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 .
Priority
This application is a 371 of PCT/CN2022/092300 (05/11/2022)
and claims foreign priority to CHINA 202110518639.9 (05/12/2021).
Status
Claims 4-8, 11-14, 16-20, 23-25 are pending.
Rejections not reiterated in this action are withdrawn.
Election/Restrictions
Applicant affirmed the election without traverse to prosecute the invention of Group I, claims 1-8, 11-14, 16-20, 23. Claims 24-25 remain withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Applicant also affirmed the elected the species of Compound 42 shown below:
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with A as morpholinyl and B as cyclohexyl R2 3-chlorophenyl, reading on claims 4-8, 11-14, 16-20, 23.
As detailed in the following rejections, the generic claim encompassing the elected species was not found patentable. Therefore, the provisional election of species is given effect, the examination is restricted to the elected species only, and claims not reading on the elected species are held withdrawn.
Should applicant, in response to this rejection of the Markush-type claim, overcome the rejection through amendment, the amended Markush-type claim will be reexamined to the extent necessary to determine patentability of the Markush-type claim. See MPEP 803.02.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 4-8, 11-14, 16-20, 23 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention.
Applicant amended claim 4 to add the following proviso language:
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while stating support for the added claim limitation is found:
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The PGPUB has as follows for [0086]:
Preferably, in Formula I, R2 is a 3-8-membered cycloalkyl or 6-14-membered aryl, more preferably phenyl or naphthyl. Preferably. R2 is optionally substituted by 1-3 substituents selected from the group consisting of hydroxyl, halogen, C1-C4 alkyl, halogenated C1-C4 alkyl, hydroxyl-substituted C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy, C2-C4 alkenyl, C2-C4 alkynyl, —NRaRb, carboxyl, cyano, 6-14 membered aryl, 5-10 membered heteroaryl, 4-10 membered heterocyclic group and C1-C6 acyl, wherein said Ra and Rb are each independently selected from the group consisting of H, C1-C4 alkyl, halogenated C1-C4 alkyl and hydroxyl-substituted C1-C4 alkyl. More preferably, R2 is optionally substituted by 1-3 substituents selected from the group consisting of C1-C4 alkoxy, halogen, C1-C4 alkyl, halogenated C1-C4 alkyl and halogenated C1-C4 alkoxy. More preferably, R2 is optionally substituted by 1-3 substituents selected from the group consisting of F, C1, C1-C3 alkyl, C1-C3 alkoxy, fluorinated or chlorinated C1-C3 alkyl, fluorinated or chlorinated C1-C3 alkoxy. In some embodiments, when the 6-14 membered aryl especially phenyl is substituted, the substituent does not include 4-Cl or 3-CF.
which does not support the new claim language. In addition, based on the original disclosure one of skill in the art would not recognize that Applicant possessed such a scope.
As per MPEP 2163 II A: With respect to newly added or amended claims, applicant should show support in the original disclosure for the new or amended claims. See, e.g., Hyatt v. Dudas, 492 F.3d 1365, 1370, n.4 (Fed. Cir. 2007) (citing MPEP § 2163.04 which provides that a "simple statement such as ‘applicant has not pointed out where the new (or amended) claim is supported, nor does there appear to be a written description of the claim limitation ‘___’ in the application as filed’ may be sufficient where the claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported."); see also MPEP §§ 714.02 and 2163.06 ("Applicant should ... specifically point out the support for any amendments made to the disclosure."); and MPEP § 2163.04 ("If applicant amends the claims and points out where and/or how the originally filed disclosure supports the amendment(s), and the examiner finds that the disclosure does not reasonably convey that the inventor had possession of the subject matter of the amendment at the time of the filing of the application, the examiner has the initial burden of presenting evidence or reasoning to explain why persons skilled in the art would not recognize in the disclosure a description of the invention defined by the claims."). The inquiry into whether the description requirement is met is a question of fact that must be determined on a case-by-case basis. AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1297, 111 USPQ2d 1780, 1788 (Fed. Cir. 2014) ("Whether a patent claim is supported by an adequate written description is a question of fact."); In re Smith, 458 F.2d 1389, 1395, 173 USPQ 679, 683 (CCPA 1972) ("Precisely how close [to the claimed invention] the description must come to comply with Sec. 112 must be left to case-by-case development."); In re Wertheim, 541 F.2d at 262, 191 USPQ at 96 (inquiry is primarily factual and depends on the nature of the invention and the amount of knowledge imparted to those skilled in the art by the disclosure).
The examiner could not locate support for such a new limitation, nor does there appear to be a written description of the limitation in the application as filed. See Hyatt v. Dudas, 492 F.3d 1365, 1370, 83 USPQ2d 1373, 1376 (Fed. Cir. 2007) (holding that "[MPEP] § 2163.04 (I)(B) as written is a lawful formulation of the prima facie standard for a lack of written description rejection."). There is no literal support for the added limitation and one of skill in the art would not recognize that Applicant possessed the claim scope. Thus, claim 4 and those that depend therefrom are rejected.
Claim Rejections - 35 USC § 102
Claims 4-8, 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Balsamo et al. (CAPLUS Abstract of European Journal of Medicinal Chemistry (1983), 18(6), 563-6).
Balsamo teaches the compound:
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corresponding to claim 4’s Formula (II) when X1 is O; X2 is NH; n,m=2; R2 is phenyl.
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, 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.
Claims 4-8, 11-14, 16-20, 23 are rejected under 35 U.S.C. 103 as being unpatentable over Elhallaoui et al. (J Mol Model (2002) 8:65-72) in view of Warawa (US4046892), White et al. (US4387097), and Wermuth (“The Practice of Medicinal Chemistry”, 4th ed. (2015), Ch. 8, pages 181-241 provided).
Elhallaoui teaches antagonists of NMDA receptor for modeling the pharmacophore to aid in design of NMDA receptor antagonists which have known activity as anesthetics and potential for treating neurological disease (p. 65). Elhallaoui developed the model based on the known activity of PDHQ having the following structure (p. 66, Figs 1-2; p. 67, Table 1; p. 68)
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.
Elhallaoui’s PDHQ compound differs from the instant claims (i.e., first compound of claim 23 shown below) by a -CH2- vs. -O- in the lower right ring
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“4a-phenyloctahydro-2H-benzo[b][1,4]oxazine”.
Warawa teaches anesthetic compounds of the following formula (claim 2 R=H; claim 3 R=Me):
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.
White teaches Example 14 “(4aR*,8aS)-3-(Octahydro-4-methyl-2H-1,4-benzoxazin-8a-yl)phenol” with the following structure:
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corresponding to claim 1’s formula (I) when: with A as N-methyl-morpholinyl and B as cyclohexyl, and R2 3-hydroxyphenyl. White also teaches the compound as an analgesic pharmaceutical composition (claim 10-11).
Wermuth teaches the well-known technique in the art known as bioisosterism which is routinely used by those of ordinary skill in the art in the development of pharmaceuticals. Wermuth specifically teaches interchanging divalent atoms among -CH2-, -O-, and -NH- with an expectation of similar activity (p. 182: “Figure 8.1 reports clozapine and two analogs as an example of classic isosteric replacement of NH with O”; p. 188: “A first series of frequently interchanged divalent atoms or groups is represented by O, S, NH, and CH2 … changes can be applied to cyclic series, for example, to a series such as piperidine-morpholine-thiomorpholine-piperazine or in introducing oxygen or sulfur atoms into cyclic ketoprofen analogs”).
One of ordinary skill in the art following the teaching of Elhallaoui would have considered the structurally related compounds of Warawa and White sharing the same pharmaceutical utility applied the known technique of bioisosterism as taught by Wermuth to form the 1,4-oxazine ring and arrive at the claimed invention.
As evidenced by Elhallaoui and Wermuth, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed before the effective filing date with a reasonable expectation of success. Thus, the claims are prima facie obvious.
Response to Remarks - 35 USC § 103
Applicant argues that Elhallaoui teaches activities of PDHQ and MK801 which would not allow one of ordinary skill in the art to predict that modified PDHQ would result in an active compound. This argument is not persuasive because one of ordinary skill in the art in view of the cited art including Elhallaoui’s teaching of experimental activity and the structurally similar compounds taught by Warawa and White and further Wermuth would have expected bioisosteres to have similar IC50 values and therefore be similarly active. Thus, one of ordinary skill in the art had a reasonable expectation of success.
Applicant argues regarding the activity of MK801 and ketamine as being superior to PDHQ. This argument is not persuasive because the superiority of other known compounds does not constitute a teaching away considering the context of Elhallaoui’s teaching. MPEP 2145 (A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In reGurley, 27 F.3d 551, 553, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994)).
Applicant makes reference to toxicity data of compounds 9, 11, 41-44 compared to ketamine but does not articulate how this renders the claims nonobvious. Regardless, even if it were alleged as an unexpected result, such a result is not commensurate in scope with the claimed invention.
Applicant also argues that a prima facie case of obviousness was not established because no “reasoning with rational underpinning as to why a person of skill in the art would have been prompted to combine the structure of PDHQ in view of Warawa and White” to arrive at the claimed invention. This argument is not persuasive because a prima facie case was established. One of ordinary skill in the art following the teaching of Elhallaoui would have recognized that PDHQ was an active compound showing pharmacological activity and considered the structurally related compounds of Warawa and White sharing the same pharmaceutical utility and would have applied the known technique of bioisosterism as taught by Wermuth to form the 1,4-oxazine ring and arrive at the claimed invention with a reasonable expectation of success in the compound sharing the same pharmacological acitivity.
Conclusion
No claims allowed.
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 ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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, Kortney Klinkel can be reached at (571) 270-5293. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626
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