DETAILED ACTION
This office action is in response to applicant’s filing dated July 15, 2026.
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 .
Status of claims
Claims 1, 8 – 17 and 19 are pending in the instant application. Acknowledgment is made of Applicant’s amendments filed July 15, 2026.
Objections and/or Rejections and Response to Arguments
Applicants' arguments, filed on July 15, 2026, have been fully considered but they are not deemed to be persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
Maintained Objections and/or Rejections
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 (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1 and 8 – 17 are rejected under 35 U.S.C. 103 as being unpatentable over Velazquez et al (Aging Cell. 2019; 18:e13037, hereinafter Velazquez, the reference is of record) in view of Lin et al (Neuron 98, 1141–1154, June 27, 2018, hereinafter Lin, the reference is of record) and Blusztajn et al (Nutrients 2017, 9, 815, hereinafter Blusztajn).
Regarding claims 1 and 12 - 14, drawn to a method of treating a subject for Alzheimer' s disease comprising determining the presence or absence of an ApoE4 gene in a subject and delivering to the subject an effective amount of choline supplementation in the form of choline chloride, if the subject has an ApoE4 gene, wherein the choline supplementation is the only active agent, and wherein the effective amount is an effective daily dose of about 550 mg to 1000 mg, administered to a subject one to three times a day. According to the said method, the effective amount of choline supplementation is an effective amount for decreasing lipid droplet accumulation in the liver of the subject.
Velazquez teaches an effect of choline supplementation throughout life, where the effect of choline supplementation was tested on the APP/PS1 mouse model of AD (page 1, abstract), where mice received choline supplemented diet in concentration of choline chloride 1.1 g/kg and 5.0 g/kg in their daily diet (page 9, § 4.1). Recalculating mice dosage into human equivalent dosage according to “Guidance for Industry”, choline supplementation was given in the amount 800 mg per day and 3.65 g per day for 60 kg adult. (Examiner corrects here an inadvertent error, and thanks an applicant for pointing it out, as “dietary concentration of choline chloride 5.0 g/kg” means 5.0 g of choline chloride per kg of food). Velazquez further teaches current established adequate intake level of choline for adult (>19 years of age) women is 425 mg/day and 550 mg/day for adult men, and the tolerable upper limit (TUL) of choline unlikely to cause side effects for adult females and males (>19 years of age) is 3,500 mg/day (page 8, 2nd paragraph). The effective amount of choline taught by Velasquez overlaps or lies within the ranges of instant claims. MPEP 2144.05 states: In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
Summarizing the results of the experiment, Velazquez concludes that “additional dietary choline is a putative treatment option that may prevent AD progression” (page 2, 3rd paragraph).
Velazquez does not teach determining the presence or absence of an ApoE gene in the subject suffering from Alzheimer’s disease.
However, Lin teaches the apolipoprotein E4 (APOE4) variant as the single greatest genetic risk factor for sporadic Alzheimer’s disease (sAD) (page 1142, summary), where sporadic Alzheimer’s disease accounts for more than 90% of the disease cases according to Barykin et al (Front. Genet. 8:58. doi: 10.3389/fgene.2017.00058, reference of record).
Moreover, Blusztajn teaches that dietary choline intake may influence cognitive function in AD patients, and is associated with higher memory performance, and resistance to cognitive decline (abstract). Blusztajn describes the experiment of effects of choline supplementation on APPswe/PS1dE9 (APP.PS1; MGI ID: 3524957) AD mouse model. APP.PS1 mice are characterized by: (1) high production of amyloid Aβ peptides in brain and accumulation of amyloid plaques by 4–6 months of age; (2) cognitive impairments; (3) cholinergic defects; and (4) evidence of abnormal methylation of several genes (page 5, 2.3.5). While the study, described by Blusztajn, used an AD model caused by genes mutated in the familial human disease, the vast majority of AD cases are sporadic, with no known causes (page 6, 1st paragraph). However, subjects with the APOE4 genotype carry the major genetic risk factor for AD, where vulnerability to AD may be modified by early-life choline supplementation (page 8, 1st paragraph).
Thus, since Velazquez teaches delivering an effective amount of choline to the subject with Alzheimer’s disease generically, without identifying presence of ApoE4 allele, Lin and Blusztajn teach presence APOE4 allele as a major genetic factor of development of AD, where choline supplementation intake helps retard the disease progression, a person of ordinary skill in the art would have recognized that determining the presence of E4 allele of the APOE, would be beneficial in targeting a subject with the higher genetic risk factor for developing AD.
Regarding claim 12 limitation, which recites the method “where an effective amount of choline supplementation is an effective amount for decreasing lipid droplet accumulation in the liver of the subject”, Velasquez teaches an amount of choline supplementation which overlaps or falls within the ranges of an effective amount of choline supplementation recited by instant claims, thus amount of choline supplementation taught by prior art is sufficient to decrease lipid droplet accumulation in the liver of the subject as evidenced by instant claim 1.
Regarding claim 14 limitation, which recites the method where an effective amount of choline supplementation is administered to a subject one to three times a day. Velasquez teaches the method, where mice receive choline supplementation in the concentration 5.0 g/kg in their daily diet, which indicates that mice received and effective amount of choline at least once a day.
Taking all together, it would be prima facie obvious to one of ordinary skill in the art before effective filing date of the claimed invention to modify the method of treating a subject with Alzheimer’s disease comprising administering choline chloride taught by Velazquez to further identify the presence of APOE4, since the prior art teaches the presence of APOE4 is known to be a genetic risk factor of developing AD conditions. Thus, resulting in the practice of the method of claims 1 and 12 – 14 with the reasonable expectation of success.
Regarding claims 8 and 9, drawn to a method where the effective amount of choline supplementation is an effective amount for altering phosphatidylcholine (PC) metabolism in the subject, wherein altering PC metabolism in a subject comprises increased expression of one or more of the following genes Pld3, Sipr1 , or Plpp3 in astrocytes.
Lin teaches disfunction of genes in APOE4 astrocytes, such as PLPP3, associated with lipid metabolism. (page 1146, left column, 1st paragraph; Figure 3D).
Blusztajn teaches dietary choline intake in the adult may also influence cognitive function via an effect on PC (phosphatidylcholine) containing eicosapentaenoic and docosahexaenoic acids; polyunsaturated species of PC whose levels are reduced in brains from AD patients. One possible explanation for the effect of concurrent choline intake on cognition in adults lies in its function as a precursor of the phospholipid phosphatidylcholine (PC), a major constituent of all biological membranes, including those in neurons and glial cells. Evidence that phospholipid metabolism is abnormal in AD originated with postmortem brain sample studies dating to the 1980s and 1990s which showed reduced levels of PC in the cerebral cortex of AD patients (page 7, 2nd paragraph).
Velasquez teaches an amount of choline supplementation which overlaps or falls within the ranges of an effective amount of choline supplementation recited by instant claims, thus amount of choline supplementation taught by prior art is sufficient for altering phosphatidylcholine (PC) metabolism in the subject as evidenced by instant claim 1.
Thus, prior art teaches, that regular intake of an effective amount of choline supplies cells with material to build membrane phospholipids (PC), where PC level is reduced in AD patients.
Regarding claims 10 and 11, drawn to a methos where the effective amount of choline supplementation is an effective amount for normalizing microglial activation in the subject, and wherein normalizing microglial activation comprises decreased expression of IL-lb induction following activation with interferon gamma relative to a control.
Velasquez teaches that lifelong Ch+ (choline intake) reduces the levels of activated microglia which are increased in AD, thereby mitigating the detrimental effects of brain inflammation associated with AD-like pathology (page 4, right column, 1st paragraph).
Regarding claim 11 limitation, which recites the method where “normalizing microglial activation comprises decreased expression of IL-lb induction following activation with interferon gamma relative to a control”, the prior art is silent regarding “normalizing microglial activation comprises decreased expression of IL-1b induction following activation with interferon gamma relative to control”. However: “normalizing microglial activation comprises decreased expression of IL-1b induction following activation with interferon. gamma relative to control " will naturally flow from the teachings of (or method made obvious by) the prior art (see above rejection), since the same compound (choline) is being administered to the same subjects (subjects suffering from Alzheimer’s disease). In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances.
In other words, even though the prior art is silent regarding "normalizing microglial activation comprises decreased expression of IL-1b induction following activation with interferon gamma relative to control ", by practicing the method made obvious by the prior art: "the administration of an effective amount of choline to a patient suffering from Alzheimer’s disease ", one will also be "decreasing expression of IL-1b induction following activation with interferon gamma ", even though the prior art was not aware of it.
Apparently, Applicant has discovered a new property or advantage ("normalizing microglial activation comprising decreased expression of IL-1b induction following activation with interferon gamma ") of the method made obvious by the prior art ("the administration of an effective amount of choline to a subject, having an APOE4 allele and suffering from Alzheimer’s disease ").
MPEP 2145 II states: "The fact that Applicant 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. (FP 7.37.07, MPEP 707.07(f)).
Regarding claims 15 - 17, drawn to a method where the choline supplementation is administered to the subject for at least 3 months, at least 6 months or at least 12 months.
Velasquez teaches the method where mice were given choline supplemented diet starting at age 2.5 months until 10 months of age (page 2, “results”, Fig.1). This data indicates that mice were fed choline supplemented diet during 7.5 months, which falls within the claimed range “at least 3 months or at least 6 months”.
Regarding claim 17 limitation, which recites the method where the choline supplementation is administered to the subject for at least 12 months, Velasquez teaches “lifelong choline supplementation”. Since human’s lifespan is considered to be over 70 years, the term “lifelong” falls within the claimed range “at least 12 months. MPEP 2144.05 states: In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Amenta et al (Journal of the Neurological Sciences 322 (2012) 96–101, hereinafter Amenta) in view of Lin et al (Neuron 98, 1141–1154, June 27, 2018) and Blusztajn et al (Nutrients 2017, 9, 815).
Instant claim is drawn to a method of treating a subject for Alzheimer's disease comprising determining the presence or absence of an ApoE4 gene in a subject and delivering an effective amount of choline supplementation and a cholinesterase inhibitor to the subject if the subject has an ApoE4 gene, wherein the choline supplementation and the cholinesterase inhibitor are the only active agents, and wherein the effective amount of choline supplementation is an effective daily dose of about 550 mg to 1000 mg.
Amenta teaches multicenter, randomized, placebo-controlled, double-blind clinical trial ASCOMALVA, where 183 subjects with AD (105 female and 78 male), aged between 56 and 91 years (average 75) were recruited. The study protocol includes the treatment of patients with cholinesterase inhibitor (donepezil 10 mg/day) + precursor cholinergic (choline alphoscerate 1200 mg/day) (treatment group) or donepezil+ placebo (control group) for 24 months starting from enrolment in the study (page 97, “methods”). The amount 1200mg/day, taught by prior art, is close to the claimed range daily dose of about 550 mg to 1000 mg. MPEP 2144.05.I. states: […]a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). See also Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 41 USPQ2d 1865 (1997) (under the doctrine of equivalents, a purification process using a pH of 5.0 could infringe a patented purification process requiring a pH of 6.0-9.0); 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%).
Amenta does not teach determining the presence or absence of an ApoE gene in the subject suffering from Alzheimer’s disease.
However, Lin teaches the apolipoprotein E4 (APOE4) variant as the single greatest genetic risk factor for sporadic Alzheimer’s disease (sAD) (page 1142, summary), where sporadic Alzheimer’s disease accounts for more than 90% of the disease cases according to Barykin et al (Front. Genet. 8:58. doi: 10.3389/fgene.2017.00058, reference of record).
Moreover, Blusztajn teaches that dietary choline intake may influence cognitive function in AD patients, and is associated with higher memory performance, and resistance to cognitive decline (abstract). Blusztajn describes the experiment of effects of choline supplementation on APPswe/PS1dE9 (APP.PS1; MGI ID: 3524957) AD mouse model. APP.PS1 mice are characterized by: (1) high production of amyloid Aβ peptides in brain and accumulation of amyloid plaques by 4–6 months of age; (2) cognitive impairments; (3) cholinergic defects; and (4) evidence of abnormal methylation of several genes (page 5, 2.3.5). While the study, described by Blusztajn, used an AD model caused by genes mutated in the familial human disease, the vast majority of AD cases are sporadic, with no known causes (page 6, 1st paragraph). However, subjects with the APOE4 genotype carry the major genetic risk factor for AD, where vulnerability to AD may be modified by early-life choline supplementation (page 8, 1st paragraph).
Thus, since Amenta teaches delivering an effective amount of choline and cholinesterase inhibitor to the subject with Alzheimer’s disease generically, without identifying presence of ApoE4 allele, Lin and Blusztajn teach presence of APOE4 allele as a major genetic factor of developing AD, where choline supplementation intake helps retard the disease progression, a person of ordinary skill in the art would have recognized that determining the presence of E4 allele of the APOE, would be beneficial in targeting a subject with the higher genetic risk factor for developing AD.
Taking all together, it would be prima facie obvious to one of ordinary skill in the art before effective filing date of the claimed invention to modify the method of treating a subject with Alzheimer’s disease comprising administering choline supplementation and the cholinesterase inhibitor taught by Amenta to further identify the presence of APOE4, since the prior art teaches the presence of APOE4 is known to be a genetic risk factor of developing AD conditions. Thus, resulting in the practice of the method of claim 19 with the reasonable expectation of success.
Therefore, taking all together, taught by prior art, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues:
- The skilled artisan would not have had a reasonable expectation of success in combining the cited references to produce the claimed invention. Velasquez performs a study in which mice were provided with dietary choline supplementation. The tested mice were APP/PS1, meaning they harbored the mouse APOE gene in the background. The skilled artisan would not have had a reasonable expectation that treatment in a non-humanized APOE background would have the same effects. While APOE4 is a well-established Alzheimer's risk gene in humans, it is unclear whether mouse models of AD, especially those that do not bear humanized APOE, are representative of processes covering APOE related risk.
- Applicant notes that it is unclear where Lin provides a teaching on choline supplementation and Lin and Blusztajn describes "an adequate dietary supply of choline and DHA is necessary to maintain plasma and brain PC- DHA levels". (emphasis added, Page 8, 1st paragraph).
- The data presented in the specification provides clear evidence that APOE4 risk is specifically ameliorated by choline. A novel molecular pathway specifically affected by APOE4 status was identified and it was demonstrated, that choline supplementation normalizes the APOE4-mediated dysregulation. The conclusions were validated in human model systems and in vivo in an AD mouse model. The data suggest amyloid deposition and turnover, PC metabolism, and synaptic health and inflammation are modified in APOE4 carriers given choline supplementation. In the absence of such data, the claimed invention was unpredictable.
- There would have been no reasonable expectation of success in combining the cited references to produce the claimed invention in view of the teachings found in the cited references. Velasquez study does not take into account human APOE4. While Lin and Blusztajn both describe the role of APOE4 allele as a genetic factor in the development of AD, neither provides any teaching or suggestion that choline supplementation would be effective in human APOE4 positive patients. In fact, Blusztajn actually suggests that choline supplementation may not work in APOE4 patients. On page 8, 1st paragraph Blusztajn concludes that "Not surprisingly, early intervention works better, and the response to treatment may be attenuated in subjects with the APOE4 genotype-the major genetic risk factor for AD."
- Further, in Velazquez the mice were treated with choline supplementation at dosage of 5.0 g/kg per day, which the Examiner asserts is 405 mg/kg per day in humans. The amended claims currently recite the limitation that the amount of choline used is 550 mg/day to 2,000 mg/day, which appears to be significantly lower than the amount used in the cited art. If the average human is 62-65 kg, a dose of 405 mg/kg per day would be about 25,000-26,000 mg/day.
- Regarding the rejection of claim 19, the combination of cited art does not produce the claimed invention. Claim 19, recites the limitation that the choline is administered in a dosage of 1,000 mg/day, which is 200 mg/day less than the amount of choline taught to be effective in Amenta. The Office has provided no reason why the skilled artisan would have considered an upper range value of 1,000 mg be the equivalent of 1,200 mg.
- Amenta, does not provide any guidance to the skilled artisan as to whether the combination of cholinesterase inhibitor and choline would produce a therapeutic effect in the treatment of AD in APOE4 position patients. In view of the teaching away found in Blusztajn and the knowledge in the art, the skilled artisan would not have reasonably expected the combined therapy to be useful in APOE4 patients.
Examiner’s response:
Applicant's arguments have been fully considered but they are not persuasive because: as set forth above combined prior art teachings give a clear direction to the presently claimed method. In particular, Velasquez and Blusztajn teach the method to treat the same AD associated pathologies (neurodegeneration, memory loss, microglia activation, Aβ42 plaques accumulation, reduced PC level and cholinergic deficit) with the equal or similar amount of choline supplementation. Lin teaches the apolipoprotein E4 (APOE4) variant as the single greatest genetic risk factor for sporadic Alzheimer’s disease (sAD), mostly affecting synaptic function (neurons), lipid metabolism (astrocytes), and immune response (microglia activation) (page 1141, “summary” and page 1146). Although Velasques teaches the method to treat AD patients with the effective amount of choline generically, not specifically targeting the subgroup of APOE4 carriers, since Lin teaches that majority of AD patients carry APOE4 variant, it indicates that among all AD patients, APOE4 carriers necessary present, and the effective amount of choline is already administered to that exact population. Although Blusztajn says that the response to treatment may be attenuated in subjects with the APOE4 genotype, Blusztajn does not teach away from taking choline by APOE4 carriers, as Blusztajn clearly suggests that an adequate dietary supply of choline and DHA helps to delay or ameliorate the pathogenic process in AD generically. Thus, combined prior art teaches that choline intake in the amounts which are equal or similar to the instantly claimed is beneficial to all AD patients including those carrying APOE4 variant. Moreover, Applicant did not provide any evidence that choline intake is more effective in APOE4-positive AD patients or does not work for other APOE variant carriers. MPEP 2145 states: If a prima facie case of obviousness is established, the burden shifts to the applicant to come forward with arguments and/or evidence to rebut the prima facie case. See, e.g., In re Dillon, 919 F.2d 688, 692, 16 USPQ2d 1897, 1901 (Fed. Cir. 1990) (en banc). Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.").
Regarding the argument about discovered novel molecular pathway specifically affected by APOE4 status, it is not persuasive because, prior art teaches the same method (method of treating AD associated pathologies), targeting the same cellular processes that are affected by the presence of APOE4 variant (lipid metabolism, microglia activation, Aβ42 plaques accumulation etc.) and to be practiced with the equivalent amount of same agent (choline). Thus, by practicing the method made obvious by the prior art: "the administration of an effective amount of choline to the AD patient", one will also be targeting the same molecular pathways in APOE4 carriers (majority of AD patients), even though the prior art was not aware of it, as products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances (see also MPEP 2112). Moreover, the feature “novel molecular pathway” is not recited in the claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Regarding the argument about an effective amount of choline recommended by Velasquez or Amenta, it is not persuasive, because the doses of choline recommended by Velasquez overlap or lie inside the claimed ranges, and amount of choline disclosed in Amenta is close to the instantly claimed amount, thereby rendering instantly claimed ranges obvious (see also MPEP 2144.05) (Examiner corrected the calculation error. See the rejection section above). Absent any showing of unexpected results or criticality of selected ranges, it would be within the skill of an ordinary artisan to be able to modify the amount of choline supplementation in order to obtain the desired therapeutic effect. It is noted that "[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).
The argument about lack of expectation of success are not persuasive, because as set forth above, regarding claims 1 and 8 – 17, combined prior art references of Velasquez, Lin and Blusztajn teach the same method (method of treating AD associated pathologies), targeting the same cellular processes and molecular mechanisms in the same AD patient population (APOE4 carriers) to be practiced with the equivalent amount of the same agent (choline). Regarding claim 19, the combined references of Amenta, Lin and Blusztajn teach the method for treatment of AD patients with cholinesterase inhibitor and choline alphoscerate, where choline is administered in the similar to the instantly claimed amount, and demonstrated a neuroprotective effect, where APOE4 carriers are majority of AD patient population and in need of neuroprotection. The person of ordinary skills in the art would understand that, if choline intake helps to slow down, ameliorate or reduce AD progression across general Alzheimer’s population, as evidenced by prior art teachings, the choline intake efficacy is also translated to APOE4-positive AD patients with the reasonable expectation of success, since APOE4-positive subgroup is the predominant cohort of the overall Alzheimer’s population. As stated in MPEP 2145: Absolute predictability is not a necessary prerequisite to a case of obviousness. Rather, a degree of predictability that one of ordinary skill would have found to be reasonable is sufficient. The Federal Circuit concluded that "[g]ood science and useful contributions do not necessarily result in patentability." Id. at 1364, 83 USPQ2d at 1304.
Therefore, Applicant’s arguments are not persuasive and the rejection of claims 1 and 8 – 17 as obvious over teachings of Velasquez, Lin and Blusztajn , as well as the rejection of claim 19 as obvious over teachings of Amenta, Lin and Blusztajn is maintained.
Conclusion
Claims 1, 8 – 17 and 19 are rejected. No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/E.V.V./ Examiner, Art Unit 1691
/SAVITHA M RAO/ Primary Examiner, Art Unit 1691
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