DETAILED ACTION
Status of Application
The response filed 08/21/2025 has been received, entered and carefully considered. The response affects the instant application accordingly:
Claims 11 have been amended.
Claim 13 has been added.
Applicant has previously elected the species genera of benzoxazole based compounds (W=X=Y=Z=carbon, Q=V= oxygen, and U=N) with the specific species compound election of
PNG
media_image1.png
268
378
media_image1.png
Greyscale
which was expanded to include
PNG
media_image2.png
200
400
media_image2.png
Greyscale
where R1 is an alkyl with at least 5 carbons, and R3 is a halogen and hydrogen.
Claims 1-13 are pending.
Claims 1-3, 5-9, 11-13 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 .
New grounds of rejection are set forth in the current office action as a result of amendment.
New and Standing 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 1-3, 5-9, 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Teuber et al. (U.S. Pat. Pub. 2004/0029937) as evidenced by Matschke et al. (Calcium-activated SK potassium channels are key modulators of the pacemaker frequency in locus coeruleus neurons).
Rejection:
Teuber et al. teaches a method of treating/alleviating a disease condition responsive to modulation of SKCa (calcium activated potassium channels) like cystic fibrosis in a living animal body including a human, with the administration of a compound of formula I. The modulating compounds of formula I may inhibit/block or activate the channels [29]. The compounds of formula I include
PNG
media_image3.png
200
400
media_image3.png
Greyscale
(X=O), and R1 includes alkyl which is defined to be from 1-12 carbons and more preferred C1-6 alkyl [33, 64] and R5 includes hydrogen, halogen, and -CN [35]. Teuber et al. also exemplifies and claims compounds like
PNG
media_image4.png
200
400
media_image4.png
Greyscale
(3-ethyl-5-chlorobenzoxazolone [133], R1=C2 and R5=chloride halogen), and that R5 can be absent (then R5 is hydrogen Example 1i). Teuber et al. teaches that the compounds can modulate SKCa (i.e. inhibit the calcium activated potassium channels) which as evidenced by Matschke et al. are SK1-SK4 (Page 331 first column 2nd paragraph (The SK channel family is composed of SK1 to SK4) and used to treat conditions like cystic fibrosis. Wherein it is implicit if not prima facie obvious to utilize the compounds taught to be utilized for the method of modulation/inhibition on any/all of the SKCa channels including SK4 as evidenced by Matschke et al. and taught by Teuber et al. to treat the taught conditions like cystic fibrosis ([7-8, 16-24, 29-39, 64, 122-125, 132], claims 1, 5 and 24-25).
While Teuber et al. does not expressly exemplify where R1 is at least 5 carbons, it does expressly defines the alkyl to be from 1-12 carbons including a more preferred C1-6 alkyl and exemplifies it with an alkyl (ethyl); wherein it would be prima facie obvious to exemplify the compound with the taught alkyl groups as defined such as C5 and C6 and C8 with a reasonable expectation of success absent evidence of criticality. It is also prima facie obvious to exemplify where R5 is hydrogen as R5 can be hydrogen, halogen, and -CN; and is exemplified without R5 substituent (R5 is then hydrogen) with a reasonable expectation of success absent evidence of criticality for the substituent. As the Teuber compounds defines the alkyl to be from 1-12 carbons and includes the alkyl to be from C5-C12 which falls within the claimed formula, the mechanism of activity of the compound (i.e. interacting with calmodulin PIP2 binding domain and inhibiting the SK4 channel) to treat these disease is responsive to modulation of SKCa naturally flows from the compound upon administration to the subject as the prior art teaches the method of treatment of diseases responsive to modulation of SKCa (calcium activated potassium channels) which includes SK4 like cystic fibrosis which is a condition of the instant specification, with the administration of compounds of formula I which includes
PNG
media_image3.png
200
400
media_image3.png
Greyscale
like
PNG
media_image4.png
200
400
media_image4.png
Greyscale
(exemplified/claimed) and
PNG
media_image5.png
332
401
media_image5.png
Greyscale
(alkyl is C5 within the instant claimed formula) and
PNG
media_image6.png
321
345
media_image6.png
Greyscale
(alkyl is C6 falling within the instant formula) and
PNG
media_image7.png
430
419
media_image7.png
Greyscale
(alkyl is C8 falling within the instant formula) where the same activity and mechanism of action is present as it naturally flows from the compounds are being administered for treatment of conditions like cystic fibrosis as taught by Teuber et al. which is a condition of SK4 as established by the instant specification; wherein the same activity and mechanism of action is present and the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render it patentably new to the discoverer. The claiming of a new use, new function or unknown property which is present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).
Response to Arguments:
Applicant's arguments are centered on the assertion that the inventors identified a previously untargeted region of SK4 channels, the calmodiulin-PEP2 binding domain, and have designed novel compounds that act as allosteric SK4 blocker by interfering with this domain, cites Tables 2-3 as evidence that compounds comprising an alkyl chain of at least 5 carbons in length and that compounds with a single or 2 alkyl are inactive, and the assertion that instant claim 1 requires that “one of R1 and R6 is an alkyl of at least 5 carbon atoms in length; and that when Q and U are each nitrogen, only one of R1 and R6 is the alkyl of at least 5 carbon atoms in length”, and that the documents -alone or in combination does not teach/suggests the invention as instantly claimed.
This is fully considered but not persuasive.
With regards to the assertion that inventors identified a previously untargeted region of SK4 channels, the calmodiulin-PEP2 binding domain, and have designed novel compounds that act as allosteric SK4 blocker by interfering with this domain; this is not persuasive as the prior art of Teuber teaches method of treating/alleviating a disease condition like cystic fibrosis where the disease condition is responsive to modulation of SKCa (calcium activated potassium channels) with the administration of a compound of formula I including
PNG
media_image3.png
200
400
media_image3.png
Greyscale
that may inhibit/block or activate the channels, where the alkyl for R1 is from 1-12 carbons which includes the alkyl to be from C5-C12 falling within the claimed formula.
The mechanism of activity of the compound (i.e. interacting with calmodulin PIP2 binding domain and inhibiting the SK4 channel) to treat the diseases responsive to modulation of SKCa like cystic fibrosis (a condition of the instant specification) - naturally flows from the compound upon administration to the subject. The prior art teaches the method of treatment of diseases responsive to modulation of SKCa (calcium activated potassium channels) which includes cystic fibrosis which is a SK4 condition as established by the instant specification, the administration of compounds of formula I which includes exemplified/claimed
PNG
media_image4.png
200
400
media_image4.png
Greyscale
and
PNG
media_image5.png
332
401
media_image5.png
Greyscale
(alkyl is C5 within the instant claimed formula) and
PNG
media_image6.png
321
345
media_image6.png
Greyscale
(alkyl is C6 falling within the instant formula) and
PNG
media_image7.png
430
419
media_image7.png
Greyscale
(alkyl is C8 falling within the instant formula) wherein the same activity and mechanism of action is present as it naturally flows from the compounds are being administered for treatment of conditions like cystic fibrosis as taught by Teuber et al. which is a condition of SK4 as established by the instant specification; wherein the same activity and mechanism of action is present and the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342,1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is intrinsically present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). An intrinsic feature need not be recognized at the time of the invention. There is no requirement that a person of ordinary skill in the art would have recognized the disclosure at the time of invention, but only that the subject matter is in fact present in the prior art reference. As if the compounds are physically the same it must have the same properties “products of identical chemical composition cannot have mutually exclusive properties” In re Spada, 911 F.2D 705, 709, 15 USPQ2D 1655, 1658 (FED. Cir 1990). The Examiner’s finding on the principle that product of identical chemical composition cannot have mutually exclusive properties which is a well settled principle in patent law. Therefore where the claimed and prior art compounds and their utility are identical or substantially identical, the USPTO can require an applicant to prove that the prior art product do not necessarily possess the characteristic of the claims for targeting SK4 channels and the calmodiulin-PEP2 binding domain to act as allosteric SK4 blocker by interfering with this domain.
As for the assertion Tables 2-3 are evidence that compounds comprising an alkyl chain of at least 5 carbons in length and that compounds with a single or 2 alkyl are inactive; this is fully considered but not persuasive. The compounds of Tables 2-3 are not commensurate in scope with what Applicant elected or what is claimed as Applicant’s election/expansion is for
PNG
media_image2.png
200
400
media_image2.png
Greyscale
and there is no compound that is present as a comparative in Tables 2-3 within the elected genus to demonstrate that the prior art compounds do not possess the SK4 or evidence of criticality for the specific formula being examined over the prior art. It is noted that contrary to Applicant’s arguments, compounds BA44, BA46, BA54 which are embraced by the instant claim 1 are inactive; and compounds BA43, BA45, BA53 which are embraced by the instant claims do not have any reported activity. As for the assertion that instant claim 1 requires that “one of R1 and R6 is an alkyl of at least 5 carbon atoms in length; and that when Q and U are each nitrogen, only one of R1 and R6 is the alkyl of at least 5 carbon atoms in length”, is not persuasive as instant claim 1 does not contain that provision. As for the assertion that the prior art of Teuber et al. -alone or in combination does not teach/suggests the invention as instantly claimed this is not persuasive as addressed by the prior art rejection above as Teuber et al. teaches the compounds to be useful for treating a disease condition is responsive to modulation of SKCa (calcium activated potassium channels) like cystic fibrosis with the administration of a compound of formula I including
PNG
media_image3.png
200
400
media_image3.png
Greyscale
that may inhibit/block or activate the channels, and Matschke et al. is presented merely as evidence that calcium activated potassium channels are SK1-SK4.
Accordingly, the rejection stands.
Conclusion
Claims 1-3, 5-9, 11-13 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.
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, Brian Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/GIGI G HUANG/Primary Examiner, Art Unit 1613