DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 4/27/2026 has been entered.
Claims 1-5, 7, 9, 13, 15-18, 21, 22, 29, 30, 34-37 and 41 are pending. Claims 1-5, 7, 9 and 13, drawn to a method of stapling oner or more amino acid sequences by reacting a compound of Formula I with a compound of Formula II are under examination. Claims 15-18, 21, 22, 29, 30 and 34-37 are withdrawn from examination.
This application claims priority as a 371 filing of PCT/US2021/017839 which claims priority to U.S. Provisional Application No. 62/976,599, filed February 14, 2020.
Response to Amendments
Applicants have amended the claims to overcome the rejection under 35 USC 112, second.
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 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.
Claims 1-5, 7, 9 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Pentelute et al (US 20140113871) in view of Kobayshi et al (JACS, 2016, pages 14832-14835). This rejection is maintained for reasons below.
Stapling is a strategy used to Pentelute et al teach use of thiols and fluorinated compounds in stapling strategies.
Instant claim 1 recites that the method uses Formula I
PNG
media_image1.png
134
334
media_image1.png
Greyscale
PNG
media_image2.png
116
212
media_image2.png
Greyscale
combined with Formula II to staple one or more amino acids wherein the reaction solution is at pH 8.5 or lower. As to Formula II, the claims require,
PNG
media_image3.png
124
682
media_image3.png
Greyscale
PNG
media_image4.png
26
534
media_image4.png
Greyscale
Looking to Pentelute et al, the format of SH-linker-SH meets Formula 1 WHEN p, q and r are zero. The linker of Pentelute therefore does not comprise a halo-aryl substituted group.
This same structure is seen in claim 3 as formula (IV).
PNG
media_image5.png
326
294
media_image5.png
Greyscale
PNG
media_image6.png
90
140
media_image6.png
Greyscale
Pentelute teaches as shown to the right that the structure with Formula II reacts with a fluorinated form of a peptide sequence (as recited in instant claims 4 and 5) (see 1B. approach 1).
Pentelute does not teach Formula I. However, Kobayshi provides an improved chemical reactivity group between a fluoridated compound and a thiol group by providing a reactive compound called FAcK.
We demonstrated that fluoroacetamide installed on FAcK, previously thought inert to biological functional groups, actually reacted with the thiol group of cysteine when in proximity
PNG
media_image7.png
126
77
media_image7.png
Greyscale
FAcK meets the limitation of Formula 1 and III (as recited in instant claim 2) wherein F- X2, X1= NR1 and ( )n, n=4. FAcK was incorporated into proteins such as an Affibody protein (see page 14833, col 1) and reacted with a thiol group.
Our results showed that when in close proximity, a condition often encountered when small molecules bind with large biomolecules, fluoroacetamide reacted with the Cys thiol group readily under mild physiological conditions.
This reaction is performed at a pH of 7.4 as recited in claim 1 and 9 (see page 14834, col 1).
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made to use the FAcK reactive group in place of the fluoroaryl of Pentelute. Such a modification would have resulted in a composition encompassed by claims 1-5, 7, 9 and 13. As noted above: 1) Pentelute teaches reaction of a thiol group matching Formula II in order to staple amino acid sequences; 2) Kobayshi teaches improved treatment for reacting thiol groups where the molecule reactivity is readily occurring under mild conditions. both Pentelute and Kobayshi are directed to covalent linkage between fluorinated compounds and Thiol (see abstract for Pentelute). Kobayshi teaches “we demonstrated that the “biologically inert” fluoroacetamide actually reacted with cysteine side chain selectively.” (page 14832, col 2). This is a feature that improves the reaction. Hence, one would substitute the FAcK in the scheme of Pentelute. The FAcK was incorporated (page 14833, col 2) into proteins (i.e. amino acid sequences) for linkage to a thiol group (SH). This reaction led to a bridge (staple) when tested in the same protein (see page 14835, col 1).
Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the use of FAcK would be a substitution of one known element used in similar reactions for another.
Response to Arguments
Applicants have argued that the action failed to address the limitations in the dependent claims or explain how the references relate. In order to make the teachings as they relate to the dependent claims clearer, each of the previously noted teachings are noted with the claim limitation to which they relate.
Secondly, applicants note that they have amended the claims to advance the prosecution. However, this amendment as set forth above has not been sufficient to overcome the art. This is expounded above in the claim rejection.
Conclusion
Claim 41 appears free of the art but is objected to as dependent on a rejected claim.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached 8 am - 5 pm.
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, Maria Leavitt can be reached at 571-272-1085. 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.
/MARIA MARVICH/Primary Examiner, Art Unit 1634
Prosecution Insights