DETAILED ACTION
Status of Application
The response filed 03/19/2026 has been received, entered and carefully considered. The response affects the instant application accordingly:
Claims 1, 5 have been amended.
A 132 declaration by Guangwei He is submitted.
Applicant had previously elected Group I and elected the compound species
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(n=3) which was expanded to include the homologs where n=0-6.
Claims 1-2, 4-14 are pending.
Claims 1-2, 4-6, 9 are present for examination at this time.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
All grounds not addressed in the action are withdrawn or moot as a result of amendment.
New grounds of rejection are set forth in the current office action as a result of amendment.
New Grounds of Rejection
Due to the amendment of the claims the new grounds of rejection are applied:
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.
Claims 1-2, 4-6, 9 are rejected under 35 U.S.C. 103 as being unpatentable over Piwinski et al. (U.S. Pat. 5665726) in view of Griffith et al. (U.S. Pat. 4912222).
Rejection:
Piwinski et al. teaches benzo[5,6]cyclohepta pyridine compounds with antiallergic, antiinflammatory, and antihistamine activity of formula I and its pharmaceutical salts like sodium and ammonium salts, including the exemplified compound
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in Example 7 as seen in Table VI
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(Abstract, Col. 1 line 15-Col. 2 line 10, Col. 2 line 43-46, Col. 13 line 57-68, Col. 36 line 56-Col. 37 line 15). The compounds can be formulated in compositions like tablets (Col. 43 line 5-15, see full document specifically areas cited).
Piwinski et al. does not expressly teach the benzyl substituent to be -(CH3)2 CO2H but does teach the benzyl/aryl substituent to be tert butyl.
Griffith et al. teaches that known substituents (R) for benzene rings on similar antihistamine tricyclic compounds are hydrogen, tert-butyl, -C(CH3)2CH2OH, -C(CH3)2 CO2H, or -C(CH3)2 COOalkyl that is 1-4 carbons or hydrogen (Col. 1 line 25-47).
Wherein it would be obvious to one of skill in the art before the effective filing date of the claimed invention to substitute the benzyl with -C(CH3)2 CO2H as suggested by Griffith et al. and produce the claimed invention
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; as simple substitution of one known benzyl substituent for another with antihistamine activity is prima facie obvious with a reasonable expectation for success absent evidence of criticality for the substituent.
Response to Arguments:
Applicant's arguments are centered on the assertion that the secondary reference of Griffith et al. teaches away from the claims compounds as the preferred compounds are n is 3, Y is -CH2CH2 -, X is -CH(OH)-, and R is tert-butyl in claim 2 of Griffith, that there is no reasonable expectation of success as neither Piwinski nor Griffith address cardiotoxicity (hERG toxicity) or the anticholinergic side effects of the disclosed compounds while the present application produce antihistamines with lower cardiotoxicity and lower anticholinergic side effect while maintained/improving antihistamine activity, and the assertion of unexpected results.
This is fully considered but not persuasive.
The assertion the secondary reference of Griffith et al. teaches away from the claims compounds is not persuasive as Griffith is presented merely to demonstrate that known substituents (R) for benzene rings on similar antihistamine tricyclic compounds are hydrogen, tert-butyl, -C(CH3)2CH2OH, -C(CH3)2 CO2H, or -C(CH3)2 COOalkyl that is 1-4 carbons or hydrogen as seen by the limited section cited. Additionally, as for the assertion for the preferred teaching for the tert-butyl as a teach away in Griffith et al., this is not persuasive as the general teachings of Griffith et al. are not held solely to Applicant’s cited embodiment when the general teaching of well-known known substituents (R) for benzene rings on similar antihistamine tricyclic compounds is for a specific finite grouping of which includes -C(CH3)2 CO2H as seen by the section cited and contrary Applicant’s assertion as Griffith exemplifies the C(CH3)2 CO2H substituent embodiment (i.e. example 26) which expressly teaches it.
As for the assertion that there is no reasonable expectation of success as neither Piwinski nor Griffith address cardiotoxicity (hERG toxicity) or the anticholinergic side effects of the disclosed compounds, this is fully considered but not persuasive as the claims are compound claims wherein the effects of the compound need not be recognized at the time of the prior art but that the properties present and are the natural result of the combination of the prior art elements. Piwinski expressly teaches benzo[5,6]cyclohepta pyridine compounds with antiallergic, antiinflammatory, and antihistamine activity of formula I including the exemplified compound
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in Example 7 and Griffith et al. teaches that known substituents (R) for benzene rings on similar antihistamine tricyclic compounds are hydrogen, tert-butyl, -C(CH3)2CH2OH, -C(CH3)2 CO2H, or -C(CH3)2 COOalkyl that is 1-4 carbons or hydrogen; wherein simple substitution of one known benzyl substituent for another with antihistamine activity is prima facie obvious with a reasonable expectation for success absent evidence of criticality for the substituent.
Applicant’s assertion of unexpected results citing the 132 declaration by Guangwei He submitted on 03/19/2026 that the claimed compounds are unexpected in comparison to compound 2 of WO 89/12443 which is a compound from Griffith et al.
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verses the compound 21
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and compound 29
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of the specification which Applicant asserts has unexpected results is fully considered but not persuasive. First, it is not the closes prior art of Piwinski. Second, the assertion is based on the allegation that the compounds 21 and 29 of the specification are unexpected over compound 2 of WO 89/12443 which is a compound from Griffith et al. which is not the persuasive. One must first establish what is to be expected to determine what is unexpected. While there are differences in compound 21 and compound 29 of the specification from that of the prior art, Applicant did not demonstrate that they were unexpected. In fact, Compound 21 is not of the formula instantly claimed – it is a compound that is analogous to those of Griffith as it has the same/similar chemical core to those of Griffith et al. and essentially a homolog/analog (U.S. 4912222 and WO 89/12443) which exemplifies compounds like 4-[4-[4-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-1-hydroxybutyl]-α, α-dimethylbenzeneacetic acid
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in example 26 which has the
-C(CH3)2 CO2H substituent wherein there is a clear teaching for utilizing this substituent on the benzene supporting the prima facie case of obviousness presented. Additionally Applicant has demonstrated with compound 21
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which is analogous as it has a similar if not identical core to Griffith (i.e.
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) and is in line with those teachings like the exemplified
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demonstrates that there would have a reasonable expectation of success and establishes what properties would be expected for that substituent -C(CH3)2 CO2H as seen in the specification and declaration. As compound 21 establishes what would be expected in compounds like Griffith with the -C(CH3)2 CO2H substituent
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, the showing of compound 29 are not unexpected - as while there is a difference between compound 29 that falls within the instant claims verses compound 21 which is not instantly claimed, it does not show unexpected results between these compounds particularly as compound 21 is similar to the teaching of Griffith et al. and then establishes what was to be expected with the -C(CH3)2 CO2H substituent that is taught for the benzene wherein the prima facie case of obviousness stand absent evidence of criticality. It is also noted that even if one were to assert that compound 21 and compound 29 were different from the prior art, and the testing was different; Applicant still must establish what was to be expected in order to determine what is unexpected. while there is a difference between compound 29 and the prior art- it is not a showing of unexpected results for the instant claimed formula is significantly broader that the compounds tested in the instant specification and broader than compound 29 cited in the declaration.
Accordingly, the rejection of stands.
Conclusion
Claims 1-2, 4-6, 9 are rejected.
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 GIGI GEORGIANA HUANG whose telephone number is (571)272-9073. The examiner can normally be reached Monday-Thursday 9:00-5:00pm.
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/GIGI G HUANG/Primary Examiner, Art Unit 1613
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