DETAILED ACTION
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 .
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 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.
Status of the Claims
In the reply filed 8/6/25, Applicants amended claims 18, 20-29 and canceled claims 30-41. Claims 42-50 were newly added.
In the reply filed 5/11/26, Applicants amended claim 18 and added new claims 51-53.
Claims 18-29 and 42-53 are pending and are under consideration.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/11/26 was considered by the examiner.
Claim Objections-Withdrawn
The objection to claims 46-50 is withdrawn.
Claim Rejections-Withdrawn
The rejection of claims 18-29 and 42-50 under 35 U.S.C. 103 as being unpatentable over Caltagirone et al. (Aging Clin Exp Res. Vol 24 no. 6, 9/5/12) in view of Cho et al. (WO 2015/120233) and Kong et al. (US 2008/0146642 A1) is withdrawn due to amendment of the claims.
Claim Rejections - 35 USC § 103-New
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 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 18-29 and 42-50 are rejected under 35 U.S.C. 103 as being unpatentable over Caltagirone et al. (Aging Clin Exp Res. Vol 24 no. 6, 9/5/12) in view Kong et al. (US 2008/0146642 A1). This is a NEW rejection necessitated by amendment of the claims.
Caltagirone et al. teach the therapeutic efficacy of homotaurine in AD has been investigated in a pivotal Phase III clinical study that did not reach its pre-defined primary endpoints. Caltagirone et al. teach that post-hoc analysis have shown positive and significant effects of homotaurine on secondary endpoints and subgroups of patients, including a reduction in hippocampal volume loss and lower decline in memory function in the overall cohort, as well as a reduction in global cognitive decline in APOE4 allele carriers, suggesting a disease modifying effect (Abstract). Fig. 1 discloses homotaurine is tramiprosate (p. 585). With respect to the new limitation “treating Alzheimer’s disease in an ApoE4 position patient”, Caltagirone et al. teach that the benefit of cognitive function was more prominent in a homogenous population of ApoE4 positive patients (Fig. 6, p. 585), therefore tramiprosate was administered to ApoE4 positive patients. Caltagirone et al. teach long term administration of tramiprosate was safe and well tolerated (p. 586, 2nd col.).
Caltagirone et al. does not teach the administration of the Formula of claim 18, however the teachings of Kong et al. cure this deficiency.
Kong et al. teach prodrugs of 3APS (tramiprosate) for the treatment of AD (Abstract). In particular, Kong et al. teach the prodrug, compound A2 that meets the structural limitations of the Formula in claim 18 (Table 1 on page 13, paragraph [0146]; Compound A2, left column, second compound). Kong et al. teach the preferred prodrugs include compounds A2, A4, A6, A7 and A18 [0146]. Kong et al. teach that compound A2 was helpful in increasing the bioavailability of 3APS (tramiprosate) suggesting this compound was more readably absorbed than 3APS or was able to prevent first pass metabolism of 3APS. Kong et al. also compared the bioavailability of compound A2 with 3APS and teach the relative bioavailability (F %) of Compound A2 and 3APS were respectively of 51% and to 32%. A 2-fold increase in plasma concentration (Cmax) of 3APS was observed when orally administering Compound A2 compared to 3APS. Brain concentration of 3APS was observed after oral administration of 0.18 mmol/kg for Compound A2 whereas the concentration could not be quantified after oral administration of the same molar equivalent of APS ([0404], Table 10).
With respect to claims 18 and 50, It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to administer the compound A2 for the tramiprosate taught by Caltagirone et al. for treatment of AD. A person would be motivated to administer the prodrug compound A2 because Kong et al. teach that compound A2 has improved properties compared to tramiprosate, such as relative bioavailability, increased plasma concentration and brain concentration. There is a reasonable expectation of success given that Caltagirone et al. disclosed significant improvement of cognitive function of ApoE4 positive AD patients and Kong et al. disclose the pharmacokinetic benefits of compound A2.
With respect to claim 19, Caltagirone et al. teach that the benefit of cognitive function was more prominent in a homogenous population of ApoE4 positive patients (Fig. 6, p. 585), meeting the limitation of “ reduces cognitive decline in the ApoE4 positive patient”. As indicated above, it would be obvious to administer the compound of A2 in place of tramiprosate because it has improved properties, such as increased bioavailability, increased plasma and brain concentration.
With respect to claims 20-21, Caltagirone et al. teach the Phase III clinical study, where patients were administered 100 mg tramiprosate, 150 mg tramiprosate or placebo b.i.d. for 70 consecutive weeks (p. 584, 2nd col. 3rd para.), meeting the limitation of “a period of greater than 13 weeks” and “twice daily”. Kong et al. further teach that administration of the compounds of the present invention to a subject to be treated can be carried out using known procedures, at dosages and periods of time effective to achieve a desired purpose (e.g. prevention or treatment of AD). Therefore, Kong et al. indicates that the frequency and length of treatment is a result effective variable and the determination of the optimum or workable ranges of said variable maybe characterized by routine experimentation (Please see MPEP 2144 II-Optimization of Ranges). In the instant case, Caltagirone et al. teach administration of tramiprosate twice a day for 70 consecutive weeks. It would have been obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize the frequency and length of the prodrug of tramiprosate to arrive at the limitations of claims 20-21.
With respect to claims 22-25, Kong et al. teach the suitable formulations include oral [0239]. Kong et al. state that preferably, the compounds of the invention are administered orally and formulations of the invention include those suitable for oral administration [0241]. Kong et al. teach the formulations of the invention suitable for oral administration include capsules, cachets, pills, tablets etc. [0242]. Kong et al. teach PK brain and plasma levels of oral administration of compound A2 [0404].
With respect to claims 26-29, Caltagirone et al. teach the Phase III clinical study, patients were administered 100 mg tramiprosate, 150 mg tramiprosate or placebo b.i.d. for 70 consecutive weeks (p. 584, 2nd col. 3rd para.). Kong et al. teach exemplary doses include about 100mg, about 150mg, about 200mg or about 250mg [0254]. Kong et al. further teach that administration of the compounds of the present invention to a subject to be treated can be carried out using known procedures, at dosages and periods of time effective to achieve a desired purpose (e.g. prevention or treatment of AD) and dosage can be adjusted to provide the optimum therapeutic response. Therefore, Kong et al. indicates that the dosage is a result effective variable. The concentration of the active agent for treatment of a disease is a result-effective variable and the determination of the optimum or workable ranges of said variable maybe characterized by routine experimentation (Please see MPEP 2144 II-Optimization of Ranges). In the instant case, Caltagirone et al. teach the patients were administered 100 mg tramiprosate or 150 mg tramiprosate. Kong et al. teach exemplary doses include about 100mg, about 150mg, about 200mg or about 250mg [0254]. It would have been obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize the dose of the prodrug, to arrive at the dose ranges of claims 26-29.
With respect to NEW claims 42-49, Kong et al. teach the suitable formulations include oral [0239]. Kong et al. state that preferably, the compounds of the invention are administered orally and formulations of the invention include those suitable for oral administration [0241]. Caltagirone et al. teach the Phase III clinical study, patients were administered 100 mg tramiprosate, 150 mg tramiprosate or placebo b.i.d. for 70 consecutive weeks (p. 584, 2nd col. 3rd para.). Kong et al. teach exemplary doses include about 100mg, about 150mg, about 200mg or about 250mg [0254]. Kong et al. further teach that administration of the compounds of the present invention to a subject to be treated can be carried out using known procedures, at dosages and periods of time effective to achieve a desired purpose (e.g. prevention or treatment of AD) and dosage can be adjusted to provide the optimum therapeutic response. Therefore, Kong et al. indicates that the dosage is a result effective variable. The concentration of the active agent for treatment of a disease is a result-effective variable and the determination of the optimum or workable ranges of said variable maybe characterized by routine experimentation (Please see MPEP 2144 II-Optimization of Ranges). In the instant case, Caltagirone et al. teach the patients were administered 100 mg tramiprosate or 150 mg tramiprosate. Kong et al. teach exemplary doses include about 100mg, about 150mg, about 200mg or about 250mg [0254]. It would have been obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize the dose of the prodrug, to arrive at the dose ranges of claims 42-49.
NEW Claims 51 and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Caltagirone et al. (Aging Clin Exp Res. Vol 24 no. 6, 9/5/12) in view of Cho et al. (WO 2015/120233) and Kong et al. (US 2008/0146642 A1).
Caltagirone et al. teach the therapeutic efficacy of homotaurine in AD has been investigated in a pivotal Phase III clinical study that did not reach its pre-defined primary endpoints. Caltagirone et al. teach that post-hoc analysis have shown positive and significant effects of homotaurine on secondary endpoints and subgroups of patients, including a reduction in hippocampal volume loss and lower decline in memory function in the overall cohort, as well as a reduction in global cognitive decline in APOE4 allele carriers, suggesting a disease modifying effect (Abstract). Fig. 1 discloses homotaurine is tramiprosate (p. 585). Caltagirone et al. teach that the benefit of cognitive function was more prominent in a homogenous population of ApoE4 positive patients (Fig. 6, p. 585). Caltagirone et al. teach long term administration of tramiprosate was safe and well tolerated (p. 586, 2nd col.).
Although Caltagirone et al. teaches treatment of AD in ApoE4 positive subjects, Caltagirone et al. analyzed the effect of tramiprosate in ApoE4 positive patients after the study was completed. Caltagirone et al. does not teach step a) evaluating the patient’s ApoE4 status; b) selecting the patient for treatment only if the patient is ApoE4-positive, step c) administering to the ApoE4 positive patient a compound of the Formula in an amount effective to treat the disease. However, the teachings of Caltagirone et al. are suggestive of the limitation. Moreover, the teachings of Cho et al. are also suggestive of the limitation.
Cho et al. teach that ApoE4 allele is strongly associated with late-onset familial and sporadic AD, with reported allele frequency of 50-65% in patient with AD [0004]. Cho et al. teach patients who carry the ApoE4 allele may represent an etiologically distinct population of patients with AD [0004]. Cho et al. that phase two clinical studies in AD patients described demonstrate that the drug, crenzumab slows progression of disease in mild to moderate AD and has an even stronger effect in ApoE4 positive patients [0008]. Cho et al. teach Fig. 4 with the patients enrolled in the clinical trial, tabulating the number of patients enrolled, ApoE4 status and stage of AD [0019]. Cho et al. teach the patients can be ApoE4 positive or ApoE4 negative [00243, 0246]. Cho et al. specifically states that the patients were stratified according to ApoE4 status (carrier vs non-carrier) [0279].
With respect to claim 51 and 53, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to evaluate the ApoE4 status of a patient and select that patient population (ApoE4 positive) to administer an effective amount of tramiprosate because Caltagirone et al. teach a more prominent improvement in cognitive function in ApoE4 carriers administered tramiprosate. Moreover, Cho et al. teach ApoE4 positive patients are an etiologically distinct population in patients with AD and specifically states that patients with AD were stratified according to their ApoE4 status (carriers vs. non-carriers). Therefore, a person of ordinary skill in the art would look to the teaching of Caltagirone et al. and Cho et al. and would be motivated to stratify the patient population based on ApoE4 status and administer the compound to only the ApoE4 positive population since there was an effect in that population. There is a reasonable expectation of success given that Caltagirone et al. disclosed that long term administration of tramiprosate was safe and well tolerated. Moreover, methods of identification and stratification of patients based on their ApoE4 status is well known and exemplified in Cho et al.
Caltagirone et al. does not teach the administration of the Formula of claim 51, however the teachings of Kong et al. cure this deficiency.
Kong et al. teach prodrugs of 3APS (tramiprosate) for the treatment of AD (Abstract). In particular, Kong et al. teach the prodrug, compound A2 that meets the structural limitations of the Formula in claim 18 (Table 1 on page 13, paragraph [0146]; Compound A2, left column, second compound). Kong et al. teach the preferred prodrugs include compounds A2, A4, A6, A7 and A18 [0146]. Kong et al. teach that compound A2 was helpful in increasing the bioavailability of 3APS (tramiprosate) suggesting this compound was more readably absorbed than 3APS or was able to prevent first pass metabolism of 3APS. Kong et al. also compared the bioavailability of compound A2 with 3APS and teach the relative bioavailability (F %) of Compound A2 and 3APS were respectively of 51% and to 32%. A 2-fold increase in plasma concentration (Cmax) of 3APS was observed when orally administering Compound A2 compared to 3APS. Brain concentration of 3APS was observed after oral administration of 0.18 mmol/kg for Compound A2 whereas the concentration could not be quantified after oral administration of the same molar equivalent of APS ([0404], Table 10).
With respect to claims 51 and 53, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to administer the compound A2 for the tramiprosate taught by Caltagirone et al. for treatment of AD. A person would be motivated to administer the prodrug compound A2 because Kong et al. teach that compound A2 has improved properties compared to tramiprosate, such as relative bioavailability, increased plasma concentration and brain concentration. There is a reasonable expectation of success given that Caltagirone et al. disclosed significant improvement of cognitive function of ApoE4 positive AD patients and Kong et al. disclose the pharmacokinetic benefits of compound A2.
New claim 52 is rejected under 35 U.S.C. 103 as being unpatentable over Caltagirone et al. (Aging Clin Exp Res. Vol 24 no. 6, 9/5/12), Cho et al. (WO 2015/120233) and Kong et al. (US 2008/0146642 A1) as applied to claims 51 and 53 above, and further in view of Calero et al. (Journal of Neuroscience Methods 183(2009) 238-240). ‘
Although Caltigarone et al. and Cho et al. teach the patient population is ApoE4 positive, the references do not teach how the patients were genotyped. However, the teachings of Calero et al. cure this deficiency.
Calero et al. ApoE polymorphism genotyping is an important predictive of Alzheimer’s disease (Abstract). Calero et al. teach a simple, fast, cost-effective and suited for high throughput protocol for determining ApoE4 genotype (Abstract).
It would have been obvious to one of ordinary skill in the art to use the genotyping method of Calero et al. for determining the ApoE4 status of Alzheimer’s patients. A person of ordinary skill in the art would be motivated to use the method of Calero et al. because it is simple, fast and cost-effective. There is a reasonable expectation of success given that Calero et al. teach the methods of genotyping for ApoE4 status.
Response to Arguments
Applicant's arguments filed 5/1/26 have been fully considered but they are not persuasive. Applicants argue that claim 18 was amended to recite a method of treating AD in an ApoE4 positive patient in the preamble and no feature in the claim reads on treatment of ApoE4 negative patients. Applicants argue that the Examiner conceded on the record that Caltigarone does not teach limiting treatment to ApoE4 positive patients (interview 8/15/24). Applicants argue that the Office has not identified any teachings in the Kong reference that would suggest limiting to ApoE4 positive patients. Applicants argue that Cho teaches a different drug and stratifying subject after treatment for analysis, not withholding treatment from a subgroup as recited in the claims. Applicants argue that even for the sake of argument that the combined teachings suggest the claimed method, the rejection would nevertheless be overcome for additional reasons, such as unexpected results and long-felt need.
These arguments are not persuasive because Caltagirone disclosed that the treated population included ApoE4 positive patients as demonstrated by the stratification during analysis. Amended claim 18 does not require identifying, selecting or determining that a patient is ApoE4 positive before treatment nor does it limit treatment exclusively to ApoE4 patients. Rather, the claim requires only that the claimed method is carried out in an ApoE4 positive patient, a limitation satisfied because the reference teaches administration to a population that includes ApoE4 positive patients. The timing of genotype analysis does not change the fact that ApoE4 positive patients received the claimed treatment. Furthermore, the claims are drafted using “comprising” language which does not exclude additional steps (MPEP 2111.03). Therefore, the claims do not affirmatively prohibit administration of the compound to subjects who do not possess ApoE4.The claim merely requires that subjects who do possess the allele are selected for treatments and administered the compound. The arguments regarding unexpected results and long felt need are not persuasive for the reasons presented in the last office action. The Examiner responded to the declarations in detail in the previous office action. With respect to new claims 51-53, the claim requires identifying and selecting the patient population based on ApoE4 status. These limitations are obvious by Caltagirone, Kong and Cho (please see 103 above In other words, the prior art teaches a particular genetic subgroup is more likely to benefit from a known therapy and it would be obvious to limit administration to the identified responsive subgroup. Although Caltagirone analyzed the ApoE4 status after administration, the clinical significance of ApoE4 status and AD is known in the art. A person of ordinary skill in the art would have recognized the benefit of the predictive biomarker to guide treatment selection.
Double Patenting-Maintained
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. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); 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); 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) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
The rejection of claims 18-29 and 42-50 on the ground of nonstatutory double patenting as being unpatentable over claims 18-19 and 24-35 of copending Application 18/462,238 is maintained and extended to claims 51-53. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending Application claims a method of treating AD comprising administered valyl-3-amino-1-propanesulfonic acid or pharmaceutically acceptable salt thereof, wherein the composition is administered twice daily (claims 18-19, 27, 29,31, 33), wherein the subject is ApoE4 homozygous (claim 24), wherein the subject is ApoE4 heterozygous (claim 25), wherein the composition comprises 200-300mg of compound (claims 26, 28, 30, 32). Therefore, the copending Application claims treatment of AD with the same compound (valyl-3-amino-1-propanesulfonic acid is the same compound as instantly claimed) in subjects that are ApoE4 homozygous or heterozygous. Although the copending Application does not specifically claim the “assessing” step, the step would necessarily have been done in order to identify the ApoE4 status of the patients. The dose range of the copending application meets the limitation of claims 18-29 and 42-53.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The rejection of claims 18-29 and 42-50 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-6, 8, 11, 15-17, 19, 21, 31-33,35-36 of copending Application No. 18/717,139 (reference application) is maintained and extended to claims 51-53. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending application meets the limitations of the instant claims. The copending Application claims a method of treating AD having an MMSE score of 21 or less with 700 mg/day of ALZ-801 (claims 1-6, 8, 11, 15-17, 19, 21, 31-33,35). ALZ-801 is the same compound as instantly claimed. The copending Application claims the subject is APOE4 homozygous. Although the copending Application does not specifically claim the “assessing” step, the step would necessarily have been done in order to identify the ApoE4 status of the patients. The dose and length of treatment is a result-effective variable and the determination of the optimum or workable ranges of said variable maybe characterized by routine experimentation (Please see MPEP 2144 II-Optimization of Ranges). In the instant case, the copending Application teaches 400-800 mg/day for a first and second period of time. It would have been obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize the dose and length of treatment, to arrive at the limitations of claims 18-29 and 42-53.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The rejection of claims 18-29 and 42-50 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18/793,452 (reference application) is maintained and extended to claims 51-53. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending application meets the limitations of the instant claims. The copending Application claims a method of selecting and treating a subject with AD comprising selected the subject if the concentration of 3-SPA in the CNS fluid is less than 25 ng/ml and administering Formula I. When AA1 is Val and t is 0, the Formula meets the limitations of the instantly claimed compound. The compound of claims 39-44 is identical to the compound instantly claimed. The copending Application the subject is only administered the compound if the subject is ApoE4 homozygous (claims 30-32). Although the copending Application does not specifically claim the “assessing” step, the step would necessarily have been done in order to identify the ApoE4 status of the patients. The dose and length of treatment is a result-effective variable and the determination of the optimum or workable ranges of said variable maybe characterized by routine experimentation (Please see MPEP 2144 II-Optimization of Ranges). It would have been obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize the dose and length of treatment, to arrive at the limitations of claims 18-29 and 42-53.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The rejection of claims 18-29 and 42-50 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 6-22 of copending Application No. 19/135,046 (reference application) is maintained and extended to new claims 51-53. The copending Application claims a method of treating AD comprising administering tramiprosate or tramiprosate prodrug and co-administering an amyloid plaque clearing agent (Claim 1). Please note that the instant claims use “open” comprising language and the claim does not preclude other agents co-administered with the compound. The instant compound is a tramiprosate prodrug and is identical to the compound of the copending claims 3 and 22. The copending Application claims the subject is only treated if the subject is ApoE4 positive or homozygous (claims 19-20). Although the copending Application does not specifically claim the “assessing” step, the step would necessarily have been done in order to identify the ApoE4 status of the patients. The dose and length of treatment is a result-effective variable and the determination of the optimum or workable ranges of said variable maybe characterized by routine experimentation (Please see MPEP 2144 II-Optimization of Ranges). It would have been obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize the dose and length of treatment, to arrive at the limitations of claims 18-29 and 42-53.
Response to Arguments
Applicant's arguments filed 5/1/26 have been fully considered but they are not persuasive. Applicants request abeyance of the double patenting rejection until allowable subject matter is indicated.
These arguments were considered but are not persuasive as the no allowable subject matter has been indicated.
The rejection of claims 18-29 and 42-50 on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12,083,082 in view of Kong et al. is maintained and extended to new claims 51-53. The USPN claims a method of treating AD comprising administering 3-APS (claims 1-5 and 8-9). The USPN claims 3-APS is administered the compound only if ApoE4 homozygous or heterozygous (claims 6-7). Although the copending Application does not specifically claim the “assessing” step, the step would necessarily have been done in order to identify the ApoE4 status of the patients. The dose and length of treatment is a result-effective variable and the determination of the optimum or workable ranges of said variable maybe characterized by routine experimentation (Please see MPEP 2144 II-Optimization of Ranges). It would have been obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize the dose and length of treatment, to arrive at the limitations of claims 18-29 and 42-50. The USPN does not claim the compound is ALZ-801, however the teachings of Kong et al. cure this deficiency. The teachings of Kong et al. are presented in detail above (103 rejection). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to administer the compound A2 for the 3APS taught by the USPN for treatment of AD. A person would be motivated to administer the prodrug compound A2 because Kong et al. teach that compound A2 has improved properties, such as relative bioavailability, increased plasma concentration and brain concentration. There is a reasonable expectation of success given that Kong et al. disclose the pharmacokinetic benefits of compound A2.
Response to Arguments
Applicant's arguments filed 5/1/26 have been fully considered but they are not persuasive. Applicants argue that the rejection has been overcome because of the amendments and arguments presented above.
These arguments were considered but are not persuasive for the reasons presented above.
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 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 TARA L MARTINEZ whose telephone number is (571)270-1470. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/TARA L MARTINEZ/Primary Examiner, Art Unit 1654
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