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 .
Status of the Application
This Office Action is in response to applicant’s arguments filed on 4/27/26. Claims 1-31 are pending. Claims 3, 8-10, 19, 30-31 have been amended. Claims 5-6, 22 have been withdrawn. Claims 1-4, 7-21, 23-31 are examined herein.
The claim amendments have rendered the claim objection and 112 rejection of the last Office Action moot, therefore hereby withdrawn.
Applicant’s arguments have been fully considered but found not persuasive. The rejection of the last Office Action is maintained for reasons of record and modified below due to the claim amendments. repeated below for Applicant’s convenience.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-4, 7-12, 15-19, 23-31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Buntinx (EP 1 541 197, of record).
Buntinx teaches the use of the D4 and 5-HT2A receptor antagonist, pipamperone, (paragraphs 0010-0011) for treating a mood or anxiety disorder, wherein 5-15 mg of pipamperone is administered simultaneously, separate, or sequentially to augment the therapeutic effect with a second active agent selected from an SNDRI, SNRI, or SSRI (paragraph 0012), for example the SSRI, citalopram or escitalopram (paragraphs 0031-0034). For example, pipamperone can be administered 1-12 months before administration of the second active agent (paragraph 0085). An example of a mood disorder is depression, which are commonly treated with SSRIs. However, these compounds can give rise to side effects. Moreover, a substantial problem is the non-response to SSRIs or delayed therapeutic effect (paragraph 0048). It was found that this non-response to SSRIs in depression may be declared by partial inhibition of the 5-HT2A stimulation, therefore 5-HT2A antagonism appears to be the answer (paragraph 0050). Examples 2-3, 6 and Figures 3-11 shows the effect of pipamperon as an add-on treatment in comparison to using SSRIs or SNRI in treating major depression for 8 weeks. Some side effects include central and peripheral nervous system, gastrointestinal, musculoskeletal, psychiatric, respiratory, skin and appendages, vascular, and urinary in nature (paragraph 0157). Specifically, Figures 3 and 6 show remission rates form the combo treatment for major depression (paragraph 0129). The term “treatment” or “treating” encompasses prevention or recurrence or relapse-prevention of the disease or symptoms associated therewith (paragraph 0074). In Example 6, the Hamilton Depression Rating Scale score was reduced by at least 20% more than reached with conventional known antidepressants as well as preventing significantly more relapses during 48 weeks following treatment (paragraphs 0184). Tables 3 and 4 show an active controlled randomized relapse prevention study for 36 weeks, where the active mono and combo therapy was continued (paragraph 0185).
Response to Arguments
Applicant argues that Buntinx does not disclose the treatment of subjects which are partially responsive to antidepressant treatment.
This is not persuasive because Buntinx teaches this subset patient population through the teaching that some subjects with depression being treated with SSRIs are non-responsive or have a delayed therapeutic effect (paragraph 0048), which is considered partially responsive. Furthermore, Buntinx teaches the term “treatment” or “treating” to encompass recurrence of the disease or symptoms associated therewith (paragraph 0074), which is also considered partially responsive.
Applicant argues that Buntinx does not disclose pipamperone for resolving side effects typically associated with other anti-depressant adjunctive therapies. Side effects associated with primary anti-depressant therapy are different from side effects associated with adjunctive therapy.
This is not persuasive because whether the side effects are associated with primary anti-depressant therapy or with adjunctive therapy matters little since the instant claim encompasses prevention. Therefore, the side effects need not be present, making the origin of the side effects irrelevant. Applicant is also reminded that Buntinx teaches both primary and secondary active agents along with a general teaching that side effects are known.
Applicant argues that the limitations regarding “reducing hedonic impairment during antidepressant therapy” and “maintaining remission or preventing relapse of depression after antidepressant therapy” and “improving treatment adherence” are not disclosed by Buntinx.
This is not persuasive because these limitations are drawn to a mechanism of action or a property of the claimed active agents, therefore will necessarily occur since all the elemental steps of the method claims have been taught by Buntinx.
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 of this title, 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 13-14, 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Buntinx (EP 1 541 197, of record), as applied to claims 1-4, 7-12, 15-19, 23-31, in view of Papaetropoulos et al. (“The effect of depression on motor function and disease severity of Parkinson’s disease,” Clinical Neurology and Neurosurgery, 2006, 108, 465-469) and Pan et al. (“Bidirectional Association Between Depression and Metabolic Syndrome,” Diabetes Care, 2012, 35, 1171-1180, of record).
The instant claims are directed to a method for treating a subject with depression by administering a dopamine D4 and 5HT2A receptor antagonist, reverse agonist, or partial agonist, wherein the subject is partially responsive to antidepressant therapy.
Buntinx teaches as discussed above, however, fail to disclose wherein the side effects comprise motor symptoms or metabolic syndrome.
Papaetropoulos et al. teach that depression can have a profound negative impact on a patient’s motor functioning (abstract).
Pan et al. teach the bidirectional association between depression and metabolic syndrome (abstract).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have selected a subject with the side effects, motor symptoms and metabolic syndrome, as taught by Papaetropoulos and Pan et al., in the method of treating depression by administering pipamperone, as taught by Buntinx.
A person of ordinary skill in the art would have been motivated to select a subject having the side effects, motor symptoms and metabolic syndrome, because Papaetropoulos and Pan et al. teach that subjects suffering from depression have a high likelihood of also having motor symptoms and metabolic syndrome. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success in treating depression in a subject with motor symptoms and metabolic syndrome by administering pipamperone.
Response to Arguments
Applicant argues unexpected results in that pipamperone is superior to other anti-depressant adjunctive therapies, not only in the sense that side effects (for example anhedonia) are virtually absent, but even that side effects associated with other adjunctive therapies can be resolved. Furthermore, pipamperone does not suffer from reduced treatment adherence, rather to the contrary, demonstrating adherence for up to 11 years.
This is not persuasive because Applicant has not provided any factual evidence why this result would be considered unexpected. Regarding the establishment of unexpected results or synergism, a few notable principles are well settled. The Applicant has the initial burden to explain any proffered data and establish how any results therein should be taken to be unexpected and significant. See MPEP 716.02 (b). It is applicant’s burden to present clear and convincing factual evidence of nonobviousness or unexpected results, i.e., side-by-side comparison with the closest prior art in support of nonobviousness for the instant claimed invention over the prior art. The claims must be commensurate in the scope with any evidence of unexpected results. See MPEP 716.02 (d). With regard to synergism, a prima facie case of synergism has not been established if the data or result is not obvious. The synergism should be sufficient to overcome the obviousness, but must also be commensurate with the scope of the claims. Further, if the Applicant provides a DECLARATION UNDER 37 CFR 1.132, it must compare the claimed subject matter with the closest prior art in order to be effective to rebut a prima facie case of obviousness. See MPEP 716.02 (e).
Conclusion
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 extension fee 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 Yong S. Chong whose telephone number is (571)-272-8513. The examiner can normally be reached Monday to Friday: 9 AM to 5 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached at (571)-270-7674. The fax phone number for the organization where this application or proceeding is assigned is (571)-273-8300.
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/Yong S. Chong/Primary Examiner, Art Unit 1623
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