breadth of the claims.
Breadth of Claims
Applicants’ claims are broad. The claims are directed to the improvement of cognitive performance (e.g., reduction in memory loss, forgetfulness, etc.) in a mammalian subject by administration of the claimed lipid composition to the subject. In particular, the claims are broad with respect to the patient population, the desired outcome, dosage for administration, and timing of administration. The claims as currently written do not recite any dosage for administration nor does it recite a timing for administration (e.g., what stage of cognitive function). The scope of the claimed patient population is broad in that it encompasses all mammals, with dependent claims limiting to still broad subsets of companion animals and humans (children and adults). Such subsets are broad in that it encompasses, for example, humans of all ages at any cognitive starting point, with and without comorbidities, health conditions, and/or age-associated conditions such as Alzheimer’s Disease and Parkinson’s Disease. Furthermore, “improvement” of cognitive performance in the independent claims do not limit to only a reduction in the conditions recited in the instant dependent claims, but would also encompass, for example, increased cognitive function, beyond normal memory functions.
Nature of the invention/State of the Prior Art
Generally, the state of the art for improvement of cognitive function such as the intended outcomes recited in the dependent claims, is a lack of predictability in that the causes of a cognitive disfunction are multifaceted and due to a wide range of known and not fully understood mechanisms of action.
Wood (European Journal of Nutrition; published 2022) discloses that cognitive impairment and Alzheimer’s Disease (AD) present major challenges for clinical medicine, with multi-faceted pathologies that are still not understood. Evidence from observational studies appear promising for prevention of cognitive decline. Regular consumption of LC omega 3-PUFA rich foods in healthy populations without pre-existing AD or dementia suggests a protective effect against future AD or dementia. Conversely, clinical trials that primarily focus on participants already diagnosed with AD consistently report no effect. Large-scale trials of long duration (greater than or equal to 5 months) using higher dosage supplements (900 mg DHA/day) across diverse populations are required to validate these findings, to improve generalizability, and determine safe and optimum dosage (p.601, Conclusion).
Ewumi (What to know about medications for memory loss, published April 4, 2024) notes that the National Institute of Aging (NIA) states that people should avoid any treatment that promises to restore brain function, prevent brain disorders, and improve memory. Certain medications can help ease symptoms and help a person manage the condition’s progression. However, no drug treatment can effectively cure memory loss (p.2, Can medication help slow memory loss?). Ewumi discloses that there are presently no disease-modifying medications for memory loss. Cholinesterase inhibitors and NMDA glutamate regulators can only stop memory loss symptoms for a short time, but they cannot stop or reverse the progression of the condition (p.9, Outlook). Few medications are available to help manage memory loss. The severity of a person’s memory loss and the underlying cause will indicate the most suitable drug therapy (p.10, para.1).
Zhang (Am J Clin Nutr; published 2016) discloses that while the intake of fish and polyunsaturated fatty acids (PUFAs) may benefit cognitive function, optimal intake recommendations for protection are unknown. While Fishery products are recommended as dietary sources and are associated with lower risk of cognitive impairment, marine-derived DHA was associated with lower risk of dementia and Alzheimer’s Disease, it was without a linear dose-response relation (p.330, col.1). Zhang also discloses that benefits of PUFAs, especially of EPA and DHA, in preventing cognitive problems have been of public interest. However, studies have reported inconsistent outcomes and induced extensive controversy. Some clinical trials have shown the cognitive-enhancing effects of n-3 PUFAs during infant development, childhood, and adulthood as well as in the elderly with neurodegenerative diseases such as AD. However, other trials have indicated that dietary DHA intake from the perinatal period to adulthood has not revealed a clear memory improvement in humans (p.330, col.2, par.1)
Chiu (Progress in Neuro-psychopharmaceutical & Biological Psychiatry; published 2008) discloses that their preliminary study suggest that conducting a study with omega-3 PUFAs monotherapy in patients with AD or MCI is feasible. Omega-3 fatty acids may improve general clinical function in patients with mild or moderate AD and MCI, but not their cognitive function (p.1543, col.1, para.3).
Chen (Frontiers in Neuroscience, published 2022) discloses that various pharmacological and non-pharmacological interventions have been proposed for cognitive impairment in older people. Although a variety of new drug targets has been identified for cognition enhancement in older adults, the new drug is still in development. The existing potential drug targets should be further exploited, and discovering new drug targets could be a solution to the lack of effective drugs. Most non-pharmacological interventions showed a small to moderate beneficial effect on cognitive function in cognitive impairment old people. However, it is noted that isolated supplementation with omega-3 fatty acid showed no effect on cognitive decline over 3 years (p.8, Table 3; p.9-10, Conclusion).
Level of One of Ordinary Skill & Predictability/Unpredictability in the Art
MPEP 2141.03 states (in part), “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (disagreeing with the examiner’s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering).
There is a general lack of predictability in the pharmaceutical art. In re Fisher, 427, F. 2d 833, 166, USPQ 18 (CCPA 1970).
Guidance/Working Examples
There appears to be no guidance or working examples of an improvement in cognitive performance—in general or the specific limitations recited in the dependent claims—in the instant Specification. While the specification appears to disclose examples of administration of the lipid composition, the administration was only to rats, which is not representative of the scope of the claimed patient population, which encompass companion animals and humans (children and adults) and humans with and without comorbidities, health conditions, and/or age-associated conditions such as Alzheimer’s Disease and Parkinson’s Disease. Furthermore, although the examples discuss the difference in bioavailability and bioefficacy between administration of the claimed lipid composition and a fish oil, does not appear to connect it to its effect in the claimed cognitive performance measurements.
Claims 2-18 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.
As discussed above, the claims are broadly directed to the improvement of cognitive performance (e.g., reduction in memory loss, forgetfulness, etc.) in a mammalian subject by administration of the claimed lipid composition to the subject. In particular, the claims are broad with respect to the patient population, the desired outcome, dosage for administration, and timing of administration. The claims as currently written do not recite any dosage for administration nor does it recite a timing for administration (e.g., what stage of cognitive function). The scope of the claimed patient population is broad in that it encompasses all mammals, with dependent claims limiting to still broad subsets of companion animals and humans (children and adults). Such subsets are broad in that it encompasses, for example, humans of all ages at any cognitive starting point, with and without comorbidities, health conditions, and/or age-associated conditions such as Alzheimer’s Disease and Parkinson’s Disease. Furthermore, “improvement” of cognitive performance in the independent claims do not limit to only a reduction in the conditions recited in the instant dependent claims, but would also encompass, for example, increased cognitive function, beyond normal memory functions.
While Applicant describes administration of their claimed lipid composition to rats, Applicant does not appear to describe dosages, timing of administration, and/or patient populations to arrive at the intended outcomes recited in the preamble of the independent claims and the limitations as recited in the dependent claims. As discussed above, generally, the state of the art for improvement of cognitive function such as the intended outcomes recited in the dependent claims, is a lack of predictability in that the causes of a cognitive disfunction are multifaceted and due to a wide range of known and not fully understood mechanisms of action. The further discussion of the state of the art are set forth above and incorporated herein.
Applicant fails to describe a representative number of dosages and patient populations for the intended outcome of the claimed method. While Applicant discusses the changes in the bioavailability and bioefficacy of the claimed lipid composition, Applicant does not appear to describe how that relates to the claimed improvements in cognitive function. Thus, the specification fails to provide an adequate written description to support the breadth of the claims.
Response to Arguments
Applicant's arguments filed May 5, 2025 have been fully considered but they are not persuasive.
(1) With regards to the rejection regarding the lack of enablement of the claims, Applicant argues that the Nguyen reference (Exhibit 1) validates that deficiency in omega-3 fatty acids in the brain is directly linked to cognitive decline and that the supply of omega-3 fatty acids to the brain is mediated by transport of lysophosphatidylcholine molecules across the blood-brain barrier. In particular, Applicant points to Nguyen’s teaching that the Mfsd2a is the transporter for lysophosphatidylcholine molecules containing omega-3 fatty acids to the brain, and when Mfsd2a was knocked out, behavioral tests indicated that the knockout mice had severe deficits in learning, short- and long-term memory, and severe anxiety. Thus, Applicant argues that a person of ordinary skill in the art would recognize that the instant claims are enabled as the specification teaches how to make and use the claims lysophosphatidylcholine molecule compositions to improve cognitive performance in a subject in need thereof.
With regards to Applicant’s argument (1), the traversal argument is not found persuasive. The claims are currently written are directed to a method of improving cognitive performance in a mammalian subject in need thereof. As discussed above, the claims are broad with respect to the patient population, the desired outcome, dosage for administration, and timing of administration. The claims as currently written do not recite any dosage for administration nor does it recite a timing for administration (e.g., what stage of cognitive function). The scope of the claimed patient population is broad in that it encompasses all mammals, with dependent claims limiting to still broad subsets of companion animals and humans (children and adults). Such subsets are broad in that it encompasses, for example, humans of all ages at any cognitive starting point, with and without comorbidities, health conditions, and/or age-associated conditions such as Alzheimer’s Disease and Parkinson’s Disease.
Generally, the state of the art (including post-filing art) for improvement of cognitive function such as the intended outcomes recited in the dependent claims, is a lack of predictability in that the causes of a cognitive disfunction are multifaceted and due to a wide range of known and not fully understood mechanisms of action. The references cited in the rejection set forth above evidence that there is a lack of predictability even after the priority date of the instant application. For example, the Wood reference discloses that clinical trials (involving consumption of LC omega 3-PUFA rich foods) that primarily focus on participants already diagnosed with AD consistently report no effect; the Zhang references discloses that trials have indicated that dietary DHA intake from the perinatal period to adulthood has not revealed a clear memory improvement in humans (a patient population encompassed by the instantly claimed method); the Chiu references discloses that omega-3 fatty acids may improve general clinical function in patients with mild or moderate AD and MCI, but not their cognitive function; and the Chen references discloses that isolated supplementation with omega-3 fatty acid showed no effect on cognitive decline over 3 years.
Furthermore, while the instantly claimed method recites administration of a specific lysophosphatidylcholine molecule composition, as disclosed by Wood, cognitive impairment and Alzheimer’s Disease (AD) present major challenges for clinical medicine, with multi-faceted pathologies that are still not understood. There appears to be no guidance or working examples of an improvement in cognitive performance—in general or the specific limitations recited in the dependent claims—in the instant Specification. While the specification appears to disclose examples of administration of the lipid composition, the administration was only to rats, which is not representative of the scope of the claimed patient population, which encompass companion animals and humans (children and adults) and humans with and without comorbidities, health conditions, and/or age-associated conditions such as Alzheimer’s Disease and Parkinson’s Disease.
With regards to Applicant’s cited Nguyen reference (Exhibit 1), the reference is looking only at mice, which is not representative of the scope of the claimed population, and Nguyen further specifically notes that dietary DHA treatment did not rescue knockout phenotypes, such as brain size and anxiety (p.506, col.1, para.4). Furthermore, with regards to Applicant’s argument regarding Nguyen’s teaching that Mfsd2a is the transporter for lysophosphatidylcholine molecules containing omega-3 fatty acids to the brain and that behavioral tests indicated that the Mfsd2a knockout mice had severe deficits in learning, short- and long-term memory, and severe anxiety, such a model is not representative of the instantly claimed population nor representative of all causes of cognitive decline or disfunction.
The instant claims also encompass, for example, treating those with Alzheimer’s Disease. Shiekh (Neuroscience; published 2015), for example, discloses that lysophosphatidylcholine (LPC) increases oligomer formation of Aβ1-42, the major Aβ peptide found in Alzheimer’s disease (abstract), and concluded that their results showed that increased LPC level induced Aβ peptide oligomer formation and subsequently neurodegeneration. Sheikh discloses that because Aβ-induced neurodegeneration is the main pathological feature of AD, LPC might play a role in the pathological process of the disease (p.168, Conclusion). Thus, it cannot be concluded that the lack of LPC in the brain is the sole cause of cognitive decline, nor that supplementation with LPC will improve cognitive decline.
Moreover, as discussed above, the instant claims, as currently written, recite “improving cognitive performance in a mammalian subject in need thereof.” “Improvement” of cognitive performance in the independent claims do not limit to only a reduction in the conditions recited in the instant dependent claims, but would also encompass, for example, increased cognitive function in those without a cognitive disfunction to beyond normal memory functions. Thus, Nguyen’s knockout mouse model is not representative of the patient population encompassed by the instant claims and does not provide evidence of enablement of the instantly claimed method.
(2) With regards to the rejection regarding the lack of adequate written description, Applicant argues that specification provides detailed methods on how to synthesize the claimed lysophosphatidylcholine molecule compositions, how to administer them to a mammalian subject, and describes the claimed uses of the lysophosphatidylcholine molecule compositions.
With regards to Applicant’s argument (2), the traversal argument is not found persuasive. The instant claims are not directed merely to a composition, how to synthesize the compositions, or how to administer the composition. Rather, the claims are directed to a method with particular intended outcomes, and as discussed in the rejection set forth above, the application does not provide adequate written description for how to achieve the intended outcomes recited in the preamble of the independent claims and the limitations as recited in the dependent claims.
As discussed above, generally, the state of the art for improvement of cognitive function, such as the intended outcomes recited in the dependent claims, lacks predictability in that the causes of a cognitive disfunction are multifaceted and due to a wide range of known and not fully understood mechanisms of action. Applicant fails to describe a representative number of dosages and patient populations for the intended outcome of the claimed method. While Applicant discusses the changes in the bioavailability and bioefficacy of the claimed lipid composition, Applicant does not appear to describe how that relates to the claimed improvements in cognitive function. Thus, the specification fails to provide an adequate written description to support the breadth of the claims.
Conclusion
Claims 2-18 are rejected. No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MONICA A. SHIN whose telephone number is (571)272-7138. The examiner can normally be reached Monday-Friday (9:00AM-5:00PM EST).
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/MONICA A SHIN/Primary Examiner, Art Unit 1616