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 .
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to a compound of formula (I)
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or formula (II)
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; and compound 5 having the structure of:
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as the elected compound species are maintained.
Claims 3, 10, 33, 38-39, 44-47, 49 and 66 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim.
Expansion of Election of Species Requirement
A reasonable and comprehensive search of the elected species conducted by the Examiner determined that the prior art at the time of the present invention was such that it did not anticipate and renders obvious the elected compound species:
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.
In light of this discovery, the search is expanded to the subject matter of the subgenus of the elected compound species, i.e., the compound having the structure of:
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in addition to the elected compound species such that it does not encompass the full scope of the claims.
Status of Claims
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on December 19, 2025, wherein claims 1, 4, 10-11, 13, 16, 19, 30, 32-33, 38-39, 43-47 and 66 are unchanged; claims 2-3 and 42 are amended; and claims 5-9, 12, 14-15, 17-18, 20-29, 31, 34-37, 40-41, 48, 50-65 and 67-81 are cancelled. Specifically, applicant amends claims 2-3 from the recitation of “comprises formula” to “is of formula”; and further amends claim 42 by deleting the recitation of “comprises a compound of Table 1”, and recites chemical structure of compound no. 1-9.
Claims 1-4, 10-11, 13, 16, 19, 30, 32-33, 38-39, 42-47, 49, and 66 are pending.
Claims 3, 10, 33, 38-39, 44-47, 49 and 66 remain withdrawn.
Claims 1-2, 4, 11, 13, 16, 19, 30, 32, and 42-43 are under examination in accordance to the elected species along with the expanded compound sets forth in the Expansion of Species section above.
Action Summary
Claim 42 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention are withdrawn in light of the claim amendments.
Claim 2 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends are withdrawn in light of the claim amendments.
Claims 1-2, 4, 11, 13, 16, 19, 30, 32 and 42-43 rejected under 35 U.S.C. 103 as being unpatentable over Backes et al. (US 2021/0198238 A1) are maintained.
Priority
The instant application 17/275,609 filed on March 11, 2021 is a 371 of PCT/US2019/050698 filed on September 11, 2019, which claims priority to, and the benefits of Foreign Application No. PCT/CN2018/105184 filed on September 12, 2018.
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 (i.e., changing from AIA to pre-AIA ) 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 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 1-2, 4, 11, 13, 16, 19, 30, 32 and 42-43 remain rejected under 35 U.S.C. 103 as being unpatentable over Backes et al. (US 2021/0198238 A1).
Backes et al. teaches a compound 96 is a compound of formula (Ib) that inhibits the activity of IRE1[Symbol font/0x61] kinase, IRE1[Symbol font/0x61] RNase and IRE1[Symbol font/0x62] kinase shown below:
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(see e.g., compound 96 in Table 1; [0009]). Backes et al. further teaches a pharmaceutical composition comprising the compound and one or more pharmaceutically acceptable excipients (see e.g., [0010]; [0272]-[0273]).
"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). In the present case, the difference between the compound 96 of Backes et al. and the claimed compound having formula (I), in this case, compound no. 1 of the instant specification, lies on the position of the nitrogen atom shown below (see shaded):
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; However, in the absence of showing unobvious results, it would have been prima facie obvious to one of ordinary skill in the art at the time of the application was filed when faced with the compound 96 of Backes et al. to make the instantly claimed derivative of a known product, in this case, compound no. 1 of instant application. The instantly claimed compounds and prior art compounds are common derivatives known as position isomers. Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) 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). See MPEP 2144.09(11).
Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979). In the present case, the compound 96 of Beckes et al. and the claimed compound no. 1 are both directed to compounds that inhibits IRE1[Symbol font/0x61] kinase activities. As noted above, the only structural difference between the compound 96 of Beckes et al. and the claimed compound no. 1 is the position of the nitrogen atom in the pyrazine moiety of Beckes et al. (
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, see diagram shown above). The similarity between the chemical structures and properties is sufficiently close that one of ordinary skill in the art would have been motivated to make the claimed compound in searching for IRE1[Symbol font/0x61] kinase inhibitor. See MPEP 2144.09 (111).
Guided by the teaching of Backes et al., one of ordinary skill in the art would be able to make similar compounds by making isomers of the known compound; and incorporate said isomers with a pharmaceutically acceptable excipients to form a pharmaceutical composition. The motivation would be to prepare similar compounds that are pharmacologically active compounds that can inhibits IRE1[Symbol font/0x61] kinase; and prepare similar pharmaceutical composition useful for the same purpose. Therefore, it would have been prima facie obvious to one of the ordinary skilled in the art at the time the application was filed to arrive at the claimed invention, absent factual evidence to the contrary.
Response to Arguments
Applicant's arguments filed on December 19, 2025 with respect to the rejection of claims 1-2, 4, 11, 13, 16, 19, 30, 32 and 42-43 under 35 U.S.C. 103 as being unpatentable over Backes et al. (US 2021/0198238 A1) have been fully considered but they are not persuasive for the reasons set forth below.
In Summary, Applicant argues there is (i) no evidence showing that one of ordinary skill in the art would have selected Compound 96 of Backes et al. as a lead compound; (ii) no evidence that one of ordinary skill in the art would have a reasonable expectation of success in making the necessary modification to compound 96 of Backes et al.; and (iii) one of ordinary skill in the art would not have been motivated to modify Backes' Compound 96 based upon the teachings in Brooks. Applicant further argues Backes et al. also teaches other compounds species in the embodiment, such as compounds 47, 20, and 67 having a thiazole ring at the position corresponding to a pyrazine ring in Compound 96 that exhibit better IRE 1-alpha kinase inhibition than Compound 96; and therefore, there is no reason to compound 96 as a lead compound to modify. Applicant further argues changing the pyrazine ring in Compound 96 of Backes to the pyridazine ring of instant Compound I is not related to position isomerism; and the data from the present application cannot be used to support a reasonable expectation of success in modifying a compound of Backes to reach the presently claimed compounds. Applicant further argues Backes et al. fails to show how one would modify the synthesis of Compound 96 to arrive at the claimed invention, thus, one would not have a reasonable expectation of success to arrive at the claimed invention.
In response, applicant’s argument is not persuasive for the reasons sets forth below:
In response to applicant’s argument that there is no reason to select compound 96 of Backes et al. as the lead compound because the prior art also teaches other compound species having thiazole ring
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rather than pyrazine ring
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in the embodiments. Specifically, applicant directs attention to compounds of structural formula (Ia):
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described in Table 1, including compound 47 having the structure of:
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that has an IC50 value of 7.3 µM for inhibiting IRE1[Symbol font/0x61] kinase (see e.g., p. 83, Table 1, compound 47), which is better than the IC50 value of compound 96. It may well be true that some compound species of structural formula (Ia) have better IC50 value than compound 96; However, according to MPEP 2123, “[d]isclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). ‘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 re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994)… Furthermore, ‘[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….’ In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).”. In the present case, just because Backes et al. teaches more than one alternatives, including some compounds of structural formula (Ia) that are superior to compound 96 as the compound of structural formula (Ib), it does not mean compound 96 cannot be selected as the compound of structural formula (Ib). In fact, Backes et al. clearly teaches compound 96 can be chosen as the compound of structural formula (Ia) or (Ib) in the preferred embodiment (see claim 27); and that provides guidance to interchange compound of structural formula (Ia) with formula (Ib) even though it is not preferred. In other words, one of ordinary skill in the art would have reasonably expected that compound 96 as the compound of structural formula (Ib) would have successfully inhibit IRE1[Symbol font/0x61] kinase activities even though it is not the best performing IRE1 kinase inhibitor among all the compound species taught by Backes et al.
In addition, according to MPEP 2144.09, I, “[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)”. In the present case, the rejection is formed on the basis that the compound 96 of Backes et al. is a compound with close structural similarity and a position isomer. As noted in the rejection above, the only structural difference between the compound 96 of Backes et al. and the claimed compound 1 (see instant claim 42) is that the prior art compound contains a diazine with different nitrogen placement, specifically the prior art teaches pyrazine ring
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rather than pyridazine ring
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shown below (see shaded):
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. According to MPEP 2144.09, “[c]ompounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) …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). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) … Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979)”. Applicant’s assertion that pyrazine and pyridazine are not position isomers appears to be mere argument without supported by appropriate evidence, the pyrazine of the compound 96 of Backes et al. and the pyridazine of the claimed compound 1 are clearly position isomers that differs in the relative position of the two nitrogen atoms in the six-membered ring noted above. Therefore, one of ordinary skill in the art would have been motivated to make the position isomers of compound 96 of Beckes et al. with an expectation that said compounds with very close structural similarities would possess similar properties in inhibiting IRE1[Symbol font/0x61] kinase activities just like the compound 96 of Beckes et al. It is noted that the properties of inhibiting IRE1[Symbol font/0x61] kinase activities relies on the fact that Beckes et al. teaches the IC50 value of compound 96 for inhibiting IRE1[Symbol font/0x61] kinase activities rather than in light of the disclosure of the instant application. In other words, since compound 96 of Beckes et al. is capable of inhibiting IRE1[Symbol font/0x61] kinase activities, one would have reasonably expected that position isomers of compound 96 with close structural similarities would have similar properties of inhibiting IRE1[Symbol font/0x61] kinase activities, in the absence of unexpected results.
In response to applicant’ argument that there is no reasonable expectation of success to arrive at the claimed invention, because Backes et al. fails to show how one would modify the synthesis of Compound 96 to arrive at the claimed invention. It may well be true that Backes et al. does not provide explicit teachings to modify the method of synthesizing Compound 96; However, the examiner recognize that obviousness may be established by modifying the teachings of the prior art to produce the claimed invention where there is some teachings, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In the present case, what matter is whether a person of ordinary skill in the pertinent art would have found it obvious to modify the prior art compound to produce the claimed invention based on what's already known to the skilled artisan at the relevant time. A person of ordinary skill in the art, knowing the closely related structure, would have found it routine or obvious to arrive at the claimed compound. The lack of synthesis does not negate obviousness if the structural guidance is strong enough. It is noted that Backes et al. clearly teaches the examples described therein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims (see e.g., [0498]; and further teaches individual isomers are encompassed within the scope of the disclosure (see e.g., [0073]); and the term “isomers” refers to compounds having the same number and kind of atoms, and hence the same molecular weight, but differing in respect to the structural arrangement or configuration of the atoms (see e.g., [0074]). If Applicant asserts that a person of ordinary skill in the art do not have the knowledge of modifying the synthesis method without explicit teachings, then applicant is not in the possession of compound 7-9 because there are no working examples describing the method of synthesis these compound species in the specification. In addition, there is also no disclosure for the method of synthesizing other compound species of formula (I) or formula (II) besides compound 1-6.
Therefore, the rejection has been maintained for the same reasons on the record and for the reasons sets forth herein.
Free of the Art
To the extent that claim 42 is drawn to a compound having the structure of:
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, which is the elected compound species; said claim is free of the art rejection.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 Chihyi Lee whose telephone number is (571)270-0663. The examiner can normally be reached Monday - Friday 8:30 am - 5:00 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L. Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628