DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed August 3, 2026. Currently, claims 1, 9, 18, 27 are pending.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow.
Any objections and rejections not reiterated below are hereby withdrawn.
The 103 rejection has been withdrawn in view of the statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
The DP rejection over U.S. Patent No. 10,471,029 or U.S. Patent No. 11,053,192 or U.S. Patent No. 12,187,668 or copending Application No. 17/877,380 in view of Shuff et al. (Brain – A journal of Neurology, Vol. 132, pages 1067-1077, 2009) or KR20180078032 (July 9, 2018) and Jia et al (WO 2018/157014, August 30, 2018) have been withdrawn in view of the amendments to the claims and arguments.
Priority
This application claims priority to
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Applicant should contact the filing receipt branch for guidance on the inconsistent data.
Drawings
The drawings are acceptable.
Claim Interpretation
The claims have been interpreted to require a determination of APOE4 alleles, and hippocampal volume or cortical thickness. The claims do not encompass an inherent property of a subject to have a hippocampal volume or cortical thickness below a threshold. Some sort of determination is required to have been performed.
Claim Objections
Claim 1 and the claims dependent thereon are objected to because the claim contains more than one period (see 609.01(m)). Periods may not be used elsewhere in the claims except for abbreviations. For example, a. b. i. ii. Iii. Iv. contains a period and the end of the claim contains a period. This objection may be overcome by amending a. to read a) (see MPEP 608.01(m)).
The response filed August 3, 2026 does not address this objection.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the "right to exclude" granted by a patent and to prevent possible harassment by multiple assignees. See In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970);and, In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-7, 9-12, 14-15, are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12083,082 in view of Shuff et al. (Brain – A journal of Neurology, Vol. 132, pages 1067-1077, 2009) or KR20180078032 (July 9, 2018) and Jia et al (WO 2018/157014, August 30, 2018).
‘082 claims methods of preventing and treating using ALZ-801 (valyl-3-amino-1-propanesulfonic acid), a small molecule prodrug of tramiprosate in patients with MMSE score of 30, with APOE4/4 homozygous.
The patent claims do not teach determining a hippocampal volume or cortical thickness and selecting a subject with hippocampal volume or cortical thickness below a threshold.
However, Schuff et al teaches MRI of hippocampal volume loss in early Alzheimer’s disease in relation to ApoE genotype. Schuff teaches hippocampal volume change over time has huge potential as a maker for Alzheimer’s disease. Schuff teaches studying the hippocampal loss over 6-12 months (abstract). Table 2 illustrates hippocampal baseline volumes and rates of volume loss by group for different time frames (page 1071). Schuff teaches increased rates of hippocampal loss were associated with presence of the ApoE allele E4 gene in Alzheimer’s disease (abstract). Figure 3 illustrates rates of hippocampal volume loss in carriers and non-carriers of APpoE4 (page 1072). Figure 2 illustrates the rate of volume loss over different time periods of 1-6 and 6-12 months (page 1072). Each of Figure 2 and 3 illustrates the normal baseline that the comparison may be made to, i.e. 5% and 10% below normal. Schuff teaches amyloid AB1-42 are a major component of amyloid plaques that are directly related to Alzheimer’s disease pathology. Schuff teaches that amyloid burden and high rates of hippocampal loss implies the two measures provide complementary information about the presence of Alzheimer’s disease pathology. Schuff teaches the higher hippocampal loss in presence of ApoE4 and reduced amyloid protein supports the concept that increased hippocampal loss is an indicator of Alzheimer’s disease pathology and a potential marker to assess therapeutic interventions in Alzheimer’s disease (page 1076).
However, KR20180078032 teaches shrinking cerebral cortex for Alzheimer’s disease. KR20180078032teaches cortical thickness is a risk factor for Alzheimer’s disease. Figure 2 teaches the cortical thickness from brain imaging of Alzheimer’s disease and normal patients. KR20180078032 teaches cortical atrophy refers to a value obtained by converting cortical thickness of Alzheimer’s disease patients based on a standard score calculated from cortical thickness values from a normal population. The cortical thickness may be calculated from the normal group based on the image of the normal group.
Additionally, Jia teaches measuring cortical thickness and hippocampal volume using MRI measurements. Mean values of volume, cortical thickness in 11 Alzheimer’s related brain regions were used as phenotypes (para 83). Jia teaches performing linear regression using APOE e4 status as a covariate. Jia teaches determining a baseline total cerebral cortex for use in analysis (para 85). Jia teaches hippocampal volume and cortical thickness are markers for Alzheimer’s disease.
Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention to have analyzed a human subject for APOE4 alleles, hippocampal volume, cortical thickness and amyloid status to select a patient at risk of Alzheimer’s disease. The patents and patent applications teach selecting patients at risk for Alzheimer’s disease and treating with tramiprosate prodrugs and metabolites allows for prevention of Alzheimer’s disease. The instant invention provides a set of markers, namely APOE4 alleles, hippocampal volume, cortical thickness and amyloid deposits that were previously known to be associated with Alzheimer’s disease. It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have modified the methods claimed so as to have surveyed additional markers known to be associated with Alzheimer’s disease, in order to provide a more complete picture of the potential of Alzheimer’s disease in a patient for known markers. It is prima facie obvious to combine elements, each of which is taught by the prior art to be useful for the same purpose. See MPEP 2144.06. The claims of the patent and applications select patients at risk for Alzheimer’s disease, namely APOE4 positive patients may be treated with tramiprosate to prevent Alzheimer’s disease. Jia teaches hippocampal volume and cortical thickness are also markers for Alzheimer’s diseases. Here all of the recited markers were known in the prior art to be associated with Alzheimer’s disease and tramiprosate slows the progression of Alzheimer’s. The ordinary artisan would have been motivated to combine this method with other known markers associated with Alzheimer’s disease like hippocampal volume and amyloid deposits to select and treat adults and prevent Alzheimer’s disease.
Response to Arguments
The response traverses the rejection. The response asserts the references do not teach the selected patient is asymptomatic for AD characterized by an MMSE score of 29 or greater. This argument has been reviewed but is not persuasive. ‘082 specifically provides the subject has a MMSE score of 30, is APOE4/4 homozygous (see Claim 2 of ‘082). Claims 8 and 9 are further directed to preventing. Thus, it is follows prevention occurs before the phenotype occurs. Thus, the subject has a MMSE score of 29 or greater and is thus defined as asymptomatic.
If Applicant is arguing unexpected results of the hippocampal volume loss or cortical thickness below a threshold, the arguments are not commensurate in scope with the claims because the claims are not drawn to these thresholds. Additionally, Tables 2 and 3 in the specification is directed to a difference in ApoE 3/3 and 4/4 subjects and hippocampus volume for mild AD and mild cognitive impairment. The specification does not study and provide analysis of patients with MMSE score of 29 or greater and CDR-global score of less than 0.5. The specification does not consider heterozygotes, as encompassed by the claims (pages 30 and 32 of the specification).
The cited prior art provides hippocampal volume and cortical thickness are each associated with Alzheimer’s and thus, analyzing the hippocampal volume and cortical thickness were a marker for Alzheimer’s disease and would provide a clear picture of Alzheimer’s status for a patient. Each of Figure 2 and 3 in Shuff, illustrates the normal baseline that the comparison may be made to, i.e. 5% and 10% below normal. The prior art, including Shuff, teaches normal patients are MMSE above 29, thus, determining a patient is normal or asymptomatic for Alzheimer’s disease by determining MMSE is 29 or 30 was known in the art.
Thus, for the reasons above and those already of record, the rejection is maintained.
Conclusion
No claims allowable.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Abushakra et al. J. of Prevention of Alzheimer’s Disease “Clinical effects of tramiprosate in APOE4/4 homozygous patients with mild Alzheimer’s disease suggest disease modification potential”. Vol. 4, No. 3, pages 149-156, 2017.
Abushakra et al. J. Prevention of Alzheimer’s Disease, Vol. 3, No. 4, pages 219-228, 2016. Abushakra 2016 teaches clinical benefits of tramiprosate in Alzheimer’s disease are associated with higher number of APOE4 alleles.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng (Winston) Shen can be reached on (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
August 19, 2026
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