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 .
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.
Current Status of 18/333,872
This Office Action is responsive to the amended claims received 28 August 2026.
Claims 1 and 7-15 are currently pending.
Priority
Applicant’s claim for the benefit of the prior-filed patent applications 63/366,377 (filed 14 June 2022) under 35 U.S.C. 119(e), 120, 121, 365(c), or 386(c) is acknowledged.
Response to Amendments
The 35 U.S.C. 103 rejections to the claims, present in the previous office action, are maintained herein, although they have been amended as necessitated by Applicant’s amendments.
Response to Arguments and Declaration
The Examiner acknowledges the receipt of a second declaration from SIAW SHI BOON on 28 August 2026, being one of the inventors of the instant application.
The declaration argues that HPV-associated cancers are different from non-HPV-associated cancers. The declaration argues that chemotherapy is broadly cytotoxic, whereas the claimed treatment specifically attacks E7 oncoprotein which was a “previously unaddressed vulnerability” and is a “novel therapeutic approach”. The declaration argues that blocking deubiquitination of E6/E7 is not a predictable evolution of previous therapies. The declaration argues that using the instantly claimed compound allows for the additional targeting of Aurora kinase A. The declaration that the claimed compound is novel alone and novel in combination with other therapeutics. The declaration again argues at length that HPV-associated cancers are different from non-HPV-associated cancers. The declaration discusses shortcomings of clinical trials focusing on oropharyngeal squamous cell carcinoma. The declaration argues that treatment strategies for cancers of the colon, rectum, and anus are completely different.
The declaration acknowledges that DONATO teaches inhibition of a deubiquitinase for the treatment of EBV-induced nasopharyngeal carcinoma or colon cancer. The declaration argues that, while REVERDY teaches using HBX19818 (an inhibitor of deubiquitinase USP7) for the treatment of cancers, it does not specify that the cancers are virally-induced cancers. The declaration again argues that HPV-associated cancers are different from non-HPV-associated cancers. The declaration argues that, even though the nasopharynx and oropharynx are “proximal”, cancers arising at these sites are different. The declaration then argues that the Examiner’s cited references in combination do not teach the instant claims and an artisan would not have had a reasonable expectation of success. The arguments submitted along with the declaration repeat the arguments within the declaration.
DONATO taught the inhibition of USP7 before the instant filing date. If that process also inhibits HPV E7, it would have been practiced by one of ordinary skill in the art performing the method taught by DONATO. DONATO teaches the treatment of colon cancer (claim 18) that may have been caused by a virus (claim 17; paragraph [0062]), specifically papillomavirus (claims 27 and 29; paragraph [0063]). It is not clear why the declaration repeatedly admits that DONATO teaches the treatment of EBV-induced cancers, but entirely ignores the fact that DONATO teaches the treatment of papillomavirus-induced cancer. The Examiner is not disagreeing that cancers in different locations within the body are different and may require different therapies. The Examiner is arguing that it would have been obvious for one of ordinary skill in the art to have read “a method of treating colon cancer” and immediately envisaged the treatment of rectal cancer. The anatomical location of the colon includes the rectum. The new declaration does not appear to address this. REVERDY is not relied upon within the rejections to provide teachings related to papillomavirus, but REVERDY is relied upon to provide the effective USP7 inhibitor HBX 19818.
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.
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 and 7-15 are rejected under 35 U.S.C. 103 as being unpatentable over:
DONATO (WO 2012/040527 A2; International Publication Date 29 March 2012)
in view of:
REVERDY (Reverdy, C.; Conrath, S.; Lopez, R.; et al. “Discovery of Specific Inhibitors of Human USP7/HAUSP Deubiquitinating Enzyme” Chemistry & Biology 19, 467–477, April 20, 2012).
DONATO teaches a method of treating a condition that is due to a pathogenic infection, through the use of a deubiquitinase inhibitor (claims 21 and 23). DONATO then specifies that the condition is a virus-induced cancer (claim 24). DONATO also specifies that the virus is a papillomavirus (claim 27). Claims 38 and 39 of DONATO specify that the cells being treated are human cells. One of ordinary skill in the art would read the teachings of DONATO, which specify a papillomavirus infection within a human cell, and would understand that the papillomavirus must be a human papillomavirus.
DONATO teaches the identification of a human having a condition due to a pathogenic infection and administering an effective amount of a compound thereto (paragraph [0054]). DONATO teaches specific types of cancers contemplated therein in paragraph [0068]. The cancers specified by DONATO therein include melanoma, nasopharyngeal carcinoma, and colon cancer (paragraph [68] and claim 18). DONATO teaches USP7 as a specific deubiquitinase that may be inhibited (paragraphs [0009] and [0011]). DONATO teaches the inhibition of proliferation in a cancer cell using a deubiquitinase inhibitor therein (claims 15, 16, and 19). DONATO teaches compound WP1130 as a deubiquitinase inhibitor therein (paragraphs [00123]-[00124] and [00147]), which was administered in the form of a 5 μM solution to cells (paragraph [00147]). One of ordinary skill in the art would understand that, when DONATO teaches a 5 μM solution of WP1130, this indicates an aqueous solution of the compound.
DONATO does not specifically teach the treatment of cancer of the rectum, but does teach treatment of cancer of the colon (paragraph [68] and claim 18). The anatomical location of the colon includes the rectum, and one of ordinary skill in the art would have read the teachings of DONATO and immediately envisaged the treatment of cancer of the rectum.
DONATO does not specifically teach compound HBX 19818.
REVERDY teaches that USP7, a deubiquitinating enzyme, is an attractive viral and oncology target (1st paragraph of discussion section). REVERDY teaches that they identified a selective inhibitor of USP7, referred to as HBX 19,818 (2nd paragraph of discussion section). REVERDY goes on to teach the benefits of HBX 19,818, such as the absence of off-target activity and the ability to replicate the effects of USP7 silencing (3rd paragraph of discussion section).
It would have been obvious, before the effective filing date of the instant application, to replace the deubiquitinase inhibitor present in the method of treating a cancer caused by papillomavirus through inhibition of USP7, taught by DONATO, with the selective USP7 deubiquitinase inhibitor taught by REVERDY, HBX 19,818, for the purpose of improving the efficacy of the cancer treatment method. One of ordinary skill in the art would have expected success in this replacement, because DONATO teaches that the inhibition of USP7 is useful for the methods taught therein, and REVERDY provides an optimized inhibitor for USP7.
Regarding claims 1 and 7-8: The outcomes within instant claims 1 and 7-8 are solely the result of administering the inhibitor therein to a human patient having a papillomavirus infection. There are no positive steps recited therein that would alter these outcomes unrelated to administering the inhibitor of instant claim 1 to a human patient having a papillomavirus infection. Because the method of administering the inhibitor of instant claim 1 to a patient having a papillomavirus infection has been found to be rendered obvious, these direct outcomes are also rendered obvious.
Regarding claims 9-11: DONATO teaches the use of siRNA as an effective strategy to knockdown USP deubiquitinase enzymes, such as USP9x and USP5 in paragraphs [00132], [00133], [00151], and [00152].
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to combine both the siRNA and small-molecule-based downregulation approaches, both taught by DONATO, for the purpose of achieving a greater downregulation of whichever USP enzyme was currently being targeted for downregulation, such as USP9x, USP5, or USP7. The artisan would have expected success in this combination, because the small-molecule-based approach and the siRNA approach are each separately known to downregulate the same target enzyme.
Regarding claim 12: Downregulation of USP7 will reasonably result in a decrease in the concentration of HPV E7, because less USP7 will be available to act as a deubiquitinase enzyme for the HPV E7 protein. DONATO renders obvious the downregulation of USP7, and in turn renders obvious the downregulation of HPV E7, being a reasonable consequence of the first action.
Additionally, the outcome within instant claim 12 is solely the result of administering the inhibitor and siRNA therein to a human patient having a papillomavirus infection. There are no positive steps recited therein that would alter the outcome unrelated to administering the inhibitor and siRNA of instant claims 1 and 11 to a human patient having a papillomavirus infection. Therefore, because the method of administering the inhibitor and siRNA of instant claims 1 and 11 to a patient having a papillomavirus infection has been found to be obvious, this direct outcome is also rendered obvious.
Conclusion
No claims are currently allowable.
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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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