DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment of 1/9/26 has been entered in full. Claims 1, 6, 10 and 12-13 are amended. Claims 2-3, 5, 7, 19-20, 22 and 39-40 are cancelled.
Clams 1, 6, 8 and 10-17 are pending.
Applicants' election without traverse of Invention I, currently all pending claims, was previously acknowledged. Applicants’ elections of the following species were also previously acknowledged: (1) immune checkpoint inhibitor as the species of cancer immunotherapy agent; (2) chemical entity that blocks PD-1 as the species of immune checkpoint inhibitor; (3) pembrolizumab as the species of anti-PD-1 antibody; and (4) breast cancer as the species of cancer. Claims 10-14 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1, 6, 8 and 15-17 are under consideration, as they read upon the elected species.
Withdrawn Objections and/or Rejections
The following page numbers refer to the previous Office Action (10/27/25).
The objection to the specification at pages 2-3 is withdrawn in view of the amendments to the specification.
All rejections of canceled claims 2-3, 5 and 7 are moot.
The rejection of claims 1, 6, 8 and 15-17 at pages 3-7 under 35 U.S.C. 112(a) for failing to comply with the written description requirement is withdrawn in view of the amendments to the claims that limit the scope of the claim with respect to the administered to that which is indicated is the rejection of record as meeting the written description requirement.
Maintained Objections and/or Rejections
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 6 and 15-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shen et al, 2021, Cell. 184: pages 352-369 and e1-10; published on-line 12/23/20 (see page 366) (cited on the 4/10/23 IDS). The earliest date to which the instant application claims priority is 1/20/22. This rejection was set forth previously at pages 7-8 of the 10/27/25 Office action.
The rejection of record is first restated in view of Applicants’ amendments to the claims, and then Applicants’ arguments against the rejection are addressed.
Independent claim 1 has been amended to narrow each of the administered components; specifically, the inhibitor of FBXO44 has been limited to a nucleic acid, and the cancer immunotherapy agent has been narrowed to an antibody that binds to one of four targets, including the elected species of PD-1.
Shen teaches “FBXO44 inhibitors” as “enhancers of immunotherapy response” in “cancer treatment” (page 366), and that FBXO44 “targeting sensitized normally refractory cancer cells to anti-PD-1 therapy” (page 366). Shen further teaches treatment of cancer in an animal model by administering two components: “FBXO44 KD [knockdown]” and “anti-PD-1” (page 362). Shen further teaches that the results of this are shown in Figure 6F, which describes this as “shFBXO44 + anti-PD-1”. shRNA is small hairpin RNA, which is a nucleic acid, and anti-PD-1 is an antibody. Thus, Shen teaches a method of claim 1, as amended, encompassing treating cancer in an individual in need thereof, comprising administering to the individual two components: (1) a nucleic acid inhibitor of F-box protein FBXO44 (i.e., shFBXO44) and (2) a cancer immunotherapy agent that is an anti-PD-1 antibody.
Claim 6 depends from claim 1 and is directed to the anti-PD-1 antibody alternative of claim 1. As such, claim 6 is anticipated by Shen for the same reasons as parent claim 1.
Claim 15 encompasses a method of claim 1 wherein the cancer is breast cancer. The studies of Shen utilize “4T1 breast cancer cells” (page 362), and Shen further teaches that “FBXO44 was expressed at low levels in normal breast tissues and increased with tumor stage” and “High FBXO44 expression correlated with poor patient outcome in several major cancer types” in Figure 7C, including breast cancer, indicating that the teachings of Shen are directed to treatment of breast cancer. As such, the teachings of Shen also anticipate claim 15.
Claims 16 and 17 encompass a method of claim 1 wherein the cancer is treatment resistant (claim 16) and wherein the individual was previously treated with another cancer immunotherapy agent. As described above, Shen teaches that FBXO44 targeting “sensitized normally refractory cancer cells to anti-PD-1 therapy” (page 366). Shen further teaches that FBXO44 inhibition as converting “‘‘cold’’ tumors, which are poorly immunogenic and non-responsive to immunotherapy, to ‘‘hot’’” (page 366). As such, Shen teaches treatment of cancer that resistant and non-responsive to anti-PD-1 therapy alone, which is encompassed by “another cancer immunotherapy agent”. As such, the teachings of Shen also anticipate claims 16 and 17.
Applicants’ arguments (1/9/26; pages 7-9) as they pertain to the rejection have been fully considered but are not deemed to be persuasive for the following reasons.
In the response, Applicants first describe the amendments to the claims and argue that Shen “doesn’t disclose at least these features of claim 1 as currently amended” (page 7). Applicants quote a sentence from page 366 of Shen about FBXO44 inhibitors converting “cold” tumors to “hot” tumors.
This argument has been fully considered but is not found persuasive. The rejection has been restated above in view of Applicants’ amendments, and explains how the teachings of Shen meet the limitations of the claims as amended. It is not clear how the quotation from page 366 supports the argument because it is directed to how the FBXO44 inhibitors function in treatment, rather than pointing out a limitation of the claims that is not taught by Shen.
Applicants next argue that the examples in Shen “are primarily directed to an inhibitor of SUV39H1 and not a nucleic acid inhibitor of F-Box protein FBXO44” (page 7). Applicants point to several teachings of Shen directed to the chemical inhibitor of SUV39H1 known as F5446, which is “not a nucleic acid inhibitor of F-Box protein FBXO44” (page 8).
This argument has been fully considered but is not found persuasive. While it is acknowledged that Shen contains teachings directed to use of an inhibitor of SUV39H1, Shen also provides teachings directed to use of a nucleic acid inhibitor of FBXO44 in combination with an anti-PD-1 antibody, as described above in the rejection. The teachings directed to inhibition of SUV39H1 do not take away from the other teachings directed to inhibition of FBXO44. Per MPEP 2123, “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments” and “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments”.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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.
Claim 8 is rejected under 35 U.S.C. 103(a) as being unpatentable over Shen et al, 2021, Cell. 184: pages 352-369 and e1-10; published on-line 12/23/20 (see page 366) (cited on the 4/10/23 IDS), as applied to parent claims 1-3, 5 and 6, and further in view of Li et al, 2021 (Oncology Reports. 45: 5-12; published on-line 11/3/20; cited previously). This rejection was set forth previously at page 9 of the 10/27/25 Office action.
The rejection of record is first restated in view of Applicants’ amendments to the claims, and then Applicants’ arguments against the rejection are addressed.
Claim 8 encompasses a method of claim 6 wherein the anti-PD-1 antibody is Pembrolizumab.
The teachings of Shen that anticipate parent claims 1 and 6 are set forth above. Shen does not further teach at the anti-PD-1 antibody is Pembrolizumab.
Li teaches that Pembrolizumab is a monoclonal antibody that targets PD-1 (page 6) and that has been used in a number of clinical trials (Table I).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method of treating a cancer with a nucleic acid inhibitor of FBXO44 and a cancer immunotherapy agent that is an anti-PD-1 antibody as taught by Shen, and modify it to use Pembrolizumab as the anti-PD-1 antibody as taught by Li. The person of ordinary skill in the art would have been motivated to make such a change because Shen teaches anti-PD-1 antibodies in general, but does not specify a particular anti-PD-1 antibody, and Li provides this information. The person of ordinary skill in the art would have had a reasonable expectation of success because such a modification represents a simple and predictable substitution use of a known species where use of a known genus is taught. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Applicants’ arguments (1/9/26; page 9) as they pertain to the rejection have been fully considered but are not deemed to be persuasive for the following reasons.
In the response, Applicants argue that “Li fails to remedy the deficiencies of Shen discussed above with respect to the novelty rejection”, and therefore “a prima facie case of obviousness of claim 8 over Shen in view of Li has not been properly established” (page 9).
This argument has been fully considered but is not found persuasive, because the novelty rejection over Shen is not deficient for the reasons set forth above. As such, the obviousness of claim 8 over the teachings of Shen in view of Li has been properly established and maintained for the reasons set forth herein.
New Claim Objections
Claims 1, 6, 8 and 15-17 are objected to because of the following informalities:
In claim 1, line 4, there is a comma missing between “B7-1” and “B7-2”.
The remaining claim(s) are objected to for depending from an objected claim.
Appropriate correction is required.
Note on Withdrawn Claims
In withdrawn claim 12, it is noted that as amended, the claim limits the cancer immunotherapy agent of claim 1 to a “chemical entity that blocks CTLA-4”, but this is broader in scope than parent claim 1 with respect to CTLA-4 inhibitors, which in the alternative limits the agent to an antibody that binds to CTLA-4.
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 extension fee 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 ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674