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 .
Detailed Action
Response to Amendments
The amendments made to the claims 10/01/2025 have been entered.
The amendments made to the specification 10/01/2025 have been entered.
Status of Claims
Claims currently pending and under examination are claims 7-15.
Specification
In view of the amendments made, the objection to the specification has been withdrawn.
Modified Rejection
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 7-15 is/are under 35 U.S.C. 103 as obvious over Puzzo (J. Neurosci, 2009, 29(25), of the record).
Puzzo is drawn to phosphodiesterase 5 Inhibition as a method of improving synaptic function, memory, and Amyloid-β Load in Alzheimer’s disease (title). Puzzo throughout the reference discusses the PDE5 inhibitor sildenafil.
In regards to claim 7, Puzzo on p. 8085, left col., para 2 states “Our findings strongly support the hypothesis that inhibition of PDE5 can be beneficial against cognitive loss in [Alzheimer’s Disease].
Regarding the limitation regarding administering sildenafil or mirodenafil daily over 4 weeks, Puzzo in sec. Drug Administration, para. 1 states “For assessment of long-term effects, sildenafil was given daily by intraperitoneal injection at a concentration of 3mg/kg for 3 weeks, and then treatment was stopped 9-12 weeks before behavioral testing.” Additionally, Puzzo on p. 6, text of Fig. 2, Bullet D states “The minimum concentration of sildenafil needed to improve spatial working memory in APP/PS1 mice is 3 mg/kg for 3 weeks.” Since Puzzo teaches a minimum daily administration over 3 weeks, one of ordinary skill in the art would find it obvious to extend this period to 4 weeks.
In regards to claim 15, Puzzo on p. 8078-8079, sec. Acute effects of sildenafil on the cognitive function of APP/Pδ1 mice teaches that “Sildenafil treatment improved contextual learning in the transgenic animals.”
In regards to claims 8-14, the language of the claims implies that the claimed elements are effects that are brought on by the composition of claim 16. Essentially, the claim elements are consequence of administering the composition comprising sildenafil and would be made obvious by the combination Puzzo which makes obvious administering sildenafil to treat Alzheimer’s Disease.
Therefore, it would have been prima facie obvious at the time of the effective filing date for one of ordinary skill in the art to have taken the teachings of Puzzo and arrive at the instant claims with a reasonable assumption of success. Puzzo teaches administering a PDE5 inhibitor, specifically sildenafil, to treat cognitive loss associated with Alzheimer’s Disease.
Response to Arguments
Applicant argues that “Puzzo is drawn to PDE5 inhibition generally, where a PDE5 inhibitor may improce sunaptic function, memory, and amyloid-beta load in a transgenic mouse model.” Applicant continues “Sildenafil is selected in Puzzo merely because it is known to cross the blood—brain barrier. While memory loss, synaptic dysfunction, and accumulation of amyloid beta-peptides are major indicators of Alzheimer’s Disease, Puzzo, as a whole, is, at best, speculative that PDE5 inhibitors in general,…can be beneficial against cognitive loss in Alzheimer’s Disease. Simply put, Puzzo does not show an expectation of success that using any PDE5 inhibitor would treat Alzheimer’s Disease in a human subject let alone sildenafil.”
Puzzo’s full title is “Phosphodiesterase 5 Inhibition Improves Synaptic Function, Memory, and Amyloid-β Load in an Alzheimer’s Disease mouse model.” Additionally, Puzzo in its Introduction states “Alzheimer’s disease (AD) is characterized by neuronal loss, extracellular senile plaques, and intracellular neurofibrillary tangles, leading to memory loss.” Puzzo in sec. Discussion further states “The present study shows novel findings demonstrating that a treatment with the PDE5 inhibitor sildenafil rescues synaptic and memory deficits in a transgenic mouse model of amyloid deposition. Sildenafil also re-establishes the increase in phosphorylation of the transcription factor and memory molecule CREB. In addition, the inhibitor counteracts the negative effects pf high levels of Aβ on synaptic function, memory, and CREB phosphorylation, not only immediately, but also for a prolonged period beyond the drug administration.
The instant specification discusses treatment, but never explicitly defines “treatment”. The broadest reasonable interpretation includes amelioration of symptoms characteristic to Alzhiemer’s Disease, which includes those symptoms discussed by Puzzo. Therefore, the teachings of Puzzo read on the instant claims as Puzzo teaches symptom amelioration and/or cognitive improvement from administering sildenafil.
Applicant’s emphasis on treatment within a human subject is also not persuasive. The pharmaceutical arts rely on animal models and in vitro models largely to test the potential effectiveness of compounds and/or compositions in human subjects. As the art indicates effectiveness within an animal model, one of ordinary skill would then find it obvious to apply the method towards a human subject.
Maintained Claim Rejection - 35 USC § 103
Claim(s) 7-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Puzzo (J. Neurosci, 2009, 29(25), of the record) in view of Naef (WO2018/215433 A1, of the record).
Puzzo is drawn to phosphodiesterase 5 Inhibition as a method of improving synaptic function, memory, and Amyloid-β Load in Alzheimer’s disease (title). Puzzo throughout the reference discusses the PDE5 inhibitor sildenafil.
In regards to claim 7, Puzzo on p. 8085, left col., para 2 states “Our findings strongly support the hypothesis that inhibition of PDE5 can be beneficial against cognitive loss in [Alzheimer’s Disease].
Regarding the limitation regarding administering sildenafil or mirodenafil daily over 4 weeks, Puzzo in sec. Drug Administration, para. 1 states “For assessment of long-term effects, sildenafil was given daily by intraperitoneal injection at a concentration of 3mg/kg for 3 weeks, and then treatment was stopped 9-12 weeks before behavioral testing.” Additionally, Puzzo on p. 6, text of Fig. 2, Bullet D states “The minimum concentration of sildenafil needed to improve spatial working memory in APP/PS1 mice is 3 mg/kg for 3 weeks.” Since Puzzo teaches a minimum daily administration over 3 weeks, one of ordinary skill in the art would find it obvious to extend this period to 4 weeks.
In regards to claim 15, Puzzo on p. 8078-8079, sec. Acute effects of sildenafil on the cognitive function of APP/Pδ1 mice teaches that “Sildenafil treatment improved contextual learning in the transgenic animals.”
Puzzo does not explicitly teach mirodenafil. This is addressed by Naef.
Naef discusses phosphodiesterase (PDE) inhibitors in combination with guanylate cyclase activators. Naef on p. 144, Table 1 teaches the % inhibition and IC50 of the compound sildenafil and mirodenafil. These values were measured in a Phosphodiesterase-5 activity assay as discussed on p. 143-144, Example 110.
Mirodenafil showed a % inhibition (at 5.0E-09 M) of 64.9% compared to sildenafil’s 49.9%. The IC50 value for mirodenafil was also measured at 3.4x10-10, which is an improvement over sildenafil’s 5.4x10-9.
Therefore, one of ordinary skill in the art would find motivation to replace sildenafil with mirodenafil for its improve pharmacokinetic values.
In regards to claims 8-14, the language of the claims implies that the claimed elements are effects that are brought on by the composition of claim 16. Essentially, the claim elements are consequence of administering the composition comprising mirodenafil and would be made obvious by the combination Puzzo and Naef which makes obvious administering mirodenafil to treat Alzheimer’s Disease.
Therefore, it would have been prima facie obvious at the time of the effective filing date for one of ordinary skill in the art to have combined the teachings of Puzzo and Naef and arrive at the instant claims with a reasonable assumption of success. Puzzo teaches administering a PDE5 inhibitor, specifically sildenafil, to treat cognitive loss associated with Alzheimer’s Disease and Naef teaches the improved properties of mirodenafil over sildenafil.
One of ordinary skill in the art would find motivation to use mirodenafil in place of sildenafil as Naef teaches improved pharmacokinetic properties of mirodenafil.
Response to Arguments
Applicant argues that “one skilled in the art would replace Puzzo’s sildenafil with Naef’s dual-pharmacology NO-releasing inhibitor” instead of replacing sildenafil with mirodenafil.
This is not persuasive because the test for obvious is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Naef may focus on its own dual pharmacological NO-releasing inhibitor, but in its teaching it also teaches the pharmacokinetic properties of mirodenafil. These properties are superior to sildenafil which is sufficient motivation to modify the method in Puzzo.
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 7-15 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 9,271,916 in view of Puzzo (J. Neurosci, 2009, 29(25), of the record) in view of Naef (WO2018/215433 A1, of the record).
Dependent reference claim 3 states “The method of claim 2, wherein the PDE5 inhibitor is mirodenafil, or a pharmaceutically acceptable salt, solvate, or hydrate.”
Puzzo teaches the effectiveness of PDE inhibitors against Alzheimer’s Disease. Naef teaches improved properties of mirodenafil. Puzzo also teaches daily administration over the course of a minimum of 3 weeks. Therefore, the instant claims are made obvious over the reference claims in view of the references cited.
Response to Arguments
In response to applicant's argument that US Pat. 9,271,916 is non-analogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, the U.S. Patent. ‘916 is drawn to a method for reducing skin wrinkles in a subject comprising administering a phosphodiesterase 5 (PDE5) inhibitor. The instant claims are drawn to a method of treating Alzheimer’s Disease comprising administering a PDE5 inhibitor. The critical difference between the claims are simply the intended use. Both claim sets still involve administering a PDE5 inhibitor. As Puzzo teaches the effectiveness of one PDE5 inhibitor towards treating Alzheimer’s disease, one of ordinary skill would find it obvious to repurpose the method of U.S. Patent. ‘916 towards treating Alzheimer’s disease.
The MPEP section 2112, subsection I states:
“[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
The rejection is maintained.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. 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.
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/L.G./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624