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.
Please note this is a 2nd Non-Final to address NEW Double patenting rejections.
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 are newly added.
Claims 18-29 and 42-50 are pending and are under consideration.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/6/25 was considered by the examiner.
Claim Rejections - Withdrawn
The rejection of claims 18 and 30 under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter is withdrawn due to amendment of the claims
Claim Objections
New claims 46-50 are objected to because of the following informalities: the claims are missing a period at the end of the claim. Appropriate correction is required.
Claim Rejections - 35 USC § 103-Maintained
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.
The rejection of claims 18-29 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 maintained and extended to NEW claims 42-50.
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) selecting the patient for treatment on the basis of the patient being ApoE4-positive, step b)administering to the ApoE4 positive patient a compound of the Formula in an amount effective to treat the disease and the limitation “wherein if the patient is ApoE4 negative, the patient is not administered the compound. 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 18, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to receive the information on 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 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 30, 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, Caltigirone 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 42-50, 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 42-50.
Response to Arguments
Applicant's arguments filed 8/6/25 have been fully considered but they are not persuasive. Applicants argue that the claimed method selects for treatment only those patients with one or more ApoE4 alleles and withholds treatment from all patients without ApoE4 allele. Applicants argue that Caltagirone merely shows that Apo-E4 positive patients with tramiprosate show reduced decline in one particular measure of AD—ADAs-cog scores as compared with placebo. Applicants argue that the Examiner does not mention such treatment should be limited to ApoE4 positive patients. Applicants state that Declaration by Dr. Sampalis (previously submitted) supports Applicants position. Applicants argue that the Declaration the ApoE4 subgroup analysis in Fig. 6 (of Caltagirone) would not suggest limiting tramiprosate treatment of apoE4 positive AD patients. Applicants argue that the Declaration states that while the ApoE4 positive subgroup demonstrated a significant overall treatment effect in favor of tramiprosate for ADAS-cog, the authors did not suggest omitting AD subject from tramiprosate treatment (ApoE4 negative patients). Applicant argue that separately analyzing ApoE4 positive patients in the first place was completely unrelated to analyzing or looking for some type of patient stratification, but rather it was based on statistical needs. Applicants argue that assessing the treatment effects of tramiprosate in subgroups of patients that are genetically and possibly phenotypically homogenous, the effect of known and unknown covariates that can artificially increase the variability in response to outcome assessments. Applicants argue that the results are a statistically clearer standard error and does not suggest that tramiprosate treatment was effective in only that subgroup of patients. Applicants argue that Dr. Sampalis is uniquely qualified to provide this insight because he oversaw the early statistical analysis of the data from those trials. Applicants argue its counterintuitive and defies reasonableness to withhold treatment from a patient class (ApoE4 negative patients) that have been shown to reap benefits from the treatment, even if the benefits are not as qualitatively or quantitively as beneficial. Applicants argue that since Caltigarone is reporting some positive benefits in some subjects, the art effectively teaches away from the instant claims. Applicants argue that the Examiner has failed to explain why PHOSITA after seeing the data in Caltagirone on the benefits to the entire cohort would conclude that the ApoE4 negative patients should not be treated. Applicant argue that Cho does not define “stratify”. Applicants argue that the ordinary meaning of “stratify” is to divide or arrange a group into subpopulations (strata).Applicants argue that Cho merely teaches patients were subdivided into subpopulations based on their ApoE4 status. Applicants argue that there was no motivation to achieve the claimed invention. Applicants also argue that Cho does not suggest withholding treatment from ApoE4 negative subjects and the compound is different than what is instantly claimed. Applicants argue that the combined references of Caltagirone, Cho and Kong does not suggest selecting for ApoE4 positive patients and treating only those patients with ALZ-801, while not treating negative patients. Applicants further argue that administration of ALZ-801 exhibited pronounced and statistically significant effects in patients with one or more ApoE4 alleles. Applicants argue that the previously presented declaration by Dr. Abushakra discloses a significant and meaningful benefit on a composite cognitive and functional measure over 78 weeks of treatment compared to placebo in patients with one ApoE4 allele. Applicants argue that there was no clinical benefit in a dementia rating scale in ApoE4 negative patients. Applicants argue that the absence of a property which a claimed invention would have been expected to possess based on the teaching of the prior art is evidence of nonobviousness. Applicants argue that PHOSITA would have expected tramiprosate and ALZ-801 to be effective in treating AD in ApoE4 negative patients. However, the data in Fig. 8 (instant application) and in the Abushakra declaration show that tramiprosate has no positive effect. Applicants further discuss the Hey Declaration that was previously submitted disclosing long felt need and failure of others. The Hey Declaration disclosed treatment options of AD at the filing date of the instant application were limited to agents that treated certain symptoms of AD, however the treatments were not curative of disease modifying.
These arguments are not persuasive because the claims do not require withholding treatment of ApoE4 negative patients. The instant claims do not preclude treatment of all patients with ALZ-801 because the claims do not disclaim treatment of ApoE4 negative patients. 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 claims do not preclude or disclaim treatment of all subjects. The argument that it effectively teaches away is not persuasive because the references do not criticize, discredit or otherwise discourage treatment of ApoE4 negative patients.
Importantly, Caltagirone et al. teach that post-hoc analysis have shown positive and significant effects of tramiprosate on subgroups of patients, including a reduction in global cognitive decline in APOE4 allele carriers, suggesting a disease modifying effect (Abstract). 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). Fig. 6 of Caltagirone disclose a significant overall treatment effect in favor of tramiprosate for ADAS-cog in the ApoE4+ subgroup. Therefore, a person of ordinary skill in the art would be motivated to receive the information on 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. Cho et al. teach that ApoE4 allele is strongly associated with late-onset familial and sporadic AD and patients who carry the ApoE4 allele may represent an etiologically distinct population of patients with AD. Cho et al. teach 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 and ApoE4 status. Cho et al. specifically states that the patients were stratified according to ApoE4 status (carrier vs non-carrier) [0279]. 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. 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 identifying and stratification of patients based on their ApoE4 status is well known and exemplified in Cho et al. The arguments about the definition of “stratify” is not persuasive. Cho et al. specifically states that the patients were stratified according to ApoE4 status (carrier vs non-carrier) [0279]. 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 the ApoE4 positive population since there was an effect in that population.
With respect to the Declaration by Dr. Sampalis: it would have been obvious to receive the information on 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 and 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. 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. There is a reasonable expectation of success given that the methods of identified and stratification of patients based on their ApoE4 status is well known and exemplified in Cho et al. Although Dr. Sampalis states that the data was analyzed based on ApoE4 status for statistical reasons, a person of ordinary skill in the art would look to the data presented (more prominent improvement in cognitive function in ApoE4 carriers administered tramiprosate) and be justified in treating AD based on ApoE4 status. Data disclosing a more prominent effect in a subpopulation would be sufficient to suggest stratifying the patient population based on ApoE4 status.
With respect to the Declaration by Dr. Abushuka: it would have been obvious to receive the information on 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 and 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. Therefore, the results in the Declaration are not surprising or unexpected, since 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). MPEP 716.02(c) II states: II. EXPECTED BENEFICIAL RESULTS ARE EVIDENCE OF OBVIOUSNESS “Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof.” In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967) (resultant decrease of dental enamel solubility accomplished by adding an acidic buffering agent to a fluoride containing dentifrice was expected based on the teaching of the prior art); Ex parte Blanc, 13 USPQ2d 1383 (Bd. Pat. App. & Inter. 1989) (Claims at issue were directed to a process of sterilizing a polyolefinic composition which contains an antioxidant with high-energy radiation. Although evidence was presented in appellant’s specification showing that particular antioxidants are effective, the Board concluded that these beneficial results would have been expected because one of the references taught a claimed antioxidant is very efficient and provides better results compared with other prior art antioxidants.). In the instant case, the results are expected in view of the teachings of Caltagirone et al. and Cho et al.
With respect to the Hey Declaration: the declaration was insufficient to overcome the rejection of the claims because the claims are obvious over Caltagirone et al. and Cho et al. The MPEP 2141 states “The mere fact that an applicant has presented evidence does not mean that the evidence is dispositive of the issue of obviousness. The question of obviousness must be resolved on the basis of the factual inquiries set forth above. While each case is different and must be decided on its own facts, these factual inquiries, including secondary considerations when present, are the controlling inquiries in any obviousness analysis.”. In the instant case, a strong case of obviousness was presented in the 103 rejection above. Importantly, the same drug as claimed (Tramiprosate) was shown in Caltagirone et al. as a potential treatment for AD. The data from Fig. 8 is not sufficient to disclose unexpected results because the ApoE4 group comprises both ApoE4 +/+ and ApoE4 +/. As seen in the figure there is a significant different in the ApoE4 +/+ group and the non ApoE4 group. However, there is no data presented that discloses unexpected results for Apo E4 +/- group. Importantly, Caltigarone et al. and Cho et al. make obvious administering tramiprosate to the same population. The population of Caltagirone et al. do not stratify based on ApoE4 homozygous or heterozygous. The MPEP 2145 states: “Evidence pertaining to secondary considerations must be taken into account whenever present: however, it does not necessarily control the obviousness conclusion”. The evidence was considered by the Examiner, however the teachings of Caltagirone et al. and Cho et al. make obvious the claimed invention.
For the reasons presented above, the rejection is maintained.
New Rejections
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. 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.
Claims 18-29 and 42-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18-19 and 24-35 of copending Application 18/462,238. 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 42-50.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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). 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 42-50.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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). 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 42-50.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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). 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-adminstered 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 42-50.
Claims 18-29 and 42-50 are rejected 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. 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.
Conclusion
No claims are allowed.
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/TARA L MARTINEZ/Examiner, Art Unit 1654