DETAILED ACTION
This action is in response to Applicant’s submission dated December 18, 2025, in which Applicant elected the invention of Group I without traverse and amended claim 19 to correct a typographical error regarding dependency.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Information Disclosure Statement
The references contained in the IDS dated September 21, 2022 are made of record.
Election/Restriction
Claims 18-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 18, 2025.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-17 are examined. A complete reply to the final rejection must include cancellation of non-elected claims or other appropriate action (37 CFR 1.144) See MPEP § 821.01.
Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be amended in compliance with 37 CFR 1.48(b) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. Any amendment of inventorship must be accompanied by a request under 37 CFR 1.48(b) and by the fee required under 37 CFR 1.17(i).
Claim Rejections - 35 USC § 112
The following is a quotation of the second paragraph of 35 U.S.C. 112:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3, 6, 9, 12, and 16 are rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention. Claims must, under modern claim practice, stand alone to define an invention. Ex parte Fressola, 27 USPQ 2d 1608 (1993).
In the instant case, dependent claims 3, 6, 9, 12, and 16 recite “FIG. X” without providing these figures in the rejected claims. As a result, one must refer back to the specification to define the claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 non-obviousness.
Determining the scope and contents of the prior art.
Claims 1, 8-10, and 17 are rejected under 35 U.S.C. § 103(a) as being unpatentable over WO 03/029232 in view of Berge, et al., Pharmaceutical Salts, J. of Pharm. Sciences (1977).
Applicant claims various HBr salts of 1-[2-(2,4-dimethylphenyl-sulfanyl)phenyl]piperazine. These pharmaceutical compositions are characterized by different X-ray powder diffraction patterns having different diffraction peaks.
WO 03/029232 discloses the compound 1-[2-(2,4-dimethylphenyl-sulfanyl)phenyl]piperazine (example 1e) as a compound having SERT activity. See page 21. The only issue and potential difference between what is taught in the reference and the present claims is that the instant claims are directed towards a new crystalline form of a HBr salt of 1-[2-(2,4-dimethylphenyl-sulfanyl)phenyl]piperazine, characterized by an XRPD profile as shown in FIG. 4.
Table I of Berge, et al. discloses FDA-approved commercially marketed salts, including hydrobromide salt.
Ascertaining the difference between the prior art and the claims at issue.
The biological activity of a compound depends primarily on its molecular structure. To reach its target it will at some point be in solution, e.g. in body fluids, where all differences among polymorphs disappear. The skilled polymorphism chemist would thus expect that all polymorphs of compound 1-[2-(2,4-dimethylphenyl-sulfanyl)phenyl]piperazine possess the same activity, at least to a certain extent. From common general knowledge it is known that the systematic investigation of a compound determines whether it is prone to polymorphism is routine practice in the pharmaceutical industry. It is also known that most substances when investigated for a sufficiently long time will reveal more than one polymorph. See Mino, et al., Crystalline Polymorphism of Organic Compounds, Topics in Current Chemistry, Vol. 198, pp. 163-208, XP008166276, ISSN: 0340-1022 (1998), particularly the paragraph bridging pages 165-166. Furthermore, the methods to screen for polymorphs are well known in the art. The skilled polymorphism chemist investigating the therapeutic application of compound 1-[2-(2,4-dimethylphenyl-sulfanyl)phenyl]piperazine would thus routinely screen for polymorphs thereof. If such routine work yields another polymorph, e.g. the present polymorph gamma salt, then its provision is an obvious solution of said routine experimentation.
Any skilled polymorphism chemist would be incentivized to look for further crystalline forms of 1-[2-(2,4-dimethylphenyl-sulfanyl)phenyl]piperazine in view of the already known property of the latter to give a new crystalline form, so that by trial and error would arrive at the new crystalline form having a stability equivalent to that known in the art from WO 03/029232.
As far as we know, this crystalline form gamma salt is disclosed in the reference. Applicants have to show that the instant compounds are different from the reference, by providing evidence such as melting point, or other physical or chemical characteristics.
“Mere recitation of newly-discovered function or property, inherently possessed by things in prior art, does not cause claim drawn to those things to distinguish over prior art; Patent Office can require applicant to prove that subject matter shown to be in prior art does not possess characteristic relied on where it has reason to believe that functional limitation asserted to be critical for establishing novelty in claimed subject matter may be inherent characteristic of prior art; this burden of proof is applicable to product and process claims reasonably considered as possessing allegedly inherent characteristics.” In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977).
Regarding the claims reciting the x-ray diffraction - these properties are inherently present in reference compounds. This compound disclosed in the reference renders the claims of the instant application obvious to one skilled in the art. See instant
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comparing the X-ray peak positions between the crystalline base and the hydrobromide gamma salt, all four peaks are within .77 of one another. The subject matter of the rejected claims differs from the primary reference due to the characterization by X-ray powder diffraction patterns; however, one skilled in the art would find the differences in the teaching to be negligible.
Resolving the level of skill in the art.
The Court has addressed this obviousness issue: “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 12 (2007). “When there is a design need or market pressure to solve a problem and there are finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, … the fact that a combination was obvious to try might show that it was obvious”. Id. at 17. That is exactly the case here. The scope of polymorphs is a very finite list and Applicant was not left to pick and choose from a generic disclosure which compound(s) should be tested against the claimed polymorphs. The instant polymorphic form of the present claims thus is reasonably expected to share the same properties as that taught in the reference given the express equivalency teaching recited.
Considering objective evidence present in the application indicating obviousness or non-obviousness.
In the absence of any substantiated unexpected property or properties, or other secondary considerations over the prior art of the claimed hydrobromide gamma salt of 1-[2-(2,4-dimethylphenyl-sulfanyl)phenyl]piperazine, which is relevant in comparison with the closest related crystalline base of compound 1-[2-(2,4-dimethylphenyl-sulfanyl)phenyl]piperazine, then non-obviousness cannot be acknowledged for the claimed hydrobromide gamma salt of 1-[2-(2,4-dimethylphenyl-sulfanyl)phenyl]piperazine and subject matter referring thereto.
Thus, it would have been obvious to one of ordinary skill in the art at the time of invention to combine the teachings of WO 03/029232 with those of Berge, et al. to obtain the HBr gamma salt of 1-[2-(2,4-dimethylphenyl-sulfanyl)phenyl]piperazine in the instant application. Obviousness based on similarity of structure and functions entails motivation to make the claimed compound in expectation that compounds similar in structure will have similar properties. Therefore, one of ordinary skill in the art would be motivated to make the claimed compounds in searching for new salt forms as SERT inhibitors. See In re Payne, 203 USPQ 245 (CCPA 1979).
Double Patenting
The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory 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 1, 5-7, and 17 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claim 5 of Bang-Andersen, et al., United States Patent No. 8,722,684. Although the conflicting claims are not identical, they are not patentably distinct from each other in each case the claims are directed to a composition comprising 1-[2-(2,4-dimethylphenyl-sulfanyl)phenyl]piperazine HBr salt in a crystalline form which is characterized by XRPD reflections at 6.89, 9.73, 13.78 and 14.64 +/-0.10° θ, which is identical to the (β) HBr salt in the present application.
Claim Objections
Claims 2, 4-5, 7, 11, and 13-15 are objected to as being dependent upon rejected independent claim 1, but would be allowable if rewritten in independent form including all of the limitations of the base claims and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ERICH A LEESER whose telephone number is (571) 272-9932. The Examiner can normally be reached Monday through Friday from 10-6 PST, M-F. PST.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Mr. James Alstrum-Acevedo can be reached at (571) 272-5548. The fax number for the organization where this application is assigned is 571-273-8300.
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/ERICH A LEESER/Primary Examiner, Art Unit 1622
United States Patent and Trademark Office
Tel. No.: (571) 272-9932