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 .
Claims 1-18 are currently pending in this Application. Therefore, claims 10-13, 17 and 18 are withdrawn from further consideration by the Examiner, 37 C.F.R. § 1.142(b), as being drawn to a non-elected invention. The withdrawn subject matter is patentably distinct from the elected subject matter as it differs in structure and element and would require separate search considerations. In addition, a reference, which anticipates one group, would not render obvious the other.
Priority
CONTINUING DATA
This application is a 371 of PCT/EP2022/059527 04/08/2022
FOREIGN APPLICATIONS
EPO EP21167690.3 04/09/2021
EPO EP21181134.4 06/23/2021
Information Disclosure Statement
Applicant’s Information Disclosure Statement, filed on October 06, 2026 has been considered. Please refer to Applicant’s copies of the 1449 submitted herewith.
Response to Restriction
Applicants’ election, with traverse, the invention of Group I, claims 1-9 and 14-16, drawn to a products of Formula
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, and the compound,
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depicted un claim 16, as the elected species, in response filed on March 13, 2026 is acknowledged. The traversal is on the ground(s) that there is not a showing of both independence and distinctness in the Restriction Requirement, and that there is no undue burden to search all of the claimed inventions.
This is not found persuasive because as pointed out in the previous Office Action, restriction for examination purposes as indicated is proper because there would be a serious search and examination burden if restriction were not required because one or more of the following reasons apply:
(a) the inventions have acquired a separate status in the art in view of their different classification;
(b) the inventions have acquired a separate status in the art due to their recognized divergent subject matter;
(c) the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries);
(d) the prior art applicable to one invention would not likely be applicable to another invention;
(e) the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph.
For example A, B, C each could represent a heterocyclic group which are different from the elected group wherein A is a cycloalkyl group; B is a substituted phenyl group and C is a substituted phenyl group. This recognized chemical diversity of the functional groups can be seen by the various classifications of these functional groups in the U.S. classification system and requires different resources for searching, and raise different non-prior art issues. Therefore, the restriction requirement is considered proper and is maintained.
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 petition under 37 CFR 1.48(b) and by the fee required under 37 CFR 1.17(i).
The scope of the invention of the elected subject matter is as follows:
Examination will begin with the elected species. In accordance with the MPEP 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species and the claims drawn to the elected species are allowable, the search of the Markush-type claim will be extended (see MPEP 803.02). If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. Id. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. Id. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final. Id.
The elected species was not found to be free of prior art and therefore, the scope of the examined subject matter was limited to include products of Formula I,
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, depicted in claim 1, wherein:
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; B is an optionally substituted phenyl group; C is an optionally substituted phenyl group and the rest of the variables ( R1, R2 and X) are as defined.
As result of the election and the corresponding scope of the invention identified supra, the remaining subject matter of claims 1-9 and 14-15, are withdrawn from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to non-elected inventions. The withdrawn compounds contain varying functional groups, which are chemically recognized to differ in structure and function from the elected R4 variable.
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 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 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.
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 1-9 and 14-16, are rejected under 35 U.S.C. 103(a) as being unpatentable over U.S. Patent No. 7,247,736 B2 in view of Dyck et al, Effects of Deuterium Substitution on the Catabolism of beta-Phenylethylamine:Journal of Neurochemistry, 46(2) (1986) 399-404]., U.S. Patent no. 6,603,008, U.S. Patent no. 6,221,335, U.S. PGPub no. 20070082929, U.S. PGPub no. 20070197695, U.S. Patent no. 7,517,990, Tonn et al., Haskins et al., Wolen et al., Browne et al., Baillie et al., U.S. Patent no. 6,440,710, Gouyette et al., Cherrah et al., Pieniaszek et al., and Honma et al.
The primary reference U.S. Patent No. 7,247,736 B2, teach the following products:
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;
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; and
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which are capable of binding to the ubiquinone binding site of DHODH.
The rejected claims differ from the primary reference in that the claimed compound is deuterated.
The secondary references discuss the advantage of replacing H by deuterium.
For example, Dyck et al., [Dyck, L.E., Effects of Deuterium Substitution on the Catabolism of beta-Phenylethylamine: An In Vivo Study, Journal of Neurochemistry, 46(2) (1986) 399-404] states, “Thus, deuterium substitution seems to be a useful strategy to enhance the pharmacological effects of a compound without significantly altering its basic chemical structure.”
U.S. Patent no. 6,603,008 teaches "[S]ubstitution with heavier isotopes such as deuterium, i.e. 2H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances" (see col. 6, lines 59-67 and col. 7, lines 11-16).
U.S. Patent no. 6,221,335 teaches that “by deuterating drugs, we have likely … increased the lipophilic nature of the molecule” and, via the deuterium isotope effect, produced a derivative “less easily cleaved by metabolic (or destructive) processes. Hence, the elimination half life of the drug is prolonged and the drug's therapeutic effects are increased.”
U.S. PGPub 20070082929, paragraph 0014 states, “Deuteration of pharmaceuticals to improve pharmacokinetics (PK), pharmacodynamics (PD), and toxicity profiles, has been demonstrated previously with some classes of drugs.
U.S. PGPub 20070197695 states, “Deuteration can yield pharmaceuticals having improved bioavailability and reduced the toxicity.”
U.S. Patent no. 7,517,990 states, “a deuterated compound is very useful in elucidation of reaction mechanism and substance metabolism and used widely as a labeled compound. Said compound is also known to be useful as drugs, pesticides … and the like due to change in stability and property itself by isotope effect thereof.”
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. See MPEP 2143. 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.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel. Here one or more of rationales (C) and (G) apply.
Hence, it is clear that, “a person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and that there would have been a reasonable expectation of success." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 80 USPQ2d 1641, 1645.
Moreover, given that there is always a need to enhance the pharmacological effects of a compound (e.g. increased in vivo half-life) without significantly altering its basic chemical structure, or that there is always a need to reduce the time, cost, risk, and statistical imprecision of pharmacokinetic studies (e.g. measure bioavailability or identify metabolites), and that there is only a limited number of ways that this can be done, it would be obvious to pursue a potential solution that has a reasonable expectation of success. See e.g. KSR International Co. v. Teleflex Inc., 1385, 1397; Pfizer, Inc. v. Apotex, Inc., 82 USPQ2d 1321; Alza Corp. v. Mylan Laboratories, Inc., 80 USPQ2d 1001; In re Kubin, 90 USPQ2d 1417; In re O’Farrell, 7 USPQ2d 1673, 1681; In re Eli Lilly & Co., 14 USPQ2d 1741; In re Ball Corp., 18 USPQ2d 1491.
In addition, it is clear that deuteration per se is a known improvement technique for getting a more useful version of the pharmaceutical, and that the improvement is of a predictable nature, as is seen by the success reported in the various secondary references. Thus, it would have been obvious to one of ordinary skill in the pharmaceutical art to have applied this known improvement technique in the same way to the compound of the primary reference to obtain the results reasonably predictable from the secondary references. See e.g. KSR International Co. v. Teleflex Inc., 1385, 1396; Ruiz v. AB Chance Co., 69 USPQ2d 1686; In re Nilssen, 7 USPQ2d 1500.
Accordingly the rejected claims are deemed obvious.
Some dependent claims specify various levels of deuteration. Selecting and optimizing the level of deuteration, up to and including full deuteration, would be within the skill of one seeking to achieve either of the goals set forth in the secondary references. For example, setting 100% deuteration at one position is routinely done, and as seen by the references cited above, di-deuteration and higher levels are also employed.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Accordingly, claims 1-9 and 14-16 are rendered obvious in view of the references above. Applicant may wish to consider providing evidence of unexpected results to overcome the obviousness rejection.
Claim Objections
Claims1-9 and 14-15 are objected for containing non-elected subject matter.
Telephone Inquiry
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAMAL A SAEED whose telephone number is (571) 272-0705.
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, Adam C 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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/Kamal A Saeed/
Primary Examiner, Art Unit 1626
Prosecution Insights