DETAILED ACTION
Notice of 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 .
Election/Restrictions
Applicant’s election without traverse of a single method in the reply filed on 3/30/2026 is also acknowledged.
The elected species read upon claims 1, 26, 29, 31-33, 35-36, 40, 65, 68, 70-72 and 76-78. Claims 5, 27, 44 and 66 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
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.
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, 26, 29, 31-33, 35-36, 40, 65, 68, 70-72 and 76-78 are rejected under 35 U.S.C. 103(a) as being unpatentable over Cotman et al (US 2018/0228808) in view of Castello et al (PLOS ONE 9:e91453, (8 pages), 2014) and Safieh et al (BMC Medicine 17:64 (17 pages), March 20, 2019).
Claims 1 and 40 (drafted independently) are drawn methods of preventing/delaying the onset of an Alzheimer’s disease in a subject in need thereof (claim 1) and improving cognition in a subject at risk of developing Alzheimer’s disease (claim 40), the methods comprising administering to the subject a composition comprising ETP69, wherein:
the subject has at least one genetic risk factor associated with sporadic Alzheimer’s disease (more specifically, wherein the genetic risk factor is an apolipoprotein (APOE) e4 allele (claims 26 and 65)); and
the subject is asymptomatic of Alzheimer’s disease (claims 29 and 68)).
Cotman et al teach “treating cognitive dysfunction via administration of a SUV39H1 inhibitor referred to as ETP69” (Paragraph 00024), in particular, “cognitive deficits related to... Alzheimer’s disease” (Paragraph 0006; see also Paragraph 0042: “to ameliorate cognitive deficits associated with Alzheimer’s disease”).
As such, Cotman et al teach a method of treating Alzheimer’s disease in a subject in need thereof and/or improving cognition in a subject suffering from Alzheimer’s disease, the method comprising administering to the subject a composition comprising ETP69.
However, Cotman et al do not teach preventing/delaying the onset of an Alzheimer’s disease and/or improving cognition in a subject having an apolipoprotein (APOE) e4 allele that is asymptomatic of Alzheimer’s disease, as claimed.
Yet, as further taught by Cotman et al, treatment of mice with ETP69 “increases spine density” (Paragraph 0087). In particular, Cotman et al demonstrate that, “in the CA1 of the hippocampus” (Paragraph 0089), “ETP69 treated mice had 45% more total number of spines per length of dendrite (µm) compared to controls” (Paragraph 0090). And, as further disclosed by Cotman et al, “[t]ransient increases in spine density have been associated with improved learning and memory, particularly in the hippocampus of aged mice” (Paragraph 0095).
Notably, as taught by Castello et al, in CaM/Tet-DTA mice (which exhibit a “pattern and degree of neuronal loss [that] emulates... AD” (Page 2, Column 1)), treatment with 7,8-DHF “induced a significant and selective increase in the density of thin spines in CA1 of lesioned mice” (Abstract) and “significantly improves hippocampus-dependent behavior” (Page 4, Column 1), including “spatial learning and memory” (Page 4, Figure 2). As further taught by Castello et al, the “increase in the density of dendritic spines... may underlie the improvements in cognition” (Page 4, Column 1).
And, as taught by Safieh et al, “carriers of APOE4 are more likely to develop AD [Alzheimer’s disease]” and “the cognitive changes in APOE4 carriers... occur several years earlier” (Page 2, Column 1), wherein one “feature of AD that is probably linked very significantly to memory impairment and cognitive decline is synaptic failure” (Page 6, Column 2). In particular, Safieh et al teach that “[c]linical studies suggest that APOE4 carriers have lower levels of dendritic spine density in the hippocampus”, and related studies in apoE4 mice suggest “an early onset of apoE4-driven alteration of neuronal circuitry” (Page 6, Column 2).
In view of all of the foregoing, it would have been prima facie obvious to extend the method of treating Alzheimer’s disease in a subject in need thereof comprising administering to the subject a composition comprising ETP69, as taught Cotman et al, to:
a subject having an apolipoprotein (APOE) e4 allele that is asymptomatic of Alzheimer’s disease in order to prevent/delay the onset of an Alzheimer’s disease in said subject with a reasonable expectation of success (as recited by claims 1, 26 and 29); and/or
a subject having an apolipoprotein (APOE) e4 allele that is at risk of but asymptomatic of Alzheimer’s disease in order to improve cognition in said subject with a reasonable expectation of success (as recited by claims 40, 65 and 68).
At the outset, based on Safieh et al, a person of ordinary skill in the art would have recognized that carriers of APOE4 are more likely to develop AD (i.e., are at risk of developing AD) and that the cognitive changes in APOE4 carriers occur several years earlier than the development of AD (i.e., when the subject in asymptomatic of AD). And it would have been prima facie obvious to treat this patient population with ETP69 further considering that, as taught by Safieh et al, APOE4 carriers have lower levels of dendritic spine density in the hippocampus, and as taught by Cotman et al, ETP69 increases spine density in the CA1 of the hippocampus which, as taught by Castello et al, has been shown to improve hippocampus-dependent behavior including spatial learning and memory in CaM/Tet-DTA mice (which exhibit a “pattern and degree of neuronal loss [that] emulates... AD”).
As such, claims 1, 26, 29, 40, 65 and 68 are rejected as prima facie obvious.
Claims 31-33 are drawn to the method of claim 1, wherein the delaying onset of Alzheimer’s disease comprises a delay in onset of at least one symptom of AD (claim 31), more specifically, by at least about 6 months (claim 32), wherein the symptom is memory loss, difficulty concentrating, etc. (claim 33).
Regarding claims 31-33, although it is recognized that “[i]nherency may not be established by probabilities or possibilities” (In re Robertson, 169 F.3d 743 (Fed. Cir. 1999)), Applicant is also reminded that the U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the infinite number of ways that a subsequent Applicant may present previously unmeasured characteristics. When, as here, the prior art appears to contain the exact same elements as those instantly claimed, the burden is properly shifted to Applicant to show otherwise. As stated in In re Best, Bolton, and Shaw, “[w]here… the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product" 562 F2d 1252 (CCPA 1977). In the instant case, the claimed and prior art products are substantially identical. As such, absent evidence to the contrary, it is asserted that the prima facie obvious administration of ETP69 to a subject having an apolipoprotein (APOE) e4 allele that is asymptomatic of Alzheimer’s disease in order to prevent/delay the onset of an Alzheimer’s disease in said subject, as taught by the prior art, would necessarily delay the onset of at least one symptom of AD, as recited by claims 31-33 (see also In re Fitzgerald 619 F2d 67 (CCPA 1980): the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on”; see also Hoffer v. Microsoft Corp. (405 F.3d 1326 (Fed. Cir. 2005)): a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited” (quoting Minton v. Nat ' l Ass ' n of Securities Dealers, Inc., 336 F.3d 1373 (Fed. Cir. 2003))).
As such, claims 31-33 are also rejected as prima facie obvious.
Claims 35-36, 70, 72 and 76-78 are drawn to the methods of claim 1 or 40, wherein the treatment results in improvement in a mental status test and/or a neuroimaging test relative to a score obtained prior to administration of the composition, more specifically wherein the mental status test is a MMSE, Mini-Cog test, etc. (claims 35-36 and 72); wherein the method improves memory loss wherein the improvement comprises an improved score relative to a score obtained prior to administration of the composition (claim 70); and wherein the administration results in increased synaptic integrity and/or dendritic spine density in the subject as compared to synaptic integrity and/or dendritic spine density measured prior to administration of the composition (claims 76-78).
Although the claims recite an improvement and/or increase in mental status, memory loss, synaptic integrity, and/or dendritic spine density relative to and/or as compared to scores/measures thereof obtained prior to administration of the composition, the claims, as currently drafted, do not require the active steps of measuring and comparing those parameters prior to and following treatment. As such, claims 35-36, 70, 72 and 76-78 are rejected for largely the same reasons as discussed regarding claims 31-33. Namely, absent evidence to the contrary, it is asserted that the prima facie obvious administration of ETP69 to a subject having an apolipoprotein (APOE) e4 allele that is asymptomatic of Alzheimer’s disease in order to prevent/delay the onset of an Alzheimer’s disease and/or improve cognition in said subject in said subject, as taught by the prior art, would necessarily result in the improvements and/or increases relative to/as compared to measures/scores of those parameters prior to said administration, as recited by claims 35-36, 70, 72 and 76-78 (see also In re Fitzgerald 619 F2d 67 (CCPA 1980): the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on”; see also Hoffer v. Microsoft Corp. (405 F.3d 1326 (Fed. Cir. 2005)): a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited” (quoting Minton v. Nat ' l Ass ' n of Securities Dealers, Inc., 336 F.3d 1373 (Fed. Cir. 2003))).
As such, claims 35-36, 70, 72 and 76-78 are also rejected as prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CRAIG D RICCI whose telephone number is (571) 270-5864. The examiner can normally be reached on Monday through Thursday, and every other Friday, 7:30 am - 5:00 pm ET. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached on (571) 272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CRAIG D RICCI/Primary Examiner, Art Unit 1611
Prosecution Insights