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
Claims 43, 45-46, 49, 51, 55-56, 58-59, 63-66 and 68-73 are pending in the present application.
AMENDMENTS
The amendments and reply filed 06/27/2025 have been acknowledged and entered in the present application file.
Previous Claim Rejections - 35 USC § 112
Claims 55-56 were previously rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Applicant has amended claims 55 and 56 to remove the indefinite subject matter.
The rejection of 02/27/2025 is withdrawn.
Previous Claim Rejections - 35 USC § 103
Claims 43-49, 51-52, 58-59 and 63-69 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2006/035034 A1 (Peters et al.), in view of Higgins (Higgins, A., et al. Drug, healthcare and patient safety (2010): 141-150.) and US 2011/0201617 A1 (Moore et al.).
Claims 55-56 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2006/035034 A1 (Peters et al.), in view of Higgins (Higgins, A., et al. Drug, healthcare and patient safety (2010): 141-150.), US 2011/0201617 A1 (Moore et al.) and Mazzilli (Mazzilli, R., et al. Archivio Italiano di Urologia e Andrologia 90.1 (2018): 44-48.).
Applicant has amended the claims and traversed the previous rejections on grounds the compound of present formula (I) as disclosed by Peters functions by mechanisms known to induce erectile dysfunction (ED), there was a long, unmet need for treating ED that arose as a result of treatment with an antidepressant, and there was no reasonable expectation of success in treating antidepressant treatment-emergent ED using the compound of Peters. See pages 8-9 and 12-13 of Applicant’s remarks filed 06/27/2025. Applicant alleges “there is no evidence that any compound could or would successfully treat antidepressant treatment-emergent ED”. See Applicant’s remarks Applicant refers to examples where the compound of present formula (I) is alleged as suitable for combination treatment of ED and depression as well as clinical trial data where some subjects also under treatment with SSRIs saw improvements in symptoms of ED. See pages 9 and 10 of Applicant’s remarks filed 06/27/2025.
The Examiner has considered the amendment and traversal fully but must disagree for the following reasons.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). See MPEP 2145, Section IV. The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006). See MPEP 2144, Section IV.
With regards to the compound of present formula (I) as disclosed by Peters being known to induce erectile dysfunction (ED), Moore also discloses compounds which inhibit serotonin reuptake as suitable for the treatment of ED in a patient who has previously received, or is concurrently taking, an antidepressant. See paragraph 37-38, 49, 54, and 59 of Moore.
Conclusive proof of efficacy is not required to show a reasonable expectation of success. See MPEP 2143.02, Section I. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")).
Peters discloses instant formula (I) as suitable for treatment of diseases response to monoamine neurotransmitter re-uptake in the CNS, including anxiety, depression, sexual dysfunction, major depressive disorder, mild depression and low mood. One of skill in the art would have a reasonable expectation that the compound of Peters, having potentially similar activity disclosed as the compounds of Moore, would provide similar benefit to a patient experiencing ED who has previously received, or is concurrently taking, an antidepressant.
Although Peters may have disclosed ED in a list of diseases, this does not alter the conclusion of obviousness based on the combination of references, which provides the motivation for one of skill in the art to administer a compound of present formula (I) to a subject having ED, whether or not previously treated with an antidepressant. Peters also includes a number of diseases related to sexual dysfunction of both males and females, adding to the reasonable expectation of success towards the usefulness of the compound of present formula (I).
The remarks filed 06/27/2025 as they relate to unexpected results have been considered but they are not found persuasive since they are arguments of counsel, which cannot take the place of evidence in the record. See MPEP 716.01(c). The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. Applicant’s arguments rebutting a reasonable expectation of success regarding the clinical trial data is not persuasive as the data does not qualify as relevant prior art having been published after the effective filing date of the present application. Further consideration of compound of formula (I) as improving sexual dysfunction in said subjects not considered in analysis of obviousness.
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). See MPEP 716.02 (d) and MPEP 716.02 (e). Applicant refers to alleged unexpected results; however, even if the results were considered unexpected, the results would not be commensurate in scope with the scope claims. Further, the results provided do not occur over the entire claimed range (a method for treatment, prevention, or alleviation of antidepressant treatment-emergent ED comprising any amount of dosage of a compound of present formula (I) administered in any dosing schedule) of present claim 43.
With regards to there was a long, unmet need for treating ED that arose as a result of treatment with an antidepressant, while the persistent need for such treatment has existed, Moore and Mazzilli disclose inventions which meet the need for treating treatment-emergent ED. Moore discloses 1-[2-(2,4-dimethylphenyl-sulfanyl)-phenyl]piperazine, as suitable for the treatment erectile dysfunction in a patient who has previous received treatment with an antidepressant such as selective serotonin reuptake inhibitors (SSRIs) or selective noradrenalin reuptake inhibitor (SNRIs/NRIs). Mazzilli discloses the efficacy of PDE5-i in relieving ED in patients with psychotropic-associated ED who continue on their psychotropic medication.
The fact the claims encompass treatment as well as prevention means practicing the method of the prior art would entail administration to a patient population embraced by the instant claims, subjects experiencing depressive symptoms unrelated to substance or addictive disorders. One of ordinary skill would have a reasonable expectation of success towards treating or preventing erectile dysfunction in a subject previously treated with an antidepressant based on the guidance provided by the combination of Peter, Moore and Higgins, and further still Mazzilli.
Therefore, the claims remain prima facie obvious and the rejections of 02/27/2025 are maintained in an amended form due to Applicant’s amendments.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 43, 45-46, 49, 51, 58-59, 63-66 and 69-73 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2006/035034 A1 (Peters et al.), in view of Higgins (Higgins, A., et al. Drug, healthcare and patient safety (2010): 141-150.) and US 2011/0201617 A1 (Moore et al.).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Peters discloses compounds of formula (I), comprising instant formula (I), exo-7-(8-Methyl-8-aza-bicyclo[3.2.1]oct-3-yloxy)-chromen-2-one, as suitable for treating, preventing or alleviating anxiety, depression and sexual dysfunction. See page 15, Method D where Peters discloses the preparation of a HCl salt of a compound of instant formula (I) as well as claims 1, 9 and 12-13. Peters also discloses instant formula (I) as suitable for treatment of diseases response to monoamine neurotransmitter re-uptake in the CNS. See page 13, third paragraph; page 8-9. Peters provides where a compound of instant formula (I) can be administered orally, topically or parenterally (see present claims 58-59). See page 9, line 30 to page 12, line 33. Peters also discloses where the compounds of the invention are suitable for the treatment of erectile difficulty, erectile dysfunction, major depressive disorder, mild depression, low mood and anxiety in claim 13 (see present claims 63-67).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Peters does not disclose a method of treatment, prevention or alleviation of erectile dysfunction in a subject treated with an antidepressant comprising administering a compound of present formula (I). Peters also does not disclose where the subject was treated with a selective serotonin reuptake inhibitor (SSRI) or selective noradrenalin reuptake inhibitor (SNRI) antidepressant agent.
Finding of prima facie obviousness --- rationale and motivation (See
MPEP § 2142-2143)
Higgins discloses where sexual dysfunction is a common side effect of antidepressants, particularly of selective serotonin reuptake inhibitor (SSRIs) and serotonin norepinephrine reuptake inhibitor (SNRIs) medications (see present claims 46 and 68). See abstract and page 142, column 1. Higgins discloses in Table 1 where the administration of SSRIs (fluoxetine, paroxetine, etc.) and SNRIs (venlaxifene and duloxetine) causes treatment-emergent erectile dysfunction in men (see present claims 51-52).
Moore discloses compound (I), 1-[2-(2,4-dimethylphenyl-sulfanyl)-phenyl]piperazine, as suitable for the treatment of depression, anxiety and erectile dysfunction in a patient who has previous received treatment with an antidepressant such as selective serotonin reuptake inhibitors (SSRIs) or selective noradrenalin reuptake inhibitor (SNRIs/NRIs). See paragraphs 26, 37, 49, 54, 59 and claims 1 and 28. Moore discloses where compound (I) is an antidepressant with serotonin reuptake inhibitor activity.
Moore teaches that treatment with anti-depressants in general and SSRI's in particular may be associated with sexual dysfunction and which frequently leads to discontinuation of the treatment. See paragraph 46 of Moore.
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
As Peters, Higgins and Moore disclose compositions comprising instant formula (I) and either selective serotonin reuptake inhibitor (SSRIs) or selective noradrenalin reuptake inhibitor (SNRIs) as antidepressant agents, it would have been obvious to combine the two compositions to form a fourth composition with similar suitability for treating depression.
Higgins and Moore teach where erectile dysfunction is an adverse event which emerges from the treatment of depression with SSRI or SNRI agents. Moore provides methods for treating erectile dysfunction in a subject previously treated with a SSRI or SNRI agent. Peters discloses where a compound of instant formula (I) is suitable for the treatment of sexual dysfunction and further still erectile dysfunction.
The instant claims would be embraced when one of ordinary skill in the art is administering instant formula (I) in combination with an antidepressant agent, such as paroxetine or duloxetine, as the claims are directed to treatment and prevention and a male patient would reasonably be expected to have erectile dysfunction from the antidepressant agents or require prevention thereof. There would be a reasonable expectation that the compound of Peters, having potentially similar activity disclosed as the compounds of Moore, would provide similar benefit to a patient experiencing ED who has previously received, or is concurrently taking, an antidepressant. One of ordinary skill would have a reasonable expectation of success towards treating or preventing erectile dysfunction in a subject previously treated with an antidepressant based on the guidance provided by the combination of Peter, Moore and Higgins.
Regarding claims 70-73, Peters discloses where the compound of present formula (I) is suitable for treatment and prevention of both ED and depression. The combination of Peters, Higgins and Moore disclose a composition for treating depression comprising a compound of formula (I). One of skill in the art would have a reasonable expectation of success towards treating depression based on the combination of references as well as treating ED based on the diseases disclosed as treatable by the compound of Peters. Nonetheless, claims 70-73 include the term prevention which a male patient would reasonably be expected to have depression, requiring treatment with antidepressant agents, and/or erectile dysfunction from the antidepressant agents or require prevention thereof. There would be a reasonable expectation that the compound of Peters, having potentially similar activity disclosed as the compounds of Moore, or the combined composition of Peters, Higgins and Moore for depression, would provide similar benefit to a patient experiencing ED who has previously received, or is concurrently taking, an antidepressant.
Therefore, the present claims are prima facie obvious.
Claims 55-56 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2006/035034 A1 (Peters et al.), in view of Higgins (Higgins, A., et al. Drug, healthcare and patient safety (2010): 141-150.), US 2011/0201617 A1 (Moore et al.) and Mazzilli (Mazzilli, R., et al. Archivio Italiano di Urologia e Andrologia 90.1 (2018): 44-48.).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Peters discloses compounds of formula (I), comprising instant formula (I), exo-7-(8-Methyl-8-aza-bicyclo[3.2.1]oct-3-yloxy)-chromen-2-one, as suitable for treating, preventing or alleviating anxiety, depression and sexual dysfunction. See page 15, Method D where Peters discloses the preparation of a HCl salt of a compound of instant formula (I) as well as claims 1, 9 and 12-13. Peters also discloses instant formula (I) as suitable for treatment of diseases response to monoamine neurotransmitter re-uptake in the CNS. See page 13, third paragraph; page 8-9. Peters provides where a compound of instant formula (I) can be administered orally, topically or parenterally. See page 9, line 30 to page 12, line 33. Peters also discloses where the compounds of the invention are suitable for the treatment of major depressive disorder, mild depression, low mood and anxiety in claim 13.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Peters does not disclose a method of treatment, prevention or alleviation of erectile dysfunction in a subject treated with an antidepressant comprising administering a compound of present formula (I). Peters does not disclose where the subject is a male below 40 years of age or over the age of 20.
Finding of prima facie obviousness --- rationale and motivation (See
MPEP § 2142-2143)
Higgins discloses where sexual dysfunction is a common side effect of antidepressants, particularly of selective serotonin reuptake inhibitor (SSRIs) and serotonin norepinephrine reuptake inhibitor (SNRIs) medications. See abstract and page 142, column 1. Higgins discloses in Table 1 where the administration of SSRIs (fluoxetine, paroxetine, etc.) and SNRIs (venlaxifene and duloxetine) causes treatment-emergent erectile dysfunction in men.
Moore discloses compound (I), 1-[2-(2,4-dimethylphenyl-sulfanyl)-phenyl]piperazine, as suitable for the treatment of depression, anxiety and erectile dysfunction in a patient who has previous received treatment with an antidepressant such as selective serotonin reuptake inhibitors (SSRIs) or selective noradrenalin reuptake inhibitor (SNRIs/NRIs). See paragraphs 26, 37, 49, 54, 59 and claims 1 and 28. Moore discloses where compound (I) is an antidepressant with serotonin reuptake inhibitor activity.
Moore teaches that treatment with anti-depressants in general and SSRI's in particular may be associated with sexual dysfunction and which frequently leads to discontinuation of the treatment. See paragraph 46 of Moore.
Mazzilli discloses the prevalence of erectile dysfunction (ED) in patients ages 18 to 75 treated with an antidepressant as well as the efficacy of PDE5-i in relieving ED in patients with psychotropic-associated ED who continue on their psychotropic medication. See page 45, column 1, paragraph 2 to page 46, column 1, paragraph 2. Mazzilli discloses where 9.5% of all patients with erectile dysfunction have also been treated with an antidepressant for at least 3 months. See page 47, column 1, paragraphs 1-2.
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
As Peters, Higgins and Moore disclose compositions comprising instant formula (I) and either selective serotonin reuptake inhibitor (SSRIs) or selective noradrenalin reuptake inhibitor (SNRIs) as antidepressant agents, it would have been obvious to combine the two compositions to form a fourth composition with similar suitability for treating depression. Higgins and Moore teach where erectile dysfunction is an adverse event which emerges from the treatment of depression with SSRI or SNRI agents. Moore and Mazzilli disclose inventions which meet the need for treating treatment-emergent ED. Moore discloses 1-[2-(2,4-dimethylphenyl-sulfanyl)-phenyl]piperazine, as suitable for the treatment erectile dysfunction in a patient who has previous received treatment with an antidepressant such as selective serotonin reuptake inhibitors (SSRIs) or selective noradrenalin reuptake inhibitor (SNRIs/NRIs). Mazzilli discloses the efficacy of PDE5-i in relieving ED in patients with psychotropic-associated ED who continue on their psychotropic medication. Peters discloses where a compound of instant formula (I) is suitable for the treatment of sexual dysfunction and further still erectile dysfunction.
The instant claims would be embraced when one of ordinary skill in the art is administering instant formula (I) in combination with an antidepressant agent, such as paroxetine or duloxetine, as the claims are directed to treatment and prevention and a male patient would reasonably be expected to have erectile dysfunction from the antidepressant agents or require prevention thereof. There would be a reasonable expectation that the compound of Peters, having potentially similar activity disclosed as the compounds of Moore, would provide similar benefit to a patient experiencing ED who has previously received, or is concurrently taking, an antidepressant. One of ordinary skill would have a reasonable expectation of success towards treating or preventing erectile dysfunction in a subject previously treated with an antidepressant based on the guidance provided by the combination of Peter, Moore and Higgins.
Regarding present claims 55-56, Mazzilli teaches where ED occurs in male subjects aged 18-75. One of ordinary skill in the art would have a reasonable expectation of treating ED in a patient treated with an antidepressant above 20 years of age and below 40 years of age based on the data provided by Mazzilli as well as the disclosures provided by Peters, Higgins and Moore.
Therefore, the present claims are prima facie obvious.
Conclusion
Claims 43, 45-46, 49, 51, 55-56, 58-59, 63-66 and 68-73 are rejected.
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 QUINCY A MCKOY whose telephone number is (703)756-4598. The examiner can normally be reached Monday - Thursday 8:00 - 6:00.
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/QUINCY A. MCKOY/
Patent Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626
/JOSEPH K MCKANE/Supervisory Patent Examiner, Art Unit 1626