DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-5, 8-9, 11-13, 15, 18-22, 27-28, 31 and 33 are pending.
Claims 1-5, 8 and 11 are examined herein.
Claims 9, 12, 13, 15, 18-22, 27-28, 31 and 33 are withdrawn (see restriction/election below).
Priority
This application is filed 03/05/2024, and claims the benefit of domestic priority as below:
PNG
media_image1.png
56
545
media_image1.png
Greyscale
Information Disclosure Statements
Two IDS(s) received on 03/05/2024, and 04/01/2024 have been considered unless marked with a strikethrough.
Election/Restrictions
Applicant elects Group I, claims 1-5, 8, 9, and 11, directed to products of the Markush Formula . Applicant further elects the “Urea, N'-ethyl-N-methyl-N-[3-phenyl-3-[4 (trifluoromethyl)phenoxy] propyl]-“ disclosed in claim 8 as the elected species, in the reply filed on 6/22/2026 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The claims 1-5, 8 and 11 are readable on the elected species, as Applicant asserts.
If the elected species is not identified in the prior arts, the elected species would be allowable if
an independent claim were drafted with that species alone. (see MPEP 802.03)
The elected species was not identified in the prior art. Further, the Examiner expanded the
search to alternative species within the genus of Formula (I) and subsequent examination is based on alternative species expansion. (see 35 USC 102 below and MPEP 818)
Accordingly, claims 1-5, 8 and 11 read on the elected species and alternative species, and will be examined on their merits. Claim 9 in Group I is withdrawn from consideration because claim 9 does not read on the elected and alternative species.
With respect to the expanded species, the art is rejected under 35 USC 102 and 35 USC 103 below.
Abstract
The abstract of the disclosure is objected to because the abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. Currently, the abstract has 36 words.
The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. The current submitted abstract is the front pages of PCT application. Examiner requests to bring in narrative form to satisfy the abstract requirement.
Correction is required. See MPEP § 608.01(b).
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because:
The lines, numbers and lettering are not clean, well-defined, sufficiently dense and dark, and uniformly thick and well defined in Figure(s) 1, 2, 3, and 4. See 37 CFR 1.84(l) and (q). In particular, the text in Fig 1 is illegible, and the shaped images in graphs cannot be readily understood. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Claim interpretation
Claims are interpreted in accordance with the broadest reasonable interpretation (BRI) standard consistent with the specification (See MPEP 2111).
The product claims are interpreted to cover the compound per se. Any statement of use dose not distinguish the claimed product from an otherwise identical prior are product. In addition, under MPEP 2144, the prior art does not need to suggest the combination for the same advantage or result discovered by applicant.
With respect to claims 1 and 2, the alkyl group is generally categorized as recited straight, branched or cyclic. Therefore, the phrase “may be” does not appear to create indefiniteness under 35 USC 112(b). However, for clearer claim language, it would be preferable to replace “may be” with “is selected from”.
Claim Objections
Claims 3 and 11 are objected to because of the following informalities:
Claim 3 is objected to because the period is missing.
Claim 11 is objected to because the word “and” is needed in the claim, but it has been deleted.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 5 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 5 depends from claim 2 that limits R1 to alkyl from claim 1. The recited 4-methylphenyl as R1 in claim 5 does not fall within the limitations of claim 2 because 4-methylphenyl is an aryl group, not an alkyl group. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Safwat et al.
(Synthesis and antidepressant activity of some novel fluoxetine derivatives, Bull. Pharm. Sci., Assiut University, 30, Part 1, 63-80, pub’d 10/07/2007).
With respect to claims 1-3, the claims recites that a compound having the structure: Formula wherein R1 is -C(O)-NH-(alkyl), or -SO2-(alkyl) wherein the alkyl may be straight, branched or cyclic, or -SO2- (aryl) in claim 1. The Alkyl group further limits to C1-C8 alkyl in claim 3. Safwat teaches that a cyclohexyl alkyl group at R1 position. Safwat further teaches that the compound has potential as a serotonin reuptake inhibitor by measuring potentiation of 5-HTP induced neurotoxicity, and some compounds have potential as norepinephrine reuptake inhibitors by measuring yohimbine-induced mortality in mice to calculate 5-HTP/NE ratio as a parameter for selectivity to inhibit serotonin reuptake.
PNG
media_image2.png
159
228
media_image2.png
Greyscale
PNG
media_image3.png
160
283
media_image3.png
Greyscale
Instant Formula Safwat’s compound
As discussed the claim interpretation, the product claims are interpreted to cover the compound per se. Moreover, although the prior art reference does not explicitly disclose the functional property recited in the instant application, the prior art compound is structurally identical to the claimed compound. A prior art compound that is structurally identical to the claimed compound is presumed to possess the same inherent properties as the claimed compound. The discovery of a previously unrecognized property of a prior art compound does not render the old compound patentable. (See MPEP 2112)
Claims 1 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tao et al.
(Fe(OTf)3-catalyzed tandem Meyer-Schuster rearrangement/intermolecular hydroamination of 3-aryl propargyl alcohols for the synthesis of acyclic β-Aminoketones, Tetrahedron, 73, 1762-1768, pub’d 02/16/2017).
With claims 1 and 5, the claims recites that a compound having the structure of Formula, wherein R1 is -C(O)-NH-(alkyl), or -SO2-(alkyl) wherein the alkyl may be straight, branched or cyclic, or -SO2- (aryl) wherein the aryl is optionally substituted with one or more -(alkyl), -O-(alkyl), halogen, -CF3, -OCF3 or -CN, in claim 1. The -SO2- (aryl) group is further limited -SO2-(methyl), or -SO2-(4-methylphenyl) in claim 5. Tao teaches Fe(OTf)3-catalyzed synthesis of acyclic beta-aminoketones from 3-aryl propargyl alcohols and nitrogen nucleophiles, and Tao synthesizes compound 5, which has the corresponding -SO2-(4-methylphenyl) group.
PNG
media_image4.png
226
377
media_image4.png
Greyscale
Tao’s compound 5
As discussed the claim interpretation, the product claims are interpreted to cover the compound per se. Moreover, although the prior art reference does not explicitly disclose the functional property recited in the instant application, the prior art compound is structurally identical to the claimed compound. A prior art compound that is structurally identical to the claimed compound is presumed to possess the same inherent properties as the claimed compound. The discovery of a previously unrecognized property of a prior art compound does not render the old compound patentable. (See MPEP 2112)
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
This 35 USC 103 rejection is made in the alternative to the 35 USC 102 rejection, and addresses any limitation not found to be expressly disclosed by the anticipated references.
Claim(s) 1-5, 8, and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Safwat et al. (Synthesis and antidepressant activity of some novel fluoxetine derivatives, Bull. Pharm. Sci., Assiut University, 30, Part 1, 63-80, pub’d 10/07/2007), in view of Yoon et al., (N-methyl amine-substituted fluoxetine derivatives: new dopamine transporter inhibitors, Arch Pharm Res., 32(12), 1663-71, pub’d 08/29/2009), and in further view of Fuller et al. (EP 0369685 A2, pub’d 01/16/1991).
With respect to independent claim 1, the claim recites that a compound having the Formula,
Wherein R1 is -C(O)-NH-(alkyl), -SO2-(alkyl) wherein the alkyl may be straight, branched or cyclic or -SO2- (aryl) wherein the aryl is optionally substituted with one or more -(alkyl), -O-(alkyl), halogen, -CF3, -OCF3 or -CN or a pharmaceutically acceptable salt thereof.
Safwat teaches fluoxetine derivatives based on the 3-phenyl-3-(4-trifluoromethylphenoxy) propylamine scaffold (table 1). Safwat further teaches that preparation of N-substituted fluoxetine derivatives, including substituted ureas and thioureas, by reacting fluoxetine with isocyanates and isothiocyanates (scheme and table 1). Thus, Safwat teaches modification of the fluoxetine terminal amine to provide compounds of the general type N(Me)C(X)NHR, where X may be O in the urea analogs and X may be S in the thiourea analogs. Safwat shows examples in which X is O and R is cyclohexyl, and examples in which X is S and R is ethyl. Accordingly, Safwat teaches both the carbonyl urea linker, X=O, and the ethyl substituent, R=ethyl, within the same N-substituted fluoxetine urea/thiourea derivative series. Safwat also identifies the compounds as part of a fluoxetine derivative program for evaluating biologically active antidepressant analogs.
PNG
media_image5.png
325
466
media_image5.png
Greyscale
PNG
media_image6.png
149
318
media_image6.png
Greyscale
Instant compound in claim 8
Safwat’s derivatives
Safwat fails to teach the exact compound in which X is O and R is ethyl.
Yoon teaches N-methyl amine substituted fluoxetine derivatives and identifies substitution at the N-methyl amine portion of fluoxetine as a known strategy for preparing biologically active fluoxetine analogs, including dopamine transporter inhibitors (abstract, and introduction). Thus, Yoon reinforces that the terminal amine portion of fluoxetine is a recognized SAR modification site and that analogs modification at that site could retain or improve biological activity. Thus, Yoon provides additional motivation to modify the N-methyl amine portion of fluoxetine as a known strategy for preparing biologically active fluoxetine analogs.
The combination of Safwat and Yoon fails to teach the pharmaceutical relevance of norfluoxetine type amine scaffolds and their pharmaceutically acceptable forms.
Fuller teaches norfluoxetine, pharmaceutically acceptable salts and solvates thereof, and pharmaceutical compositions containing such compounds (claims 1-4). Therefore, Fuller confirms that norfluoxetine type amine scaffolds and their pharmaceutically acceptable forms are known pharmaceutical compounds Fuller further supports the conclusion that fluoxetine/norfluoxetine type scaffolds are recognized in the art as pharmacologically relevant scaffolds suitable for pharmaceutical development.
It would have been obvious to a PHOSITA at the time of the invention to prepare the ethyl urea analog of the fluoxetine/norfluoxetine scaffold by selecting X=O, and R=ethyl in Safwat’s N(Me)C(X)NHR derivatives. The motivation would have been to obtain an additional biologically active fluoxetine/norfluoxetine analog by applying Safwat’s known and predictable terminal amine urea/thiourea derivatization strategy, with the expected advantages of retaining or improving biological activity in a known pharmacologically active fluoxetine scaffold. Yoon supports that expectation because it teaches that N-methyl amine substitution of fluoxetine can produce biologically active analogs. Fuller further supports the pharmaceutical relevance of the norfluoxetine type scaffold and its pharmaceutically acceptable forms. As discussed the claim interpretation, and under MPEP 2144, the prior art need not suggest the combination for the same advantage or result discovered by applicant.
The references is directed to the same field of endeavor and address related to the application. The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Consistently, applying KSR example rationale (E) in the independent claim 1, it would have been prima facie obvious because Safwat presents a finite and identified set of predictable choices within the same derivatives series: X=O or X=S, and specific R substituents including ethyl. A person of ordinary skill would have had reason to pursue the ethyl urea member, X=O and R=ethyl, as a predictable additional member of that series with a reasonable expectation of success. This rationale is also consistent with MPEP 2144.08 and 2144.09 because the claimed compound is closely structurally related to Safwat’s exemplified urea and thiourea fluoxetine analogs, and Safwat attributes biological utility to have derivatives series. (see MPEP 2141)
With respect to claims 2-3, the claim 2 recites that the further limitation of R1 that is -C(O)-NH-(alkyl) or -SO2-(alkyl), wherein the alkyl may be straight, branched or cyclic; or a pharmaceutically acceptable salt thereof, and claim 3 recites that alkyl of claim 2 is C1-C8 alkyl.
Safwat teaches that alkyl is a cyclohexyl, which is C6 alkyl group.
With respect to claims 4-5, and 8, the claim 4 independently recites that R1 is -C(O)-NH-(ethyl) or -SO2-(methyl), and claims 5 and 8 depend from claim 2, and they recites that R1 is -C(O)-NH-(ethyl), -SO2-(methyl), or -SO2-(4-methylphenyl) in claim 5, and R1 is -C(O)-NH-(ethyl), -SO2-(methyl) in claim 8.
Combination teachings of Safwat and Yoon fail to teach that R1 is -C(O)-NH-(ethyl), -SO2-(methyl), or -SO2-(4-methylphenyl).
However, as discussed above with respect to claim 1, Safwat teaches the relevant urea framework, X=O, and also teaches the ethyl as the R group in the corresponding thiourea series. Because Safwat presents ureas and thioureas as members of the same fluoxetine derivatives program, a person of ordinary skill would have been motivated to prepare the corresponding ethyl urea analog by replacing X=S with the expressly taught X=O urea linker, as same relational with respect to claim 1.
With respect to claim 11, the claim recites that a pharmaceutical composition comprising the
compound of claim 1 and a pharmaceutically acceptable carrier.
Combination teachings of Safwat and Yoon fail to teach a pharmaceutically acceptable carrier.
Fuller teaches that a process for preparing a pharmaceutical Formulation comprising admixing (S)-norfluoxetine, or a pharmaceutically acceptable salt or solvate thereof, with one or more pharmaceutically acceptable carriers, diluents or excipients therefor (claim 4). Once the compounds of instant claim 1, including the ethyl urea species, are rendered obvious by the combination of Safwat, Yoon, and Fuller, formulating that compound with a pharmaceutically acceptable carrier would have been obvious. The motivation would have been to place the biologically active fluoxetine/norfluoxetine analog into a conventional pharmaceutically administrable form, with the expected advantage of enabling therapeutic administration using known pharmaceutical carriers.
Art of Record but not Applied
WO 2007/056457 A2, which claims teaches the use of norfluoxetine related SSRI analogs for treating COPD. However, it is not applied in the 103 rejection because the examined claims at issue are directed to compounds and compositions, not to a method of treating COPD or inhibiting MMP-1.
Conclusion
Claims 3, and 11 are objected to.
Claims 1-5, 8 and 11 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEONG JONG KIM whose telephone number is (571)272-6918. The examiner can normally be reached 7:00am-3:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A. Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SEONG JONG KIM/ Examiner, Art Unit 1621
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
Prosecution Insights