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 .
This is a Final Office Action.
Claims 1-13, 80 and 81 are pending and under consideration.
Claim Rejections - 35 USC § 112
The rejection of claims 1-6 and 9-12 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for the “and/or” for isomers and solvates is withdrawn based on the amendments.
The rejection of claims 5 and 11 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for the phrase, “the compound is the E-isomer” is withdrawn based on the amendments.
The rejection of claims 1-13, 80 and 81 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement for isomers, is withdrawn based on the amendments.
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
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 1-13, 80 and 81 are 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 pre-AIA the applicant regards as the invention.
In claims 1-6 and 9-12, the phrase
“
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” is vague and confusing. The claims are drawn to a compound, and not a mixture, and therefore, the “combination” is an issue. Thus, all claims are rejected based on the dependency to claims 1 and 9.
With regards to claims 1-6 and 9-12, the terms, “E/Z” and R/S” is ambiguous. Does the “/” mean “or” or “and?” compound is the E-isomer” is vague. The formulas are shown as only the E-isomer. Thus, said claims are rejected.
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.
Claim Rejections - 35 USC § 102
The rejection of claim(s) 1-3, 5 and 8 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shrader et al. (Bioorg. Med. Chem. Lett., 2011, 21, 3693-3698), is withdrawn based on the amendments..
Claim Rejections - 35 USC § 103
The following is a quotation of 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 of this title, 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 negatived 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(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-5 and 7-8 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Shrader et al. (Bioorg. Med. Chem. Lett., 2011, 21, 3693-3698) in view of Cross et al. (US 3585216), and Berge et al. (J. Pharm. Sciences, 1977, 66(1), 1-19).
The present application claims the following compounds:
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.
The Shrader reference teaches the following species:
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, see page 3695, as a redox silenced version or chemically locked in a single state version, of α-tocotrienol quinone, see page 3694, right-hand column, first paragraph. This compound was used as a control to determine the relationship between the redox-cycling for compound efficacy, see page 3696, left-hand column, last sentence, and right-hand column, Figure 2b.
The only difference between the claimed and cited compound is the ketone protecting group on the phenyl ring, Piv ((CH₃)₃CCO- (pivaloyl)) versus Applicant’s tetrahydro pyranyl ether (six-membered ring with an oxygen as part of the ring) at the 1- and 4-position of the phenyl ring.
The Cross reference teaches similar compounds with Applicant’s tetrahydro pyranyl ether, see column 3, compound (III).
Thus, it would be obvious to use the tetrahydro pyranyl ether protecting group as taught by Cross et al. to lock the single state redox version of the compound for use as a control as taught by Shrader et al.
The present application claims the (R) and (S) isomers of the subformulas in claims 3 and 4. Preparing, isolating and testing the different stereoisomers is considered obvious, unless there is evidence to the contrary, see MPEP § 2144.09 that teaches that stereoisomers are prima facie obvious, see also In re May, 574 f.2d 1082, 197 USPQ 601 (CCPA 1978).
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Shrader does not teach the lithium salt, which is addressed with the Berge reference. Salts are commonly made throughout different synthetic steps to help recover or purify intermediates.
Berge et al teaches lithium as an FDA-approved salt, see page 2, Table 1, cation section.
Therefore, it would be obvious to make the presently claimed compound since Cross teaches similar compounds with the same protecting group and Shrader teaches the compounds as controls for pharmacological experiment.
Thus, said claims are obvious over Shrader, Cross and Berge.
Applicant states, “The Examiner acknowledges that Shrader et al. only describes a constitutional isomer of the compound of claim 1, but neither Shrader et al. nor the Examiner has provided motivation for why a person of skill in the art would replace the Piv groups of the compound of Shrader et al. with pyran groups to afford the compound of claim 1 wherein R is
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. Berge et al., a general reference directed to pharmaceutical salts, does not remedy this deficiency.”
This is not persuasive as noted in the rejection as amended.
Thus, the rejection is maintained.
Claims 1 and 6 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Kobayashi et al. (JP 02248953).
The present application claims the formula of claim 1, wherein R is methyl.
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The ‘953 patent teaches the following species:
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, see page 6, bottom left column.
The only difference between the claimed compound and the cited compound is a H at positions 3 and 6 of the phenyl ring versus Applicant’s methyl group. Since a methyl group is considered a homolog of hydrogen these compounds are considered equivalent. The MPEP 2144.09 states “Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
Thus, said claims are obvious.
Applicant traverses the rejection by stating, “According to the Federal Circuit, whether a new chemical compound would have been prima facie obvious over prior art compounds follows a two-part analysis: first, the court determines whether a chemist of ordinary skill would have selected the asserted prior art compounds as lead compounds; and second, the court determines whether the prior art would have suppled one of ordinary skill in the art with a reason or motivation to modify a lead compound to make the claimed compound with a reasonable expectation of success. Otsuka Pharmaceutical Co., Ltd. v. Sandoz, Inc. (Fed. Cir. 2012), citing Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed. Cir. 2007); see also MPEP § 2143(B), Examples 8-11. The Examiner has not satisfied the requirements for demonstrating prima facie obviousness of Applicant's claimed compounds.”
This is not persuasive.
The choice of a lead compound need not be constrained to the most preferred embodiment, nor to the compound with the highest activity. “The Federal Circuit in Eisai makes it clear that from the perspective of the law of obviousness, any known compound might possibly serve as a lead compound: ‘Obviousness based on structural similarity thus can be proved by identification of some motivation that would have led one of ordinary skill in the art to select and then modify a known compound (i.e. a lead compound) in a particular way to achieve the claimed compound.’ Eisai, 533 F.3d at 1357.” and “Obviousness of a chemical compound in view of its structural similarity to a prior art compound may be shown by identifying some line of reasoning that would have led one of ordinary skill in the art to select and modify a prior art lead compound in a particular way to produce the claimed compound. It is not necessary for the reasoning to be explicitly found in the prior art of record, nor is it necessary for the prior art to point to only a single lead compound.” Thus “any known compound my serve as a lead compound when there is some reason for starting with that lead compound and modifying it to obtain the claimed compound (Federal Register, 2010, 75(169), page 53651 and 53653).
MPEP 2144.09 states “Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
Furthermore, "Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homolog because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties." (see MPEP § 2144.08c). In addition, homologs are generally so structurally similar that "without more" such structural similarity could give rise to prima facie obviousness (see In re Wilder, 563 F.2d 457, 195 USPQ 426).
MPEP 2144.09 states, Top of Form
Bottom of Form
“A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990).” Similar compounds with similar properties would provide a reasonable expectation of success.
Thus, the rejection is maintained.
Conclusion
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 SUSANNA MOORE whose telephone number is (571)272-9046. The examiner can normally be reached Monday - Friday, 10:00 am to 7:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached on 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SUSANNA MOORE/Primary Examiner, Art Unit 1624
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